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Background: The BNT162b2 vaccine against coronavirus disease 2019 (Covid-19) has been authorized for use in children 5 to 11 years of age and adolescents 12 to 17 years of age but in different antigen doses.Methods: We assessed the real-world effectiveness of the BNT162b2 vaccine against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among children and adolescents in Qatar. To compare the incidence of SARS-CoV-2 infection in the national cohort of vaccinated participants with the incidence in the national cohort of unvaccinated participants, we conducted three matched, retrospective, target-trial, cohort studies - one assessing data obtained from children 5 to 11 years of age after the B.1.1.529 (omicron) variant became prevalent and two assessing data from adolescents 12 to 17 years of age before the emergence of the omicron variant (pre-omicron study) and after the omicron variant became prevalent. Associations were estimated with the use of Cox proportional-hazards regression models.Results: Among children, the overall effectiveness of the 10-μg primary vaccine series against infection with the omicron variant was 25.7% (95% confidence interval [CI], 10.0 to 38.6). Effectiveness was highest (49.6%; 95% CI, 28.5 to 64.5) right after receipt of the second dose but waned rapidly thereafter and was negligible after 3 months. Effectiveness was 46.3% (95% CI, 21.5 to 63.3) among children 5 to 7 years of age and 16.6% (95% CI, -4.2 to 33.2) among those 8 to 11 years of age. Among adolescents, the overall effectiveness of the 30-μg primary vaccine series against infection with the omicron variant was 30.6% (95% CI, 26.9 to 34.1), but many adolescents had been vaccinated months earlier. Effectiveness waned over time since receipt of the second dose. Effectiveness was 35.6% (95% CI, 31.2 to 39.6) among adolescents 12 to 14 years of age and 20.9% (95% CI, 13.8 to 27.4) among those 15 to 17 years of age. In the pre-omicron study, the overall effectiveness of the 30-μg primary vaccine series against SARS-CoV-2 infection among adolescents was 87.6% (95% CI, 84.0 to 90.4) and waned relatively slowly after receipt of the second dose.Conclusions: Vaccination in children was associated with modest, rapidly waning protection against omicron infection. Vaccination in adolescents was associated with stronger, more durable protection, perhaps because of the larger antigen dose. (Funded by Weill Cornell Medicine-Qatar and others.). [ABSTRACT FROM AUTHOR]

Background: Waning of vaccine protection against coronavirus disease 2019 (Covid-19) and the emergence of the omicron (or B.1.1.529) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have led to expedited efforts to scale up booster vaccination. Protection conferred by booster doses of the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines in Qatar, as compared with protection conferred by the two-dose primary series, is unclear.Methods: We conducted two matched retrospective cohort studies to assess the effectiveness of booster vaccination, as compared with that of a two-dose primary series alone, against symptomatic SARS-CoV-2 infection and Covid-19-related hospitalization and death during a large wave of omicron infections from December 19, 2021, through January 26, 2022. The association of booster status with infection was estimated with the use of Cox proportional-hazards regression models.Results: In a population of 2,239,193 persons who had received at least two doses of BNT162b2 or mRNA-1273 vaccine, those who had also received a booster were matched with persons who had not received a booster. Among the BNT162b2-vaccinated persons, the cumulative incidence of symptomatic omicron infection was 2.4% (95% confidence interval [CI], 2.3 to 2.5) in the booster cohort and 4.5% (95% CI, 4.3 to 4.6) in the nonbooster cohort after 35 days of follow-up. Booster effectiveness against symptomatic omicron infection, as compared with that of the primary series, was 49.4% (95% CI, 47.1 to 51.6). Booster effectiveness against Covid-19-related hospitalization and death due to omicron infection, as compared with the primary series, was 76.5% (95% CI, 55.9 to 87.5). BNT162b2 booster effectiveness against symptomatic infection with the delta (or B.1.617.2) variant, as compared with the primary series, was 86.1% (95% CI, 67.3 to 94.1). Among the mRNA-1273-vaccinated persons, the cumulative incidence of symptomatic omicron infection was 1.0% (95% CI, 0.9 to 1.2) in the booster cohort and 1.9% (95% CI, 1.8 to 2.1) in the nonbooster cohort after 35 days; booster effectiveness against symptomatic omicron infection, as compared with the primary series, was 47.3% (95% CI, 40.7 to 53.3). Few severe Covid-19 cases were noted in the mRNA-1273-vaccinated cohorts.Conclusions: The messenger RNA (mRNA) boosters were highly effective against symptomatic delta infection, but they were less effective against symptomatic omicron infection. However, with both variants, mRNA boosters led to strong protection against Covid-19-related hospitalization and death. (Funded by Weill Cornell Medicine-Qatar and others.). [ABSTRACT FROM AUTHOR]

Objectives: Scant data are available on syphilis infection within migrant populations worldwide and in the population of the Middle East and North Africa region. This study investigated the prevalence of both lifetime and recent syphilis infections among migrant craft and manual workers (MCMWs) in Qatar, a diverse demographic representing 60% of the country's population., Methods: Sera specimens collected during a nationwide cross-sectional survey of SARS-CoV-2 seroprevalence among the MCMW population, conducted between 26 July and 9 September 2020, were analysed. Treponema pallidum antibodies were detected using the Mindray CL-900i Chemiluminescence Immunoassay Analyzer. To differentiate recent infections, rapid plasma reagin (RPR) testing was performed, with an RPR titre of ≥1:8 considered indicative of recent infection. Logistic regression analyses were employed to identify factors associated with lifetime syphilis infection. Sampling weights were incorporated into all statistical analyses to obtain population-level estimates., Results: T. pallidum antibodies were identified in 38 of the 2528 tested sera specimens. Prevalence of lifetime infection was estimated at 1.3% (95% CI 0.9% to 1.8%). Among the 38 treponemal-positive specimens, 15 were reactive by RPR, with three having titres ≥1:8, indicating recent infection. Prevalence of recent infection was estimated at 0.09% (95% CI 0.01 to 0.3%). Among treponemal-positive MCMWs, the estimated proportion with recent infection was 8.1% (95% CI: 1.7 to 21.4%). The adjusted OR for lifetime infection increased with age, reaching 8.68 (95% CI 2.58 to 29.23) among those aged ≥60 years compared with those ≤29 years of age. Differences in prevalence were observed by nationality and occupation, but no differences were found by educational attainment or geographic location., Conclusions: Syphilis prevalence among MCMWs in Qatar is consistent with global levels, highlighting a disease burden with implications for health and social well-being. These findings underscore the need for programmes addressing both sexually transmitted infections and the broader sexual health needs of this population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: This study provides a head-to-head comparison of the protection provided by the BNT162b2 and mRNA-1273 vaccines against SARS-CoV-2 infection and against severe COVID-19, covering primary series and third dose/booster vaccinations over up to 3 years of follow-up, both before and after the emergence of the omicron variant., Methods: Two national, matched, retrospective cohort studies were conducted on Qatar's vaccinated population from December 16, 2020, to February 18, 2024. Subgroup analyses by pre-vaccination SARS-CoV-2 infection history, as well as sensitivity analyses, were also conducted., Results: The adjusted hazard ratio (AHR) comparing infection incidence in those vaccinated with BNT162b2 versus mRNA-1273 was 1.03 (95% CI: 1.02-1.05) after the primary series and 1.11 (95% CI: 1.09-1.13) after the third (booster) dose. The corresponding AHRs for any severe, critical, or fatal COVID-19 were 1.31 (95% CI: 0.81-2.11) and 1.00 (95% CI: 0.20-4.94), respectively. Subgroup analyses by prior infection status hinted at a dose-dependent immune imprinting effect, where a combination of two types of immunity, pre-omicron and omicron, offered greater protection against infection than one type alone, with this effect being amplified by the higher antigen dose of mRNA-1273 compared to BNT162b2. Sensitivity analyses confirmed the study findings., Conclusions: BNT162b2 provided slightly less protection against infection than mRNA-1273 following both primary series and booster vaccinations while offering comparable protection against severe COVID-19 outcomes. The findings suggested that the vaccine antigen dose in interaction with infection history may determine the extent of immune protection against infection., (© 2024 The Author(s). Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

The COVID-19 pandemic has highlighted the need to use infection testing databases to rapidly estimate effectiveness of prior infection in preventing reinfection ($P{E}_S$) by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Mathematical modeling was used to demonstrate a theoretical foundation for applicability of the test-negative, case-control study design to derive $P{E}_S$. Apart from the very early phase of an epidemic, the difference between the test-negative estimate for $P{E}_S$ and true value of $P{E}_S$ was minimal and became negligible as the epidemic progressed. The test-negative design provided robust estimation of $P{E}_S$ and its waning. Assuming that only 25% of prior infections are documented, misclassification of prior infection status underestimated $P{E}_S$, but the underestimate was considerable only when > 50% of the population was ever infected. Misclassification of latent infection, misclassification of current active infection, and scale-up of vaccination all resulted in negligible bias in estimated $P{E}_S$. The test-negative design was applied to national-level testing data in Qatar to estimate $P{E}_S$ for SARS-CoV-2. $P{E}_S$ against SARS-CoV-2 Alpha and Beta variants was estimated at 97.0% (95% CI, 93.6-98.6) and 85.5% (95% CI, 82.4-88.1), respectively. These estimates were validated using a cohort study design. The test-negative design offers a feasible, robust method to estimate protection from prior infection in preventing reinfection., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Background: Vaccines were developed and deployed to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to characterize patterns in the protection provided by the BNT162b2 and mRNA-1273 mRNA vaccines against a spectrum of SARS-CoV-2 infection symptoms and severities., Methods: A national, matched, test-negative, case-control study was conducted in Qatar between January 1 and December 18, 2021, utilizing a sample of 238,896 PCR-positive tests and 6,533,739 PCR-negative tests. Vaccine effectiveness was estimated against asymptomatic, symptomatic, severe coronavirus disease 2019 (COVID-19), critical COVID-19, and fatal COVID-19 infections. Data sources included Qatar's national databases for COVID-19 laboratory testing, vaccination, hospitalization, and death., Results: Effectiveness of two-dose BNT162b2 vaccination was 75.6% (95% CI: 73.6-77.5) against asymptomatic infection and 76.5% (95% CI: 75.1-77.9) against symptomatic infection. Effectiveness against each of severe, critical, and fatal COVID-19 infections surpassed 90%. Immediately after the second dose, all categories-namely, asymptomatic, symptomatic, severe, critical, and fatal COVID-19-exhibited similarly high effectiveness. However, from 181 to 270 days post-second dose, effectiveness against asymptomatic and symptomatic infections declined to below 40%, while effectiveness against each of severe, critical, and fatal COVID-19 infections remained consistently high. However, estimates against fatal COVID-19 often had wide 95% confidence intervals. Analogous patterns were observed in three-dose BNT162b2 vaccination and two- and three-dose mRNA-1273 vaccination. Sensitivity analyses confirmed the results., Conclusion: A gradient in vaccine effectiveness exists and is linked to the symptoms and severity of infection, providing higher protection against more symptomatic and severe cases. This gradient intensifies over time as vaccine immunity wanes after the last vaccine dose. These patterns appear consistent irrespective of the vaccine type or whether the vaccination involves the primary series or a booster., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Limited data exist on viral hepatitis among migrant populations. This study investigated the prevalence of current hepatitis B virus (HBV) infection and lifetime hepatitis C virus (HCV) infection among Qatar's migrant craft and manual workers (CMWs), constituting 60% of the country's population. Sera collected during a nationwide COVID-19 population-based cross-sectional survey on CMWs between July 26 and September 9, 2020, underwent testing for HBsAg and HCV antibodies. Reactive samples underwent confirmatory testing, and logistic regression analyses were employed to explore associations with HBV and HCV infections. Among 2528 specimens tested for HBV infection, 15 were reactive, with 8 subsequently confirmed positive. Three samples lacked sufficient sera for confirmatory testing but were included in the analysis through multiple imputations. Prevalence of current HBV infection was 0.4% (95% CI 0.2-0.7%). Educational attainment and occupation were significantly associated with current HBV infection. For HCV infection, out of 2607 specimens tested, 46 were reactive, and 23 were subsequently confirmed positive. Prevalence of lifetime HCV infection was 0.8% (95% CI 0.5-1.2%). Egyptians exhibited the highest prevalence at 6.5% (95% CI 3.1-13.1%), followed by Pakistanis at 3.1% (95% CI 1.1-8.0%). Nationality, geographic location, and occupation were significantly associated with lifetime HCV infection. HBV infection is relatively low among CMWs, while HCV infection falls within the intermediate range, both compared to global and regional levels., (© 2024. The Author(s).)

Introduction: Reinfections are increasingly becoming a feature in the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, accurately defining reinfection poses methodological challenges. Conventionally, reinfection is defined as a positive test occurring at least 90 days after a previous infection diagnosis. Yet, this extended time window may lead to an underestimation of reinfection occurrences. This study investigated the prospect of adopting an alternative, shorter time window for defining reinfection., Methods: A longitudinal study was conducted to assess the incidence of reinfections in the total population of Qatar, from February 28, 2020 to November 20, 2023. The assessment considered a range of time windows for defining reinfection, spanning from 1 day to 180 days. Subgroup analyses comparing first versus repeat reinfections and a sensitivity analysis, focusing exclusively on individuals who underwent frequent testing, were performed., Results: The relationship between the number of reinfections in the population and the duration of the time window used to define reinfection revealed two distinct dynamical domains. Within the initial 15 days post-infection diagnosis, almost all positive tests for SARS-CoV-2 were attributed to the original infection. However, surpassing the 30-day post-infection threshold, nearly all positive tests were attributed to reinfections. A 40-day time window emerged as a sufficiently conservative definition for reinfection. By setting the time window at 40 days, the estimated number of reinfections in the population increased from 84,565 to 88,384, compared to the 90-day time window. The maximum observed reinfections were 6 and 4 for the 40-day and 90-day time windows, respectively. The 40-day time window was appropriate for defining reinfection, irrespective of whether it was the first, second, third, or fourth occurrence. The sensitivity analysis, confined to high testers exclusively, replicated similar patterns and results., Discussion: A 40-day time window is optimal for defining reinfection, providing an informed alternative to the conventional 90-day time window. Reinfections are prevalent, with some individuals experiencing multiple instances since the onset of the pandemic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chemaitelly, Ayoub, Tang, Yassine, Al Thani, Hasan, Coyle, Al-Kanaani, Al-Kuwari, Jeremijenko, Kaleeckal, Latif, Shaik, Abdul-Rahim, Nasrallah, Al-Kuwari, Butt, Al-Romaihi, Al-Thani, Al-Khal, Bertollini and Abu-Raddad.)

Objectives: We assessed short-, medium-, and long-term all-cause mortality risks after a primary SARS-CoV-2 infection., Methods: A national, matched, retrospective cohort study was conducted in Qatar to assess risk of all-cause mortality in the national SARS-CoV-2 primary infection cohort compared with the national infection-naïve cohort. Associations were estimated using Cox proportional-hazards regression models. Analyses were stratified by vaccination status and clinical vulnerability status., Results: Among unvaccinated persons, within 90 days after primary infection, the adjusted hazard ratio (aHR) comparing mortality incidence in the primary-infection cohort with the infection-naïve cohort was 1.19 (95% confidence interval 1.02-1.39). aHR was 1.34 (1.11-1.63) in persons more clinically vulnerable to severe COVID-19 and 0.94 (0.72-1.24) in those less clinically vulnerable. Beyond 90 days after primary infection, aHR was 0.50 (0.37-0.68); aHR was 0.41 (0.28-0.58) at 3-7 months and 0.76 (0.46-1.26) at ≥8 months. The aHR was 0.37 (0.25-0.54) in more clinically vulnerable persons and 0.77 (0.48-1.24) in less clinically vulnerable persons. Among vaccinated persons, mortality incidence was comparable in the primary-infection versus infection-naïve cohorts, regardless of clinical vulnerability status., Conclusions: COVID-19 mortality was primarily driven by an accelerated onset of death among individuals who were already vulnerable to all-cause mortality, but vaccination prevented these accelerated deaths., Competing Interests: Declaration of competing interests Dr. Butt has received institutional grant funding from Gilead Sciences unrelated to the work presented in this paper. The remaining authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: We investigated the contribution of age, coexisting medical conditions, sex, and vaccination to incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and of severe, critical, or fatal COVID-19 in older adults since pandemic onset., Methods: A national retrospective cohort study was conducted in the population of Qatar aged ≥50 years between February 5, 2020 and June 15, 2023. Adjusted hazard ratios (AHRs) for infection and for severe coronavirus disease 2019 (COVID-19) outcomes were estimated through Cox regression models., Results: Cumulative incidence was 25.01% (95% confidence interval [CI]: 24.86-25.15%) for infection and 1.59% (95% CI: 1.55-1.64%) for severe, critical, or fatal COVID-19 after a follow-up duration of 40.9 months. Risk of infection varied minimally by age and sex but increased significantly with coexisting conditions. Risk of infection was reduced with primary-series vaccination (AHR: 0.91, 95% CI: 0.90-0.93) and further with first booster vaccination (AHR: 0.75, 95% CI: 0.74-0.77). Risk of severe, critical, or fatal COVID-19 increased exponentially with age and linearly with coexisting conditions. AHRs for severe, critical, or fatal COVID-19 were 0.86 (95% CI: 0.7-0.97) for one dose, 0.15 (95% CI: 0.13-0.17) for primary-series vaccination, and 0.11 (95% CI: 0.08-0.14) for first booster vaccination. Sensitivity analysis restricted to only Qataris yielded similar results., Conclusion: Incidence of severe COVID-19 in older adults followed a dynamic pattern shaped by infection incidence, variant severity, and population immunity. Age, sex, and coexisting conditions were strong determinants of infection severity. Vaccine protection against severe outcomes showed a dose-response relationship, highlighting the importance of booster vaccination for older adults., (© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Laboratory evidence suggests a possibility of immune imprinting for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We investigated the differences in the incidence of SARS-CoV-2 reinfection in a cohort of persons who had a primary Omicron infection, but different vaccination histories using matched, national, retrospective, cohort studies. Adjusted hazard ratio for reinfection incidence, factoring adjustment for differences in testing rate, was 0.43 [95% confidence interval (CI): 0.39 to 0.49] comparing history of two-dose vaccination to no vaccination, 1.47 (95% CI: 1.23 to 1.76) comparing history of three-dose vaccination to two-dose vaccination, and 0.57 (95% CI: 0.48 to 0.68) comparing history of three-dose vaccination to no vaccination. Divergence in cumulative incidence curves increased markedly when the incidence was dominated by BA.4/BA.5 and BA.2.75* Omicron subvariants. The history of primary-series vaccination enhanced immune protection against Omicron reinfection, but history of booster vaccination compromised protection against Omicron reinfection. These findings do not undermine the public health utility of booster vaccination.

Background: Protection against SARS-CoV-2 symptomatic infection and severe COVID-19 of previous infection, mRNA two-dose vaccination, mRNA three-dose vaccination, and hybrid immunity of previous infection and vaccination were investigated in Qatar for the Alpha, Beta, and Delta variants., Methods: Six national, matched, test-negative, case-control studies were conducted between January 18 and December 18, 2021 on a sample of 239,120 PCR-positive tests and 6,103,365 PCR-negative tests., Findings: Effectiveness of previous infection against Alpha, Beta, and Delta reinfection was 89.5% (95% CI: 85.5-92.3%), 87.9% (95% CI: 85.4-89.9%), and 90.0% (95% CI: 86.7-92.5%), respectively. Effectiveness of two-dose BNT162b2 vaccination against Alpha, Beta, and Delta infection was 90.5% (95% CI, 83.9-94.4%), 80.5% (95% CI: 79.0-82.0%), and 58.1% (95% CI: 54.6-61.3%), respectively. Effectiveness of three-dose BNT162b2 vaccination against Delta infection was 91.7% (95% CI: 87.1-94.7%). Effectiveness of hybrid immunity of previous infection and two-dose BNT162b2 vaccination was 97.4% (95% CI: 95.4-98.5%) against Beta infection and 94.5% (95% CI: 92.8-95.8%) against Delta infection. Effectiveness of previous infection and three-dose BNT162b2 vaccination was 98.1% (95% CI: 85.7-99.7%) against Delta infection. All five forms of immunity had >90% protection against severe, critical, or fatal COVID-19 regardless of variant. Similar effectiveness estimates were observed for mRNA-1273. A mathematical model accurately predicted hybrid immunity protection by assuming that the individual effects of previous infection and vaccination acted independently., Interpretation: Hybrid immunity, offering the strongest protection, was mathematically predicted by assuming that the immunities obtained from previous infection and vaccination act independently, without synergy or redundancy., Funding: The Biomedical Research Program and the Biostatistics, Epidemiology, and the Biomathematics Research Core, both at Weill Cornell Medicine-Qatar, Ministry of Public Health, Hamad Medical Corporation, Sidra Medicine, Qatar Genome Programme, Qatar University Biomedical Research Center, and Qatar University Internal Grant ID QUCG-CAS-23/24-114., Competing Interests: Declaration of interests Dr. Butt has received institutional grant funding from Gilead Sciences unrelated to the work presented in this paper. Otherwise, we declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Limited data exists on herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections in migrant populations. This study investigated HSV-1 and HSV-2 seroprevalences and associations among craft and manual workers (CMWs) in Qatar who constitute 60% of Qatar's population., Methods: A national population-based cross-sectional seroprevalence survey was conducted on the CMW population, all men, between July 26 and September 9, 2020. 2,612 sera were tested for anti-HSV-1 IgG antibodies using HerpeSelect 1 ELISA IgG kits and for anti-HSV-2 IgG antibodies using HerpeSelect 2 ELISA IgG kits (Focus Diagnostics, USA). Univariable and multivariable logistic regression analyses were conducted to identify associations with HSV-1 and HSV-2 infections., Results: Serological testing identified 2,171 sera as positive, 403 as negative, and 38 as equivocal for HSV-1 antibodies, and 300 sera as positive, 2,250 as negative, and 62 as equivocal for HSV-2 antibodies. HSV-1 and HSV-2 seroprevalences among CMWs were estimated at 84.2% (95% CI 82.8-85.6%) and 11.4% (95% CI 10.1-12.6%), respectively. HSV-1 infection was associated with nationality, educational attainment, and occupation. HSV-2 infection was associated with age, nationality, and educational attainment., Conclusions: Over 80% of CMWs are infected with HSV-1 and over 10% are infected with HSV-2. The findings highlight the need for sexual health programs to tackle sexually transmitted infections among the CMW population., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Waning of natural infection protection and vaccine protection highlight the need to evaluate changes in population immunity over time. Population immunity of previous SARS-CoV-2 infection or of COVID-19 vaccination are defined, respectively, as the overall protection against reinfection or against breakthrough infection at a given point in time in a given population., Methods: We estimated these population immunities in Qatar's population between July 1, 2020 and November 30, 2022, to discern generic features of the epidemiology of SARS-CoV-2. Effectiveness of previous infection, mRNA primary-series vaccination, and mRNA booster (third-dose) vaccination in preventing infection were estimated, month by month, using matched, test-negative, case-control studies., Findings: Previous-infection effectiveness against reinfection was strong before emergence of Omicron, but declined with time after a wave and rebounded after a new wave. Effectiveness dropped after Omicron emergence from 88.3% (95% CI: 84.8-91.0%) in November 2021 to 51.0% (95% CI: 48.3-53.6%) in December 2021. Primary-series effectiveness against infection was 84.0% (95% CI: 83.0-85.0%) in April 2021, soon after introduction of vaccination, before waning gradually to 52.7% (95% CI: 46.5-58.2%) by November 2021. Effectiveness declined linearly by ∼1 percentage point every 5 days. After Omicron emergence, effectiveness dropped from 52.7% (95% CI: 46.5-58.2%) in November 2021 to negligible levels in December 2021. Booster effectiveness dropped after Omicron emergence from 83.0% (95% CI: 65.6-91.6%) in November 2021 to 32.9% (95% CI: 26.7-38.5%) in December 2021, and continued to decline thereafter. Effectiveness of previous infection and vaccination against severe, critical, or fatal COVID-19 were generally >80% throughout the study duration., Interpretation: High population immunity against infection may not be sustained beyond a year, but population immunity against severe COVID-19 is durable with slow waning even after Omicron emergence., Funding: The Biomedical Research Program and the Biostatistics, Epidemiology, and the Biomathematics Research Core, both at Weill Cornell Medicine-Qatar, Ministry of Public Health, Hamad Medical Corporation, Sidra Medicine, Qatar Genome Programme, Qatar University Biomedical Research Center, and Qatar University Internal Grant ID QUCG-CAS-23/24-114., Competing Interests: We declare no competing interests., (© 2023 The Author(s).)

Background: Long-term effectiveness of COVID-19 mRNA boosters in populations with different previous infection histories and clinical vulnerability profiles is inadequately understood. We aimed to investigate the effectiveness of a booster (third dose) vaccination against SARS-CoV-2 infection and against severe, critical, or fatal COVID-19, relative to that of primary-series (two-dose) vaccination over a follow-up duration of 1 year., Methods: This observational, matched, retrospective, cohort study was done on the population of Qatar in people with different immune histories and different clinical vulnerability to infection. The source of data are Qatar's national databases for COVID-19 laboratory testing, vaccination, hospitalisation, and death. Associations were estimated using inverse-probability-weighted Cox proportional-hazards regression models. The primary outcome of the study is the effectiveness of COVID-19 mRNA boosters against infection and against severe COVID-19., Findings: Data were obtained for 2 228 686 people who had received at least two vaccine doses starting from Jan 5, 2021, of whom 658 947 (29·6%) went on to receive a third dose before data cutoff on Oct 12, 2022. There were 20 528 incident infections in the three-dose cohort and 30 771 infections in the two-dose cohort. Booster effectiveness relative to primary series was 26·2% (95% CI 23·6-28·6) against infection and 75·1% (40·2-89·6) against severe, critical, or fatal COVID-19, during 1-year follow-up after the booster. Among people clinically vulnerable to severe COVID-19, effectiveness was 34·2% (27·0-40·6) against infection and 76·6% (34·5-91·7) against severe, critical, or fatal COVID-19. Effectiveness against infection was highest at 61·4% (60·2-62·6) in the first month after the booster but waned thereafter and was modest at only 15·5% (8·3-22·2) by the sixth month. In the seventh month and thereafter, coincident with BA.4/BA.5 and BA.2·75* subvariant incidence, effectiveness was progressively negative albeit with wide CIs. Similar patterns of protection were observed irrespective of previous infection status, clinical vulnerability, or type of vaccine (BNT162b2 vs mRNA-1273)., Interpretation: Protection against omicron infection waned after the booster, and eventually suggested a possibility for negative immune imprinting. However, boosters substantially reduced infection and severe COVID-19, particularly among individuals who were clinically vulnerable, affirming the public health value of booster vaccination., Funding: The Biomedical Research Program and the Biostatistics, Epidemiology, and the Biomathematics Research Core (both at Weill Cornell Medicine-Qatar), Ministry of Public Health, Hamad Medical Corporation, Sidra Medicine, Qatar Genome Programme, and Qatar University Biomedical Research Center., Competing Interests: Declaration of interests AAB has received institutional grant funding from Gilead Sciences unrelated to the work presented in this paper. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The future of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic hinges on virus evolution and duration of immune protection of natural infection against reinfection. We investigated the duration of protection afforded by natural infection, the effect of viral immune evasion on duration of protection and protection against severe reinfection, in Qatar, between 28 February 2020 and 5 June 2022., Methods: Three national, matched, retrospective cohort studies were conducted to compare the incidence of SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19) severity among unvaccinated persons with a documented SARS-CoV-2 primary infection, to incidence among those infection-naïve and unvaccinated. Associations were estimated using Cox proportional hazard regression models., Results: Effectiveness of pre-Omicron primary infection against pre-Omicron reinfection was 85.5% [95% confidence interval (CI): 84.8-86.2%]. Effectiveness peaked at 90.5% (95% CI: 88.4-92.3%) in the 7th month after the primary infection, but waned to ~ 70% by the 16th month. Extrapolating this waning trend using a Gompertz curve suggested an effectiveness of 50% in the 22nd month and < 10% by the 32nd month. Effectiveness of pre-Omicron primary infection against Omicron reinfection was 38.1% (95% CI: 36.3-39.8%) and declined with time since primary infection. A Gompertz curve suggested an effectiveness of < 10% by the 15th month. Effectiveness of primary infection against severe, critical or fatal COVID-19 reinfection was 97.3% (95% CI: 94.9-98.6%), irrespective of the variant of primary infection or reinfection, and with no evidence for waning. Similar results were found in sub-group analyses for those ≥50 years of age., Conclusions: Protection of natural infection against reinfection wanes and may diminish within a few years. Viral immune evasion accelerates this waning. Protection against severe reinfection remains very strong, with no evidence for waning, irrespective of variant, for over 14 months after primary infection., (© International Society of Travel Medicine 2022. Published by Oxford University Press.)

Background: Understanding protection conferred by natural SARS-CoV-2 infection versus COVID-19 vaccination is important for informing vaccine mandate decisions. We compared protection conferred by natural infection versus that from the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines in Qatar., Methods: We conducted two matched retrospective cohort studies that emulated target trials. Data were obtained from the national federated databases for COVID-19 vaccination, SARS-CoV-2 testing, and COVID-19-related hospitalisation and death between Feb 28, 2020 (pandemic onset in Qatar) and May 12, 2022. We matched individuals with a documented primary infection and no vaccination record (natural infection cohort) with individuals who had received two doses (primary series) of the same vaccine (BNT162b2-vaccinated or mRNA-1273-vaccinated cohorts) at the start of follow-up (90 days after the primary infection). Individuals were exact matched (1:1) by sex, 10-year age group, nationality, comorbidity count, and timing of primary infection or first-dose vaccination. Incidence of SARS-CoV-2 infection and COVID-19-related hospitalisation and death in the natural infection cohorts was compared with incidence in the vaccinated cohorts, using Cox proportional hazards regression models with adjustment for matching factors., Findings: Between Jan 5, 2021 (date of second-dose vaccine roll-out) and May 12, 2022, 104 500 individuals vaccinated with BNT162b2 and 61 955 individuals vaccinated with mRNA-1273 were matched to unvaccinated individuals with a documented primary infection. During follow-up, 7123 SARS-CoV-2 infections were recorded in the BNT162b2-vaccinated cohort and 3583 reinfections were recorded in the matched natural infection cohort. 4282 SARS-CoV-2 infections were recorded in the mRNA-1273-vaccinated cohort and 2301 reinfections were recorded in the matched natural infection cohort. The overall adjusted hazard ratio (HR) for SARS-CoV-2 infection was 0·47 (95% CI 0·45-0·48) after previous natural infection versus BNT162b2 vaccination, and 0·51 (0·49-0·54) after previous natural infection versus mRNA-1273 vaccination. The overall adjusted HR for severe (acute care hospitalisations), critical (intensive care unit hospitalisations), or fatal COVID-19 cases was 0·24 (0·08-0·72) after previous natural infection versus BNT162b2 vaccination, and 0·24 (0·05-1·19) after previous natural infection versus mRNA-1273 vaccination. Severe, critical, or fatal COVID-19 was rare in both the natural infection and vaccinated cohorts., Interpretation: Previous natural infection was associated with lower incidence of SARS-CoV-2 infection, regardless of the variant, than mRNA primary-series vaccination. Vaccination remains the safest and most optimal tool for protecting against infection and COVID-19-related hospitalisation and death, irrespective of previous infection status., Funding: The Biomedical Research Program and the Biostatistics, Epidemiology, and Biomathematics Research Core, Weill Cornell Medicine-Qatar; Qatar Ministry of Public Health; Hamad Medical Corporation; Sidra Medicine; Qatar Genome Programme; and Qatar University Biomedical Research Center., Competing Interests: Declaration of interests AAB has received institutional grant funding from Gilead Sciences unrelated to the work presented in this paper. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

In 2021, Qatar experienced considerable incidence of SARS-CoV-2 infection that was dominated sequentially by the Alpha, Beta, and Delta variants. Using the cycle threshold (Ct) value of an RT-qPCR-positive test to proxy the inverse of infectiousness, we investigated infectiousness of SARS-CoV-2 infections by variant, age, sex, vaccination status, prior infection status, and reason for testing in a random sample of 18,355 RT-qPCR-genotyped infections. Regression analyses were conducted to estimate associations with the Ct value of RT-qPCR-positive tests. Compared to Beta infections, Alpha and Delta infections demonstrated 2.56 higher Ct cycles (95% CI: 2.35-2.78), and 4.92 fewer cycles (95% CI: 4.67- 5.16), respectively. The Ct value declined gradually with age and was especially high for children <10 years of age, signifying lower infectiousness in small children. Children <10 years of age had 2.18 higher Ct cycles (95% CI: 1.88-2.48) than those 10-19 years of age. Compared to unvaccinated individuals, the Ct value was higher among individuals who had received one or two vaccine doses, but the Ct value decreased gradually with time since the second-dose vaccination. Ct value was 2.07 cycles higher (95% CI: 1.42-2.72) for those with a prior infection than those without prior infection. The Ct value was lowest among individuals tested because of symptoms and was highest among individuals tested as a travel requirement. Delta was substantially more infectious than Beta. Prior immunity, whether due to vaccination or prior infection, is associated with lower infectiousness of breakthrough infections, but infectiousness increases gradually with time since the second-dose vaccination., Competing Interests: AB has received institutional grant funding from Gilead Sciences unrelated to the work presented in this paper. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Qassim, Hasan, Tang, Chemaitelly, Ayoub, Yassine, Al-Khatib, Smatti, Abdul-Rahim, Nasrallah, Al-Kuwari, Al-Khal, Coyle, Gillani, Kaleeckal, Shaik, Latif, Al-Kuwari, Jeremijenko, Butt, Bertollini, Al-Romaihi, Al-Thani and Abu-Raddad.)

Beta (B.1.351)-variant coronavirus disease 2019 (COVID-19) disease was investigated in Qatar. Compared with the Alpha (B.1.1.7) variant, odds (95% confidence interval) of progressing to severe disease, critical disease, and COVID-19-related death were 1.24-fold (1.11-1.39), 1.49-fold (1.13-1.97), and 1.57-fold (1.03-2.43) higher, respectively, for the Beta variant., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

There is significant genetic distance between SARS-CoV-2 Omicron (B.1.1.529) variant BA.1 and BA.2 sub-lineages. This study investigates immune protection of infection with one sub-lineage against reinfection with the other sub-lineage in Qatar during a large BA.1 and BA.2 Omicron wave, from December 19, 2021 to March 21, 2022. Two national matched, retrospective cohort studies are conducted to estimate effectiveness of BA.1 infection against reinfection with BA.2 (N = 20,994; BA.1-against-BA.2 study), and effectiveness of BA.2 infection against reinfection with BA.1 (N = 110,315; BA.2-against-BA.1 study). Associations are estimated using Cox proportional-hazards regression models after multiple imputation to assign a sub-lineage status for cases with no sub-lineage status (using probabilities based on the test date). Effectiveness of BA.1 infection against reinfection with BA.2 is estimated at 94.2% (95% CI: 89.2-96.9%). Effectiveness of BA.2 infection against reinfection with BA.1 is estimated at 80.9% (95% CI: 73.1-86.4%). Infection with the BA.1 sub-lineage appears to induce strong, but not full immune protection against reinfection with the BA.2 sub-lineage, and vice versa, for at least several weeks after the initial infection., (© 2022. The Author(s).)

We developed a Coronavirus Disease 2019 (COVID-19) risk score to guide targeted RT-PCR testing in Qatar. The Qatar national COVID-19 testing database, encompassing a total of 2,688,232 RT-PCR tests conducted between February 5, 2020-January 27, 2021, was analyzed. Logistic regression analyses were implemented to derive the COVID-19 risk score, as a tool to identify those at highest risk of having the infection. Score cut-off was determined using the ROC curve based on maximum sum of sensitivity and specificity. The score's performance diagnostics were assessed. Logistic regression analysis identified age, sex, and nationality as significant predictors of infection and were included in the risk score. The ROC curve was generated and the area under the curve was estimated at 0.63 (95% CI: 0.63-0.63). The score had a sensitivity of 59.4% (95% CI: 59.1%-59.7%), specificity of 61.1% (95% CI: 61.1%-61.2%), a positive predictive value of 10.9% (95% CI: 10.8%-10.9%), and a negative predictive value of 94.9% (94.9%-95.0%). The concept and utility of a COVID-19 risk score were demonstrated in Qatar. Such a public health tool can have considerable utility in optimizing testing and suppressing infection transmission, while maximizing efficiency and use of available resources., Competing Interests: The authors have declared that no competing interests exist.

Background: The protection conferred by natural immunity, vaccination, and both against symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with the BA.1 or BA.2 sublineages of the omicron (B.1.1.529) variant is unclear., Methods: We conducted a national, matched, test-negative, case-control study in Qatar from December 23, 2021, through February 21, 2022, to evaluate the effectiveness of vaccination with BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna), natural immunity due to previous infection with variants other than omicron, and hybrid immunity (previous infection and vaccination) against symptomatic omicron infection and against severe, critical, or fatal coronavirus disease 2019 (Covid-19)., Results: The effectiveness of previous infection alone against symptomatic BA.2 infection was 46.1% (95% confidence interval [CI], 39.5 to 51.9). The effectiveness of vaccination with two doses of BNT162b2 and no previous infection was negligible (-1.1%; 95% CI, -7.1 to 4.6), but nearly all persons had received their second dose more than 6 months earlier. The effectiveness of three doses of BNT162b2 and no previous infection was 52.2% (95% CI, 48.1 to 55.9). The effectiveness of previous infection and two doses of BNT162b2 was 55.1% (95% CI, 50.9 to 58.9), and the effectiveness of previous infection and three doses of BNT162b2 was 77.3% (95% CI, 72.4 to 81.4). Previous infection alone, BNT162b2 vaccination alone, and hybrid immunity all showed strong effectiveness (>70%) against severe, critical, or fatal Covid-19 due to BA.2 infection. Similar results were observed in analyses of effectiveness against BA.1 infection and of vaccination with mRNA-1273., Conclusions: No discernable differences in protection against symptomatic BA.1 and BA.2 infection were seen with previous infection, vaccination, and hybrid immunity. Vaccination enhanced protection among persons who had had a previous infection. Hybrid immunity resulting from previous infection and recent booster vaccination conferred the strongest protection. (Funded by Weill Cornell Medicine-Qatar and others.)., (Copyright © 2022 Massachusetts Medical Society.)

SARS-CoV-2 Omicron BA.1 and BA.2 subvariants are genetically divergent. We conducted a matched, test-negative, case-control study to estimate duration of protection of the second and third/booster doses of mRNA COVID-19 vaccines against BA.1 and BA.2 infections in Qatar. BNT162b2 effectiveness was highest at 46.6% (95% CI: 33.4-57.2%) against symptomatic BA.1 and at 51.7% (95% CI: 43.2-58.9%) against symptomatic BA.2 infections in the first three months after the second dose, but declined to ~10% or below thereafter. Effectiveness rebounded to 59.9% (95% CI: 51.2-67.0%) and 43.7% (95% CI: 36.5-50.0%), respectively, in the first month after the booster dose, before declining again. Effectiveness against COVID-19 hospitalization and death was 70-80% after the second dose and >90% after the booster dose. mRNA-1273 vaccine protection showed similar patterns. mRNA vaccines provide comparable, moderate, and short-lived protection against symptomatic BA.1 and BA.2 Omicron infections, but strong and durable protection against COVID-19 hospitalization and death., (© 2022. The Author(s).)

Introduction. The cycle threshold (Ct) value in real-time PCR (RT-PCR) is where a target-specific amplification signal becomes detectable and can infer viral load, risk of transmission and recovery. Use of Ct values in routine practice is uncommon. Gap Statement. There is a lack of routine use of Ct values when reporting RT-PCR results in routine practice. Aim. To automatically insert Ct values and interpretive comments when reporting SARS-CoV-2 RT-PCR to improve patient management. Methodology. Routine Ct values across three different RT-PCR platforms were reviewed for concordance at presentation and clearance in patients with COVID-19. An indicative threshold (IT) linked to viral clearance kinetics was defined at Ct30 to categorize Ct values as low and high, reflecting high and low viral loads respectively. Results. The different gene targets of each platform showed high correlation and kappa score agreement ( P <0.001). Average Ct values were automatically generated with values ≤Ct30 reported as positive and >Ct30 as reactive; interpretive comments were added to all reports. The new reporting algorithm impacted on: physician interpretation of SARS-CoV-2 results; patient management and transfer; staff surveillance; length of stay in quarantine; and redefinition of patient recovery. Conclusion. Incorporation of Ct values into routine practice is possible across different RT-PCR platforms and adds useful information for patient management. The use of an IT with interpretive comments improves clinical interpretation and could be a model for reporting other respiratory infections. Withholding Ct values wastes useful clinical data and should be reviewed by the profession, accreditation bodies and regulators.

Background: The effective reproduction number, R t , is a tool to track and understand pandemic dynamics. This investigation of R t estimations was conducted to guide the national COVID-19 response in Qatar, from the onset of the pandemic until August 18, 2021., Methods: Real-time "empirical" R t Empirical was estimated using five methods, including the Robert Koch Institute, Cislaghi, Systrom-Bettencourt and Ribeiro, Wallinga and Teunis, and Cori et al. methods. R t was also estimated using a transmission dynamics model ( R t Model-based ). Uncertainty and sensitivity analyses were conducted. Correlations between different R t estimates were assessed by calculating correlation coefficients, and agreements between these estimates were assessed through Bland-Altman plots., Results: R t Empirical captured the evolution of the pandemic through three waves, public health response landmarks, effects of major social events, transient fluctuations coinciding with significant clusters of infection, and introduction and expansion of the Alpha (B.1.1.7) variant. The various estimation methods produced consistent and overall comparable R t Empirical estimates with generally large correlation coefficients. The Wallinga and Teunis method was the fastest at detecting changes in pandemic dynamics. R t Empirical estimates were consistent whether using time series of symptomatic PCR-confirmed cases, all PCR-confirmed cases, acute-care hospital admissions, or ICU-care hospital admissions, to proxy trends in true infection incidence. R t Model-based correlated strongly with R t Empirical and provided an average R t Empirical ., Conclusions: R t estimations were robust and generated consistent results regardless of the data source or the method of estimation. Findings affirmed an influential role for R t estimations in guiding national responses to the COVID-19 pandemic, even in resource-limited settings., Competing Interests: Competing interests: Dr Butt has received institutional grant funding from Gilead Sciences unrelated to the work presented in this paper. The authors have completed the ICMJE Declaration of Interest Form (available upon request from the corresponding author), and declare no further conflicts of interest., (Copyright © 2022 by the Journal of Global Health. All rights reserved.)

This study investigated the performance of a rapid point-of-care antibody test, the BioMedomics COVID-19 IgM/IgG Rapid Test, in comparison with a high-quality, validated, laboratory-based platform, the Roche Elecsys Anti-SARS-CoV-2 assay. Serological testing was conducted on 709 individuals. Concordance metrics were estimated. Logistic regression was used to assess associations with seropositivity. SARS-CoV-2 seroprevalence was 63.5% (450/709; 95% CI 59.8%-67.0%) using the BioMedomics assay and 71.9% (510/709; 95% CI 68.5%-75.2%) using the Elecsys assay. There were 60 discordant results between the two assays, all of which were seropositive in the Elecsys assay, but seronegative in the BioMedomics assay. Overall, positive, and negative percent agreements between the two assays were 91.5% (95% CI 89.2%-93.5%), 88.2% (95% CI 85.1%-90.9%), and 100% (95% CI 98.2%-100%), respectively, with a Cohen's kappa of 0.81 (95% CI 0.78-0.84). Excluding specimens with lower (Elecsys) antibody titers, the agreement improved with overall, positive, and negative percent concordance of 94.4% (95% CI 92.3%-96.1%), 91.8% (95% CI 88.8%-94.3%), and 100% (95% CI 98.2%-100%), respectively, and a Cohen's kappa of 0.88 (95% CI 0.85-0.90). Logistic regression confirmed better agreement with higher antibody titers. The BioMedomics COVID-19 IgM/IgG Rapid Test demonstrated good performance in measuring detectable antibodies against SARS-CoV-2, supporting the utility of such rapid point-of-care serological testing to guide the public health responses and vaccine prioritization., Competing Interests: The authors have declared that no competing interests exist.

SARS-CoV-2 breakthrough infections in vaccinated individuals and in those who had a prior infection have been observed globally, but the transmission potential of these infections is unknown. The RT-qPCR cycle threshold (Ct) value is inversely correlated with viral load and culturable virus. Here, we investigate differences in RT-qPCR Ct values across Qatar's national cohorts of primary infections, reinfections, BNT162b2 (Pfizer-BioNTech) breakthrough infections, and mRNA-1273 (Moderna) breakthrough infections. Our matched-cohort analyses of the randomly diagnosed infections show higher mean Ct value in all cohorts of breakthrough infections compared to the cohort of primary infections in unvaccinated individuals. The Ct value is 1.3 (95% CI: 0.9-1.8) cycles higher for BNT162b2 breakthrough infections, 3.2 (95% CI: 1.9-4.5) cycles higher for mRNA-1273 breakthrough infections, and 4.0 (95% CI: 3.5-4.5) cycles higher for reinfections in unvaccinated individuals. Since Ct value correlates inversely with SARS-CoV-2 infectiousness, these differences imply that vaccine breakthrough infections and reinfections are less infectious than primary infections in unvaccinated individuals. Public health benefits of vaccination may have been underestimated, as COVID-19 vaccines not only protect against acquisition of infection, but also appear to protect against transmission of infection., (© 2022. The Author(s).)

Background: The epidemiology of the SARS-CoV-2 B.1.1.7 (or Alpha) variant is insufficiently understood. This study's objective was to describe the introduction and expansion of this variant in Qatar and to estimate the efficacy of natural infection against reinfection with this variant., Methods and Findings: Reinfections with the B.1.1.7 variant and variants of unknown status were investigated in a national cohort of 158,608 individuals with prior PCR-confirmed infections and a national cohort of 42,848 antibody-positive individuals. Infections with B.1.1.7 and variants of unknown status were also investigated in a national comparator cohort of 132,701 antibody-negative individuals. B.1.1.7 was first identified in Qatar on 25 December 2020. Sudden, large B.1.1.7 epidemic expansion was observed starting on 18 January 2021, triggering the onset of epidemic's second wave, 7 months after the first wave. B.1.1.7 was about 60% more infectious than the original (wild-type) circulating variants. Among persons with a prior PCR-confirmed infection, the efficacy of natural infection against reinfection was estimated to be 97.5% (95% CI: 95.7% to 98.6%) for B.1.1.7 and 92.2% (95% CI: 90.6% to 93.5%) for variants of unknown status. Among antibody-positive persons, the efficacy of natural infection against reinfection was estimated to be 97.0% (95% CI: 92.5% to 98.7%) for B.1.1.7 and 94.2% (95% CI: 91.8% to 96.0%) for variants of unknown status. A main limitation of this study is assessment of reinfections based on documented PCR-confirmed reinfections, but other reinfections could have occurred and gone undocumented., Conclusions: In this study, we observed that introduction of B.1.1.7 into a naïve population can create a major epidemic wave, but natural immunity in those previously infected was strongly associated with limited incidence of reinfection by B.1.1.7 or other variants., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: A.A.B. has received institutional grant funding from Gilead Sciences unrelated to the work presented in this paper, otherwise, the authors declare no competing interests.

Background: Waning of vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 (Covid-19) is a concern. The persistence of BNT162b2 (Pfizer-BioNTech) vaccine effectiveness against infection and disease in Qatar, where the B.1.351 (or beta) and B.1.617.2 (or delta) variants have dominated incidence and polymerase-chain-reaction testing is done on a mass scale, is unclear., Methods: We used a matched test-negative, case-control study design to estimate vaccine effectiveness against any SARS-CoV-2 infection and against any severe, critical, or fatal case of Covid-19, from January 1 to September 5, 2021., Results: Estimated BNT162b2 effectiveness against any SARS-CoV-2 infection was negligible in the first 2 weeks after the first dose. It increased to 36.8% (95% confidence interval [CI], 33.2 to 40.2) in the third week after the first dose and reached its peak at 77.5% (95% CI, 76.4 to 78.6) in the first month after the second dose. Effectiveness declined gradually thereafter, with the decline accelerating after the fourth month to reach approximately 20% in months 5 through 7 after the second dose. Effectiveness against symptomatic infection was higher than effectiveness against asymptomatic infection but waned similarly. Variant-specific effectiveness waned in the same pattern. Effectiveness against any severe, critical, or fatal case of Covid-19 increased rapidly to 66.1% (95% CI, 56.8 to 73.5) by the third week after the first dose and reached 96% or higher in the first 2 months after the second dose; effectiveness persisted at approximately this level for 6 months., Conclusions: BNT162b2-induced protection against SARS-CoV-2 infection appeared to wane rapidly following its peak after the second dose, but protection against hospitalization and death persisted at a robust level for 6 months after the second dose. (Funded by Weill Cornell Medicine-Qatar and others.)., (Copyright © 2021 Massachusetts Medical Society.)

With the global expansion of the highly transmissible SARS-CoV-2 Delta (B.1.617.2) variant, we conducted a matched test-negative case-control study to assess the real-world effectiveness of COVID-19 messenger RNA vaccines against infection with Delta in Qatar's population. BNT162b2 effectiveness against any, symptomatic or asymptomatic, Delta infection was 45.3% (95% CI, 22.0-61.6%) ≥14 d after the first vaccine dose, but only 51.9% (95% CI, 47.0-56.4%) ≥14 d after the second dose, with 50% of fully vaccinated individuals receiving their second dose before 11 May 2021. Corresponding mRNA-1273 effectiveness ≥14 d after the first or second dose was 73.7% (95% CI, 58.1-83.5%) and 73.1% (95% CI, 67.5-77.8%), respectively. Notably, effectiveness against Delta-induced severe, critical or fatal disease was 93.4% (95% CI, 85.4-97.0%) for BNT162b2 and 96.1% (95% CI, 71.6-99.5%) for mRNA-1273 ≥ 14 d after the second dose. Our findings show robust effectiveness for both BNT162b2 and mRNA-1273 in preventing Delta hospitalization and death in Qatar's population, despite lower effectiveness in preventing infection, particularly for the BNT162b2 vaccine., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Importance: The effect of prior SARS-CoV-2 infection on vaccine protection remains poorly understood., Objective: To assess protection from SARS-CoV-2 breakthrough infection after mRNA vaccination among persons with vs without prior SARS-CoV-2 infection., Design, Setting, and Participants: Matched-cohort studies in Qatar for the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines. A total of 1 531 736 individuals vaccinated with either vaccine between December 21, 2020, and September 19, 2021, were followed up beginning 14 days after receiving the second dose until September 19, 2021., Exposures: Prior SARS-CoV-2 infection and COVID-19 vaccination., Main Outcomes and Measures: Incident SARS-CoV-2 infection, defined as a polymerase chain reaction (PCR)-positive nasopharyngeal swab regardless of reason for PCR testing or presence of symptoms. Cumulative incidence was calculated using the Kaplan-Meier estimator method., Results: The BNT162b2-vaccinated cohort comprised 99 226 individuals with and 290 432 matched individuals without prior PCR-confirmed infection (median age, 37 years; 68% male). The mRNA-1273-vaccinated cohort comprised 58 096 individuals with and 169 514 matched individuals without prior PCR-confirmed infection (median age, 36 years; 73% male). Among BNT162b2-vaccinated persons, 159 reinfections occurred in those with and 2509 in those without prior infection 14 days or more after dose 2. Among mRNA-1273-vaccinated persons, 43 reinfections occurred in those with and 368 infections in those without prior infection. Cumulative infection incidence among BNT162b2-vaccinated individuals was an estimated 0.15% (95% CI, 0.12%-0.18%) in those with and 0.83% (95% CI, 0.79%-0.87%) in those without prior infection at 120 days of follow-up (adjusted hazard ratio for breakthrough infection with prior infection, 0.18 [95% CI, 0.15-0.21]; P < .001). Cumulative infection incidence among mRNA-1273-vaccinated individuals was an estimated 0.11% (95% CI, 0.08%-0.15%) in those with and 0.35% (95% CI, 0.32%-0.40%) in those without prior infection at 120 days of follow-up (adjusted hazard ratio, 0.35 [95% CI, 0.25-0.48]; P < .001). Vaccinated individuals with prior infection 6 months or more before dose 1 had statistically significantly lower risk for breakthrough infection than those vaccinated less than 6 months before dose 1 (adjusted hazard ratio, 0.62 [95% CI, 0.42-0.92]; P = .02 for BNT162b2 and 0.40 [95% CI, 0.18-0.91]; P = .03 for mRNA-1273 vaccination)., Conclusions and Relevance: Prior SARS-CoV-2 infection was associated with a statistically significantly lower risk for breakthrough infection among individuals receiving the BNT162b2 or mRNA-1273 vaccines in Qatar between December 21, 2020, and September 19, 2021. The observational study design precludes direct comparisons of infection risk between the 2 vaccines.

Background: Risk of reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. We assessed the risk and incidence rate of documented SARS-CoV-2 reinfection in a cohort of laboratory-confirmed cases in Qatar., Methods: All SARS-CoV-2 laboratory-confirmed cases with at least 1 polymerase chain reaction-positive swab that was ≥45 days after a first positive swab were individually investigated for evidence of reinfection. Viral genome sequencing of the paired first positive and reinfection viral specimens was conducted to confirm reinfection., Results: Out of 133 266 laboratory-confirmed SARS-CoV-2 cases, 243 persons (0.18%) had at least 1 subsequent positive swab ≥45 days after the first positive swab. Of these, 54 cases (22.2%) had strong or good evidence for reinfection. Median time between the first swab and reinfection swab was 64.5 days (range, 45-129). Twenty-three of the 54 cases (42.6%) were diagnosed at a health facility, suggesting presence of symptoms, while 31 (57.4%) were identified incidentally through random testing campaigns/surveys or contact tracing. Only 1 person was hospitalized at the time of reinfection but was discharged the next day. No deaths were recorded. Viral genome sequencing confirmed 4 reinfections of 12 cases with available genetic evidence. Reinfection risk was estimated at 0.02% (95% confidence interval [CI], .01%-.02%), and reinfection incidence rate was 0.36 (95% CI, .28-.47) per 10 000 person-weeks., Conclusions: SARS-CoV-2 reinfection can occur but is a rare phenomenon suggestive of protective immunity against reinfection that lasts for at least a few months post primary infection., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

The SARS-CoV-2 pandemic resulted in considerable morbidity and mortality as well as severe economic and societal disruptions. Despite scientific progress, true infection severity, factoring both diagnosed and undiagnosed infections, remains poorly understood. This study aimed to estimate SARS-CoV-2 age-stratified and overall morbidity and mortality rates based on analysis of extensive epidemiological data for the pervasive epidemic in Qatar, a country where < 9% of the population are ≥ 50 years. We show that SARS-CoV-2 severity and fatality demonstrate a striking age dependence with low values for those aged < 50 years, but rapidly growing rates for those ≥ 50 years. Age dependence was particularly pronounced for infection criticality rate and infection fatality rate. With Qatar's young population, overall SARS-CoV-2 severity and fatality were not high with < 4 infections in every 1000 being severe or critical and < 2 in every 10,000 being fatal. Only 13 infections in every 1000 received any hospitalization in acute-care-unit beds and < 2 in every 1000 were hospitalized in intensive-care-unit beds. However, we show that these rates would have been much higher if Qatar's population had the demographic structure of Europe or the United States. Epidemic expansion in nations with young populations may lead to considerably lower disease burden than currently believed., (© 2021. The Author(s).)

The SARS-CoV-2 pandemic continues to be a global health concern. The mRNA-1273 (Moderna) vaccine was reported to have an efficacy of 94.1% at preventing symptomatic COVID-19 due to infection with 'wild-type' variants in a randomized clinical trial. Here, we assess the real-world effectiveness of this vaccine against SARS-CoV-2 variants of concern, specifically B.1.1.7 (Alpha) and B.1.351 (Beta), in Qatar, a population that comprises mainly working-age adults, using a matched test-negative, case-control study design. We show that vaccine effectiveness was negligible for 2 weeks after the first dose, but increased rapidly in the third and fourth weeks immediately before administration of a second dose. Effectiveness against B.1.1.7 infection was 88.1% (95% confidence interval (CI): 83.7-91.5%) ≥14 days after the first dose but before the second dose, and was 100% (95% CI: 91.8-100.0%) ≥14 days after the second dose. Analogous effectiveness against B.1.351 infection was 61.3% after the first dose (95% CI: 56.5-65.5%) and 96.4% after the second dose (95% CI: 91.9-98.7%). Effectiveness against any severe, critical or fatal COVID-19 disease due to any SARS-CoV-2 infection (predominantly B.1.1.7 and B.1.351) was 81.6% (95% CI: 71.0-88.8%) and 95.7% (95% CI: 73.4-99.9%) after the first and second dose, respectively. The mRNA-1273 vaccine is highly effective against B.1.1.7 and B.1.351 infections, whether symptomatic or asymptomatic, and against any COVID-19 hospitalization and death, even after a single dose., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The study objective was to the assess level of detectable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in the urban population of Qatar. Antibody testing was performed on residual blood specimens for 112,941 individuals (∼10% of Qatar's urban population) attending for routine/other clinical care between May 12 and September 9, 2020. Seropositivity was 13.3% (95% confidence interval [CI] = 13.1-13.6%) and was independently associated with sex, age, nationality, clinical care encounter type, and testing date. Median optical density (antibody titer) among antibody-positive persons was 27.0 (range = 1.0-150.0), with higher values associated with age, nationality, clinical care encounter type, and testing date. Seropositivity by nationality was positively correlated with the likelihood of having higher antibody titers (Pearson correlation coefficient = 0.85; 95% CI = 0.47-0.96). Less than two in every 10 individuals in Qatar's urban population had detectable antibodies against SARS-CoV-2, suggesting this population is still far from herd immunity and at risk of subsequent infection waves. Higher antibody titer appears to be a biomarker of repeated exposures to the infection., (© 2021 The Author(s).)

Performance of three automated commercial serological IgG-based assays was investigated for assessing SARS-CoV-2 "ever" (past or current) infection in a population-based sample in a high exposure setting. PCR and serological testing was performed on 394 individuals. SARS-CoV-2-IgG seroprevalence was 42.9% (95% CI 38.1-47.8%), 40.6% (95% CI 35.9-45.5%), and 42.4% (95% CI 37.6-47.3%) using the CL-900i, VidasIII, and Elecsys assays, respectively. Between the three assays, overall, positive, and negative percent agreements ranged between 93.2-95.7%, 89.3-92.8%, and 93.8-97.8%, respectively; Cohen's kappa statistic ranged from 0.86 to 0.91; and 35 specimens (8.9%) showed discordant results. Among all individuals, 12.5% (95% CI 9.6-16.1%) had current infection, as assessed by PCR. Of these, only 34.7% (95% CI 22.9-48.7%) were seropositive by at least one assay. A total of 216 individuals (54.8%; 95% CI 49.9-59.7%) had evidence of ever infection using antibody testing and/or PCR during or prior to this study. Of these, only 78.2%, 74.1%, and 77.3% were seropositive in the CL-900i, VidasIII, and Elecsys assays, respectively. All three assays had comparable performance and excellent agreement, but missed at least 20% of individuals with past or current infection. Commercial antibody assays can substantially underestimate ever infection, more so when infection rates are high.

Introduction: Lymphoid enhancer-binding factor 1 (LEF-1) overexpression has been recently remarkably reported in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and has shown utility in distinguishing CLL/SLL from other B-cell lymphomas. CLL has a well-defined immunophenotype, yet, some cases of CLL demonstrate atypical morphology/ phenotype reflected by low Matutes score (atypical CLL). Till date, LEF1 expression has not been systematically studied in cases of CLL with atypical features., Methods: In this study, LEF-1 expression was assessed by two different techniques, (immunohistochemistry and flow cytometry), to investigate the expression profile of LEF-1 in cases of CLL/SLL, in comparison with other low-grade B-lymphomas and CLL with atypical features, including atypical immunophenotype and CLL with increased prolymphocytes or morphologically atypical cells., Results: We found that LEF-1 expression is downregulated in CLL with atypical immunophenotype/features compared to classic CLL; Chi-Square P < .0001. The ratio for LEF-1 expression in malignant B-cells/NK (by flow cytometry) in CLL/SLL with classic immunophenotype was higher than atypical CLL and is significantly higher in other small B-cell lymphomas (P < .01). Absence of LEF-1 expression in CLL/SLL is correlated (P < .05) with downregulation of CD5, CD23, CD200, expression of FMC7, brighter expression of CD79b, brighter expression of surface light chain, increased prolymphocytes and lower Matutes score., Conclusion: As downregulation of LEF-1 expression is well correlated with atypical CLL, we suggest adding LEF-1 to Matutes score as a beneficial marker to differentiate classic from atypical CLL LEF-1 could also serve as a potential prognostic indicator for CLL clinical course., (© 2020 The Authors. International Journal of Laboratory Hematology published by John Wiley & Sons Ltd.)