Latest Development

ACT-Accelerator Facilitation Council co-chairs welcome financial and policy commitments made at the Second Global COVID-19 Summit

23 May 2022

Statement

Geneva, Switzerland

The Second Global COVID-19 Summit showed that the world could come together around a global public good – ending the COVID-19 pandemic, and establishing a solidarity-based system to prevent, prepare for and respond to future health emergencies.

The display of unity by the Summit co-hosts – Belize, Germany, Indonesia, Senegal, and the United States, representing CARICOM, the G7, the G20 and the African Union - and the concrete commitments made by governments, the private sector and civil society, is further evidence of a reignited common purpose.

As Co-Chairs of the council of the ACT-Accelerator, a multi-partner group aimed at developing and facilitating equitable access to COVID-19 tools, we welcome this strong evidence of our shared determination to bring the pandemic to an end and prepare better to prevent and respond to the next health emergency.

The number of COVID-19 cases is now increasing globally, indicating that the pandemic is far from over, particularly for high-risk groups in lower-income countries. The reduction in testing rates makes it harder to track the trajectory of the virus, making it more likely that new variants will go undetected.

At the Summit, global leaders pushed back against complacency and committed to investing in the rollout out of vaccines, strengthening health systems, and facilitating access to treatments and tests.

New commitments of around US$ 1 billion were made to ACT-A’s constituent agencies, including a generous fair share pledge from Canada, and contributions from Italy, Belgium, France, the European Commission, New Zealand, the UAE, Denmark and Colombia.

These are in addition to pledges made at the recent AMC Summit, Germany’s commitment to meet its fair share in March and Norway’s early contribution to kick off the second budget cycle. All these contributions will prove crucial in driving the partnership’s work to ensure equitable access to COVID-19 tools.

Building momentum for expanding access to oral antivirals, the Clinton Health Access Initiative (CHAI) announced at the Summit a lower price for the treatment nirmatrelvir/ ritonavir - known under the brand name Paxlovid - with CHAI committing to work with ACT-Accelerator agencies to accelerate delivery.

The G7 Summit at the end of June provides the final major opportunity to meet the remaining financing needs of the ACT-Accelerator. The projected funding gap is now US$ 12.1 billion – with US$ 7.5 billion especially urgent. A failure to fund the partnership’s remaining needs will see vulnerable people go unvaccinated, untested, untreated, and unprotected.

Fully funding the ACT-Accelerator will support its life-saving work to expand access to life-saving tools, from new oral antivirals to booster vaccine doses, to ensure the most at-risk are protected wherever they live in the world. No-one is safe until everyone is safe.

COVAX calls for urgent action to close vaccine equity gap

20 May 2022

Statement

Geneva/New York/Oslo

COVAX has access to enough COVID-19 vaccines to help protect 70% of the population in 91 lower income countries.

Demand and uptake are low, with low-income countries remaining furthest behind.

To close the global vaccine equity gap, COVAX calls on countries to set ambitious targets for implementation and on all partners to ensure countries have the resources needed to accelerate and expand national strategies.

Nearly 18 months after the first administration of a COVID-19 vaccine, incredible progress has been made – with lower-income countries administering billions of COVID-19 vaccines in a historic global rollout that is unprecedented in terms of speed, scale and demographics reached. Yet despite this progress, and the easing of global supply constraints, inequities between lower and higher income countries are continuing to cost lives and are prolonging the pandemic by increasing the threat posed by the emergence of new, potentially more dangerous variants of the virus.

Only 16% of people in low-income countries have received a single vaccine dose – compared to 80% in high-income countries. In certain lower-income countries, many of the most at-risk people in society – healthcare workers, the elderly and those with underlying health conditions – are going unprotected while young, healthy adults receive booster doses in wealthier countries.

The world must act urgently to close this equity gap.

After a year of severe constraints, we are now in a situation that two years ago would have seemed impossible: namely global supply is now high enough to underpin the overarching objective of supporting equitable, full vaccination of all adult and adolescent populations globally. COVAX has access to more than enough doses needed to enable 91 lower-income countries that are supported by the COVAX Advance Market Commitment (AMC) – which provides donor-funded doses of a wide variety of COVID-19 vaccines – to meet their targets in light of the WHO global target of protecting 70% of the population in each country. We can support these countries to meet individual targets and prioritize full coverage of high-risk groups. In accordance with the updated SAGE roadmap of January 2022 – which recommends boosters for priority groups – COVAX is now open to and encouraging requests for doses for booster campaigns from countries.

COVAX is also well-placed to deliver these doses so they reach those in need. In just 15 months, COVAX – as the Vaccines Pillar of the ACT-Accelerator partnership for equitable access to COVID-19 tools – has shipped over 1.3 billion vaccines to 87 low and lower-middle income countries around the world. COVAX shipments account for 82% of vaccines delivered to low-income countries and the majority of COVID-19 vaccines administered in humanitarian settings. Through driving the fastest, largest and most complex global vaccination effort in history, COVAX’s work has helped raise the average proportion of people protected by a full course of vaccines in these low- and lower-middle income countries to 46%.

The onus now is on building on this foundation to help countries to fully protect high risk groups, meet national vaccination targets, and close the global COVID-19 vaccine equity gap for good. However, hurdles now remain: demand and uptake are low, with low-income countries remaining the furthest behind.

Demand and delivery

With more than 3.8 billion COVID-19 doses administered to-date, national governments in lower-income countries have led the way. The number of countries with coverage under 10% of the population has decreased from 34 in January to 18 today. Some AMC-supported countries – for example, Bhutan, Cambodia, Viet Nam, Maldives, Fiji and Bangladesh – have coverage above 70%.

Building on country readiness efforts undertaken so far, the countries furthest behind are receiving tailored support. In January 2022, WHO, UNICEF and Gavi established the COVID-19 Vaccine Delivery Partnership (CoVDP), an inter-agency initiative building on existing resources globally, regionally and in-country to support COVID-19 vaccine delivery in lower-income countries. CoVDP specifically provides urgent operational support to the 34 countries that were at or below 10% full vaccination coverage in January 2022, many of which are in Africa. By mid-April 2022, a total of US$29 million of urgent funding was coordinated and disbursed - within 15 working days or less - to ten countries across the three agencies. The CoVDP has driven political engagement with several countries with low vaccination rates to keep vaccine delivery on top of the political agenda and identify opportunities for bundling COVID-19 vaccinations with other health interventions.

While CoVDP and other efforts are helping lower-income countries make progress, challenges still need to be addressed. In many countries Omicron has reduced the perceived risk of the virus and there are other health priorities that people and governments are focused on. The option of integrating COVID-19 vaccination with other health systems activities – for example, measles and polio campaigns, or the distribution of malaria bed nets, – therefore becomes more important. COVID-19 vaccination is also an opportunity to strengthen health systems including training health workers, enhancing health management information systems, further improving the cold chain, and forging new ways of working in fragile and conflict settings.

Through our continuous dialogue with AMC-supported countries, we know that demand is highly dynamic and difficult to predict, even for countries themselves. Thanks to input from national governments, COVAX is able to make some initial estimates of overall demand from AMC-supported countries. From our analysis of the latest demand planning forecasts provided to us by these countries, estimated country demand from now through early 2023 currently stands at approximately 330 million doses from COVAX, in addition to what has already been delivered or accepted by countries. However, these continue to be dynamic figures, and will evolve with situations on the ground as well as the occurrence of new variants. As such, COVAX will be working with national governments to continuously update these estimates.

In order for the world to continue to make meaningful progress on closing the global vaccine equity gap, we urgently call on countries to set ambitious targets backed by concrete plans for implementation – prioritising full coverage of high risk groups – and on all partners to coordinate on providing countries with the resources needed to accelerate and expand national strategies, stimulate demand and overcome operational bottlenecks. The next 3-4 months are crucial for accelerating COVID-19 vaccination campaigns, alongside moving to integrate COVID-19 vaccination efforts into routine primary health systems.

Supply

It is testament to the ground-breaking work of the scientific and manufacturing communities that there is now enough global supply to meet needs, as is the fact that it took only 327 days to go from the SARS-CoV-2 virus being sequenced and published to bringing a COVID-19 vaccine into emergency use.

As we strive to help countries deploy more doses, we must also work ensure supply remains available, at the right times. COVAX experienced delays securing doses in 2021. With many doses from advance purchase agreements now becoming available alongside donated doses, and the dynamic nature of country demand coupled with global oversupply, it is highly likely that overall supply will exceed demand. However, COVAX is working with manufacturers to help make supply more responsive to the changing demand environment.

That both global and COVAX supply now exceed demand is an advantageous situation in a pandemic, as it guarantees all countries long term availability of supply and choice of product. Protecting populations rapidly must now take priority. This is fundamental, given that 2021 clearly demonstrated the impact ad hoc, unpredictable supply had on the ability for countries with more limited health systems resources to plan and roll-out vaccination campaigns. Certainty of supply enables countries to plan national vaccination campaigns with more confidence, ensures a rolling buffer of stock can be available in-country and aids smooth and efficient roll outs.

While every effort should be taken to minimize wastage and expiry, lower income countries should also be able to accept doses, and to aim high, without being stigmatized when there is wastage, which is an inevitable part of immunization efforts against any disease, in any country.

COVAX is committed to providing countries with long-term, predictable supply, catering to all contexts and maintaining reserves to ensure supply can keep up with shifts in demand. This includes working with manufacturers and donors to ensure any new, variant-adapted vaccines reach COVAX at the same time as higher income countries.

We call on donor countries and manufacturers to support COVAX by ensuring the volume and timing of deliveries match as closely as possible the needs of lower-income countries. Donors should support COVAX in maintaining a diverse portfolio, including variant-adapted vaccines if necessary. Manufacturers should work with COVAX to re-phase or re-size supply from existing advance purchase agreements.

A world beset by numerous challenges and crises does not change the fact that the pandemic – our collective crisis – is far from over. Closing the vaccine equity gap must continue to be an urgent priority for the international community.

NOTES TO EDITORS

About COVAX

COVAX, the vaccines pillar of the Access to COVID-19 Tools (ACT) Accelerator, is co-led by CEPI, Gavi, WHO and UNICEF – working in partnership with developed and developing country vaccine manufacturers, PAHO, the World Bank, and others. It is the only global initiative that is working with governments and manufacturers to ensure equitable access to COVID-19 vaccines.

CEPI’s role in COVAX

CEPI is leading on the COVAX vaccine research and development portfolio, investing in R&D across a variety of promising candidate to support the development of safe and effective vaccines which can be made available to countries participating in the COVAX Facility. As part of this work, CEPI has secured first right of refusal for the COVAX Facility to access doses of multiple vaccines, and made strategic investments in vaccine manufacturing, which includes reserving capacity to manufacture doses of COVAX vaccines at a network of facilities. CEPI is also investing in ‘next generation’ and ‘variant-proof’ vaccine candidates, which will give the world additional options to control COVID-19 in the future.

Gavi’s role in COVAX

Gavi leads on procurement and delivery at scale for COVAX: designing and managing the COVAX Facility and the Gavi COVAX AMC and working with its traditional Alliance partners UNICEF and WHO, along with governments, on country readiness and delivery.

As part of this role, Gavi hosts the Office of the COVAX Facility to coordinate the operation and governance of the mechanism as a whole, holds financial and legal relationships with 193 Facility participants, and manages the COVAX Facility deals portfolio: negotiating advance purchase agreements with manufacturers of promising vaccine candidates to secure doses on behalf of all COVAX Facility participants.

Gavi also coordinates design, operationalisation and fundraising for the Gavi COVAX AMC, the mechanism that provides access to donor-funded doses of vaccine to 92 lower-income economies. As part of this work, Gavi provides funding and oversight for UNICEF procurement and delivery of vaccines to all AMC participants – operationalising the advance purchase agreements between Gavi and manufacturers – as well as support for partners’ and governments work on readiness and delivery. This includes tailored support to governments, UNICEF, WHO and other partners for cold chain equipment, technical assistance, syringes, vehicles, and other aspects of the vastly complex logistical operation for delivery. Gavi also co-designed, raises funds for and supports the operationalisation of the AMC’s no fault compensation mechanism as well as the COVAX Humanitarian Buffer.

WHO’s role in COVAX

WHO has multiple roles within COVAX: It provides normative guidance on vaccine policy, regulation, safety, R&D, allocation, and country readiness and delivery. Its Strategic Advisory Group of Experts (SAGE) on Immunization develops evidence-based immunization policy recommendations. Its Emergency Use Listing (EUL) / prequalification programmes ensure harmonized review and authorization across member states. It provides global coordination and member state support on vaccine safety monitoring. It developed the target product profiles for COVID-19 vaccines and provides R&D technical coordination. WHO leads, together with UNICEF, the Country Readiness and Delivery workstream, which provides support to countries as they prepare to receive and administer vaccines. Along with Gavi and numerous other partners working at the global, regional, and country-level, the CRD workstream provides tools, guidance, monitoring, and on the ground technical assistance for the planning and roll-out of the vaccines. Along with COVAX partners, WHO has developed a no-fault compensation scheme as part of the time-limited indemnification and liability commitments.

UNICEF’s role in COVAX

UNICEF is leveraging its experience as the largest single vaccine buyer in the world and working with manufacturers and partners on the procurement of COVID-19 vaccine doses, as well as freight, logistics and storage. UNICEF already procures more than 2 billion doses of vaccines annually for routine immunisation and outbreak response on behalf of nearly 100 countries. In collaboration with the PAHO Revolving Fund, UNICEF is leading efforts to procure and supply doses of COVID-19 vaccines for COVAX. In addition, UNICEF, Gavi and WHO are working with governments around the clock to ensure that countries are ready to receive the vaccines, with appropriate cold chain equipment in place and health workers trained to dispense them. UNICEF is also playing a lead role in efforts to foster trust in vaccines, delivering vaccine confidence communications and tracking and addressing misinformation around the world.

About ACT-Accelerator

The Access to COVID-19 Tools ACT-Accelerator, is a new, ground-breaking global collaboration to accelerate the development, production, and equitable access to COVID-19 tests, treatments, and vaccines. It was set up in response to a call from G20 leaders in March and launched by the WHO, European Commission, France and The Bill & Melinda Gates Foundation in April 2020.

The ACT-Accelerator is not a decision-making body or a new organisation, but works to speed up collaborative efforts among existing organisations to end the pandemic. It is a framework for collaboration that has been designed to bring key players around the table with the goal of ending the pandemic as quickly as possible through the accelerated development, equitable allocation, and scaled up delivery of tests, treatments and vaccines, thereby protecting health systems and restoring societies and economies in the near term. It draws on the experience of leading global health organisations which are tackling the world’s toughest health challenges, and who, by working together, are able to unlock new and more ambitious results against COVID-19. Its members share a commitment to ensure all people have access to all the tools needed to defeat COVID-19 and to work with unprecedented levels of partnership to achieve it.

The ACT-Accelerator has four areas of work: diagnostics, therapeutics, vaccines and the health system connector. Cross-cutting all of these is the workstream on Access & Allocation.

WHO validates 11th vaccine for COVID-19

19 May 2022

News release

Today, the World Health Organization (WHO) issued an emergency use listing (EUL) for CONVIDECIA, a vaccine manufactured by CanSino Biologics, China, adding to a growing portfolio of vaccines validated by WHO for the prevention of COVID-19 caused by SARS-CoV-2.

WHO’s EUL procedure assesses the quality, safety and efficacy of COVID-19 vaccines as a prerequisite for COVAX vaccine supply. It also allows countries to expedite their own regulatory approval to import and administer COVID-19 vaccines.

CONVIDECIA was assessed under the WHO EUL procedure based on the review of data on quality, safety, efficacy, a risk management plan, programmatic suitability and a manufacturing site inspection conducted by WHO. The Technical Advisory Group for Emergency Use Listing, convened by WHO and made up of regulatory experts from around the world, has determined that the vaccine meets WHO standards for protection against COVID-19 and that the benefits of the vaccine far outweigh risks.

CONVIDECIA is based on a modified human adenovirus that expresses the spike S protein of SARS-CoV-2. It is administered as a single dose.

CONVIDECIA was also reviewed earlier this month by WHO’s Strategic Advisory Group of Experts on Immunization (SAGE), which formulates vaccine specific policies and recommendations for vaccines’ use in populations (i.e. recommended age groups, intervals between shots, specific groups such as pregnant and lactating women).

The SAGE recommends use of the vaccine as a single (0.5ml) dose, in all age groups 18 and above.

CONVIDECIA was found to have 58% efficacy against symptomatic disease and 92% against severe COVID-19.

WHO emergency use listing

The emergency use listing (EUL) procedure assesses the suitability of novel health products during public health emergencies. The objective is to make medicines, vaccines and diagnostics available as rapidly as possible to address the emergency while adhering to stringent criteria of safety, efficacy and quality. The assessment weighs the threat posed by the emergency as well as the benefit that would accrue from the use of the product against any potential risks.

The EUL pathway involves a rigorous assessment of late phase II and phase III clinical trial data as well as substantial additional data on safety, efficacy, quality and a risk management plan. These data are reviewed by independent experts and WHO teams who consider the current body of evidence on the vaccine under consideration, the plans for monitoring its use, and plans for further studies.

As part of the EUL process, the company producing the vaccine must commit to continue to generate data to enable full licensure and WHO prequalification of the vaccine. The WHO prequalification process will assess additional clinical data generated from vaccine trials and deployment on a rolling basis to ensure the vaccine consistently meets the necessary standards of quality, safety and efficacy for broader availability.

See all EUL listings

SAGE

SAGE is the principal advisory group to WHO for vaccines and immunization. It is charged with advising WHO on overall global policies and strategies, ranging from vaccines and immunization technology, research and development, to delivery of immunization and its linkages with other health interventions. SAGE is concerned not just with childhood vaccines and immunization, but all vaccine-preventable diseases.

SAGE assesses evidence on safety, efficacy, effectiveness, impact and programmatic suitability, considering both individual and public health impact. SAGE Interim recommendations for EUL products provide guidance for national vaccination policy makers. These recommendations are updated as additional evidence becomes available and as there are changes to the epidemiology of disease and the availability of additional vaccines and other disease control interventions.


Interim statement on the use of additional booster doses of Emergency Use Listed mRNA vaccines against COVID-19

17 May 2022

Statement

The World Health Organization, with the support of the Strategic Advisory Group of Experts (SAGE) on Immunization and its COVID-19 Vaccines Working Group, continues to review the emerging evidence on the need for and timing of additional booster doses for the currently available COVID-19 vaccines which have received Emergency Use Listing (EUL). The statements and conclusions in this document will be updated as new data become available.

The objective of this statement is to review the evidence on additional booster doses. In considering additional booster doses, there are two main scenarios to assess: 1) the use of additional booster doses in those who are not able to mount and sustain adequate immune responses and 2) considerations for additional booster doses to be administered in order to protect high risk populations and health workers in order to maintain the health system during periodic waves of disease surges.

WHO's current Recommendations: (1) initial booster doses:

Booster doses should be offered based on evidence that doing so would have substantial impact on reducing hospitalization, severe disease and death, and to protect health systems. The order of implementing booster doses to different population groups should follow that which has been laid out for the primary vaccination series – i.e., booster doses should be prioritized for higher priority-use groups before lower priority-use groups, unless there is adequate justification not to do so. Such justification may include programmatic constraints or acceptability obstacles to uptake in higher priority-use groups that would result in vaccine wastage. In such cases, strategies should be prioritized to improve vaccine delivery, community engagement, and social mobilization efforts to reach higher priority-use groups.

Within a given priority-use group, primary series vaccination will have greater impact per dose than additional doses. Across priority-use groups, the benefits of additional doses for higher priority-use groups versus primary series doses for lower priority-use groups depends on country conditions, including supply and roll-out timelines, past epidemic dynamics and infection-induced immunity, vaccine product, vaccine effectiveness, and waning of protection. When high primary series coverage rates have been achieved among subgroups at higher risk of severe disease and death (e.g., older adults), additional doses for these subgroups may yield greater reductions in severe disease and death than use of equivalent vaccine supply for primary series vaccination of lower priority-use groups.

The optimal interval between completion of a primary series and administration of additional doses has yet to be determined, and depends on epidemiological setting, vaccine product, targeted age groups, background seroprevalence, and circulation and frequency of specific variant of concerns (VoC). As a general principle, an interval of 4–6 months since completion of the primary series could be considered, especially in the context of Omicron.

Booster doses should be considered for all COVID-19 vaccines having received EUL as per WHO’s product specific interim recommendations.

WHO`s current Recommendations: (2) Additional Doses in Immunocompromised persons

Available data for WHO EUL COVID-19 vaccine products suggest that vaccine effectiveness and immunogenicity are lower in immunocompromised persons (ICPs), compared to persons without immunocompromising conditions. An additional dose included in an extended primary series enhances immune responses in some ICPs (2, 3). Given the significant risk of severe COVID-19 for ICPs, if infected, WHO has already issued a recommendation for an extended primary series (i.e. third dose) as well as a booster dose (i.e. fourth dose) for ICPs, for all COVID-19 vaccines (1, 4). Homologous (same vaccine platform) and heterologous (different vaccine platform) vaccines can be used for such booster doses (5).

Considerations for additional booster doses beyond the first booster (< 6 months since first booster)

Additional booster doses beyond the first booster dose are currently being offered by some countries (i.e. fourth dose to older adults and a fifth dose for immunocompromised persons). Data on the usefulness of these additional booster doses is sparse and especially limited on the duration of further protection. Data on additional booster doses as of May 2022 only exists for the mRNA vaccines, and not for other vaccine platforms. Hence, in the following we only focus on the evidence with regards to additional booster for mRNA vaccines, while encouraging more data to be accrued for all vaccine platforms.

Seven studies were available for review, six of which were from Israel (6-11) and one from Canada (12). All were conducted during a time when Omicron has been the predominant circulating strain globally. While the studies vary in their design and population investigated, most evaluated the relative effectiveness of a fourth dose 4 months after a 3rd dose of mRNA vaccine compared to those who received 3 doses. This relative vaccine effectiveness only provides evidence on the value of a fourth dose compared to individuals who already have some vaccine induced protection (3 dose recipients). The relative vaccine effectiveness depends upon the initial VE provided by 3 doses and how much subsequent waning has occurred. In contrast, earlier studies provide an absolute vaccine effectiveness comparing vaccinated versus unvaccinated individuals. The Canadian study is the only available study that provides data on absolute vaccine effectiveness (i.e., compares 4th dose schedule to those who are unvaccinated). Additionally, the maximum follow up in the available studies was short and ranged from two weeks to ten weeks after the fourth dose.

Of the seven studies that investigated the use of a 4th dose of mRNA COVID vaccine, two reported specifically on outcomes of infection and any symptomatic disease (10, 11). Both studies were conducted in Israel and included health workers (HWs) as their population of interest. One study showed an increased IgG antibodies against SARS-CoV-2 receptor-binding domain and neutralizing antibody titers by a factor of 9-10 measured after fourth dose of vaccine. This corresponded to antibody titers that were slightly higher than those achieved after the third dose, with no significant difference between the two mRNA vaccines (11). The second study investigated breakthrough infections in HWs who received 3 doses of BNT162b2 vaccine and provided a comparison to those who received a fourth dose of BNT162b2. In fourth dose recipients, there was a reduction in breakthrough infection rates compared to that observed after only a 3rd dose of mRNA vaccine (10).

Of the remaining five studies, all were conducted in individuals older than 60 years of age, excluding individuals who had previous SARS-Co-2 infection and specifically evaluated mRNA vaccines. Two of the studies were retrospective cohort studies using administrative data. The first study found that the relative vaccine effectiveness against severe disease to be 66% (95% CI, 57-72) 15 to 21 days after a fourth dose and 77% (95% CI, 62-86) 36-42 days after a fourth dose (6). The second retrospective cohort study reported on death as the outcome measure and found a relative vaccine effectiveness of 78% (95% CI 72-83) 7 or more days post fourth dose. The absolute risk reduction conferred by the fourth dose was 0.07% in the study (9). The third study used a test negative design and reported on severe disease. They found a relative vaccine effectiveness of 87% (95% CI 0-98) 49-69 days post fourth booster. This study reported that severe disease was a relatively rare event, occurring among <1% of both fourth dose and third dose only recipients (8). The fourth study reviewed was a target trial (application of trial design principles from RCTs to the analysis of observational data(13)) that provided outcome data for hospitalization, severe disease and death. They found a relative vaccine effectiveness of 62% (95% CI, 50 to 74) against severe COVID-19, and 74% (95% CI, 50 to 90) against COVID-19 related death comparing 3 dose recipients to 4 dose recipients. A further analysis of the risk of severe COVID-19 from 7 days to 30 days post fourth dose was 42.1 events per 100,000 persons, as compared with 110.8 events per 100,000 persons in the 3 dose recipient control group. This corresponds to a difference in risk of 68.8 cases per 100,000 persons (95% CI, 48.5 to 91.9)(7).

The final study, conducted in Canada, investigated not only the relative vaccine effectiveness but also the absolute vaccine effectiveness when compared to unvaccinated individuals, two dose recipients as well as three dose recipients. This study found that with each additional dose, VE increased for severe disease. Absolute VE was 82% (95%CI 75-88%) as measured more than 84 days after third dose, and 92% (95%CI 87-95%) for fourth dose recipients at greater than 7 days after the fourth dose (12).

Taken together, these studies show some short-term benefit of an additional booster dose of mRNA vaccine in health workers, those over 60 years of age or with immunocompromising conditions. Data to support an additional dose for healthy younger populations are limited; preliminary data suggest that in younger people, the benefit is minimal. Moreover, follow-up time after the additional booster dose was limited, thereby precluding conclusions about duration of protection after this dose. Therefore, there is a lack of data to guide some important questions for making policy decisions. The limited available data suggest that for highest risk groups there is a benefit that supports the administration of an additional booster dose.

Administering an additional booster dose likely comes with considerable programmatic challenges in terms of vaccine delivery in many settings. The financial and opportunity cost of such programmes must also be carefully weighed against the limited incremental benefit of an additional booster dose. In those most at risk for severe disease or death (i.e. adults above the age of 60 years, or those who are not able to mount a full immune response), the additional benefit of an additional booster dose of mRNA vaccine might be warranted.

Considerations for future additional doses:

For longer-term considerations, there are significant uncertainties related to the evolution of the virus and the characteristics of future variants. Given widespread transmission of Omicron globally, continued viral evolution with the emergence of new variants or sub lineages as is already being seen. Development of a pan-SARS-CoV-2 or pan-sarbecovirus vaccines are needed, but the timeframe for their development is uncertain (14). Meanwhile, the composition of the currently available COVID-19 vaccines may need to be updated to offer better protection against new VOCs which may be antigenically distinct (14). Current vaccines based on the index virus appear to maintain high VE against severe disease also in the context of current variants of concerns, but VE estimates against infection and symptomatic diseases are lower against Omicron. Any update to vaccine composition would aim to elicit greater breadth in the immune response against circulating and emerging variants, in addition to retaining protection against severe disease and death. The performance of any updated vaccine(s) may vary depending on the nature and magnitude of previously acquired immunity, recognizing that this immunity will be dependent upon different VOCs, different types of vaccines and their timing of administration.

While seasonality is not yet fully established for SARS-COV-2, evidence from the past two years support the notion of more substantial transmission during the winter season. Therefore, for countries with either a Northern or Southern Hemisphere winter season, plans for catch-up to improve primary series coverage and boosting for those at highest risk, campaigns should take seasonality into account. In addition, in view of the uncertainty of the characteristics of new VOC, which may emerge rapidly, there may be value in establishing vaccine induced immunity using existing vaccines (i.e. index virus) complemented by a booster dose of variant vaccine to broaden the immunological response. The Technical Advisory Group on COVID-19 Vaccine Composition will provide advice on updated vaccine composition when data is available.

To that end, in order to make sound policy decisions, data will need to be generated on the performance of current and variant-specific candidate COVID-19 vaccines, including the VE, immunogenicity and safety of an additional booster dose over time and by disease outcome and priority use groups. More research is needed on the breadth, magnitude, and durability of humoral and cell-mediated immune responses to variants. Also needed is evidence to address other gaps in the evidence regarding the need for additional booster doses, which includes the duration of VE of inactivated, subunit and viral vectored vaccines over time and by disease outcome. Finally, an understanding of the vaccine correlates of protection and correlates of durability of protection in persons with and without previous COVID-19 infection would assist policy makers in creating sound programmatic decisions.

SAGE as well as the Technical Advisory Group on COVID-19 Vaccine Composition continue to monitor the situation carefully and the WHO position will be updated accordingly.

References:

1. WHO. WHO SAGE roadmap for prioritizing uses of COVID-19 vaccines. (https://www.who.int/publications/i/item/who-sage-roadmap-for-prioritizing-uses-of-covid-19-vaccines-in-the-context-of-limited-supply, accessed 20 January 2022).

2. N Engl J Med. 2021. doi: 10.1056/NEJMc2111462.

3. Response to additional COVID-19 vaccine doses in people who are immunocompromised: a rapid review. The Lancet Global Health. 2022;10:e326-e8. doi: 10.1016/S2214-109X(21)00593-3.

4. WHO. Interim recommendations for an extended primary series with an additional vaccine dose for COVID-19 vaccination in immunocompromised persons. 2021 (https://www.who.int/publications/i/item/WHO-2019-nCoV-vaccines-SAGE_recommendation-immunocompromised-persons, accessed 26 October 2021).

5. WHO. Interim recommendations for heterologous COVID-19 vaccination schedules. (https://www.who.int/news/item/16-12-2021-interim-recommendations-for-heterologous-covid-19-vaccine-schedules, accessed 21 Dec 2021).

6. Bar-On YM, Goldberg Y, Mandel M, Bodenheimer O, Amir O, Freedman L et al. Protection by a Fourth Dose of BNT162b2 against Omicron in Israel. New England Journal of Medicine. 2022. doi: 10.1056/NEJMoa2201570.

7. Magen O, Waxman JG, Makov-Assif M, Vered R, Dicker D, Hernán MA et al. Fourth Dose of BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting. N Engl J Med. 2022. doi: 10.1056/NEJMoa2201688.

8. 2022:2022.03.24.22272835. doi: 10.1101/2022.03.24.22272835.

9. Effectiveness of a second BNT162b2 booster vaccine against hospitalization and death from COVID-19 in adults aged over 60 years. Nature Medicine. 2022. doi: 10.1038/s41591-022-01832-0.

10. 2022:2022.04.11.22273327. doi: 10.1101/2022.04.11.22273327.

11. Efficacy of a Fourth Dose of Covid-19 mRNA Vaccine against Omicron. New England Journal of Medicine. 2022;386:1377-80. doi: 10.1056/NEJMc2202542.

12. Grewal R, Kitchen SA, Nguyen L, Buchan SA, Wilson SE, Costa AP et al. Effectiveness of a Fourth Dose of COVID-19 Vaccine among Long-Term Care Residents in Ontario, Canada. medRxiv. 2022:2022.04.15.22273846. doi: 10.1101/2022.04.15.22273846.

13. Hernán MA, Robins JM. Using Big Data to Emulate a Target Trial When a Randomized Trial Is Not Available. American journal of epidemiology. 2016;183:758-64. doi: 10.1093/aje/kwv254.

14. Organization WH. Interim statement on COVID-19 vaccines in the context of the circulation of the Omicron SARS-CoV-2 variant from the WHO Technical Advisory Group on COVID-19 Vaccine Composition (TAG-CO-VAC). 2022 (https://www.who.int/news/item/08-03-2022-interim-statement-on-covid-19-vaccines-in-the-context-of-the-circulation-of-the-omicron-sars-cov-2-variant-from-the-who-technical-advisory-group-on-covid-19-vaccine-composition-(tag-co-vac)-08-march-2022.

Statement for healthcare professionals: How COVID-19 vaccines are regulated for safety and effectiveness (Revised March 2022)

Joint Statement from the International Coalition of Medicines Regulatory Authorities and World Health Organization

17 May 2022

Statement

Healthcare professionals and public health authorities have a central role in discussing vaccination against COVID-19 with their patients. Vaccines play a critical role in preventing deaths, and hospitalisation caused by infectious diseases, and are contributing to controlling the spread of the disease, thus their impact on infection and serious illness is significant. Both vaccinated and unvaccinated people also need to be aware of the additional protective behaviours required to control the pandemic locally.

The global impact of the COVID-19 pandemic has resulted in an unprecedented level of public interest in vaccines. This includes a focus on the development of vaccines and their regulatory review and safety monitoring. Much of this coverage has taken place through mass and social media. Reports of adverse events (side effects) have led some people to express concerns about getting vaccinated, delay getting vaccinated or be strongly opposed to vaccination. There are also differences in individual confidence in national safety monitoring systems. Another challenge in communicating the importance of COVID-19 vaccination is that in many, but not all, children and young adults are less clinically affected by COVID-19 infection and therefore some may see limited value in vaccinating this population. Clear and consistent communication of evidence and uncertainties is therefore essential to support people in making the critical choice to be vaccinated.

We appreciate that you, your colleagues and your patients may have a number of questions around the development, regulatory review and ongoing safety monitoring of COVID-19 vaccines.

Purpose

This joint International Coalition of Medicines Regulatory Authorities (ICMRA)* and World Health Organization (WHO) statement aims to help healthcare professionals answer questions about the role of regulators in the oversight of COVID-19 vaccines. It explains how vaccines undergo robust scientific evaluation to determine their safety, efficacy and quality and how safety is closely and continually monitored after approval.

Vaccination has been shown to contribute to reducing deaths and severe illness from COVID-19, and to reduce the transmission of COVID-19. Vaccinating as many people as possible and reducing the spread of disease is important. Vaccination of a significant proportion of the population also protects vulnerable people, including those who cannot receive vaccines, or the small proportion of people who might remain at risk of infection after vaccination. Failure to vaccinate widely also enables continued circulation of the virus and the generation of variants, including some that may pose a greater risk. Widespread vaccination has contributed to fewer people getting sick and being hospitalised, ultimately alleviating the burden of COVID-19 on healthcare systems. It has also helped allow the move back to normal societal functioning and the re-opening of economies.

Vaccines and the regulatory process

How do regulatory authorities evaluate COVID-19 vaccines?

Regulators rigorously evaluate scientific and clinical evidence provided by vaccine manufacturers. Vaccine manufactures are legally obliged to follow defined standards in the data they provide, and their clinical research and manufacturing operations are subject to regulatory oversight. Either full or summary data from clinical trials is made available to regulators as part of vaccine evaluation. Each vaccine is thoroughly assessed for safety, efficacy and quality to determine whether it can be approved for use. Regulators use available scientific evidence from preclinical laboratory research, human clinical trials, and manufacturing information to assess benefits and risks of candidate vaccines. Regulators have collaborated extensively with other global regulatory counterparts in premarket and safety reviews.

Regulators may seek additional expert advice from independent scientific advisory committees to help inform their decision on whether to approve a vaccine. These committees are made up of experts in science, medicine (including infectious diseases) and public health, and often include consumer and healthcare professional representatives. Public health agencies have a different role to regulatory authorities. They develop and deliver vaccination programmes, often working with their expert immunisation technical advisory committees. This includes prioritising and designating populations for vaccination with specific vaccines, issuing additional recommendations and providing information more broadly about vaccines and immunization. They also collaborate with regulators to monitor the safety of vaccines after they are approved for use.

Globally, the public can have confidence in the rigour of the process used to scientifically evaluate the safety, efficacy and quality of vaccines before they are approved for use in the wider population.

Safety evidence prior to potential regulatory authorisation

Safety evidence is an essential part of each regulatory submission for a COVID-19 vaccine. It is gathered during all phases of the vaccine development process. Robust assessment of safety is carried out in the clinical trials and submitted to regulators for review as part of the approval process.

All adverse events need to be examined and reported in the regulatory submission by the companies for a marketing authorisation. Typically, regulators will require that participants in clinical trials have been followed for generally at least 2 months after receiving their final vaccine dose for decisions made under emergency or provisional or conditional approval processes, with longer follow up required before full market authorisation is granted. One year or longer safety data are now available for many of the most widely used vaccines. While rare adverse events might not be recognised until after wide population use, based on both the current experience with COVID-19 vaccines and previous experience with other vaccines, most adverse events occur days to a few weeks of vaccination and will be identified in clinical trials. There will also be longer term (for example 1 to 2 years) follow up of those who participated in the clinical trials of each vaccine, which is standard practice in clinical trials, as well as population wide observational safety studies. Safety data from these longer-term trials and population studies are being carefully reviewed by regulators as part of post approval monitoring of safety. International regulators collaborate on the review of safety allowing an increase in the size of the populations for which safety data can be assessed.

Efficacy

Apart from information on the types of immune responses induced by the vaccine, companies must submit data from well-designed clinical trials to regulators to demonstrate that the vaccine prevents COVID-19. The data showed there were sufficient numbers of people included in the clinical trials receiving the vaccine so that the efficacy of the vaccine can be accurately measured (generally at least 10,000 and usually 15,000 or more people who receive the vaccine, in addition to those in the control arm). Populations in clinical trials should include a range of age groups and people with co-morbidities. Given the disproportionate impact of COVID-19 on older people, COVID-19 vaccine clinical trials have included significant numbers of older participants.

Vaccine clinical trials for a new candidate vaccine showed that vaccines very significantly reduced COVID-19 in people who were vaccinated, compared to a control group of people who did not receive the vaccine, through a reduction in numbers of laboratory confirmed SARS-CoV-2 infections. Since the population-wide roll out of COVID-19 vaccines commenced in December 2020, a significant number of effectiveness studies have been published in refereed international medical journals. The population wide effectiveness data have been in line with the findings of the clinical trial results and shown high effectiveness against infection and even higher effectiveness against serious illness, hospitalisation or death from COVID-19 infection. Progressive waning of the effectiveness of one or two doses, particularly against mild infection and against the SARS-CoV-2 Omicron variant has emphasised the importance of a third booster vaccination.

For COVID-19 vaccines, it is becoming increasingly difficult to conduct placebo-controlled disease endpoint efficacy trials in some countries, as few individuals are willing and available to participate. Appropriately designed immuno-bridging studies are an acceptable alternative approach for authorising vaccines including for variants, boosters and paediatric populations. Neutralising antibody titres may be a suitable primary endpoint to predict vaccine effectiveness. The applicant for regulatory approval must also have justified the choice of appropriate vaccine comparators, statistical criteria and population comparator groups (for example, matched by age, gender, prior vaccination/infection status). Efficacy data should also include characterisation of comparative immunogenicity profiles, including cell-mediated immunity and characterisation of comparative in vitro neutralisation against Variants of Concern.

Quality

Any COVID-19 vaccine that receives regulatory authorisation must be manufactured according to internationally accepted stringent regulatory standards of good manufacturing practices (GMP). Regulators review data to confirm that the manufacturing process at each production site is well controlled and consistent. This will include data on the composition and purity of the vaccine and its potency, as well as data on every step of manufacturing and on the controls used to ensure that each batch of vaccine is consistently of a high quality. Data on vaccine stability must also be provided before a vaccine can be approved. After approval, batches may also undergo evaluation by individual national regulatory authorities to ensure they meet national requirements, before they can be supplied.

Monitoring safety and effectiveness after vaccine approval

After a vaccine is approved for use, regulators conduct robust effectiveness monitoring as well as monitoring of safety and risk minimisation activities (pharmacovigilance). They need to continuously monitor vaccine safety to ensure that the benefits of the vaccine continue to outweigh the risks. Regulators do this by:

Reviewing and analysing adverse events reported by healthcare professionals and consumers and requiring industry vaccine companies (sometimes called “sponsors”) to report to regulators on adverse events received both within the regulator’s home country and globally;

Many regulators have implemented enhanced passive surveillance systems. These include systems to rapidly compare numbers of suspected adverse events reported with vaccines to the number of events expected to occur by chance, and includes access to near real-time data on vaccine usage in different settings. Several regulators have also implemented traceability systems for different vaccine brands and batches;

Taking rapid action to mitigate risks, also considering the information about emerging safety issues that is shared among regulators and researchers through international collaboration;

Reviewing medical literature and other sources of new safety information;

Requiring vaccine manufacturers to continue safety surveillance from the ongoing clinical trials of their products; and

Many regulators also require vaccine manufacturers to have risk management plans describing how they will monitor and minimise risks associated with their vaccines, including post authorisation safety studies that will continue to evaluate the safety and benefit-risk of their vaccine.

There has been a significant commitment by healthcare professionals and hospitals to report any adverse events they see in their patients, and it is important that this continues. Reporting of all relevant events helps regulators assess the possible role of the vaccine in causing the adverse event and assists in identifying safety issues relating to newly introduced vaccines.

As part of the safety monitoring and review of all suspected adverse events reported for vaccines, regulators have developed lists of “Adverse Events of Special Interest”. These lists include some events that have been associated with other vaccines or could be theoretically linked to the COVID-19 vaccines. They may be included on these lists because they are serious events that are important to monitor closely, even though there may be no evidence that a particular adverse event is causally associated with specific vaccines. Having information on the background rates of these events that would be expected in people who have not received a vaccine, will help ensure that any increased reporting of these events can be quickly detected, thoroughly reviewed and investigated by regulators.

The widespread use of COVID-19 vaccines, including in the elderly and in patients with underlying health conditions, means that there have been deaths and serious illnesses that are purely coincidental and unrelated to vaccinations. The job of each regulator, often supported by independent committees of relevant medical experts together with vaccine manufacturers, is to review the cases and determine if there are potential safety signals with the vaccines. There is a special focus on monitoring safety in some groups of people that may not have been included in clinical trials or included as a small number, such as pregnant women, persons with severe pre-existing illness, older people, children, and in people also receiving vaccines for prevention of other diseases.

Regulators, often in collaboration with public health authorities, can take decisive action if a safety issue is identified. These actions can include issuing safety communications for patients, healthcare professionals and the community; updating the product information or consumer information for the vaccine; preventing the release of a particular batch of vaccine; and, taking other regulatory actions such as restriction of vaccine authorisation to a particular subgroup of the community or revocation of authorisation. Regulators approve and maintain an approval of a vaccine only if they determine that the known and potential benefits of the vaccine outweigh its known and potential risks.

Commonly reported adverse events

The most commonly reported adverse events with COVID-19 vaccines are expected vaccine side effects, such as headache, fatigue, muscle and joint pain, fever and chills and pain at the site of injection. The occurrence of these adverse events is consistent with what is already known about the vaccines from clinical trials.

Adverse events of special interest associated with specific vaccines

mRNA vaccines

The most significant adverse events of special interest reported for these vaccines, which include the Pfizer and Moderna vaccines are myocarditis, pericarditis and anaphylaxis.

Myocarditis is inflammation of the heart muscle while pericarditis is an inflammation of the membrane around the heart. They can occur as very rare adverse events after vaccination with mRNA vaccines. Cases typically occur within 10 days, with symptom onset often within 5 days of vaccination. Pericarditis symptoms may occur later, typically 2 to 3 weeks after vaccination. Myocarditis and pericarditis are often mild, and symptoms usually resolve after a short time with standard treatment and rest. Some cases are more serious and need to be treated in hospital, but very few cases require intensive care.

Myocarditis has most often been reported after the second dose in 12 to 17 year old boys and men under 30. Several countries have observed higher reporting rates of myocarditis with those vaccinated with the Moderna COVID-19 vaccine than the Pfizer vaccine, but the reported difference in rates has differed between studies and countries may be influenced by a variety of factors. The benefit-risk of both of the vaccines remains positive. Pericarditis following a mRNA vaccine tends to occur at an older median age than myocarditis, but it is nonetheless more common in people under 50 years of age than in older people.

Myocarditis and pericarditis can occur after a booster dose, but this is so far reported to be more rare than after the primary doses. There is no indication that these events are more serious than after earlier doses.

Anaphylaxis has been reported with mRNA vaccines (and other COVID-19 vaccines). Anaphylaxis reports remain very rare (in the order of 1 case per 100,000 people vaccinated). Routine vaccination procedures include keeping people under observation for at least 15 minutes after vaccination and having appropriate medical treatment on hand so that anaphylaxis can be rapidly managed. Vaccines should not be given to people with a known history of a severe allergic reaction to any of the vaccine components. A second dose of any vaccine should not be given to those people who have experienced anaphylaxis after the first dose of a COVID-19 vaccine.

Adenovirus vector vaccines

These include the AstraZeneca, Janssen, Gamaleya and CanSino Biologics COVID-19 vaccines. The most significant adverse events of special interest reported for these vaccines are Thrombosis with Thrombocytopenia Syndrome (TTS), Immune Thrombocytopenic purpura (ITP) and Guillain-Barre Syndrome (GBS).

TTS is a very rare, but serious clotting syndrome involving thromboembolic events (blood clots) with thrombocytopenia (low blood platelet count). TTS symptoms usually start between 4 to 30 days after vaccination. It occurs in about 2 out of every 100,000 people after a first dose. The risk of TTS after a second vaccine dose of the AstraZeneca vaccine appears to be much lower and is under 0.5 of every 100,000 people after a second dose. Younger women, and people under 60 years seem to be slightly more likely to have serious outcomes from TTS as they more often experience clots in unusual locations, such as the brain or abdomen. Thromboembolic events with thrombocytopenia have also been reported in the United States for the Janssen vaccine, at a rate of about 2 to 3 per million doses administered.

Immune thrombocytopenia (ITP) and Guillain-Barre Syndrome (GBS) have been reported in about one in every 100,000 people following the AstraZeneca and Janssen vaccines. ITP is a rare immune reaction that occurs when platelets are mistakenly destroyed by the immune system. In suspected ITP following vaccination with the AstraZeneca vaccine, patients had an extremely low platelet count, and signs of thrombocytopenia which may include unusual bruising, a nosebleed and/or blood blisters in the mouth. About 5% of people with ITP develop severe bleeding. In a very small number of people, it can be fatal.

GBS is a rare but sometimes serious (and rarely fatal) immune disorder affecting the nerves and can result in pain, numbness, muscle weakness and difficulty walking. GBS can occur when the immune system is activated and has been associated with infections, including SARS-CoV-2, and vaccines. GBS typically occurs days or weeks after an infection or vaccination. However, sometimes a trigger for GBS cannot be identified.

Several other COVID-19 vaccines have also been authorised in some other countries. Less information is available internationally about adverse events for other manufactured vaccines. Regulators monitor and carefully review if there is a causal relationship between any of the vaccines associated with adverse events, and, if appropriate, information will be included in Product Information / Product Label of vaccines of concern.

Health care professionals are encouraged to check the approved Product label/ product information or Fact Sheets for the vaccine in their country for safety information specific to the vaccines they are administering. In addition, where a new safety issue is identified regulators communicate this to health care professionals and consumers through alerts on their websites and through social media.

Questions and Answers on COVID-19 vaccines

Q: How have the vaccines been developed so quickly? Does this mean that their safety and efficacy has been compromised?

A: The speed of development of COVID-19 vaccines has been unprecedented for several reasons, but the safety and efficacy requirements for vaccines have not been compromised, Vaccine development was facilitated by:

New technologies adapted from the development of other vaccines – mRNA vaccines were developed for COVID-19 very rapidly after the sequence of the COVID-19 virus was determined, but the underlying technology had been under development since much longer and therefore production could be scaled up very quickly. The adenovirus technology used for adenovirus vector vaccines was first tested with SARS, MERS and Ebola virus over thelast 20 years, and so was able to be adapted quickly to COVID-19, which has several similarities to these viruses.

Clinical trial successes - it has been possible to rapidly recruit large numbers of volunteers into clinical trials and, with unfortunately high rates of infection in several countries, to complete trials with 10,000 to 50,000 people in a short period of time. Under normal circumstances, it may take many months or even a few years to carry out trials of this size to determine whether a vaccine is effective.

Very close collaboration - between regulators internationally, industry and clinical researchers enabled clear indications of regulatory requirements and early access to results.

Intensive and insightful research - researchers predicted that the “spike protein” on the virus would be a good target for vaccine development, and almost all vaccines have been designed to induce a response to this protein. So far, the spike protein has produced a strong immune response in those vaccinated, and for those vaccines that have reported clinical results have been shown to be highly protective from COVID-19 disease.

The massive financial investment by governments, industry and philanthropic organisations in vaccine development and the redirection of much of the global research and commercial infrastructure for the development and manufacture of vaccines has taken place. Governments also enabled companies to take the commercial risk of manufacturing some vaccine stocks ahead of regulatory approvals.

Real world safety experience. As of March 2022, about 11 billion doses of COVID-19 vaccines have been administered globally, and so there is an immense global data base on the safety of these vaccines. The benefit-risk ratio remains overwhelmingly positive.

Q: Will mRNA vaccines affect the DNA of vaccine recipients?

A: No. The mRNA in the vaccine has not been shown to incorporate itself into the genes of vaccine recipients and breaks down in the weeks after vaccination. mRNA vaccines contain genetic instructions for our cells, which only read them and provide copies of the SARS-CoV-2 spike protein. This enables the body’s natural immune systems to cause a response in vaccine recipients if they are later exposed to the virus.

Q: How long will COVID-19 vaccination provide protection for immunised people?

A: A number of “real world” vaccine effectiveness studies have provided information on the duration of protection from different COVID-19 vaccines. Two doses of the major mRNA and adenovirus vaccines provided strong (over 75 %) protection from serious illness,hospitalisation and death from the alpha, delta and original (wild type) SARS-COV-2 variants for 6 months. However, with emergence of the Omicron variant in late November 2021, evidence suggests that a third (booster vaccination) is required to restore and maintain protection against serious illness or death. Early results indicate that protection against serious illness or death is maintained for many months or longer after a third vaccination, and at present, there is not a widespread view that a fourth vaccination (second booster) is required to maintain immunity, except for in people who are immunocompromised. While those who become infected with SARS-CoV-2 following primary vaccination typically experience milder illness, protection against the level of severity of infection does seem to decrease over time without a booster vaccination.

Q. Should the same type of vaccine be used for a booster as the original vaccine?

A: Several studies have now been published examining the use of the same vaccine as a booster (third dose) after the first two doses (homologous boosting) and the use of a different vaccine as a third dose (heterologous boosting). While virtually all combinations of booster and initial course vaccines provided significant increase in immune response, most studies have shown that the greatest increase in immune response resulted when a booster of an mRNA vaccine was used following a primary course of either an mRNA vaccine or an adenovirus vector vaccine.

Q: Are vaccines effective against COVID-19 variants?

A: Mutations in key viral proteins can result in the emergence of virus variants emerge. The SARS-CoV-2-coronavirus is prone to mutations that create variants, some of which have become established in many parts of the world. The scientific community and regulators are actively monitoring protection by vaccines against infection and disease with new variants. For example, decreases in the level and duration of protection against the Omicron variant following a two-vaccine course led to many countries adopting a third dose booster program, three or more months following the second vaccination.

A number of vaccine developers are currently developing vaccines against the range of variants, while others are attempting to develop multivalent or pan-specific vaccines, which may protect against future variants. Regulators have agreed that review of data on vaccines against variants will be facilitated based on assessment of immune response to the variant, in the same way that new seasonal influenza vaccines are evaluated each year. However, evidence to date suggests that for people who are not immunocompromised, three doses of the current vaccines provided robust protection against serious illness, hospitalisation or death from the Omicron variant.

Q: Why are there so many vaccine candidates?

A: As the global seriousness of the pandemic became rapidly apparent, development of effective vaccines for COVID-19 became the top priority of many pharmaceutical companies and medical research institutes. There was also unprecedented government and private sector investment in vaccine development. There is now a wide range of technologies for developing new vaccines and many of the organisations developing COVID-19 vaccines have experience in one or more of these technologies. This has ensured that there would still be vaccines available if some were not approved for reasons of efficacy, safety or manufacturing challenges.

Q: What if many people start getting a reaction from a particular COVID-19 vaccine?

A: Short term reactions, such as soreness at the injection site, fatigue or headache are common following any vaccination with COVID-19 vaccines. These reactions usually pass in a day or two. If new evidence becomes available that suggests a specific serious adverse event may be linked to a particular COVID-19 vaccine, then regulators will take action by working collaboratively on a global basis and liaise with public health authorities. The type of actions that can be taken depend on the nature of the adverse event, and could range from issuing safety warnings for patients, healthcare professionals and the community; updating the product information or consumer information for the vaccine to show contraindications for the use in particular patients (e.g. those with certain co-morbidities); to closely monitoring adverse events in certain groups of patients; preventing the release of a particular batch of vaccine through to temporary suspension of the use of the vaccine until more is known.

Q: Should children be vaccinated? Are COVID-19 vaccines safe in children?

A: In many children aged under 12 years, SARS-CoV-2 infection is often asymptomatic or causes a brief illness with mild symptoms. Children at increased risk of severe outcomes from COVID-19 include those with obesity, chronic pulmonary disease, congenital heart disease and neurological disease, as well as those with neurodevelopmental disorders or epilepsy. The sheer number of COVID-19 infections during the Omicron wave, including in children has meant that most countries have experienced numbers of hospitalisation of children (and sadly some deaths) following COVID-19 infection.

Vaccination is also protective against paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (also known as MIS-C), a potentially life-threatening syndrome that occurs in approximately 1 in 3,000 children after infection. In addition to a reduction in illness, vaccination can also reduce the need for isolation in

children (and therefore the disruption to education and social activities) and potentially a reduction in parental absenteeism from employment.

Experience to date with the mRNA vaccines approved for paediatric use is that they are well-tolerated vaccines; where side effects occur, they are generally mild with pain, swelling, and redness at the vaccination site being the most commonly reported side effect. In addition, while myocarditis and pericarditis cases have very rarely been found in under 12’s following vaccination, the rates seem much lower than in older teenagers and adults.

Q: Are COVID-19 vaccines safe in pregnancy?

A: Although pregnant women were not deliberately included in the clinical trials of the COVID-19 vaccines, since the roll out of the vaccines in December 2020 there has been significant experience (particularly with the mRNA vaccines) on COVID-19 vaccination and pregnancy outcomes. A series of studies in a number of countries, both those published in the medical literature and surveillance following use of COVID-19 vaccines carried out by public health bodies and regulators, examining many tens of thousands of pregnancies did not find a higher risk of severe side effects, complications, miscarriages or premature births following vaccination.

At the same time, several studies have shown that COVID-19 infection can have very serious impacts on pregnancy outcomes in certain women, and that the benefits of receiving mRNA outweigh risks for pregnant women and their unborn children. In addition, recent data shows that maternal COVID-19 vaccination is linked to a lower risk of still births, and that perinatal mortality was more than fourfold higher for women giving birth within 28 days of infection.

Q: How are regulators speeding up the time it takes to authorise a COVID-19 vaccine?

A: Many regulators globally have implemented faster access pathways for COVID-19 vaccines, without compromising on strict standards of safety, quality and efficacy.

Some countries have Emergency Use Authorisation pathways which assess the available data at the time of authorisation. Exercising these provisions is a matter for those countries, taking into account the benefits versus risks in the context of the prevailing domestic pandemic situation. Different countries may coin this pathway or authorisation routes differently but essentially, they follow the same principles.

Other countries have implemented accelerated/priority, conditional or provisional approval schemes.

Under normal circumstances, regulatory assessment begins once all information to support registration is available. For COVID-19 vaccines, many regulators have agreed to accept data on a rolling basis to enable early evaluation of data as it becomes available. Regulators will only be in a position to make a provisional or a conditional approval decision for a vaccine once there is sufficient data to support adequately the safety, quality and effectiveness of the vaccine for its intended use. If a decision is made to grant provisional or conditional approval, it will be based on the requirement for the sponsor to submit more comprehensive, longer term clinical data, stability data and other information with agreed timelines.

Q: Did our country approve this COVID-19 vaccine, or are we relying on another country’s approval?

A: Most countries are carrying out independent regulatory evaluations on the submitted data for each vaccine. However, to ensure a more efficient use of resources and expertise, regulators in different countries are communicating closely on safety, efficacy and quality data and discussing technical issues as they may arise. In many cases principles of WHO Good Reliance Practices and collaborative mechanisms leverage the output of other regulators.

Q: Why weren’t very rare blood clots with low platelets with the AstraZeneca or Janssen vaccines or myocarditis/pericarditis with mRNA vaccines picked up during clinical trials?

A: Both of these types of adverse events are very rare with one to a few cases per hundred thousand vaccinated individuals. The clinical trials of these vaccines included large numbers of people (often with 10,000 to 20,000 individuals in the active vaccine arms), but even in trials of this size it was statistically unlikely that such very rare events would be detected. As with most medicines and vaccines, very rare side effects such as TTS are not identified until there have been a large number of the population vaccinated. This shows the importance of continual safety monitoring during the use of these vaccines in real world setting, to allow very rare events to be detected and investigated further.

About ICMRA

ICMRA brings together the heads of 38 medicines regulatory authorities* from every region in the world, with the WHO as an observer. Medicines regulators recognise their role in facilitating access to safe and effective high-quality medicinal products essential to human health and well-being. This includes ensuring that benefits of vaccines outweigh their risks. ICMRA is an international executive-level coalition of key regulators from every region in the world. It provides a global strategic focus for medicines regulators and gives strategic leadership on shared regulatory issues and challenges. Priorities include coordinated response to crisis situations.

Members of ICMRA include: Therapeutic Goods Administration (TGA), Australia; National Health Surveillance (ANVISA), Brazil; Health Products and Food Branch, Health Canada (HPFB-HC), Canada; China National Medical Products Administration (NMPA), China; European Medicines Agency (EMA) and European Commission - Directorate General for Health and Food Safety (DG - SANTE), European Union; French National Agency for Medicines and Health Products Safety (ANSM), France; Paul-Ehrlich-Institute (PEI), Germany; India Ministry of Health and Family Welfare (MoHFW); Health Product Regulatory Authority (HPRA), Ireland; Italian Medicines Agency (AIFA), Italy; Ministry of Health, Labour and Welfare (MHLW) and Pharmaceuticals and Medical Devices Agency (PMDA), Japan; Ministry of Food and Drug Safety (MFDS), Korea; Federal Commission for the Protection against Sanitary Risks (COFEPRIS), Mexico; Medicines Evaluation Board (MEB), Netherlands; Medsafe, Clinical Leadership, Protection & Regulation, Ministry of Health, New Zealand; National Agency for Food Drug Administration and Control (NAFDAC), Nigeria; Health Sciences Authority (HSA) Singapore; South African Health Products Regulatory Authority (SAHPRA), South Africa; Medical Products Agency, Sweden; Swissmedic, Switzerland; Medicines and Healthcare Products Regulatory Agency (MHRA), United Kingdom; Food and Drug Administration (FDA), United States.

Associate members include: Argentina national Administration of Drugs, Foods and Medical Devices (ANMAT); Austrian Medicines and Medical Devices Agency (AGES), Colombia National Food and Drug Surveillance Institute (INVIMA); Cuba Center for State Control of Medicines, Equipment and Medical Devices (CECMED); Danish Medicines Agency (DKMA); Egyptian Drug Authority (EDA); Ghana FDA; Icelandic Medicines Agency (IMA), Israel Ministry of Health (MOH); Poland Office of Registration of Medicinal Products and Biocidal Products (URPLWMiPB); Portugal National Authority of Medicines and Health Products (INFARMED); Russia Federal Service for Surveillance in Healthcare (Roszdravnadzor); Saudi Food and Drug Authority (SFDA); Spanish Agency of Medicines and Medical Devices (AEMPS) and The State Expert Centre of the Ministry of Health of the Ukraine.

The World Health Organization is an Observer to ICMRA. For updates on ICMRA, including its role in the COVID-19 response, visit http://www.icmrahttp://www.icmra.info.info

About the World Health Organization

The World Health Organization provides global leadership in public health within the United Nations system. Founded in 1948, WHO works with 194 Member States, across six regions and from 149 offices, to promote health, keep the world safe and serve the vulnerable. Our goal for 2019-2023 is to ensure that a billion more people have universal health coverage, to protect a billion more people from health emergencies, and provide a further billion people with better health and wellbeing. For updates on COVID-19 and public health advice to protect yourself from coronavirus, visit www.who.int and follow WHO on Twitter, Facebook, Instagram, LinkedIn, TikTok, Pinterest, Snapchat, YouTube, Twitch


WHO Results Report shows global health achievements despite COVID-19 pandemic

16 May 2022

News release

Geneva

Despite the the COVID-19 pandemic, the World Health Organization’s 2020-2021 Results Report tracks WHO’s significant achievements across the global health spectrum. Released ahead of the World Health Assembly next week, the report details such accomplishments as the delivery of more than 1.4 billion vaccine doses via the COVAX facility, the recommendation for broad use of the world’s first malaria vaccine and WHO’s response to some 87 health emergencies, including COVID-19.

During 2020-2021, WHO led the largest-ever global response to a health crisis, working with 1600 technical and operational partners, and helped galvanise the biggest, fastest and most complex vaccination drive in history. The Organization spent US$1.7 billion on essential supplies to the COVID-19 response.

“Even as WHO has responded to the most severe global health crisis in a century, we have continued to support our Member States in addressing many other threats to health, despite squeezed budgets and disrupted services,” said Dr Tedros Adhanom Ghebreyesus, WHO Director-General.

“As the world continues to respond to and recover from the pandemic in the years ahead, WHO’s priority is to invest even more resources for our work in countries, where it matters most,” he continued. “Ensuring WHO has sustainable, predictable and flexible financing is essential for fulfilling our mission to promote health, keep the world safe and serve the vulnerable.”

The ACT-A partnership delivered over 1 billion COVID-19 vaccine doses by January 2022. The global rollout of crucial health materials included nearly US$500 million worth of personal protective equipment; US$ 187 million in oxygen supplies, US$4.8 million in treatments and 110 million diagnostic tests.

However, much remains to be done for the world to get on track for WHO’s target of each country vaccinating 70% of its population by July 2022.  

WHO’s performance beyond pandemic

The Results Report reveals noteworthy achievements beyond the pandemic. Mandatory policies prohibiting the use of trans fatty acids (a hazardous food compound linked to cardiovascular disease), are in effect for 3.2 billion people in 58 countries. Among these countries, 40 have best practice policies, including Brazil, Peru, Singapore, Turkey and the United Kingdom. WHO’s REPLACE initiative aims for a world free of trans-fats by the end of 2023.  

Thanks to implementation of measures mandated by WHO's Framework Convention on Tobacco Control, tobacco use is decreasing in 150 countries, saving lives and livelihoods.  

Due to efforts to scale up life-saving interventions guided by WHO guidelines, 15 countries have achieved elimination of mother-to-child transmission of HIV and/or syphilis. 

And WHO’s recommendation of widespread use of the world’s first malaria vaccine (RTS,S) has been delivered to over 1 million children. It is expected to save 40 000 to 80 000 lives a year, when used with other malaria control interventions. 

A voice for health equity

The report demonstrates WHO’s crucial role as the world’s global health guardian, speaking up for health equity in a world of widening inequalities.

The grave costs of the pandemic were felt everywhere. The report portrays a world which is clearly further off track to reach crucial global health goals. Due to myriad disruptions caused by the COVID-19 pandemic, countries have fallen behind on WHO’s “Triple Billion targets” that provide critical pathways to attain the Sustainable Development Goals (SDGs) by 2030. 

Progress on Universal health coverage and healthier populations are at about one quarter or less the pace needed to reach the Sustainable Development Goals by 2030, and no country was fully prepared for a pandemic of such scale.

COVID-19 also caused huge disruptions to health services: 117 of 127 countries surveyed reported disruption to at least one essential health service because of COVID, whilst the average disruption across those countries was a staggering 45%.

Going forward, fulfilling the triple billion targets will be WHO’s overriding goal, as a measurable means of reducing health equity gaps.

Key role of sustainable financing

The Results Report details WHO’s efforts towards transparency and accountability, providing details of expenditure. The WHO Programme Budget for 2020-2021 was $5 840.4 million.  In fact, financing reached US $7 916 million, due to COVID-19 emergency operations. The surplus was thanks to the generosity of donors, including 12 Member States which contributed approximately 71% of the total financing.

Nonetheless, the largest share of WHO financing is earmarked by donors through specified voluntary contributions. Flexible funds constituted only 20% of total financing in 2020-2021. 

If WHO is to play its full role in achieving the SDGs, delivering on universal health coverage, reducing the burden of ill health and protecting 1 billion more people from health emergencies, the share of regular, stable, predictable financing must increase.

Note to Editors

COVAX is co-led by CEPI, Gavi and WHO, alongside key delivery partner UNICEF. In the Americas, the PAHO Revolving Fund is the recognized procurement agent for COVAX.

WHO’s Triple Billion targets, by 2023: 1 billion more people benefitting from universal health coverage; 1 billion more people better protected from health emergencies; 1 billion more people enjoying better health and well-being.



WHO and MPP announce agreement with NIH for COVID-19 health technologies

12 May 2022

News release

Geneva

WHO’s COVID-19 Technology Access Pool (C-TAP) and the Medicines Patent Pool (MPP) today finalized a licensing agreement with the United States National Institutes of Health (NIH) for the development of several innovative therapeutics, early-stage vaccines and diagnostic tools for COVID-19.

The licenses, which are transparent, global and non-exclusive, will allow manufacturers from around the world to work with MPP and C-TAP to make these technologies accessible to people living in low- and middle-income countries and help put an end to the pandemic.

The 11 COVID-19 technologies offered under two licences include the stabilized spike protein used in currently available COVID-19 vaccines, research tools for vaccine, therapeutic and diagnostic development as well as early-stage vaccine candidates and diagnostics. The full list of the NIH COVID-19 technologies covered in the agreement is here.

“I welcome the generous contribution NIH has made to C-TAP and its example of solidarity and sharing,” said Dr Tedros Adhanom Ghebreyesus, WHO Director-General. “Whether it’s today’s pandemic or tomorrow’s health emergency, it’s through sharing and empowering lower-income countries to manufacture their own health tools that we can ensure a healthier future for everyone.”

“We are honoured to sign these public health-driven licence agreements with NIH under the auspices of C-TAP with the goal of providing equitable access to life-saving health products for the most vulnerable in the world,” said Charles Gore, MPP Executive Director.

“NIH were the first to share their patents with MPP for an HIV product back in 2010 when we were created, and we are delighted to continue strengthening our partnership. It is clear that MPP’s model works across different health technologies.”

The announcement was made today by the US Government at the second Global COVID-19 Summit, co-hosted by the United States, Belize, Germany, Indonesia and Senegal.

Licensing the NIH technologies to MPP under the auspices of C-TAP will allow greater access to these technologies and hopefully lead to the development of commercial products that can address current and future public health needs. In most circumstances, NIH will not collect royalties on sales of products licensed in 49 countries classified by the United Nations as Least Developed Countries.

Launched in 2020 by the WHO Director-General and the President of Costa Rica, and supported by 43 Member States, C-TAP aims to facilitate timely, equitable and affordable access to COVID-19 health products by boosting their production and supply through open, transparent and non-exclusive licensing agreements. MPP provides the licensing expertise to this initiative and holds the licences.

The 11 technologies include:

1. Prefusion spike proteins (Vaccine Development)

2. Structure-Based Design of Spike Immunogens (Research Tool for Vaccine Development)

3. Pseudotyping Plasmid (Research Tool for Vaccine Development)

4. ACE2 Dimer construct (Research Tool for Drug Development)

5. Synthetic humanized llama nanobody library and related use (Research Tool for Drug and Diagnostic Development)

6. Newcastle Disease Virus-Like Particles Displaying Prefusion-Stabilized Spikes (Vaccine Candidate)

7. Parainfluenza virus 3 based vaccine (Vaccine Candidate)

8. A VSV-EBOV-Based Vaccine (Vaccine Candidate)

9. RNASEH-Assisted Detection Assay for RNA (Diagnostic)

10. Detection of SARS-CoV-2 and other RNA Virus (Diagnostic)

11. High-Throughput Diagnostic Test (Diagnostic)

14.9 million excess deaths associated with the COVID-19 pandemic in 2020 and 2021

5 May 2022

News release

New estimates from the World Health Organization (WHO) show that the full death toll associated directly or indirectly with the COVID-19 pandemic (described as “excess mortality”) between 1 January 2020 and 31 December 2021 was approximately 14.9 million (range 13.3 million to 16.6 million).

“These sobering data not only point to the impact of the pandemic but also to the need for all countries to invest in more resilient health systems that can sustain essential health services during crises, including stronger health information systems,” said Dr Tedros Adhanom Ghebreyesus, WHO Director-General. “WHO is committed to working with all countries to strengthen their health information systems to generate better data for better decisions and better outcomes.”

Excess mortality is calculated as the difference between the number of deaths that have occurred and the number that would be expected in the absence of the pandemic based on data from earlier years.

Excess mortality includes deaths associated with COVID-19 directly (due to the disease) or indirectly (due to the pandemic’s impact on health systems and society). Deaths linked indirectly to COVID-19 are attributable to other health conditions for which people were unable to access prevention and treatment because health systems were overburdened by the pandemic. The estimated number of excess deaths can be influenced also by deaths averted during the pandemic due to lower risks of certain events, like motor-vehicle accidents or occupational injuries.

Most of the excess deaths (84%) are concentrated in South-East Asia, Europe, and the Americas. Some 68% of excess deaths are concentrated in just 10 countries globally. Middle-income countries account for 81% of the 14.9 million excess deaths (53% in lower-middle-income countries and 28% in upper-middle-income countries) over the 24-month period, with high-income and low-income countries each accounting for 15% and 4%, respectively.

The estimates for a 24-month period (2020 and 2021) include a breakdown of excess mortality by age and sex. They confirm that the global death toll was higher for men than for women (57% male, 43% female) and higher among older adults. The absolute count of the excess deaths is affected by the population size. The number of excess deaths per 100,000 gives a more objective picture of the pandemic than reported COVID-19 mortality data.


“Measurement of excess mortality is an essential component to understand the impact of the pandemic. Shifts in mortality trends provide decision-makers information to guide policies to reduce mortality and effectively prevent future crises. Because of limited investments in data systems in many countries, the true extent of excess mortality often remains hidden,” said Dr Samira Asma, Assistant Director-General for Data, Analytics and Delivery at WHO. “These new estimates use the best available data and have been produced using a robust methodology and a completely transparent approach.”

“Data is the foundation of our work every day to promote health, keep the world safe, and serve the vulnerable. We know where the data gaps are, and we must collectively intensify our support to countries, so that every country has the capability to track outbreaks in real-time, ensure delivery of essential health services, and safeguard population health,” said Dr Ibrahima Socé Fall, Assistant Director-General for Emergency Response.

The production of these estimates is a result of a global collaboration supported by the work of the Technical Advisory Group for COVID-19 Mortality Assessment and country consultations.

This group, convened jointly by the WHO and the United Nations Department of Economic and Social Affairs (UN DESA), consists of many of the world’s leading experts, who developed an innovative methodology to generate comparable mortality estimates even where data are incomplete or unavailable.

This methodology has been invaluable as many countries still lack capacity for reliable mortality surveillance and therefore do not collect and generate the data needed to calculate excess mortality. Using the publicly available methodology, countries can use their own data to generate or update their own estimates.

“The United Nations system is working together to deliver an authoritative assessment of the global toll of lives lost from the pandemic. This work is an important part of UN DESA’s ongoing collaboration with WHO and other partners to improve global mortality estimates,” said Mr Liu Zhenmin, United Nations Under-Secretary-General for Economic and Social Affairs.

Mr Stefan Schweinfest, Director of the Statistics Division of UN DESA, added: “Data deficiencies make it difficult to assess the true scope of a crisis, with serious consequences for people’s lives. The pandemic has been a stark reminder of the need for better coordination of data systems within countries and for increased international support for building better systems, including for the registration of deaths and other vital events.”

WHO recommends highly successful COVID-19 therapy and calls for wide geographical distribution and transparency from originator

22 April 2022

Statement

Geneva

Today, WHO made a strong recommendation for nirmatrelvir and ritonavir, sold under the name Paxlovid, for mild and moderate COVID-19 patients at highest risk of hospital admission, calling it the best therapeutic choice for high-risk patients to date. However, availability, lack of price transparency in bilateral deals made by the producer, and the need for prompt and accurate testing before administering it, are turning this life-saving medicine into a major challenge for low- and middle-income countries.

Pfizer’s oral antiviral drug (a combination of nirmatrelvir and ritonavir tablets) is strongly recommended for patients with non-severe COVID-19 who are at highest risk of developing severe disease and hospitalization, such as unvaccinated, older, or immunosuppressed patients.

This recommendation is based on new data from two randomized controlled trials involving 3078 patients. The data show that the risk of hospitalization is reduced by 85% following this treatment. In a high-risk group (over 10% risk of hospitalization), that means 84 fewer hospitalizations per 1000 patients.

WHO suggests against its use in patients at lower risk, as the benefits were found to be negligible.

One obstacle for low- and middle-income countries is that the medicine can only be administered while the disease is at its early stages; prompt and accurate testing is therefore essential for a successful outcome with this therapy. Data collected by FIND show that the average daily testing rate in low-income countries is as low as one-eightieth the rate in high-income countries. Improving access to early testing and diagnosis in primary health care settings will be key for the global rollout of this treatment.

WHO is extremely concerned that -- as occurred with COVID-19 vaccines -- low- and middle-income countries will again be pushed to the end of the queue when it comes to accessing this treatment.

Lack of transparency on the part of the originator company is making it difficult for public health organizations to obtain an accurate picture of the availability of the medicine, which countries are involved in bilateral deals and what they are paying. In addition, a licensing agreement made by Pfizer with the Medicines Patent Pool limits the number of countries that can benefit from generic production of the medicine.

The originator product, sold under the name Paxlovid, will be included in the WHO prequalification list today, but generic products are not yet available from quality-assured sources. Several generic companies (many of which are covered by the licensing agreement between the Medicines Pool and Pfizer) are in discussion with WHO Prequalification but may take some time to comply with international standards so that they can supply the medicine internationally.

WHO therefore strongly recommends that Pfizer make its pricing and deals more transparent and that it enlarge the geographical scope of its licence with the Medicines Patent Pool so that more generic manufacturers may start to produce the medicine and make it available faster at affordable prices.

Along with the strong recommendation for the use of nirmatrelvir and ritonavir, WHO has also updated its recommendation on remdesivir, another antiviral medicine.

Previously, WHO had suggested against its use in all COVID-19 patients regardless of disease severity, due to the totality of the evidence at that time showing little or no effect on mortality. Following publication of new data from a clinical trial looking at the outcome of admission to hospital, WHO has updated its recommendation. WHO now suggests the use of remdesivir in mild or moderate COVID-19 patients who are at high risk of hospitalization.

The recommendation for use of remdesivir in patients with severe or critical COVID-19 is currently under review.

Statement on the eleventh meeting of the International Health Regulations (2005) Emergency Committee regarding the coronavirus disease (COVID-19) pandemic

13 April 2022

Statement

The eleventh meeting of the Emergency Committee convened by the WHO Director-General under the International Health Regulations (2005) (IHR) regarding the coronavirus disease (COVID-19) pandemic took place on Monday 11 April 2022 from 12:00 to 16:30 Geneva time (CEST).

Proceedings of the meeting

Members and Advisors of the Emergency Committee were convened by videoconference.

The Director-General welcomed the Committee members and advisers. The Director-General explained that the world has tools to limit transmission, save lives, and protect health systems. He expressed hope in the current epidemiological situation, noting that the world is currently experiencing the lowest number of reported deaths in two years. However, the unpredictable behavior of the SARS-CoV-2 virus and insufficient national responses are contributing to the continued global pandemic context. The Director-General emphasized the importance of States Parties using available medical countermeasures and public health and social measures (PHSM). He highlighted the publication of the updated Strategic Preparedness, Readiness, and Response Plan which provides a roadmap for how the world can end the COVID-19 emergency in 2022 and prepare for future events.

Representatives of the Office of Legal Counsel (LEG) and the Department of Compliance, Risk Management, and Ethics (CRE) briefed the members on their roles and responsibilities. The Ethics Officer from CRE provided the members and advisers with an overview of the WHO Declaration of Interests process. The members and advisers were made aware of their individual responsibility to disclose to WHO, in a timely manner, any interests of a personal, professional, financial, intellectual or commercial nature that may give rise to a perceived or direct conflict of interest. They were additionally reminded of their duty to maintain the confidentiality of the meeting discussions and the work of the Committee. Each member who was present was surveyed. No conflicts of interest were identified.

The Secretariat turned the meeting over to the Chair, Professor Didier Houssin, who reviewed the objectives and agenda of the meeting.

The Secretariat presented on the current status of the COVID-19 pandemic and a vision for how to optimize the ongoing response to the COVID-19 pandemic for 2022. The presentation focused on:

the global epidemiological context and factors that continue to drive transmission;

updates on international traffic as well as COVID-19 proof of vaccination and test result certificates;

the status of COVID-19 vaccination; and

the strategic objectives for countries to incorporate in their COVID-19 response.

The Committee discussed key issues including SARS-CoV-2 variants; use and equitable access to antivirals; vaccine protection and global shifts in the supply and demand for COVID-19 vaccines; hybrid immunity; potential future scenarios for SARS-CoV-2 transmission and challenges posed by concurrent health emergencies; and how Member States are responding to the COVID-19 pandemic. The Committee also noted with concern the growing fatigue among communities worldwide in response to the COVID-19 pandemic and challenges posed by the lack of trust in scientific guidance and governments.

The Committee recognized that SARS-CoV-2 is a novel respiratory pathogen that has not yet established its ecological niche. SARS-CoV-2 continues to have unpredictable viral evolution, which is compounded by its wide-spread circulation and intense transmission in humans, as well as widespread introduction of infection to a range of animal species with potential for animal reservoirs to be established. SARS-COV-2 is continuing to cause high levels of morbidity and mortality, particularly among vulnerable human populations. In this context, the Committee raised concerns that the inappropriate use of antivirals may lead to the emergence of drug-resistant variants. In addition, Committee members acknowledged national, regional, and global capacities to respond to the COVID-19 pandemic context, but noted with concern that some States Parties have relaxed PHSM and reduced testing, impacting thus the global ability to monitor evolution of the virus. The Committee also noted with concern the inconsistency of global COVID-19 requirements for international travel and the negative impact that inappropriate measures may have on all forms of international travel. In this context, the Committee noted that offering vaccination to high-risk groups of international travelers on arrival could be considered a means to mitigate the risk of severe disease or death due to COVID-19 among these individuals.

The Committee stressed the importance of maintaining PHSM to protect vulnerable populations, and maintaining the capacity to scale up PHSM if the epidemiological situation changes. States Parties are advised to regularly adjust their response strategies by monitoring their epidemiological situation (including through use of rapid tests), assessing their health system capacity, and considering the adherence to and attributable impact of individual and combined PHSM.

In addition, the Committee reinforced the continued need for international cooperation and coordination for surveillance, as well as for robust and timely reporting to global systems (such as the Global Influenza Surveillance and Response System) to inform national, regional, and global response efforts. Surveillance activities require coordination between the human and animal sectors and more global attention on the detection of animal infections and possible reservoirs among domestic and wild animals. Timely and systematic monitoring and data sharing on SARS-CoV-2 infection, transmission and evolution in humans and animals will assist global understanding of the virus epidemiology and ecology, the emergence of new variants, their timely identification, and assessment of their public health risks. Continued provision of technical support and guidance from all three levels of the WHO can enable States Parties’ adjustment of COVID-19 surveillance and its integration into respiratory pathogen surveillance systems.

The Committee acknowledged that COVID-19 vaccination is a key tool to reduce morbidity and mortality and reinforced the importance of vaccination (primary series and booster doses, including through heterologous vaccine schedules). The Committee expressed appreciation for WHO and partners’ work to enhance global vaccine supply and distribution. Committee members highlighted the challenges posed by limited vaccination protection, particularly in low-income countries, as well as by waning population-level immunity. As outlined in the SAGE roadmap, vaccination should be prioritized for high-risk groups such as health workers, older adults, and immune-compromised populations, refugees, and migrants. To enhance vaccine uptake, States Parties are encouraged to address national and sub-national barriers for vaccine deployment and to ensure COVID-19 response measures align with and strengthen immunization activities and primary health services.

In addition, the Committee noted the continued importance of WHO’s provision of guidance, training, and tools to support States Parties’ recovery planning process from the COVID-19 pandemic and future respiratory pathogen pandemic preparedness planning.

The Committee unanimously agreed that the COVID-19 pandemic still constitutes an extraordinary event that continues to adversely affect the health of populations around the world, poses an ongoing risk of international spread and interference with international traffic, and requires a coordinated international response. The Committee stressed the importance for States Parties to prepare for future scenarios with the assistance of WHO and to continue robust use of the essential tools (e.g. vaccines, therapeutics, and diagnostics). The Committee concurred that the COVID-19 pandemic remains a PHEIC and offered its advice to the Director-General.

The Director-General determined that the COVID-19 pandemic continues to constitute a PHEIC. He accepted the advice of the Committee and issued the Committee’s advice to States Parties as Temporary Recommendations under the IHR.

The Emergency Committee will be reconvened within three months or earlier, at the discretion of the Director-General. The Director-General thanked the Committee for its work.

Temporary Recommendations to States Parties

The Committee identified the following actions as critical for all countries:

1. NEW: Strengthen national response to the COVID-19 pandemic by updating national preparedness and response plans in line with the priorities and potential scenarios outlined in the 2022 WHO Strategic Preparedness and Response Plan (SPRP). States Parties should conduct assessments (e.g. intra action and after action reviews) to inform current and future response and preparedness efforts. WHO Strategic Preparedness and Response Plan (SPRP)

2. MODIFIED: Achieve national COVID-19 vaccination targets in line with global WHO recommendations of at least 70% of all countries’ populations vaccinated by the start of July 2022. States Parties are requested to support global equitable access to vaccines and to prioritize vaccination of high-risk populations through a primary series and booster schedule. These populations include health workers, older people, people with underlying conditions, immune-compromised, refugees, migrants, people living in fragile settings, and individuals with insufficient access to treatment. States Parties should continually assess their vaccine coverage and epidemiological situation in relation to the COVID-19 pandemic and modify their national responses accordingly. WHO SAGE Prioritization Roadmap

3. MODIFIED: Continue to use evidence-informed and risk-based PHSM. State Parties should be prepared to scale up PHSM rapidly in response to changes in the virus and the population immunity, if COVID-19 hospitalizations, intensive care admissions, and fatalities increase and compromise the health system’s capacity. States Parties are advised to continue the risk-based use of basic PHSM (e.g. wearing masks, staying home when sick, increased hand washing, and improving ventilation of indoor spaces, even in periods of low circulation of SARS-CoV-2). Considerations for implementing and adjusting public health and social measures in the context of COVID-19

4. MODIFIED: Take a risk-based approach to mass gathering events by evaluating, mitigating, and communicating risks. Recognizing that there are different drivers and risk tolerance for mass gatherings, it is critical to consider the epidemiological context (including the prevalence of variants of concern and the intensity of transmission), surveillance, contact tracing and testing capacity, as well as adherence to PHSM when conducting this risk assessment and planning events, in line with WHO guidance. Key planning recommendations for mass gatherings in the context of COVID-19

5. MODIFIED: Adjust COVID-19 surveillance to focus on the burden and impact and prepare for sustainable integration with other surveillance systems. States Parties should collect and publicly share indicators to monitor the burden of COVID-19 (e.g. new hospitalizations, admissions to intensive care units, and deaths). States Parties should integrate respiratory disease surveillance by leveraging and enhancing the Global Influenza Surveillance and Response System (GISRS). States Parties should be encouraged to 1) maintain representative testing strategies; 2) focus on early warning and trend monitoring, such as use of wastewater surveillance; 3) monitor severity in vulnerable groups; and 4) enhance genomic surveillance to detect potential new variants and monitor the evolution of SARS-COV-2. Guidance for surveillance of SARS-CoV-2 variants; WHO global genomic surveillance strategy for pathogens with pandemic and epidemic potential 2022–2032

6. MODIFIED: Ensure availability of essential health, social, and education services. States Parties should enhance access to health, including through the restoration of health services at all levels and strengthening of social systems to cope with the impacts of the pandemic, especially on children and young adults. Within this context, States Parties should maintain educational services by keeping schools fully open with in-person learning. In addition, essential health services, including COVID-19 vaccination, should be provided to migrants and other vulnerable populations as a priority. Building health systems resilience for universal health coverage and health security during the COVID-19 pandemic and beyond: WHO position paper; The State of the Global Education Crisis | UNICEF

7. MODIFIED: Lift international traffic bans and continue to adjust travel measures, based on risk assessments. The failure of travel bans introduced after the detection and reporting of Omicron variant to limit international spread of Omicron demonstrates the ineffectiveness of such measures over time. The implementation of travel measures (such as vaccination, screening, including via testing, isolation/quarantine of travelers) should be based on risk assessments and should avoid placing the financial burden on international travelers, in accordance with Article 40 of the IHR. WHO advice for international traffic in relation to the SARS-CoV-2 Omicron variant

8. MODIFIED: Do NOT require proof of vaccination against COVID-19 for international travel as the only pathway or condition permitting international travel. States Parties should consider a risk-based approach to the facilitation of international travel. Interim position paper: considerations regarding proof of COVID-19 vaccination for international travelers; Policy considerations for implementing a risk-based approach to international travel in the context of COVID-19

9. MODIFIED: Address risk communications and community engagement challenges, proactively counter misinformation and disinformation, and include communities in decision making. To re-build trust and address pandemic fatigue, States Parties should explain clearly and transparently changes to their response strategy. WHO risk communications resources

10. MODIFIED: Support timely uptake of WHO recommended therapeutics. Local production and technology transfer should be encouraged and supported as increased production capacity can contribute to global equitable access to therapeutics. States Parties should provide access to COVID-19 treatments for vulnerable populations, particularly immunosuppressed people as this can also reduce the likelihood of new variants’ emergence. Therapeutics and COVID-19: living guideline

11. MODIFIED: Conduct epidemiological investigations of SARS-CoV-2 transmission at the human-animal interface and targeted surveillance on potential animal hosts and reservoirs. Investigations at the human animal interface should use a One Health approach and involve all relevant stakeholders, including national veterinary services, wildlife authorities, public health services, and the environment sector. To faciliate international transparency, and in line with international reporting obligations, findings from joint investigations should be reported publicly. Statement from the Advisory Group on SARS-CoV-2 Evolution in Animals

SAGE April 2022 meeting highlights

11 April 2022

Departmental news

The highlights of the SAGE plenary 4-7 April 2022 meeting have been published.

The Full report will be published in the Weekly Epidemiological Record on 10.06.2022, and only the wording of the full report should be considered as final

Suspension of supply of COVID-19 vaccine (COVAXIN®)

2 April 2022

Departmental news

Today, WHO confirmed the suspension of supply of Covaxin (Bharat Biotech) through UN procurement agencies, and recommended that countries using the vaccine take action as appropriate.

The suspension is in response to the outcome of a WHO inspection on 14–22 March 2022, and the need to conduct process and facility upgrade to address recently identified deficiencies in good manufacturing practices (GMP).

Bharat Biotech has committed to addressing the GMP deficiencies and is developing a corrective and preventive action plan for submission to the Drugs Controller General of India (DCGI) and WHO. In the interim and as a precautionary measure, the company has indicated that it will suspend production of Covaxin for export. As a consequence, supply will be interrupted for the foreseeable future.

The risk assessment to date does not indicate changes in the risk–benefit ratio. The data, available to WHO, indicate the vaccine is effective and no safety concerns exist.

For continuation of vaccination with alternative sources of COVID-19 vaccines, countries should refer to the respective SAGE recommendation: Considerations for the Assessment of COVID-19 Vaccines for Listing by WHO

WHO launches guidance on digitally documenting SARS-CoV-2 test results

31 March 2022

Departmental news

On 31 March 2022, WHO published Digital Documentation of COVID-19 Certificates: Test Result technical specifications and guidance document for countries and implementing partners on the technical requirements for issuing digital certificates for SARS-CoV-2 diagnostic test result. The full guidance can be found here. This document is the second of two guidance documents on digital documentation of COVID-19 related data of interest: vaccination status and test result.

Similar to the Digital Documentation of COVID-19 Certificates: Vaccination Status Technical Specifications and Implementation Guidance document, this guidance on test results aims to guide countries and technologist in how to develop or adopt digital systems in support of verifiable proof of test results for domestic and cross-border purpose. It provides technical specifications and implementation guidance that details

interoperability standards, facilitated by a common digital architecture, for a digitized test result certificate which can be used as proof of negative test results or proof of previous SARS-CoV-2 infection for international travel, or as a means for protection policies that reduce public health risk in public or private venues – in accordance with individual Member States’ public health policy and their risk-based approach to addressing COVID-19. Additional technical details to support the adoption of open standards for interoperability and approaches for implementing a DDCC:TR solution can be found in the WHO DDCC Health Level Seven (HL7) Fast Healthcare Interoperability Resources (FHIR) implementation guide.

A SARS-CoV-2 diagnostic test result certificate can be purely digital (for example, stored in a smartphone application) and replace the need for a paper test result certificate; or it can be implemented as a digital augmentation of the traditional paper-based record. A digital certificate should never require individuals to have a smartphone or computer.

Future directions

Digital Documentation of COVID-19 Certificates’ (DDCC) specifications (for vaccination status and test results) set the foundations for secure personal health records based on the international patient summary standard. DDCC records contain the most important health and care information needed to demonstrate verifiable proof of vaccination and test results. As countries consider adopting personal health records including digital health wallets, the HL7 FHIR international patient summary standard (IPS) is at the foundation of the DDCC; serving as an expandable approach that will evolve with the needs of the individual, the public health policies, and the health system. The specifications are designed using the IPS and architected for future use, such as preparation for future pandemics.

DDCC provides an “umbrella” specification that can be used to generate multiple representations of a test result certificate or vaccination certificate. However, a global framework to enable convenient use and interoperability of these credentials between systems – while also allowing domestic autonomy over their use – does not exist and is critically needed. Under the current G20 Indonesian presidency, G20 countries are working together on a goal for a harmonized interoperable framework for COVID-19 certificates.

To enable the establishment of interoperable trust networks and allow for trusted exchange of COVID-19 certificates and other health data (e.g. routine immunization data, home-based records) consistent with IPS between systems, the WHO will convene, in collaboration with The Organization for Economic Cooperation and Development (OECD) and the Global Digital Health Partnership (GDHP), a technical consultation on interoperability between digital health trust networks for digital COVID-19 credentials. This technical consultation will inform the development of guidance and technical artifacts to address priority needs of Member States and regional networks that are implementing digital health trust networks for COVID-19. The focus of this consultation will be on the technical underpinning of trust networks, protocols for interoperability, and the health content (including core data sets and business rules).

For any additional inquiries, please contact smartvaccination@who.int.


WHO releases 10-year strategy for genomic surveillance of pathogens

One in three countries do not have the capacity to use this critical tool

30 March 2022

News release

WHO is releasing a strategy to strengthen and scale up genomic surveillance around the world.

Historically, few countries have routinely done genomic surveillance in-country, a technology considered complicated and expensive. But COVID-19 changed that.

Genomic surveillance is the process of constantly monitoring pathogens and analyzing their genetic similarities and differences. It helps researchers, epidemiologists and public health officials to monitor the evolution of infectious diseases agents, alert on the spread of pathogens, and develop counter measures like vaccines.

The Global genomic surveillance strategy for pathogens with pandemic and epidemic potential 2022–2032 is not specific to a single pathogen or disease threat. It provides a high-level unifying framework to leverage existing capacities, address barriers and strengthen the use of genomic surveillance worldwide.

Data collected by WHO show that in March 2021, 54% of countries had this capacity. By January 2022, thanks to the major investments made during the COVID-19 pandemic, the number had increased to 68%. Even greater gains were made in the public sharing of sequence data: in January 2022, 43% more countries published their sequence data compared to a year before.

Despite this fast progress, much remains to be done. Any new technology comes with the risk of increasing inequity, which is one of the gaps this strategy targets.

Various public health programmes – from Ebola to cholera – use genomic surveillance to understand a pathogen at its molecular level, but COVID-19 has highlighted the challenges of bringing genomics to scale.

The complexities of genomics and the challenges of sustaining capacities in different settings, including workforce needs, means that most countries cannot develop these capabilities on their own. The global strategy helps keep our eyes on the horizon and provides a unifying framework for action. WHO looks forward to working with countries and partners in this important and highly dynamic field.

- Dr Tedros Adhanom Ghebreyesus

WHO Director-General

“The complexities of genomics and the challenges of sustaining capacities in different settings, including workforce needs, means that most countries cannot develop these capabilities on their own. The global strategy helps keep our eyes on the horizon and provides a unifying framework for action. WHO looks forward to working with countries and partners in this important and highly dynamic field,” said Dr Tedros Adhanom Ghebreyesus, WHO Director-General. “We will do best if we work together.”

The COVID-19 pandemic has shown that health systems need genomic surveillance so that risks are rapidly detected and addressed. This technology has been critical in this response, from the identification of a novel coronavirus, to the development of the first diagnostic tests and vaccines, to the tracking and identification of new virus variants.

“Genomic surveillance is critical for stronger pandemic and epidemic preparedness and response,” said Dr Michael Ryan, Executive Director, WHO Health Emergencies Programme. “This pandemic has laid bare the fact that we live in an interconnected world and that we are only as strong as our weakest link. Improving global disease surveillance means improving local disease surveillance. That is where we need to act, and this strategy will provide us with the foundation.”

Read more about the strategy here.

Interim Statement on COVID-19 vaccines in the context of the circulation of the Omicron SARS-CoV-2 Variant from the WHO Technical Advisory Group on COVID-19 Vaccine Composition (TAG-CO-VAC)

8 March 2022

Key messages:

The TAG-CO-VAC is reviewing available data to optimize vaccine mediated protection against prevalent circulating variants. The TAG-CO-VAC strongly supports urgent and broad access to current COVID-19 vaccines for primary series and booster doses, particularly for groups at risk of developing severe disease, given that current COVID-19 vaccines continue to provide high levels of protection against severe disease and death, even in the context of the circulation of Omicron.

However, to ensure COVID-19 vaccines provide optimal protection into the future, they may need to be updated as new, antigenically distinct variants emerge. The updated vaccines may be monovalent targeting the predominant circulating variant, or multivalent based on different variants.

Ideally, COVID-19 vaccines will prevent infection and transmission, in addition to providing protection against severe disease and death. The development of pan SARS-CoV-2 or pansarbecovirus vaccines, as well as the development of vaccines that are able to elicit mucosal immunity, may be desirable options, but the timeframe for their development and production is uncertain.

The TAG-CO-VAC continues to encourage COVID-19 vaccine manufacturers to generate and provide data to WHO on performance of current and variant-specific COVID-19 vaccines so that they can be considered as part of a broad decision-making framework on COVID-19 vaccine composition, allowing the TAG-CO-VAC to issue more specific advice to WHO on adjustments needed to COVID-19 vaccine strain composition.

The World Health Organization, with the support of the Technical Advisory Group on COVID-19 Vaccine Composition (TAG-CO-VAC), continues to review and assess the public health implications of emerging SARS-CoV-2 Variants of Concern (VOC) on the performance of COVID-19 vaccines. Since the publication of the interim statement on COVID-19 vaccines on 11 January 2022, Omicron has become the dominant VOC globally, rapidly replacing other circulating variants. This statement highlights the global epidemiological situation, challenges of updating vaccine composition and provides the current position of the TAG-CO-VAC.

Epidemiological situation

The current global epidemiological situation is characterized by rapid and relatively synchronous dominance of Omicron variant in all six WHO regions. While global cases are declining, there are reduced testing resources and capacities in some areas and the epidemiological situation remains heterogeneous, with a number of regions and countries reporting increases in new weekly cases, while others are now reporting declines.

Omicron is comprised of several genetically related sublineages, including BA.1, BA.2 and BA.3, each of which is being monitored by WHO and partners. At a global level, BA.1 has been the predominant Omicron lineage, however, the proportion of reported sequences designated as BA.2 has been increasing relative to BA.1 in recent weeks, and is the predominant Omicron lineage in several countries. BA.1 and BA.2 have some genetic differences, which may make them antigenically distinct. Reinfection with BA.2 following infection with BA.1 has been documented, however, initial data from population-level studies suggest that infection with BA.1 provides substantial protection against reinfection with BA.2, at least for the limited period for which data are available. For more details on the Omicron sublineages, please refer to the statement by WHO on the Omicron sublineage BA.2 , published on 22 February 2022.

Updating current COVID-19 vaccines

The public health goal of COVID-19 vaccination prioritizes protection against severe disease and death. Current vaccines appear to confer high levels of protection against severe disease outcomes associated with Omicron infection. The TAG-CO-VAC therefore strongly supports urgent and broad access to current COVID-19 vaccines for primary series and booster doses, particularly for groups at risk of developing severe disease. The near- and medium-term supply of the available vaccines has increased substantially, however, vaccine equity remains an important challenge and all efforts to address such inequities are strongly encouraged.

The first interim statement from the TAG-CO-VAC highlighted the need for the development of vaccines that provide protection against infection and prevent transmission, in addition to the protection from severe disease and death, as a means to achieve a greater public health impact from COVID-19 vaccination. In this context, vaccines that are able to elicit mucosal immunity, in addition to systemic immunity, are an important goal. One of the options proposed in the first statement was the development of pan SARS-CoV-2 or pansarbecovirus vaccines. Such vaccines would provide protection that would effectively be variant-proof, and work in this area should be accelerated.

Current vaccines are based on the virus that circulated early in the pandemic (ancestral virus e.g. GISAID: hCoV-19/Wuhan/WIV04/2019). Since then, there has been continuous and substantial virus evolution and it is likely that this evolution will continue, resulting in the emergence of new variants. The composition of current COVID-19 vaccines may therefore need to be updated. Any update to current COVID-19 vaccine composition would aim to, at a minimum, retain protection against severe disease and death, while ensuring the breadth of the immune response against circulating and emerging variants, which may be antigenically distinct.

The TAG-CO-VAC considered a number of issues, all of which are important in any decision on COVID-19 vaccine composition:

There are heterogeneous levels of population immunity between countries due to different waves of VOCs and different types, levels and timing of vaccination, but robust data on the global immunologic landscape are limited. The performance of any updated vaccine(s) may vary depending on the nature and magnitude of previously acquired immunity.

When updated vaccines become available, a substantial proportion of the global population will have been exposed to SARS-CoV-2, either as a result of vaccination and/or prior infection. As above, the performance of any updated vaccine(s) may vary depending on the nature and magnitude of previously acquired immunity.

There are also considerable uncertainties as to how the virus will continue to evolve and the antigenic characteristics of future variants. Given widespread transmission of Omicron globally, the possibility of its continued evolution is high and a new variant may emerge before an updated vaccine can be produced and delivered at scale.

WHO is tracking lineages under the ‘umbrella’ of Omicron, including BA.1 and BA.2. Though data are emerging, additional antigenic and virologic characterization of these lineages is needed both independently and in comparison, to the other lineages.

While the body of evidence on the immune response to Omicron following infection is rapidly growing, data on breadth, magnitude, and durability of humoral and cell-mediated immune responses to variants from variant-specific candidate vaccines using different vaccine platforms remain limited.

In addition to the current COVID-19 vaccines, there are many other COVID-19 vaccines in various stages of clinical and preclinical development. Any decision from the TAG-CO-VAC on COVID-19 vaccine composition would apply primarily to current COVID-19 vaccines.

Position of the TAG-CO-VAC

The TAG-CO-VAC welcomes, where feasible, the development and initiation of clinical trials on variant-specific candidate vaccines against WHO-designated VOCs, including Omicron. In this context, the TAG-CO-VAC is seeking evidence of robust homologous immune responses in primed and unprimed individuals and cross-reactivity data in primed individuals. The TAG-CO-VAC encourages collection of data following one and two doses of any modified vaccine across a variety of relevant vaccine platforms.

The TAG-CO-VAC continues to encourage COVID-19 vaccine manufacturers to generate and provide data to WHO on the performance of current and variant-specific candidate COVID-19 vaccines, including the breadth, magnitude, and durability of humoral and cell-mediated immune responses to variants through monovalent and/or multivalent vaccines. The TAG-CO-VAC will carefully consider these data as part of a broader decision-making framework on COVID-19 vaccine composition, allowing the TAG-CO-VAC to issue more specific advice on any adjustments that may be needed to COVID-19 vaccine strain composition, developed either as a monovalent vaccine targeting the predominant circulating variant(s) or a multivalent vaccine derived from different variants.

The TAG-CO-VAC recognizes the independent role and procedures of relevant regulatory authorities in establishing the necessary requirements for evaluation under the currently established regulatory pathways, and the role of WHO in ensuring alignment, collaboration and a continuous exchange of information between WHO and its expert groups, the TAG-CO-VAC, regulatory authorities, and COVID-19 vaccine manufacturers.

The statement reflects the current vaccine performance and landscape of vaccine development. The statement will therefore be updated as data become available.

Joint statement on the prioritization of monitoring SARS-CoV-2 infection in wildlife and preventing the formation of animal reservoirs

By Food and Agriculture Organization (FAO), World Organisation for Animal Health (OIE) and World Health Organization (WHO)

7 March 2022

As we enter the third year of the pandemic, SARS-CoV-2, the virus that causes COVID-19, is spreading between people at an intense level globally. There are many factors that are driving transmission. One of these is the emergence of highly transmissible variants of concern, the latest being Omicron. The virus continues to evolve and the risk of future emergence of variants is high.

Although the COVID-19 pandemic is driven by human-to-human transmission, the SARS-CoV-2 virus is also known to infect animal species. Current knowledge indicates that wildlife does not play a significant role in the spread of SARS-CoV-2 in humans, but spread in animal populations can affect the health of these populations and may facilitate the emergence of new virus variants.

In addition to domestic animals, free-ranging, captive or farmed wild animals such as big cats, minks, ferrets, North American white-tailed deer and great apes have thus far been observed to be infected with SARS-CoV-2. To date, farmed mink and pet hamsters have been shown to be capable of infecting humans with the SARS-CoV-2 virus and a potential case of transmission between white-tailed deer and a human is currently under review.

The introduction of SARS-CoV-2 to wildlife could result in the establishment of animal reservoirs. For example, it has been reported that, approximately one-third of wild white-tailed deer in the United States of America have been infected with SARS-CoV-2, initially via several human-to-deer transmission events. The SARS-CoV-2 lineages detected in white-tailed deer have also been circulating in close-by human populations. White-tailed deer have been shown to shed virus and transmit it between each other.

FAO, OIE and WHO call on all countries to take steps to reduce the risk of SARS-CoV-2 transmission between humans and wildlife with the aim of reducing the risk of variant emergence and for protecting both humans and wildlife. We urge authorities to adopt relevant regulations and disseminate previously released recommendations by FAO, OIE and WHO to (1) people working in close contact with or handling wildlife, including hunters and butchers; and (2) the public.

Personnel working closely with wildlife should be trained to implement measures that reduce the risk of transmission between people and between people and animals, using WHO advice on how to protect oneself and prevent the spread of COVID-19, and OIE and FAO guidelines on the use of personal protective equipment (PPE) and good hygiene practices around animals, including good hygiene practices for hunters and butchers.

Current evidence suggests that humans are not infected with the SARS-CoV-2 virus by eating meat. However, hunters should not track animals that appear sick or harvest those that are found dead. Appropriate butchering and food preparing techniques, including proper hygiene practices, can limit transmission of coronaviruses, including SARS-CoV-2, and other zoonotic pathogens.

FAO, OIE and WHO stress that the public should be educated about contact with wildlife. Some wild animals may come close to human settlements and residential areas. As a general precaution, people should not approach or feed wild animals or touch or eat those that are orphaned, sick or found dead (including road kills). Instead, they should contact local wildlife authorities or a wildlife health professional.

It is also crucial to safely dispose of uneaten food, masks, tissues, and any other human waste to avoid attracting wildlife, especially to urban areas and, if possible, keep domestic animals away from wildlife and their droppings.

We furthermore encourage countries’ national animal and human health services to adopt the following measures:

Encourage collaboration between national veterinary services and national wildlife authorities, whose partnership is key to promoting animal health and safeguarding human and environmental health.

Promote monitoring of wildlife and encourage sampling of wild animals known to be potentially susceptible to SARS-CoV-2.

Share all genetic sequence data from animal surveillance studies through publicly available databases.

Report confirmed animal cases of SARS-CoV-2 to the OIE through the World Animal Health Information System (OIE-WAHIS).

Craft messages about SARS-CoV-2 in animals with care so that inaccurate public perceptions do not negatively impact conservation efforts. No animal found to be infected with SARS-CoV-2 should be abandoned, rejected, or killed without providing justification from a country- or event-specific risk assessment.

Suspend the sale of captured live wild mammals in food markets as an emergency measure.

Our organizations emphasize the importance of monitoring mammalian wildlife populations for SARS-CoV-2 infection, reporting results to National Veterinary Services (who report these findings to the OIE) and sharing genomic sequencing data on publicly available databases. Countries should also adopt precautions to reduce the risk of establishment of animal reservoirs and potential acceleration of virus evolution in novel hosts, which could lead to the emergence of new SARS-CoV-2 variants. Such measures will preserve the health of precious wildlife as well as humans.

We invite governments and other stakeholders to bring the contents of this joint statement to the attention of competent authorities and all parties concerned.

Eighth Meeting of the Multilateral Leaders Task Force on COVID-19, 1 March 2022: "Third Consultation with the CEOs of leading vaccine manufacturers"

7 March 2022

The heads of the International Monetary Fund, World Bank Group, World Health Organization, and World Trade Organization held high-level consultations with UNICEF, Gavi, the Vaccine Alliance, the Global Lead Coordinator for the COVID-19 Vaccine Country Readiness and Delivery and the CEOs of leading vaccine manufacturers on 1 March 2022 aimed at ensuring the rapid delivery of vaccines to where they are needed the most and putting those vaccines into arms.

The Multilateral Leaders Task Force issued the following statement:

"In the past few months, we have seen unprecedented levels of disease transmission across the world due to the Omicron variant. Still, unequal access to COVID-19 vaccines, tests and treatments is rampant, prolonging the pandemic. 23 countries are yet to fully vaccinate 10% of their populations, 73 countries are yet to achieve 40% coverage and many more are projected to miss the 70% target by middle of this year.

The biggest challenges are in low-income countries (LICs), which are concentrated in Africa. Only 7% of people in LICs have been fully vaccinated, compared with 73% in high-income countries. Safeguarding the health of people living in the world’s poorest countries in the face of a changing pandemic is a key priority. We must and can ensure that these countries have the access, the means, and the capacity to vaccinate their populations, especially those who are most at risk.

Despite the challenges, there has been progress. The vaccine supply constraints from last year have eased, and export restrictions are not currently an issue. Our efforts must now focus on supporting countries to increase vaccination rates. There is no "one-size-fits-all" approach as each country faces different political, administrative, and capacity challenges.

Insufficient health care infrastructure, including warehouses, cold chain capacity; lack of trained vaccinators; complexities associated with the management of multiple vaccines; lack of data systems to support vaccination campaigns; and misinformation and vaccine hesitancy are common hurdles that governments must confront. But we have good lessons to draw on from countries around the world that have managed to overcome obstacles and rollout vaccination campaigns, including from low-income countries.

Sustained investment in geographically diversified manufacturing capacity and new technologies for vaccines, therapeutics, and diagnostics is key for ensuring more equitable, affordable, and timely access to tools for developing countries. In this context, we welcome the work of the leading vaccine manufacturers in exploring and undertaking new partnerships and call for them to work closely with international organizations (IOs) and countries to capitalize on practical solutions, sharing licenses, technology and know-how.

A top priority to end the pandemic is deploying financing quickly to accelerate the development, production, and equitable access to COVID-19 tests, treatments and vaccines in low- and middle-income countries. Fully funding the Access to COVID-19 Tools (ACT) Accelerator is critical.

As vaccine supply increases in 2022, close coordination among all stakeholders will be crucial to aligning supply with demand, reducing supply fragmentation, and deploying vaccines in the most effective way. We must adjust to constantly evolving challenges and keep working together. As the late Dr Paul Farmer said: "Any time there's a new tool developed – whether they are vaccines or therapeutics – there must also be a delivery plan."

Let us acknowledge the importance of delivery, as this is where lives are saved, families are kept whole, children continue their education, communities stay strong, and economies grow."

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About the Multilateral Leaders Task Force

This joint initiative of the International Monetary Fund, World Bank Group, World Health Organization, and World Trade Organization aims to support the roll out of COVID-19 tools by leveraging multilateral finance and trade solutions, particularly for low and middle-income countries. It supports the goals of the ACT-Accelerator and complementary initiatives in the delivery of COVID-19 diagnostics, vaccines, therapeutics, and PPE.

WHO and MPP welcome NIH’s offer of COVID-19 health technologies to C-TAP

3 March 2022


The World Health Organization (WHO) and the Medicines Patent Pool (MPP) jointly welcome the announcement that the United States National Institutes of Health (NIH) will offer several technologies to the COVID-19 Technology Access Pool (C-TAP) for potential licensing through MPP. The announcement was made today at the U.S. COVID-19 Dialogue with Ministers of Health meeting in the presence of WHO Director-General, Dr Tedros Adhanom Ghebreyesus, and NIAID Director and Chief Medical Advisor to the President of United States, Anthony Fauci.

“I thank NIH for its offer of innovative therapeutics, vaccines and diagnostic methods for COVID-19,” said WHO Director-General Dr Tedros Adhanom Ghebreyesus. “Voluntary sharing of technologies through non-exclusive agreements will not only help us put the pandemic behind us; it will also empower low- and middle-income countries to produce their own medical products and achieve equitable access.”

“NIH were the first to share their patents with MPP for an HIV product back in 2010 when we were created,” said Charles Gore, MPP Executive Director. “We will be honoured to sign public health-driven transparent non-exclusive licence agreements with NIH under the auspices of C-TAP when the negotiations have concluded, with the goal to provide access of these innovative technologies to people in need around the world and help put an end to the pandemic.”

Launched in 2020 by the WHO Director-General and the President of Costa Rica, and supported by 43 Member States, C-TAP aims to facilitate timely, equitable and affordable access to COVID-19 health products by boosting their production and supply through open, non-exclusive licensing agreements. MPP provides the licensing expertise to this initiative and holds the licences.

Ukraine due to crisis, warn WHO Director-General and WHO Regional Director for Europe

Dr Tedros Adhanom Ghebreyesus and Dr Hans Henri P. Kluge call for critical medical supplies to safely reach those who need them, and are working with partners to establish safe transit for shipments through Poland

27 February 2022

During the crisis in Ukraine, health must remain a priority pillar of the humanitarian response, with health systems and facilities remaining protected, functional, safe and accessible to all who need essential medical services, and health workers protected so they can continue to save lives.

This must include the safe and reliable provision of essential medical supplies, including life-saving medicinal oxygen supplies, which are crucial for patients with a range of conditions, including those with COVID-19 (which number 1700 in hospital now), and those with other critical illnesses (from neonates to older persons) stemming from complications of pregnancy, childbirth, chronic conditions, sepsis, and injuries and trauma.

The oxygen supply situation is nearing a very dangerous point in Ukraine. Trucks are unable to transport oxygen supplies from plants to hospitals across the country, including the capital Kyiv. The majority of hospitals could exhaust their oxygen reserves within the next 24 hours. Some have already run out. This puts thousands of lives at risk.

Further, medical oxygen generator manufacturers in several areas are also facing shortages of zeolite, a crucial, mainly imported chemical product necessary to produce safe medical oxygen. Safe deliveries of zeolite from outside Ukraine to these plants is also needed.

Compounding the risk to patients, critical hospital services are also being jeopardized by electricity and power shortages, and ambulances transporting patients are in danger of getting caught in the crossfire.

In recent years, with WHO support, Ukraine had made significant strides in strengthening its health systems under an ambitious health reform programme. This included the rapid scale-up of oxygen therapy capacity for severely ill patients during the COVID-19 pandemic. Of the over 600 health facilities nationwide assessed by WHO during the pandemic, close to half were directly supported with supplies, technical know-how and infrastructure investments, enabling health authorities to save tens of thousands of lives.

This progress is now at risk of being derailed during the current crisis.

WHO is helping health authorities identify the country’s immediate oxygen supply surge needs, assuming a 20–25% increase over previous needs before the crisis escalated last week.

Despite the challenges posed by the current situation, WHO is working to ensure a supply of oxygen-related medical devices and trauma treatment supplies.

To achieve this, WHO is actively looking at solutions to increase supplies that likely would include the importation of oxygen (liquid and cylinders) from regional networks. These supplies would need safe transit, including via a logistics corridor through Poland. It is imperative to ensure that lifesaving medical supplies – including oxygen – reach those who need them.

WHO Director-General: Deeply concerned over escalating health crisis in Ukraine

WHO releases emergency funds to purchase desperately needed medical supplies

24 February 2022

The World Health Organization (WHO) is deeply concerned for the health of the people of Ukraine in the escalating crisis. The health system must continue to function to deliver essential care to people for all health issues, from COVID-19 to cancer, diabetes and tuberculosis, to mental health issues, especially for vulnerable groups such as older persons and migrants.

Maximum care must be taken by all parties to ensure that health facilities, workers, patients, transport, and supplies are not targeted. As part of WHO’s role to document attacks on health, we will continue to monitor and report such incidents.

I also call for sustained and safe access for the delivery of humanitarian assistance.

WHO has for decades worked closely with health authorities across Ukraine. We have a deep knowledge of the capacities and needs of the country’s health system.

Today I released a further US$3.5 million from WHO’s Contingency Fund for Emergencies (CFE) to purchase and deliver urgent medical supplies. This humanitarian health support is expected to rise following further needs assessments. This new support complements the trauma and medical supplies which we prepositioned in health facilities.

We will continue to deliver care and support the people across Ukraine affected by this crisis.

Statement on Omicron sublineage BA.2

22 February 2022

As part of its on-going work to track variants, WHO's Technical Advisory Group on SARS-CoV-2 Virus Evolution (TAG-VE) met yesterday to discuss the latest evidence on the Omicron variant of concern, including its sublineages BA.1 and BA.2.

Based on available data of transmission, severity, reinfection, diagnostics, therapeutics and impacts of vaccines, the group reinforced that the BA.2 sublineage should continue to be considered a variant of concern and that it should remain classified as Omicron. The group emphasized that BA.2 should continue to be monitored as a distinct sublineage of Omicron by public health authorities.

The Omicron variant of concern is currently the dominant variant circulating globally, accounting for nearly all sequences reported to GISAID. Omicron is made up of several sublineages, each of them being monitored by WHO and partners. Of them, the most common ones are BA.1, BA.1.1 (or Nextstrain clade 21K) and BA.2 (or Nextstrain clade 21L). At a global level, the proportion of reported sequences designated BA.2 has been increasing relative to BA.1 in recent weeks, however the global circulation of all variants is reportedly declining.

BA.2 differs from BA.1 in its genetic sequence, including some amino acid differences in the spike protein and other proteins. Studies have shown that BA.2 has a growth advantage over BA.1. Studies are ongoing to understand the reasons for this growth advantage, but initial data suggest that BA.2 appears inherently more transmissible than BA.1, which currently remains the most common Omicron sublineage reported. This difference in transmissibility appears to be much smaller than, for example, the difference between BA.1 and Delta. Further, although BA.2 sequences are increasing in proportion relative to other Omicron sublineages (BA.1 and BA.1.1), there is still a reported decline in overall cases globally.

Studies are evaluating the risk of reinfection with BA.2 compared to BA.1. Reinfection with BA.2 following infection with BA.1 has been documented, however, initial data from population-level reinfection studies suggest that infection with BA.1 provides strong protection against reinfection with BA.2, at least for the limited period for which data are available.

While reaching the above determination, the TAG-VE also looked at preliminary laboratory data from Japan generated using animal models without any immunity to SARS-CoV-2 which highlighted that BA.2 may cause more severe disease in hamsters compared to BA.1. They also considered real-world data on clinical severity from South Africa, the United Kingdom, and Denmark, where immunity from vaccination or natural infection is high: in this data, there was no reported difference in severity between BA.2 and BA.1.

WHO will continue to closely monitor the BA.2 lineage as part of Omicron and requests countries to continue to be vigilant, to monitor and report sequences, as well as to conduct independent and comparative analyses of the different Omicron sublineages.

The TAG-VE meets regularly and continues to discuss available data on transmissibility and severity of variants, and their impact on diagnostics, therapeutics, and vaccines.