Articles related to Vaccination and Prevention of Covid -19

10 vaccine.pdf

Perceived COVID-19 vaccine effectiveness, acceptance, and drivers of vaccination decision-making among the general adult population: A global survey of 20 countries

Roy Rillera Marzo1,2,3, Absar AhmadID4 , Md. Saiful IslamID5,6, Mohammad Yasir Essar7 , Petra HeidlerID8,9,10, Isabel King11,12, Arulmani ThiyagarajanID13, Kittisak JermsittiparsertID14, Karnjana Songwathana15, Delan Ameen YounusID16, Radwa Abdullah El-AbasiriID17, Burcu Kucuk BicerID18, Nhat Tan PhamID19,20, Titik RespatiID21, Susan FitriyanaID22, Erwin Martinez FallerID23, Aries Moralidad BaldonadoID24, Md Arif Billah25, Yadanar AungID26,27, Shehu Muhammad Hassan28, Muhammad Mujtaba Asad29, Kareem Ahmed El-Fass30, Sudip Bhattacharya31, Sunil Shrestha32, Nouran Ameen Elsayed Hamza33,34, Pascal Friedmann35, Michael HeadID36, Yulan LinID37*, Siyan Yi38,39,40

Abstract

Background Mass vaccination campaigns have significantly reduced the COVID-19 burden. However, vaccine hesitancy has posed significant global concerns. The purpose of this study was to determine the characteristics that influence perceptions of COVID-19 vaccine efficacy, acceptability, hesitancy and decision making to take vaccine among general adult populations in a variety of socioeconomic and cultural contexts. Methods Using a snowball sampling approach, we conducted an online cross-sectional study in 20 countries across four continents from February to May 2021. Results A total of 10,477 participants were included in the analyses with a mean age of 36±14.3 years. The findings revealed the prevalence of perceptions towards COVID-19 vaccine’s effectiveness (78.8%), acceptance (81.8%), hesitancy (47.2%), and drivers of vaccination decision-making (convenience [73.3%], health providers’ advice [81.8%], and costs [57.0%]). The county-wise distribution included effectiveness (67.8–95.9%; 67.8% in Egypt to 95.9% in Malaysia), acceptance (64.7–96.0%; 64.7% in Australia to 96.0% in Malaysia), hesitancy (31.5–86.0%; 31.5% in Egypt to 86.0% in Vietnam), convenience (49.7–95.7%; 49.7% in Austria to 95.7% in Malaysia), advice (66.1–97.3%; 66.1% in Austria to 97.3% in Malaysia), and costs (16.0–91.3%; 16.0% in Vietnam to 91.3% in Malaysia). In multivariable regression analysis, several socio-demographic characteristics were identified as associated factors of outcome variables including, i) vaccine effectiveness: younger age, male, urban residence, higher education, and higher income; ii) acceptance: younger age, male, urban residence, higher education, married, and higher income; and iii) hesitancy: male, higher education, employed, unmarried, and lower income. Likewise, the factors associated with vaccination decision-making including i) convenience: younger age, urban residence, higher education, married, and lower income; ii) advice: younger age, urban residence, higher education, unemployed/student, married, and medium income; and iii) costs: younger age, higher education, unemployed/student, and lower income. Conclusions Most participants believed that vaccination would effectively control and prevent COVID-19, and they would take vaccinations upon availability. Determinant factors found in this study are critical and should be considered as essential elements in developing COVID-19 vaccination campaigns to boost vaccination uptake in the populations.

9 vaccine.pdf

Effectiveness of an inactivated virus-based SARS-CoV-2 vaccine, BBV152, in India: a test-negative, case-control study

Devashish Desai, Adil Rashid Khan, Manish Soneja, Ankit Mittal, Shivdas Naik, Parul Kodan, Ayan Mandal, Ganesh Tarachand Maher, Rohit Kumar, Ayush Agarwal, Naveen R Gowda, Vikas H, Parmeshwar Kumar, Shivam Pandey, R M Pandey, Arvind Kumar, Animesh Ray, Pankaj Jorwal, Neeraj Nischal, Aashish Choudhary, Megha Brijwal, Karan Madan, Rakesh Lodha, Sanjeev Sinha, Lalit Dar, Naveet Wig, Randeep Guleria

Summary

Background BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine that has been deployed in India. The results of the phase 3 trial have shown clinical efficacy of BBV152. We aimed to evaluate the effectiveness of BBV152 against symptomatic RT-PCR-confirmed SARS-CoV-2 infection. Methods We conducted a test-negative, case-control study among employees of the All India Institute of Medical Sciences (a tertiary care hospital in New Delhi, India), who had symptoms suggestive of COVID-19 and had an RT-PCR test for SARS-CoV-2 during the peak of the second wave of the COVID-19 pandemic in India between April 15 and May 15, 2021. Cases (test-positives) and controls (test-negatives) were matched (1:1) on the basis of age and gender. The odds of vaccination with BBV152 were compared between cases and controls and adjusted for level of occupational exposure (to COVID-19), previous SARS-CoV-2 infection, and calendar time, using conditional logistic regression. The primary outcome was effectiveness of two doses of BBV152 (with the second dose received at least 14 days before testing) in reducing the odds of symptomatic RT-PCR-confirmed SARS-CoV-2 infection, expressed as (1 –odds ratio)×100%. Findings Between April 15 and May 15, 2021, 3732 individuals had an RT-PCR test. Of these, 2714 symptomatic employees had data on vaccination status, and 1068 matched case-control pairs were available for analysis. The adjusted effectiveness of BBV152 against symptomatic COVID-19 after two doses administered at least 14 days before testing was 50% (95% CI 33–62; p<0.001). The adjusted effectiveness of two doses administered at least 28 days before testing was 46% (95% CI 22–62) and administered at least 42 days before testing was 57% (21–76). After excluding participants with previous SARS-CoV-2 infections, the adjusted effectiveness of two doses administered at least 14 days before testing was 47% (95% CI 29–61). Interpretation This study shows the effectiveness of two doses of BBV152 against symptomatic COVID-19 in the context of a huge surge in cases, presumably dominated by the potentially immune-evasive delta (B.1.617.2) variant of SARS-CoV-2. Our findings support the ongoing roll-out of this vaccine to help control the spread of SARS-CoV-2, while continuing the emphasis on adherence to non-pharmacological measures.

8 vaccine.pdf

Acute herpes zoster radiculopathy mimicking cervical radiculopathy after ChAdOx1 nCoV-19/ AZD1222 vaccination

Andrew Dermawan ,1 Matthew Jun Min Ting ,2 Thomas Chemmanam ,3,4 Chok Lui2

SUMMARY

This case report describes an 84-year-old man who presented with 3 weeks of gradually worsening right arm weakness associated with a painful vesicular rash across his arm. This occurred 3 days after his first dose of the ChAdOx1 nCoV-19/AZD1222 (University of Oxford, AstraZeneca and the Serum Institute of India) vaccine. The diagnosis was complicated by the presence of right C5–C6 foraminal stenosis compressing on the C6 nerve root sheath on non-contrast MRI, leading to an initial diagnosis of cervical radiculopathy. However, a positive varicella zoster virus-PCR test and findings of abnormal contrast enhancement of his right C5–C7 nerve roots on gadolinium-enhanced MRI resulted in a revision of his diagnosis to zoster radiculopathy. He was subsequently commenced on oral valacilovir and made significant recovery. This report aims to highlight the diagnostic dilemma between cervical radiculopathy secondary to spondylosis and zoster radiculopathy and how an erroneous diagnosis could result in inappropriate, aggressive surgical intervention and delayed treatment with antiviral therapy.

7 vaccine.pdf

Vaccination-associated immune thrombocytopenia possibly due to ChAdOx1 nCoV-19 (Covishield) coronavirus vaccine

Prakash Sivaramakrishnan, Mayank Mishra

SUMMARY

Immune thrombocytopenia (ITP) is an acquired haemorrhagic diathesis of immune-mediated destruction, impaired production or increased splenic sequestration of platelets. It can be idiopathic (primary) or secondary (infections, medications, HIV infection, malignancies, connective tissue diseases or rarely secondary to vaccination). ITP postvaccination is termed vaccine-associated ITP (VITP) and is known to be caused by vaccines against various infectious agents such as measles-mumps-rubella, Haemophilus influenzae, pneumococcus, hepatitis B virus and human papilloma virus. Cases of VITP post SARS-CoV-2 vaccination have also been reported in the literature. Various hypotheses on the occurrence of the same are theorised, but no single theory has been proven to cause VITP conclusively. Management includes routine treatment of ITP with use of agents such as steroids, intravenous immunoglobulins, or on rare occasions a thrombopoietic agent or vinca alkaloids. We present a case of VITP possibly due to ChAdOx1 nCoV-19 (Covishield) vaccination in a middle-aged woman who responded to steroid therapy.

6 vaccine.pdf

Non-arteritic anterior ischaemic optic neuropathy (NA-AION) and COVID-19 vaccination

Srinivasan Sanjay,1 Isha Acharya,1 Abdul Rawoof,2 Rohit Shetty2,3

SUMMARY

A woman in her 50s presented with diminution of vision in her left eye (OS) 4 days after COVISHIELDTM vaccination. She had been diagnosed with non-arteritic anterior ischaemic optic neuropathy (NA-AION) of right eye (OD) 8 months earlier. The present episode revealed a best-corrected visual acuity (BCVA) of 20/50 in OD and 20/20 in OS with grade 1 relative afferent pupillary defect. Fundus evaluation showed pale disc in OD and temporal disc oedema in OS. Humphrey’s visual field analysis showed incomplete inferior altitudinal defect in OD and a centro-caecal scotoma in OS. Systemic investigations were normal. OS was diagnosed with NAAION. She was started on oral aspirin 75 mg. At 1-month follow-up, disc oedema of OS had resolved with BCVA maintaining at 20/20. The patient was lost to followup later. The relationship between the vaccine and the ocular event is temporal with no causal association.

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Efficacy, safety, and immunogenicity of the DNA SARS-CoV-2 vaccine (ZyCoV-D): the interim efficacy results of a phase 3, randomised, double-blind, placebo-controlled study in India

Akash Khobragade, Suresh Bhate, Vijendra Ramaiah, Shrikant Deshpande, Krishna Giri, Himanshu Phophle, Pravin Supe, Inderjeet Godara, Ramesh Revanna, Rajnish Nagarkar, Jayesh Sanmukhani, Ayan Dey, T M Chozhavel Rajanathan, Kevinkumar Kansagra, Parshottam Koradia, on behalf of the ZyCoV-D phase 3 Study Investigator Group*

Summary

Background ZyCoV-D, a DNA-based vaccine, showed promising safety and immunogenicity in a phase 1/2 trial. We now report the interim efficacy results of phase 3 clinical trial with ZyCoV-D vaccine in India. Methods We conducted an interim analysis of a multicentre, double-blind, randomised, placebo-controlled phase 3 trial at 49 centres in India. Healthy participants aged at least 12 years were enrolled and randomly assigned (1:1) to receive either ZyCov-D vaccine (Cadila Healthcare; 2 mg per dose) or placebo. An interactive web response system was used for randomisation (blocks of four) of participants as well as to enrol those aged 60 years and older with or without comorbid conditions, and those aged 12–17 years. It was also used to identify 600 participants for immunogenicity (blocks of six). Participants, investigators, and outcome assessors were masked to treatment assignment. Three doses of vaccine or placebo were administered intradermally via a needle-free injection system 28 days apart. The primary outcome was the number of participants with first occurrence of symptomatic RTPCR-positive COVID-19 28 days after the third dose, until the targeted number of cases (interim analysis n=79, full analysis n=158) have been achieved. The analysis was done in the per-protocol population, which consisted of all participants with negative baseline SARS-CoV-2 status who received three doses of vaccine or placebo. Assessment of safety and tolerability was based on the safety population, which consisted of all enrolled participants who were known to have received at least one dose of study vaccine or placebo. This trial is registered with Clinical Trial Registry India, CTRI/2021/01/030416, and is ongoing. Findings Between Jan 16, and June 23, 2021 (data cutoff), 33194 individuals were screened, of whom 5241 did not meet screening criteria and 27703 were enrolled and randomly assigned to receive ZyCoV-D (n=13 851) or placebo (n=13 852). Per-protocol, 81 cases were eligible and included in efficacy analysis (20 of 12350 in the ZyCoV-D group and 61 of 12 320 in placebo group). The ZyCoV-D vaccine efficacy was found to be 66·6% (95% CI 47·6–80·7). The occurrence of solicited adverse events was similar between the treatment groups (623 [4·49%] in the ZyCoV-D group vs 620 [4·47%] in the placebo group). There were two deaths (one in each group) reported at the data cutoff, neither of which was considered related to the study treatments. Interpretation In this interim analysis, ZyCoV-D vaccine was found to be efficacious, safe, and immunogenic in a phase 3 trial. Funding National Biopharma Mission, Department of Biotechnology, Government of India and Cadila Healthcare, Ahmedabad, Gujarat India. Copyright © 2022 Elsevier Ltd. All rights reserved.


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Maintaining face mask use before and after achieving different COVID-19 vaccination coverage levels: a modelling study

Sarah M Bartsch, Kelly J O’Shea, Kevin L Chin, Ulrich Strych, Marie C Ferguson, Maria Elena Bottazzi, Patrick T Wedlock, Sarah N Cox, Sheryl S Siegmund, Peter J Hotez,Bruce Y Lee

Summary

Background Face mask wearing has been an important part of the response to the COVID-19 pandemic. As vaccination coverage progresses in countries, relaxation of such practices is increasing. Subsequent COVID-19 surges have raised the questions of whether face masks should be encouraged or required and for how long. Here, we aim to assess the value of maintaining face masks use indoors according to different COVID-19 vaccination coverage levels in the USA. Methods In this computational simulation-model study, we developed and used a Monte Carlo simulation model representing the US population and SARS-CoV-2 spread. Simulation experiments compared what would happen if face masks were used versus not used until given final vaccination coverages were achieved. Different scenarios varied the target vaccination coverage (70–90%), the date these coverages were achieved (Jan 1, 2022, to July 1, 2022), and the date the population discontinued wearing face masks. Findings Simulation experiments revealed that maintaining face mask use (at the coverage seen in the USA from March, 2020, to July, 2020) until target vaccination coverages were achieved was cost-effective and in many cases cost saving from both the societal and third-party payer perspectives across nearly all scenarios explored. Face mask use was estimated to be cost-effective and usually cost saving when the cost of face masks per person per day was ≤US$1·25. In all scenarios, it was estimated to be cost-effective to maintain face mask use for about 2–10 weeks beyond the date that target vaccination coverage (70–90%) was achieved, with this added duration being longer when the target coverage was achieved during winter versus summer. Factors that might increase the transmissibility of the virus (eg, emergence of the delta [B.1.617.2] and omicron [B.1.1.529] variants), or decrease vaccine effectiveness (eg, waning immunity or escape variants), or increase social interactions among certain segments of the population, only increased the cost savings or cost-effectiveness provided by maintaining face mask use. Interpretation Our study provides strong support for maintaining face mask use until and a short time after achieving various final vaccination coverage levels, given that maintaining face mask use can be not just cost-effective, but even cost saving. The emergence of the omicron variant and the prospect of future variants that might be more transmissible and reduce vaccine effectiveness only increases the value of face masks. Funding The Agency for Healthcare Research and Quality, the National Institute of General Medical Sciences, the National Science Foundation, the National Center for Advancing Translational Sciences, and the City University of New York. Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

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Protective effect conferred by prior infection and vaccination on COVID-19 in a healthcare worker cohort in South India

Malathi Murugesan1 , Prasad Mathews2 , Hema Paul1 , Rajiv Karthik3 , Joy John Mammen4 , Priscilla RupaliID3 * 1 Department of Clinical Microbiology & Hospital Infection Control Committee, Christian Medical College, Vellore, Tamil Nadu, India, 2 Department of Geriatrics & Hospital Infection Control Committee, Christian Medical College, Vellore, Tamil Nadu, India, 3 Department of Infectious Disease & Hospital Infection Control Committee, Christian Medical College, Vellore, Tamil Nadu, India, 4 Department of Transfusion Medicine, Christian Medical College, Vellore, Tamil Nadu, India * prisci@cmcvellore.ac.in

Abstract

Background: The emergence of newer variants with the immune escape potential raises concerns about breakthroughs and re-infections resulting in future waves of infection. We examined the protective effect of prior COVID-19 disease and vaccination on infection rates among a cohort of healthcare workers (HCW) in South India during the second wave driven mainly by the delta variant. Methods and findings: Symptomatic HCWs were routinely tested by RT-PCR as per institutional policy. Vaccination was offered to all HCWs in late January, and the details were documented. We set up a non-concurrent cohort to document infection rates and estimated protective efficacy of prior infection and vaccination between 16th Apr to 31st May 2021, using a Cox proportional hazards model with time-varying covariates adjusting for daily incidence. Between June 2020 and May 2021, 2735 (23.9%) of 11,405 HCWs were infected, with 1412, including 32 reinfections, reported during the second wave. 6863 HCWs received two doses of vaccine and 1905 one dose. The protective efficacy of prior infection against symptomatic infection was 86.0% (95% CI 76.7%–91.6%). Vaccination combined with prior infection provided 91.1% (95% CI 84.1%–94.9%) efficacy. In the absence of prior infection, vaccine efficacy against symptomatic infection during the second wave was 31.8% (95% CI 23.5%– 39.1%). Conclusions: Prior infection provided substantial protection against symptomatic re-infection and severe disease during a delta variant driven second wave in a cohort of health care workers.

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Effectiveness of ChAdOx1 nCoV-19 vaccine against SARS-CoV-2 infection during the delta (B.1.617.2) variant surge in India: a test-negative, case-control study and a mechanistic study of post-vaccination immune responses

RamachandranThiruvengadam, Amit Awasthi*,Guruprasad Medigeshi*, Sankar Bhattacharya, Shailendra Mani, Sridhar Sivasubbu, Tripti Shrivastava, Sweety Samal, Deepika Rathna Murugesan, Bapu Koundinya Desiraju, Pallavi Kshetrapal, Rajesh Pandey, Vinod Scaria, Praveen Kumar Malik, Juhi Taneja, Akshay Binayke, Tarini Vohra, Aymaan Zaheer, Deepak Rathore, Naseem Ahmad Khan, Heena Shaman, Shubbir Ahmed, Rajesh Kumar, Suprit Deshpande, Chandru Subramani, Nitya Wadhwa, Nimesh Gupta, Anil K Pandey, Jayanta Bhattacharya, Anurag Agrawal, Sudhanshu Vrati, Shinjini Bhatnagar, Pramod Kumar Garg, on behalf of the Department of Biotechnology India Consortium for COVID-19 research

Summary

Background: SARS-CoV-2 variants of concern (VOCs) have threatened COVID-19 vaccine effectiveness. We aimed to assess the effectiveness of the ChAdOx1 nCoV-19 vaccine, predominantly against the delta (B.1.617.2) variant, in addition to the cellular immune response to vaccination.

Methods: We did a test-negative, case-control study at two medical research centres in Faridabad, India. All individuals who had a positive RT-PCR test for SARS-CoV-2 infection between April 1, 2021, and May 31, 2021, were included as cases and individuals who had a negative RT-PCR test were included as controls after matching with cases on calendar week of RT-PCR test. The primary outcome was effectiveness of complete vaccination with the ChAdOx1 nCoV-19 vaccine against laboratory-confirmed SARS-CoV-2 infection. The secondary outcomes were effectiveness of a single dose against SARS-CoV-2 infection and effectiveness of a single dose and complete vaccination against moderate-tosevere disease among infected individuals. Additionally, we tested in-vitro live-virus neutralisation and T-cell immune responses to the spike protein of the wild-type SARS-CoV-2 and VOCs among healthy (anti-nucleocapsid antibody negative) recipients of the ChAdOx1 nCoV-19 vaccine.

Findings: Of 2379 cases of confirmed SARS-CoV-2 infection, 85 (3·6%) were fully vaccinated compared with 168 (8·5%) of 1981 controls (adjusted OR [aOR] 0·37 [95% CI 0·28–0·48]), giving a vaccine effectiveness against SARS-CoV-2 infection of 63·1% (95% CI 51·5–72·1). 157 (6·4%) of 2451 of cases and 181 (9·1%) of 1994) controls had received a single dose of the ChAdOx1 nCoV-19 vaccine (aOR 0·54 [95% CI 0·42–0·68]), thus vaccine effectiveness of a single dose against SARS-CoV-2 infection was 46·2% (95% CI 31·6–57·7). One of 84 cases with moderate-to-severe COVID-19 was fully vaccinated compared with 84 of 2295 cases with mild COVID-19 (aOR 0·19 [95% CI 0·01–0·90]), giving a vaccine effectiveness of complete vaccination against moderate-to-severe disease of 81·5% (95% CI 9·9–99·0). The effectiveness of a single dose against moderate-to-severe disease was 79·2% (95% CI 46·1–94·0); four of 87 individuals with moderate-to-severe COVID-19 had received a single dose compared with 153 of 2364 participants with mild disease (aOR 0·20 [95% CI 0·06–0·54]). Among 49 healthy, fully vaccinated individuals, neutralising antibody responses were lower against the alpha (B.1.1.7; geometric mean titre 244·7 [95% CI 151·8–394·4]), beta (B.1.351; 97·6 [61·2–155·8]), kappa (B.1.617.1; 112·8 [72·7–175·0]), and delta (88·4 [61·2–127·8]) variants than against wild-type SARS-CoV-2 (599·4 [376·9–953·2]). However, the antigen-specific CD4 and CD8 T-cell responses were conserved against both the delta variant and wild-type SARS-CoV-2.

Interpretation: The ChAdOx1 nCoV-19 vaccine remained effective against moderate-to-severe COVID-19, even during a surge that was dominated by the highly transmissible delta variant of SARS-CoV-2. Spike-specific T-cell responses were maintained against the delta variant. Such cellular immune protection might compensate for waning humoral immunity.

Funding: Department of Biotechnology India, Council of Scientific and Industrial Research India, and Fondation Botnar.

Copyright: © 2021 Elsevier Ltd. All rights reserved.

1 VACCINE.pdf

First and second doses of Covishield vaccine provided high level of protection against SARS-CoV-2 infection in highly transmissible settings: results from a prospective cohort of participants residing in congregate facilities in India

Tenzin Tsundue,1 Tenzin Namdon,1 Tenzin Tsewang,1 Sonam Topgyal,1 Tashi Dolma,2 Dekyi Lhadon,1 Tsering Choetso,1 Tenzin Woesal,1 Tenzin Yangkyi,1 Amita Gupta,3,4 David Peters ,3,4 Zorba Paster,5 Dawa Phunkyi,1 Tsetan Dorji Sadutshang,1 Richard E Chaisson,6,7 Kunchok Dorjee4,8

ABSTRACT

Objectives: This study aimed to determine the effectiveness of Covishield vaccine among residents of congregate residential facilities.

Design: A prospective cohort study in congregate residential facilities.

Setting: Dharamshala, Himachal Pradesh, India, from December 2020 to July 2021.

Participants: Residents of all ages in seven facilities— three monasteries, two old age homes and two learning centres—were enrolled.

Exposures: First and second doses of Covishield vaccine against SARS-CoV-2 infection.

Main outcomes measures: Primary outcome was development of COVID-19. Secondary outcome was unfavourable outcomes, defined as a composite of shortness of breath, hospitalisation or death. Vaccine effectiveness (%) was calculated as (1−HR)×100.

Results: There were 1114 residents (median age 31 years) participating in the study, 82% males. Twenty-eight per cent (n=308/1114) were unvaccinated, 50% (n=554/1114) had received one dose and 23% (n=252/1114) had received two doses of Covishield. The point prevalence of COVID-19 for the facilities ranged from 11% to 57%. Incidence rates (95%CI) of COVID-19 were 76 (63 to 90)/1000 person-months in the unvaccinated, 25 (18 to 35)/1000 person-months in recipients of one dose and 9 (4 to 19)/1000 person-months in recipients of two doses. The effectiveness of first and second doses of Covishield were 71% (adjusted HR (aHR) 0.29; 95%CI 0.18 to 0.46; p<0.001) and 80% (aHR 0.20; 95%CI 0.09 to 0.44; (P<0.001), respectively, against SARS-CoV-2 infection and 86% (aHR 0.24; 95%CI 0.07 to 0.82; p=0.023) and 99% (aHR 0.01; 95%CI 0.002 to 0.10; p<0.001), respectively, against unfavourable outcome. The effectiveness was higher after 14 days of receiving the first and second doses, 93% and 98%, respectively. Risk of infection was higher in persons with chronic hepatitis B (aHR 1.78; p=0.034) and previous history of tuberculosis (aHR 1.62; p=0.047).

Conclusion: Covishield was effective in preventing SARSCoV-2 infection and reducing disease severity in highly transmissible settings during the second wave of the pandemic driven by the Delta variant.

vaccine1.pdf

COVID-19 vaccine strategies must focus on severe disease and global equity

Peter B McIntyre, Rakesh Aggarwal, Ilesh Jani, Jaleela Jawad, Sonali Kochhar, Noni MacDonald, Shabir A Madhi, Ezzeddine Mohsni, Kim Mulholland, Kathleen M Neuzil, Hanna Nohynek, Folake Olayinka, Punnee Pitisuttithum, Andrew J Pollard, Alejandro Cravioto

Abstract: In the panel, we summarise our conclusions and recommendations for global COVID-19 vaccine strategies in 2022. The emergence of delta and now omicron further reinforces the importance of access to COVID-19 vaccines globally and equitably for the health of all. Constrained vaccine supply has driven opportunities for SARS-CoV-2 to mutate to be more infectious. The emergence of omicron has emphasised that further delay in widely delivering at least first doses is fraught with peril for all.

vaccine2.pdf

COVID-19 vaccine perceptions and uptake: results from the COVID-19 Global Rheumatology Alliance Vaccine Survey

*Michael Putman, Kevin Kennedy, Emily Sirotich,Jean W Liew, Sebastian E Sattui, Tarin T Moni,Akpabio A Akpabio, Deshire Alpizar-Rodriguez,Saskya Angevare, Richard P Beesley, Francis Berenbaum,Inita Bulina, Yu Pei Eugenia Chock, Richard Conway,Ali Duarte-García, Aman Dev Singh, Eimear Duff,Karen L Durrant, Tamer A Gheita, Catherine L Hill,Richard Howard, Bimba F Hoyer, Evelyn Hsieh, Lina el Kibbi,Adam Kilian, Alfred H J Kim, David F L Liew, Chieh Lo,Elsa F Mateus, Bruce Miller, Serena Mingolla, Michal Nudel,Jasvinder A Singh, Namrata Singh, Manuel F Ugarte-Gil,John Wallace, Kristen J Young, Erick Adrian Zamora-Tehozol,Suleman Bhana, Wendy Costello, Rebecca Grainger,Pedro M Machado, Philip C Robinson, Paul Sufka,Zachary S Wallace, Jinoos Yazdany, Carly Harrison,Maggie J Larché, Mitchell Levine, Gary Foster,Lehana Thabane, Jonathan S Hausmann, Jeffrey A Sparks,Julia F Simard

Abstract: In summary, in this large international survey of people with rheumatic diseases, most people with vaccine hesitancy would consider becoming vaccinated. Data regarding the safety and efficacy of COVID-19 vaccination among people with rheumatic diseases, which is delivered by rheumatologists or patient and professional organisations, might increase vaccine uptake. These findings highlight urgent research and educational priorities to combat vaccine hesitancy in people with rheumatic diseases

vaccine3.pdf

SARS-CoV-2 Reinfection Rate and Estimated Effectiveness of the Inactivated Whole Virion Vaccine BBV152 Against Reinfection Among Health Care Workers in New Delhi, India

Sumit Malhotra, MD, 1 Kalaivani Mani, PhD, 2 Rakesh Lodha, MD, 3 Sameer Bakhshi, MD, 4 Vijay Prakash Mathur, MDS, 5 Pooja Gupta, DM, 6 Saurabh Kedia, DM, 7 Jeeva Sankar, DM, 8 Parmeshwar Kumar, MHA, 9 Arvind Kumar, MD, 10 Vineet Ahuja, DM, 7 Subrata Sinha, PhD, 11 Randeep Guleria, DM, 12 and and the COVID Reinfection AIIMS Consortium

Aman Dua, MPH, 1 Shafi Ahmad, MDS, 1 Ramadass Sathiyamoorthy, MD, 1 Ajay Sharma, BSc, 1 Tabbu Sakya, MCA, 1 Vikas Gaur, PhD, 4 Shilpi Chaudhary, PhD, 4 Swetambri Sharma, MSc, 4 Divya Madan, MSc, 7 Anvita Gupta, MSc, 7 Shubi Virmani, MDS, 7 Arti Gupta, MSc, 7 Nidhi Yadav, MSc, 7 Surbhi Sachdeva, MCom, 7 Shilpi Sharma, BA, 7 Sachin Singh, BSc, 7 Abhimanyu Pandey, MPharma, 7 Mukesh Singh, PhD, 7 Divashree Jhurani, MSc, 7 Swarnabha Sarkar, MSc, 13 Amol Kumar Lokade, MDS, 5 Atif Mohammad, MDS, 5 Sabitri Pandit, BTech, 14 Ritu Dubey, MA, 3 Ajay Kumar Singh, MA, 3 Naveen Gohar, BA, 3 Divyansh Soni, MBBS, 15 Arunangshu Bhattacharyya, MBBS, 15 Sabin Rai, MBBS, 15 Snikitha Tummala, MBBS, 15 Ishan Gupta, MBBS, 15 and Sakshi Shukla, MSc 11

Abstract:

Importance:

A surge of COVID-19 occurred from March to June 2021, in New Delhi, India, linked to the B.1.617.2 (Delta) variant of SARS-CoV-2. COVID-19 vaccines were rolled out for health care workers (HCWs) starting in January 2021.

Objective:

To assess the incidence density of reinfection among a cohort of HCWs and estimate the effectiveness of the inactivated whole virion vaccine BBV152 against reinfection.

Design, Setting, and Participants:

This was a retrospective cohort study among HCWs working at a tertiary care center in New Delhi, India.

Exposures:

Vaccination with 0, 1, or 2 doses of BBV152.

Main Outcomes and Measures:

The HCWs were categorized as fully vaccinated (with 2 doses and ≥15 days after the second dose), partially vaccinated (with 1 dose or 2 doses with <15 days after the second dose), or unvaccinated. The incidence density of COVID-19 reinfection per 100 person-years was computed, and events from March 3, 2020, to June 18, 2021, were included for analysis. Unadjusted and adjusted hazard ratios (HRs) were estimated using a Cox proportional hazards model. Estimated vaccine effectiveness (1 − adjusted HR) was reported.

Results:

Among 15 244 HCWs who participated in the study, 4978 (32.7%) were diagnosed with COVID-19. The mean (SD) age was 36.6 (10.3) years, and 55.0% were male. The reinfection incidence density was 7.26 (95% CI: 6.09-8.66) per 100 person-years (124 HCWs [2.5%], total person follow-up period of 1696 person-years as time at risk). Fully vaccinated HCWs had lower risk of reinfection (HR, 0.14 [95% CI, 0.08-0.23]), symptomatic reinfection (HR, 0.13 [95% CI, 0.07-0.24]), and asymptomatic reinfection (HR, 0.16 [95% CI, 0.05-0.53]) compared with unvaccinated HCWs. Accordingly, among the 3 vaccine categories, reinfection was observed in 60 of 472 (12.7%) of unvaccinated (incidence density, 18.05 per 100 person-years; 95% CI, 14.02-23.25), 39 of 356 (11.0%) of partially vaccinated (incidence density 15.62 per 100 person-years; 95% CI, 11.42-21.38), and 17 of 1089 (1.6%) fully vaccinated (incidence density 2.18 per 100 person-years; 95% CI, 1.35-3.51) HCWs. The estimated effectiveness of BBV152 against reinfection was 86% (95% CI, 77%-92%); symptomatic reinfection, 87% (95% CI, 76%-93%); and asymptomatic reinfection, 84% (95% CI, 47%-95%) among fully vaccinated HCWs. Partial vaccination was not associated with reduced risk of reinfection.

Conclusions and Relevance:

These findings suggest that BBV152 was associated with protection against both symptomatic and asymptomatic reinfection in HCWs after a complete vaccination schedule, when the predominant circulating variant was B.1.617.2.

21.pdf

Ongoing and future COVID-19 vaccine clinical trials: challenges and opportunities

Rafael Dal-Ré, MD,a,* Linda-Gail Bekker, Prof, MD,b Christian Gluud, Prof, MD,c,d Søren Holm, Prof, MD,e Vivekanand Jha, Prof, MD,f,g Gregory A Poland, Prof, MD,h Frits R Rosendaal, Prof, MD,i Brigitte Schwarzer-Daum, Prof, MD,j Esperança Sevene, PhD,k,l Halidou Tinto, Prof, PhD,m Teck Chuan Voo, PhD,n and Nadarajah Sreeharan, MDo

Abstract:

Large-scale deployment of COVID-19 vaccines will seriously affect the ongoing phases 2 and 3 randomised placebo-controlled trials assessing SARS-CoV-2 vaccine candidates. The effect will be particularly acute in high-income countries where the entire adult or older population could be vaccinated by late 2021. Regrettably, only a small proportion of the population in many low-income and middle-income countries will have access to available vaccines. Sponsors of COVID-19 vaccine candidates currently in phase 2 or initiating phase 3 trials in 2021 should consider continuing the research in countries with limited affordability and availability of COVID-19 vaccines. Several ethical principles must be implemented to ensure the equitable, non-exploitative, and respectful conduct of trials in resource-poor settings. Once sufficient knowledge on the immunogenicity response to COVID-19 vaccines is acquired, non-inferiority immunogenicity trials—comparing the immune response of a vaccine candidate to that of an authorised vaccine—would probably be the most common trial design. Until then, placebo-controlled, double-blind, crossover trials will continue to play a role in the development of new vaccine candidates. WHO or the Council for International Organizations of Medical Sciences should define an ethical framework for the requirements and benefits for trial participants and host communities in resource-poor settings that should require commitment from all vaccine candidate sponsors from high-income countries.

33.pdf

Challenges in ensuring global access to COVID-19 vaccines: production, affordability, allocation, and deployment

Olivier J Wouters, PhD,a,* Kenneth C Shadlen, Prof, PhD,b Maximilian Salcher-Konrad, MSc,a Andrew J Pollard, Prof, FMedSci,c,d Heidi J Larson, Prof, PhD,e,f Yot Teerawattananon, PhD,g,h and Mark Jit, Prof, PhDe

Abstract:

The COVID-19 pandemic is unlikely to end until there is global roll-out of vaccines that protect against severe disease and preferably drive herd immunity. Regulators in numerous countries have authorised or approved COVID-19 vaccines for human use, with more expected to be licensed in 2021. Yet having licensed vaccines is not enough to achieve global control of COVID-19: they also need to be produced at scale, priced affordably, allocated globally so that they are available where needed, and widely deployed in local communities. In this Health Policy paper, we review potential challenges to success in each of these dimensions and discuss policy implications. To guide our review, we developed a dashboard to highlight key characteristics of 26 leading vaccine candidates, including efficacy levels, dosing regimens, storage requirements, prices, production capacities in 2021, and stocks reserved for low-income and middle-income countries. We use a traffic-light system to signal the potential contributions of each candidate to achieving global vaccine immunity, highlighting important trade-offs that policy makers need to consider when developing and implementing vaccination programmes. Although specific datapoints are subject to change as the pandemic response progresses, the dashboard will continue to provide a useful lens through which to analyse the key issues affecting the use of COVID-19 vaccines. We also present original data from a 32-country survey (n=26 758) on potential acceptance of COVID-19 vaccines, conducted from October to December, 2020. Vaccine acceptance was highest in Vietnam (98%), India (91%), China (91%), Denmark (87%), and South Korea (87%), and lowest in Serbia (38%), Croatia (41%), France (44%), Lebanon (44%), and Paraguay (51%).

58.pdf

Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomised, phase 1 trial

Raches Ella, MBBS,a Krishna Mohan Vadrevu, PhD,a,* Harsh Jogdand, DVM,a Sai Prasad, MSc,a Siddharth Reddy, MSc,a Vamshi Sarangi, BSc,a Brunda Ganneru, PhD,a Gajanan Sapkal, PhD,b Pragya Yadav, PhD,b Priya Abraham, PhD,b Samiran Panda, MD,c Nivedita Gupta, MD,c Prabhakar Reddy, MD,d Savita Verma, PhD,e Sanjay Kumar Rai, MD,f Chandramani Singh, MD,g Sagar Vivek Redkar, MD,h Chandra Sekhar Gillurkar, MD,i Jitendra Singh Kushwaha, MD,j Satyajit Mohapatra, MD,k Venkat Rao, MD,l Randeep Guleria, MD,f Krishna Ella, PhD,a and Balram Bhargava, MDc

Background

To mitigate the effects of COVID-19, a vaccine is urgently needed. BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine formulated with a toll-like receptor 7/8 agonist molecule adsorbed to alum (Algel-IMDG) or alum (Algel).

Methods

We did a double-blind, multicentre, randomised, controlled phase 1 trial to assess the safety and immunogenicity of BBV152 at 11 hospitals across India. Healthy adults aged 18–55 years who were deemed healthy by the investigator were eligible. Individuals with positive SARS-CoV-2 nucleic acid and/or serology tests were excluded. Participants were randomly assigned to receive either one of three vaccine formulations (3 μg with Algel-IMDG, 6 μg with Algel-IMDG, or 6 μg with Algel) or an Algel only control vaccine group. Block randomisation was done with a web response platform. Participants and investigators were masked to treatment group allocation. Two intramuscular doses of vaccines were administered on day 0 (the day of randomisation) and day 14. Primary outcomes were solicited local and systemic reactogenicity events at 2 h and 7 days after vaccination and throughout the full study duration, including serious adverse events. Secondary outcome was seroconversion (at least four-fold increase from baseline) based on wild-type virus neutralisation. Cell-mediated responses were evaluated by intracellular staining and ELISpot. The trial is registered at ClinicalTrials.gov (NCT04471519).

Findings

Between July 13 and 30, 2020, 827 participants were screened, of whom 375 were enrolled. Among the enrolled participants, 100 each were randomly assigned to the three vaccine groups, and 75 were randomly assigned to the control group (Algel only). After both doses, solicited local and systemic adverse reactions were reported by 17 (17%; 95% CI 10·5–26·1) participants in the 3 μg with Algel-IMDG group, 21 (21%; 13·8–30·5) in the 6 μg with Algel-IMDG group, 14 (14%; 8·1–22·7) in the 6 μg with Algel group, and ten (10%; 6·9–23·6) in the Algel-only group. The most common solicited adverse events were injection site pain (17 [5%] of 375 participants), headache (13 [3%]), fatigue (11 [3%]), fever (nine [2%]), and nausea or vomiting (seven [2%]). All solicited adverse events were mild (43 [69%] of 62) or moderate (19 [31%]) and were more frequent after the first dose. One serious adverse event of viral pneumonitis was reported in the 6 μg with Algel group, unrelated to the vaccine. Seroconversion rates (%) were 87·9, 91·9, and 82·8 in the 3 μg with Algel-IMDG, 6 μg with Algel-IMDG, and 6 μg with Algel groups, respectively. CD4+ and CD8+ T-cell responses were detected in a subset of 16 participants from both Algel-IMDG groups.

Interpretation

BBV152 led to tolerable safety outcomes and enhanced immune responses. Both Algel-IMDG formulations were selected for phase 2 immunogenicity trials. Further efficacy trials are warranted.

Funding

Bharat Biotech International.

70.pdf

Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: interim results from a double-blind, randomised, multicentre, phase 2 trial, and 3-month follow-up of a double-blind, randomised phase 1 trial

Raches Ella, MBBS,a Siddharth Reddy, MSc,a Harsh Jogdand, DVM,a Vamshi Sarangi, BSc,a Brunda Ganneru, PhD,a Sai Prasad, MBA,a Dipankar Das, PhD,a Dugyala Raju, PhD,a Usha Praturi, MSc,a Gajanan Sapkal, PhD,b Pragya Yadav, PhD,b Prabhakar Reddy, MD,c Savita Verma, MD,d Chandramani Singh, MD,e Sagar Vivek Redkar, MD,f Chandra Sekhar Gillurkar, MD,g Jitendra Singh Kushwaha, MD,h Satyajit Mohapatra, MD,i Amit Bhate, MD,j Sanjay Rai, MD,k Samiran Panda, MD,l Priya Abraham, PhD,b Nivedita Gupta, MD,l Krishna Ella, PhD,a Balram Bhargava, MD,l and Krishna Mohan Vadrevu, PhDa,*

Background

BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine (3 μg or 6 μg) formulated with a toll-like receptor 7/8 agonist molecule (IMDG) adsorbed to alum (Algel). We previously reported findings from a double-blind, multicentre, randomised, controlled phase 1 trial on the safety and immunogenicity of three different formulations of BBV152 (3 μg with Algel-IMDG, 6 μg with Algel-IMDG, or 6 μg with Algel) and one Algel-only control (no antigen), with the first dose administered on day 0 and the second dose on day 14. The 3 μg and 6 μg with Algel-IMDG formulations were selected for this phase 2 study. Herein, we report interim findings of the phase 2 trial on the immunogenicity and safety of BBV152, with the first dose administered on day 0 and the second dose on day 28.

Methods

We did a double-blind, randomised, multicentre, phase 2 clinical trial to evaluate the immunogenicity and safety of BBV152 in healthy adults and adolescents (aged 12–65 years) at nine hospitals in India. Participants with positive SARS-CoV-2 nucleic acid and serology tests were excluded. Participants were randomly assigned (1:1) to receive either 3 μg with Algel-IMDG or 6 μg with Algel-IMDG. Block randomisation was done by use of an interactive web response system. Participants, investigators, study coordinators, study-related personnel, and the sponsor were masked to treatment group allocation. Two intramuscular doses of vaccine were administered on day 0 and day 28. The primary outcome was SARS-CoV-2 wild-type neutralising antibody titres and seroconversion rates (defined as a post-vaccination titre that was at least four-fold higher than the baseline titre) at 4 weeks after the second dose (day 56), measured by use of the plaque-reduction neutralisation test (PRNT50) and the microneutralisation test (MNT50). The primary outcome was assessed in all participants who had received both doses of the vaccine. Cell-mediated responses were a secondary outcome and were assessed by T-helper-1 (Th1)/Th2 profiling at 2 weeks after the second dose (day 42). Safety was assessed in all participants who received at least one dose of the vaccine. In addition, we report immunogenicity results from a follow-up blood draw collected from phase 1 trial participants at 3 months after they received the second dose (day 104). This trial is registered at ClinicalTrials.gov, NCT04471519.

Findings

Between Sept 5 and 12, 2020, 921 participants were screened, of whom 380 were enrolled and randomly assigned to the 3 μg with Algel-IMDG group (n=190) or 6 μg with Algel-IMDG group (n=190). Geometric mean titres (GMTs; PRNT50) at day 56 were significantly higher in the 6 μg with Algel-IMDG group (197·0 [95% CI 155·6–249·4]) than the 3 μg with Algel-IMDG group (100·9 [74·1–137·4]; p=0·0041). Seroconversion based on PRNT50 at day 56 was reported in 171 (92·9% [95% CI 88·2–96·2] of 184 participants in the 3 μg with Algel-IMDG group and 174 (98·3% [95·1–99·6]) of 177 participants in the 6 μg with Algel-IMDG group. GMTs (MNT50) at day 56 were 92·5 (95% CI 77·7–110·2) in the 3 μg with Algel-IMDG group and 160·1 (135·8–188·8) in the 6 μg with Algel-IMDG group. Seroconversion based on MNT50 at day 56 was reported in 162 (88·0% [95% CI 82·4–92·3]) of 184 participants in the 3 μg with Algel-IMDG group and 171 (96·6% [92·8–98·8]) of 177 participants in the 6 μg with Algel-IMDG group. The 3 μg with Algel-IMDG and 6 μg with Algel-IMDG formulations elicited T-cell responses that were biased to a Th1 phenotype at day 42. No significant difference in the proportion of participants who had a solicited local or systemic adverse reaction in the 3 μg with Algel-IMDG group (38 [20·0%; 95% CI 14·7–26·5] of 190) and the 6 μg with Algel-IMDG group (40 [21·1%; 15·5–27·5] of 190) was observed on days 0–7 and days 28–35; no serious adverse events were reported in the study. From the phase 1 trial, 3-month post-second-dose GMTs (MNT50) were 39·9 (95% CI 32·0–49·9) in the 3μg with Algel-IMDG group, 69·5 (53·7–89·9) in the 6 μg with Algel-IMDG group, 53·3 (40·1–71·0) in the 6 μg with Algel group, and 20·7 (14·5–29·5) in the Algel alone group.

Interpretation

In the phase 1 trial, BBV152 induced high neutralising antibody responses that remained elevated in all participants at 3 months after the second vaccination. In the phase 2 trial, BBV152 showed better reactogenicity and safety outcomes, and enhanced humoral and cell-mediated immune responses compared with the phase 1 trial. The 6 μg with Algel-IMDG formulation has been selected for the phase 3 efficacy trial.

Funding

Bharat Biotech International.

93.pdf

Cytotoxic T-lymphocyte elicited vaccine against SARS-CoV-2 employing immunoinformatics framework

Neeraj Kumar, Nikita Admane, [...], and Abhinav Grover

Abstract

Development of effective counteragents against the novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains, requires clear insights and information for understanding the immune responses associated with it. This global pandemic has pushed the healthcare system and restricted the movement of people and succumbing of the available therapeutics utterly warrants the development of a potential vaccine to contest the deadly situation. In the present study, highly efficacious, immunodominant cytotoxic T-lymphocyte (CTL) epitopes were predicted by advanced immunoinformatics assays using the spike glycoprotein of SARS-CoV2, generating a robust and specific immune response with convincing immunological parameters (Antigenicity, TAP affinity, MHC binder) engendering an efficient viral vaccine. The molecular docking studies show strong binding of the CTL construct with MHC-1 and host membrane specific TLR2 receptors. The molecular dynamics simulation in an explicit system confirmed the stable and robust binding of CTL epitope with TLR2. Steep magnitude RMSD variation and compelling residual fluctuations existed in terminal residues and various loops of the β linker segments of TLR2-epitope (residues 105-156 and 239-254) to about 0.4 nm. The reduced Rg value (3.3 nm) and stagnant SASA analysis (275 nm/S2/N after 8 ns and 5 ns) for protein surface and its orientation in the exposed and buried regions suggests more compactness due to the strong binding interaction of the epitope. The CTL vaccine candidate establishes a high capability to elicit the critical immune regulators, like T-cells and memory cells as proven by the in silico immunization assays and can be further corroborated through in vitro and in vivo assays.

Subject terms: Computational biology and bioinformatics, Biophysics

137.pdf

Public health impact of delaying second dose of BNT162b2 or mRNA-1273 covid-19 vaccine: simulation agent based modeling study

Santiago Romero-Brufau, assistant professor of medicine and healthcare systems engineering, instructor,1,2 Ayush Chopra, masters student,3 Alex J Ryu, assistant professor of medicine,1 Esma Gel, associate professor,4 Ramesh Raskar, associate professor,3 Walter Kremers, associate professor biostatistics,5 Karen S Anderson, professor,4 Jayakumar Subramanian, senior research scientist,6 Balaji Krishnamurthy, principal scientist and director,6 Abhishek Singh, masters student,3 Kalyan Pasupathy, associate professor of health care systems engineering,5 Yue Dong, assistant professor,7 John C O’Horo, associate professor of medicine,1 Walter R Wilson, professor of medicine,1 Oscar Mitchell, fellow, pulmonary and critical care medicine,8 and Thomas C Kingsley, assistant professor of medicine 1

Abstract:

Objective

To estimate population health outcomes with delayed second dose versus standard schedule of SARS-CoV-2 mRNA vaccination.

Design

Simulation agent based modeling study.

Setting

Simulated population based on real world US county.

Participants

The simulation included 100 000 agents, with a representative distribution of demographics and occupations. Networks of contacts were established to simulate potentially infectious interactions though occupation, household, and random interactions.

Interventions

Simulation of standard covid-19 vaccination versus delayed second dose vaccination prioritizing the first dose. The simulation runs were replicated 10 times. Sensitivity analyses included first dose vaccine efficacy of 50%, 60%, 70%, 80%, and 90% after day 12 post-vaccination; vaccination rate of 0.1%, 0.3%, and 1% of population per day; assuming the vaccine prevents only symptoms but not asymptomatic spread (that is, non-sterilizing vaccine); and an alternative vaccination strategy that implements delayed second dose for people under 65 years of age, but not until all those above this age have been vaccinated.

Main outcome measures

Cumulative covid-19 mortality, cumulative SARS-CoV-2 infections, and cumulative hospital admissions due to covid-19 over 180 days.

Results

Over all simulation replications, the median cumulative mortality per 100 000 for standard dosing versus delayed second dose was 226 v 179, 233 v 207, and 235 v 236 for 90%, 80%, and 70% first dose efficacy, respectively. The delayed second dose strategy was optimal for vaccine efficacies at or above 80% and vaccination rates at or below 0.3% of the population per day, under both sterilizing and non-sterilizing vaccine assumptions, resulting in absolute cumulative mortality reductions between 26 and 47 per 100 000. The delayed second dose strategy for people under 65 performed consistently well under all vaccination rates tested.

Conclusions

A delayed second dose vaccination strategy, at least for people aged under 65, could result in reduced cumulative mortality under certain conditions.