key: cord-0276891-ub7ilx98 authors: Tang, P.; Hasan, M. R.; Chemaitelly, H.; YASSINE, H. M.; Benslimane, F.; Al Khatib, H. A.; AlMukdad, S.; Coyle, P.; Ayoub, H. H.; Al Kanaani, Z.; Al Kuwari, E.; Jeremijenko, A.; Kaleeckal, A. H.; Latif, A. N.; Shaik, R. M.; Abdul Rahim, H. F.; Nasrallah, G.; Al Kuwari, M. G.; Al Romaihi, H. E.; Butt, A. A.; Al-Thani, M. H.; Al Khal, A.; Bertollini, R.; Abu-Raddad, L. J. title: BNT162b2 and mRNA-1273 COVID-19 vaccine effectiveness against the Delta (B.1.617.2) variant in Qatar date: 2021-08-11 journal: nan DOI: 10.1101/2021.08.11.21261885 sha: 2610f2a91dd3e88226e0b50aa5737327cc7104b4 doc_id: 276891 cord_uid: ub7ilx98 The SARS-CoV-2 Delta (B.1.617.2) variant of concern is expanding globally. Here, we assess real-world effectiveness of the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines against this variant in the population of Qatar, using a matched test-negative, case-control study design. BNT162b2 effectiveness against any Delta infection, symptomatic or asymptomatic, was 64.2% (95% CI: 38.1-80.1%) [≥]14 days after the first dose and before the second dose, but was only 53.5% (95% CI: 43.9-61.4%) [≥]14 days after the second dose, in a population in which a large proportion of fully vaccinated persons received their second dose several months earlier. Corresponding effectiveness measures for mRNA-1273 were 79.0% (95% CI: 58.9-90.1%) and 84.8% (95% CI: 75.9-90.8%), respectively. Effectiveness against any severe, critical, or fatal COVID-19 disease due to Delta was 89.7% (95% CI: 61.0-98.1%) for BNT162b2 and 100.0% (95% CI: 41.2-100.0%) for mRNA-1273, [≥]14 days after the second dose. Both BNT162b2 and mRNA-1273 are highly effective in preventing Delta hospitalization and death, but less so in preventing infection, particularly for BNT162b2. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta (B.1.617.2) variant of concern is expanding globally 1 (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 11, 2021. ; https://doi.org/10.1101/2021.08.11.21261885 doi: medRxiv preprint and the median date at second dose was May 12, 2021 . Median time elapsed between the first and second doses was 28 days (IQR: 28-31 days), and 74.6% of individuals received their second dose ≤30 days after the first dose. Tables 1 and 2 , respectively. Median age in the study samples was 31-32 years. Qatar has unusually young, diverse demographics, in that only 9% of its residents are ≥50 years of age, and 89% are expatriates from over 150 countries 10, 11 . As of the end of the study, July 21, 2021, 54 and 249 Delta breakthrough infections had been recorded among those who received either one or two doses of BNT162b2, respectively, and 27 and 26 breakthrough infections had been recorded among those who received mRNA-1273, respectively. Also, as of July 21, 2021, 3 and 4 severe Delta COVID-19 disease cases (acute-care hospitalizations 12 ; Methods) had been recorded among those who received either one or two All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 11, 2021. ; https://doi.org/10.1101/2021.08.11.21261885 doi: medRxiv preprint doses of BNT162b2, respectively, and 3 severe disease cases had been recorded among those who received only one dose of mRNA-1273. No severe Delta disease cases were recorded among those who received two doses of mRNA-1273. Meanwhile, 1 critical Delta COVID-19 disease case (ICU-care hospitalization 12 ; Methods) had been recorded among those who received two doses of BNT162b2. No critical disease cases were recorded among those who received only one dose of BNT162b2, or among those who received one or two doses of mRNA-1273. No fatal Delta COVID-19 disease cases (COVID-19 deaths 13 ; Methods) were recorded among those who received either vaccine. Estimated BNT162b2 effectiveness against infection with Delta, defined as a polymerase chain reaction (PCR)-positive swab with the Delta variant, regardless of the reason for PCR testing or presence of symptoms (Methods), was 64.2% (95% confidence interval (CI): 38.1-80.1%) 14 or more days after the first dose, but before receiving the second dose ( Table 3) . The corresponding effectiveness for mRNA-1273 was 79.0% (95% CI: 58.9-90.1%), and for vaccination with either BNT162b2 or mRNA-1273, it was 68.9% (95% CI: 52.7-80.1%). Estimated vaccine effectiveness against any severe 12 , critical 12 , or fatal 13 COVID-19 disease due to any Delta infection (Methods), 14 or more days after the first dose, but before receiving the second dose, was 100% for BNT162b2, mRNA-1273, and either BNT162b2 or mRNA-1273, but with very wide 95% confidence intervals due to the relatively small number of severe, critical, and fatal disease cases in this analysis (Table 3) . All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Sensitivity analyses adjusting for sex, age, nationality, reason for PCR testing, and calendar week of PCR test in logistic regression analysis confirmed main analysis results, but with slightly higher estimated effectiveness (Table 4 ). An additional analysis estimated BNT162b2 effectiveness against symptomatic Delta infection at 56.1% (95% CI: 41.4-67.2%) 14 or more days after the second dose ( (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 11, 2021. ; https://doi.org/10.1101/2021.08.11.21261885 doi: medRxiv preprint vaccination with either BNT162b2 or mRNA-1273, it was 40.0% (95% CI: 18.2-56.1%). Asymptomatic infection was defined as a PCR-positive test conducted with no reported presence of symptoms compatible with a respiratory tract infection, that is, strictly, the PCR testing was done as only part of a survey, for pre-travel requirement, or at port of entry upon arrival into the country 10, 14 . Both the BNT162b2 and mRNA-1273 vaccines demonstrated robust effectiveness (≥90%) against hospitalization and death due to infection with the Delta variant, confirming recently announced estimates from the United Kingdom (UK) 15 and Israel 16 . Although there were many breakthrough infections, especially for BNT162b2, severe or critical COVD-19 disease cases among vaccinated persons were rare. Among those fully vaccinated with BNT162b2, there were only 4 severe disease cases and 1 critical disease case due to Delta, while for mRNA-1273, there were only 3 severe disease cases and no critical disease cases. No COVID-19 deaths due to Delta were recorded in a person vaccinated with either vaccine. BNT162b2 effectiveness against any infection with Delta, symptomatic or asymptomatic, 14 or more days after the first dose, was 64.2%, compared to 46.5% 17 against Beta (B.1.351) and 65.5% 17 against Alpha (B.1.1.7), in the same population of Qatar. This result is consistent with existing evidence suggesting that Beta is the most immune-evasive variant of the known variants of concern 18,19 . However, BNT162b2 effectiveness against Delta 14 or more days after the second dose was only 53.5%, compared to 75.0% 5,17 against Beta and 89.5% 5,17 against Alpha. Strikingly, estimated BNT162b2 effectiveness against Delta 14 or more days after the first dose, or 14 or more days after the second dose, were statistically similar. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 11, 2021. ; https://doi.org/10.1101/2021.08.11.21261885 doi: medRxiv preprint Emerging evidence suggests significant waning of BNT162b2 effectiveness over time [20] [21] [22] . Effectiveness against Beta was estimated at a time when nearly all persons in Qatar were newly vaccinated with BNT162b2 5,17 , but effectiveness against Delta was estimated (in the present study) at a time when a large proportion of those BNT162b2 vaccinated had received their second dose several months earlier. The unexpectedly low effectiveness against Delta among fully vaccinated persons may thus reflect some waning of BNT162b2 protection over time. This explanation is consistent with the pattern seen in emerging effectiveness estimates against Delta in other countries. Our estimate of 53.5% among fully vaccinated persons is lower than that found in the UK 23,24 and Canada 25 , where effectiveness was estimated at >75%, but higher than that in Israel at only 39% 16 and the United States (USA) at 42% 26 . With the delayed second dose in the UK and Canada, most BNT162b2-vaccinated persons received their second dose three months or so more recently than in Israel, USA, and Qatar, where the second dose was administered three weeks after the first dose. The lower effectiveness in Israel, USA, and Qatar may thus reflect waning of vaccine protection for those who received their second dose by end of 2020 or early 2021. Qatar started its mass vaccination campaign with BNT162b2 shortly after that of Israel and the USA. Another factor may also help to explain this low effectiveness. Public health restrictions have gradually been easing in Qatar over the last few weeks, coinciding with the period during which Delta incidence has been slowly increasing. Restrictions, however, have been eased differently for vaccinated and unvaccinated persons. Many social, work, and travel activities at present require evidence of vaccination (a "health pass") that is administered through a mandatory mobile app (the Ehteraz app). Vaccinated persons presumably have a higher social contact rate than unvaccinated persons, and may have also reduced their adherence to safety measures, such All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 11, 2021. ; https://doi.org/10.1101/2021.08.11.21261885 doi: medRxiv preprint as protective masks, with the perception of vaccine protection 27-29 . Such risk compensation may be even higher with increasing time since receiving the second dose, leading to progressive normalization of behavior 28-30 . Risk of exposure to the virus could thus be higher among vaccinated persons than among unvaccinated persons, thereby diminishing the observed realworld vaccine effectiveness relative to the actual biological vaccine effectiveness. mRNA-1273 effectiveness against infection with Delta was higher than that of BNT162b2, consistent with evidence suggesting that mRNA-1273 induces stronger immune response and protection 6,31-33 . mRNA-1273 effectiveness against Delta, 14 or more days after the first dose, was 79.0%, compared to 61.3% 6 against Beta and 88.1% 6 against Alpha, in the same population in Qatar. This result is also consistent with Beta's being the most immune-evasive variant 18,19 . However, mRNA-1273 effectiveness against Delta, 14 or more days after the second dose, was only 84.8%, compared to 96.4% 6 against Beta and 100% 6 against Alpha. The same factors that may explain the low BNT162b2 effectiveness against Delta among fully vaccinated persons may also explain the less-than-expected mRNA-1273 effectiveness against Delta among fully vaccinated persons. However, there has been less time for waning of vaccine immunity for mRNA-1273, as this vaccine was incorporated into the national immunization campaign nearly three months after BNT162b2 5,6,17 . There was evidence for a gradient in vaccine effectiveness by appearance of symptoms, that is, greater protection against more symptomatic or severe infections, as observed earlier for BNT162b2 and mRNA-1273 effectiveness against the Alpha and Beta variants 5, 6, 17, 25 . This study has limitations. Estimated effectiveness against severe, critical, or fatal COVID-19 disease had wider 95% confidence intervals than that against infection, as a consequence of the smaller number of such cases in the young population of Qatar 10, 34 . Data on co-morbid All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 11, 2021. ; https://doi.org/10.1101/2021.08.11.21261885 doi: medRxiv preprint conditions were not available; therefore, they could not be factored explicitly in our analysis. However, adjusting for age may have served as a proxy given that co-morbidities are associated with older age. Furthermore, with the young population of Qatar 10,11 , we anticipate that only a small proportion of the study population may have had serious co-morbid conditions. Accordingly, our findings may not be generalizable to other settings where the elderly population constitutes a sizable proportion of the population. Effectiveness was assessed using an observational test-negative case-control study design 35,36 , rather than a randomized clinical trial design where cohorts of vaccinated and unvaccinated individuals were being followed up. However, the cohort study design applied to the same population of Qatar yielded earlier similar findings to the test-negative case-control study design 5, 6 , supporting the validity of this standard approach in assessing vaccine effectiveness for respiratory tract infections 35,36 . In conclusion, both the BNT162b2 and mRNA-1273 vaccines are highly effective in preventing hospitalization and death due to infection with the Delta variant. However, effectiveness against infection was considerably lower than that against serious COVID-19 disease, particularly for the BNT162b2 vaccine. The reasons for the inferior protection against infection remain to be determined, and may not necessarily relate to immune evasion by the Delta variant. The lower effectiveness may reflect some waning of BNT162b2 vaccine protection over time, or higher risk of exposure to the virus among vaccinated persons compared to unvaccinated persons, due to higher social contact rate and less adherence to safety measures. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 11, 2021. Programme for institutional support for the reagents needed for the viral genome sequencing. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the article. Statements made herein are solely the responsibility of the authors. PT and MRH conducted the multiplex, RT-qPCR variant screening and viral genome sequencing. HC co-designed the study, performed the statistical analyses, and co-wrote the first draft of the article. LJA conceived and co-designed the study, led the statistical analyses, and cowrote the first draft of the article. HY, FMB, and HAK conducted viral genome sequencing. All authors contributed to data collection and acquisition, database development, discussion and interpretation of the results, and to the writing of the manuscript. All authors have read and approved the final manuscript. Dr. Butt has received institutional grant funding from Gilead Sciences unrelated to the work presented in this paper. Otherwise, we declare no competing interests. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 11, 2021. ; Israel All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 11, 2021. ; https://doi.org/10.1101/2021.08.11.21261885 doi: medRxiv preprint Table 1 BNT162b2 or mRNA-1273. Cases and controls were matched one-to-one by sex, 10-year age group, nationality, reason for PCR testing, and calendar week of PCR test. † Vaccine effectiveness was estimated using the test-negative, case-control study design 35, 36 . Age was included as a dichotomous variable: <50 versus ≥50. Nationality was categorized into 3 groups: Bangladeshis, Indians, Nepalese, Pakistanis, and Sri Lankans (Group 1); Qataris (Group 2); and all other nationalities (Group 3), as informed by the observed epidemiology and exposure risk assessments of SARS-CoV-2 infection in Qatar 10,39-43 . ‡ Effectiveness against severe, critical, or fatal COVID-19 disease. Severity 37 , criticality 37 , and fatality 38 were defined as per World Health Organization guidelines. § Confidence intervals could not be generated in logistic regression as there were no events among those vaccinated. Cases and controls were matched one-to-one by sex, 10-year age group, nationality, reason for PCR testing, and calendar week of PCR test. † Vaccine effectiveness was estimated using the test-negative, case-control study design 35,36 . ‡ A symptomatic infection is defined as a PCR-positive test conducted because of clinical suspicion due to presence of symptoms compatible with a respiratory tract infection. § An asymptomatic infection is defined as a PCR-positive test conducted with no reported presence of symptoms compatible with a respiratory tract infection. That is, the PCR testing was done as part of a survey, for pre-travel requirement, or at the port of entry into the country. This study was conducted in the resident population of Qatar. Coronavirus Disease 2019 (COVID-19) laboratory testing, vaccination, clinical infection data, and related demographic details were extracted from the integrated nationwide digital-health information platform that hosts the national, federated SARS-CoV-2 databases. These databases are complete and have captured all SARS-CoV-2-related data since epidemic onset. Nearly all individuals were vaccinated (free of charge) in Qatar and not elsewhere. In rare situations in which an individual received COVID-19 vaccination outside Qatar, the individual's vaccination details were still recorded in the health system at the port of entry (airport) upon return to Qatar, in order to fulfill national requirements and to benefit from privileges associated with vaccination, such as quarantine exemption. Vaccine effectiveness was estimated using the test-negative, case-control study design, a standard design for assessing vaccine effectiveness against influenza 35, 36 . Key to this design is the control of bias arising from misclassification of infection and differences in health careseeking behavior between vaccinated and unvaccinated individuals 35,36 . Cases and controls were matched one-to-one by sex, 10-year age group, nationality, reason for SARS-CoV-2 polymerase chain reaction (PCR) testing, and calendar week of PCR test. Matching of cases and controls was performed to control for known differences in the risk of exposure to infection in Qatar 10,40-42 . Effectiveness was estimated against documented infection (defined as a PCR-positive swab regardless of the reason for PCR testing or presence of symptoms) with the Delta (B.1.617.2) variant, as well as against severe, critical, or fatal COVID-19 disease due to Delta infection. Classification of COVID-19 case severity (acute-care hospitalizations) 12 , criticality (ICU All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 11, 2021. ; https://doi.org/10.1101/2021.08.11.21261885 doi: medRxiv preprint hospitalizations) 12 , and fatality 13 followed the World Health Organization guidelines, and assessments were made by trained medical personnel using individual chart reviews (see below). All records of PCR testing for those vaccinated and unvaccinated during the study duration were examined. All persons who received mixed vaccines, or who received a vaccine other than BNT162b2 or mRNA-1273 were excluded. Every case that met the inclusion criteria (a Delta case) and that could be matched to a control was included in the analysis. Both PCR-test outcomes and vaccination status were ascertained at the time of the PCR test. Each person that had a positive PCR test result and hospital admission was subject to an infection severity assessment every three days until discharge or death. Individuals who progressed to COVID-19 disease between the time of the positive PCR test result and the end of the study were classified based on their worst outcome, starting with death 13 , followed by critical disease 12 , and then severe disease 12 (see below). Institutional Review Boards with waiver of informed consent. The STROBE checklist can be found in Supplementary Table 1 . Severe COVID-19 disease was defined per WHO classification as a SARS-CoV-2 infected person with "oxygen saturation of <90% on room air, and/or respiratory rate of >30 breaths/minute in adults and children >5 years old (or ≥60 breaths/minute in children <2 months old or ≥50 breaths/minute in children 2-11 months old or ≥40 breaths/minute in children 1-5 years old), and/or signs of severe respiratory distress (accessory muscle use and inability to complete full sentences, and, in children, very severe chest wall indrawing, grunting, central All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 11, 2021. ; https://doi.org/10.1101/2021.08.11.21261885 doi: medRxiv preprint cyanosis, or presence of any other general danger signs)" 37 . Detailed WHO criteria for classifying SARS-CoV-2 infection severity can be found in the WHO technical report 37 . Critical COVID-19 disease was defined per WHO classification as a SARS-CoV-2 infected person with "acute respiratory distress syndrome, sepsis, septic shock, or other conditions that would normally require the provision of life sustaining therapies such as mechanical ventilation (invasive or non-invasive) or vasopressor therapy" 37 . Detailed WHO criteria for classifying SARS-CoV-2 infection criticality can be found in the WHO technical report 37 . COVID-19 death was defined per WHO classification as "a death resulting from a clinically compatible illness, in a probable or confirmed COVID-19 case, unless there is a clear alternative cause of death that cannot be related to COVID-19 disease (e.g. trauma). There should be no period of complete recovery from COVID-19 between illness and death. A death due to COVID-19 may not be attributed to another disease (e.g. cancer) and should be counted independently of preexisting conditions that are suspected of triggering a severe course of COVID-19". Detailed WHO criteria for classifying COVID-19 death can be found in the WHO technical report 38 . All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 11, 2021. Nasopharyngeal and/or oropharyngeal swabs (Huachenyang Technology, China) were collected for PCR testing and placed in Universal Transport Medium (UTM). Aliquots of UTM were: extracted on a QIAsymphony platform (QIAGEN, USA) and tested with real-time reversetranscription PCR (RT-qPCR) using TaqPath™ COVID-19 Combo Kits (Thermo Fisher Scientific, USA) on an ABI 7500 FAST (ThermoFisher, USA); tested directly on the Cepheid GeneXpert system using the Xpert Xpress SARS-CoV-2 (Cepheid, USA); or loaded directly into a Roche cobas® 6800 system and assayed with a cobas® SARS-CoV-2 Test (Roche, Switzerland). The first assay targets the viral S, N, and ORF1ab gene regions. The second targets the viral N and E-gene regions, and the third targets the ORF1ab and E-gene regions. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 11, 2021. ; https://doi.org/10.1101/2021.08.11.21261885 doi: medRxiv preprint All tests were conducted at the HMC Central Laboratory or Sidra Medicine Laboratory, following standardized protocols. Descriptive statistics (frequency distributions and measures of central tendency) were used to characterize the study samples. The odds ratio, comparing odds of vaccination among cases to that among controls, and its associated 95% confidence interval (CI) were calculated using the exact method. Confidence intervals were not adjusted for multiplicity. Interactions were not investigated. Vaccine effectiveness at different time frames and its associated 95% CI were then To ensure that vaccine effectiveness estimates were not biased by epidemic phase 35 (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 11, 2021. ; https://doi.org/10.1101/2021.08.11.21261885 doi: medRxiv preprint with a respiratory tract infection, that is the PCR testing was done as part of a survey, for pretravel requirement, or at port of entry into the country. The dataset of this study is a property of the Qatar Ministry of Public Health that was provided to the researchers through a restricted-access agreement that prevents sharing the dataset with a third party or publicly. Future access to this dataset can be considered through a direct application for data access to Her Excellency the Minister of Public Health (https://www.moph.gov.qa/english/Pages/default.aspx). Aggregate data are available within the manuscript and its Supplementary information. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 11, 2021. ; https://doi.org/10.1101/2021.08.11.21261885 doi: medRxiv preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 11, 2021. ; https://doi.org/10.1101/2021.08.11.21261885 doi: medRxiv preprint All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 11, 2021. ; https://doi.org/10.1101/2021.08.11.21261885 doi: medRxiv preprint All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 11, 2021. ; https://doi.org/10.1101/2021.08.11.21261885 doi: medRxiv preprint All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Tables 3-5 Main results 16 (a) Give unadjusted estimates and, if applicable, confounder-adjusted estimates and their precision (eg, 95% confidence interval). Make clear which confounders were adjusted for and why they were included 5-6, Tables 3-5 (b) Report category boundaries when continuous variables were categorized Tables 3-5 (c) If relevant, consider translating estimates of relative risk into absolute risk for a meaningful time period NA Other analyses 17 Report other analyses done-eg analyses of subgroups and interactions, and sensitivity analyses 6-7, Tables 4-5 Key results 18 Summarise key results with reference to study objectives 7-9 Limitations 19 Discuss limitations of the study, taking into account sources of potential bias or imprecision. Discuss both direction and magnitude of any potential bias 9-10 Interpretation 20 Give a cautious overall interpretation of results considering objectives, limitations, multiplicity of analyses, results from similar studies, and other relevant evidence 10 Generalisability 21 Discuss the generalisability (external validity) of the study results 9-10 Other information All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 11, 2021. ; https://doi.org/10.1101/2021.08.11.21261885 doi: medRxiv preprint Funding 22 Give the source of funding and the role of the funders for the present study and, if applicable, for the original study on which the present article is based 11 Abbreviations: NA, not applicable; Supp, Supplementary. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 11, 2021. ; https://doi.org/10.1101/2021.08.11.21261885 doi: medRxiv preprint World Health Organization. Tracking SARS-CoV-2 variants National Project of Surveillance for Variants of Concern and Viral Genome Sequencing. Qatar viral genome sequencing data. Data on randomly collected samples One year of SARS-CoV-2: Genomic characterization of COVID-19 outbreak in Qatar. medRxiv Real-Time SARS-CoV-2 Genotyping by High-Throughput Multiplex PCR Reveals the Epidemiology of the Variants of Concern in Qatar. medRxiv, 2021 Effectiveness of the BNT162b2 Covid-19 Vaccine against the B.1.1.7 and B.1.351 Variants mRNA-1273 COVID-19 vaccine effectiveness against the B.1.1.7 and B.1.351 variants and severe COVID-19 disease in Qatar Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine Ministry of Public Health. National Covid-19 Vaccination Program Data Characterizing the Qatar advanced-phase SARS-CoV-2 epidemic World Health Organization. COVID-19 clinical management: living guidance International guidelines for certification and classification (coding) of COVID-19 as cause of death Associations of Vaccination and of Prior Infection With Positive PCR Test Results for SARS-CoV-2 in Airline Passengers Arriving in Qatar Effectiveness of COVID-19 vaccines against hospital admission with the Delta (B.1.617.2) variant