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BackgroundThis study assessed the evolution of COVID-19 severity and fatality by utilizing rigorous and standardized criteria that were consistently applied throughout the pandemic in Qatar.MethodsA national cohort study was conducted on Qataris, using data on COVID-19 acute-care and ICU hospitalizations, as well as severe, critical, and fatal COVID-19 cases classified according to the World Health Organization criteria.ResultsThe cumulative incidence of severe, critical, or fatal COVID-19 after 3.14 years of follow-up was 0.45% (95% CI: 0.43-0.47%). The incidence rate for severe, critical, or fatal COVID-19 throughout the pandemic was 1.43 (95% CI: 1.35-1.50) per 1,000 person-years. In the pre-omicron phase, first omicron wave, and combined phases, it was 2.01 (95% CI: 1.90-2.13), 3.70 (95% CI: 3.25-4.22), and 2.18 (95% CI: 2.07-2.30) per 1,000 person-years, respectively. The post-first omicron phase saw a drastic drop to 0.10 (95% CI: 0.08-0.14) per 1,000 person-years, a 95.4% reduction. Among all severe, critical, and fatal cases, 99.5% occurred during the primary infection. The cumulative incidence of fatal COVID-19 was 0.042% (95% CI: 0.036-0.050%), with an incidence rate of 0.13 (95% CI: 0.11-0.16) per 1,000 person-years. In the post-first omicron phase, the incidence rate of fatal COVID-19 decreased by 90.0% compared to earlier stages. Both severity and fatality exhibited an exponential increase with age and a linear increase with the number of coexisting conditions.ConclusionsThe conclusion of the first omicron wave was a turning point in the severity of the pandemic. While vaccination and enhanced case management reduced severity gradually, the rapid accumulation of natural immunity during the initial omicron wave appears to have played the crucial role in driving this shift in severity.

SummaryBackgroundWaning 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.MethodsWe 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.FindingsPrevious-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 immediately 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 of 2021. Effectiveness declined linearly by ∼1 percentage point every 5 days. After Omicron emergence, effectiveness dropped suddenly from 52.7% (95% CI: 46.5-58.2%) in November 2021 to negligible levels in December 2021. Booster effectiveness dropped immediately 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.InterpretationHigh population immunity may not be sustained beyond a year. This creates fertile grounds for repeated waves of infection to occur, but these waves may increasingly exhibit a benign pattern of infection.FundingThe 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.Research in contextEvidence before this studySARS-CoV-2 infection induces protection against reinfection, but this protection wanes with time since last infection. Similarly, COVID-19 primary-series and booster vaccination induce protection against SARS-CoV-2 infection, but this protection also wanes with time since last dose. These immunity patterns demonstrate the need for the concept ofpopulation immunityto track evolution of overall immune protection over time in a given population. Previous-infection and vaccine population immunities in a specific country can be defined as the overall protection against infection at a given point in time in the full national population. A search of PubMed, Google Scholar, and the International Vaccine Access Center’s VIEW-hub databases up to April 21, 2023 using the keywords “vaccination”, “infection”, “immunity”, “protection”, “SARS-CoV-2”, and “COVID-19” did not identify studies that investigated this epidemiological concept for a national population throughout the COVID-19 pandemic.Added value of this studyThis study analyzed the national federated databases for SARS-CoV-2 infection and COVID-19 vaccination in Qatar, a country that experienced SARS-CoV-2 waves dominated by different pre-Omicron variants and Omicron subvariants. Using a matched, test-negative study design, population immunity against infection of each of previous infection, primary-series vaccination, and booster vaccination were characterized at the national level month by month for two calendar years to discern generic features of the epidemiology of SARS-CoV-2. The three forms of population immunity showed rapid variation over time driven by waning of protection. Vaccine-derived population immunity declined by 1 absolute percentage point every 5 days. Omicron introduction immensely reduced the three forms of population immunity within one month by about 50 absolute percentage points. Meanwhile, previous-infection and vaccine population immunities against severe COVID-19 were durable with slow waning even after Omicron emergence.Implications of all available evidenceBoth previous-infection and vaccine population immunities vary rapidly at a national level creating fertile grounds for repeated waves of infection to occur even within months of each other. High levels of population immunity may not be sustained for more than a year or so. Preventing infection/reinfection, transmission, or future waves of infection cannot sustainably be done with current vaccines nor by the entire population being infected. Timely administration of boosters for those vulnerable to severe COVID-19 may remain essential for years to come. Repeated waves of infection may also facilitate further evolution of the virus and continual immune evasion. Emergence of a new variant that is substantially different from circulating variants can suddenly and immensely reduce population immunity leading to large epidemic waves. However, the durability of population immunity against severe COVID-19 will likely curtail the severity of future waves.

BackgroundProtection 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.MethodsSix national, matched, test-negative, case-control studies were conducted between January 18-December 18, 2021 on a sample of 239,120 PCR-positive tests and 6,103,365 PCR-negative tests.ResultsEffectiveness 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.ConclusionsAll forms of natural and vaccine immunity prior to Omicron introduction provided strong protection against infection and severe COVID-19. Hybrid immunity conferred the strongest protection and its level was consistent with previous-infection immunity and vaccine immunity acting independently of each other.

Qatar introduced COVID-19 bivalent vaccination for persons ≥12 years old using the 50-μg mRNA-1273.214 vaccine combining SARS-CoV-2 ancestral and omicron BA.1 strains. We estimated effectiveness of this bivalent vaccine against SARS-CoV-2 infection using a matched, retrospective, cohort study. Matched cohorts included 11,482 persons in the bivalent cohort and 56,806 persons in the no-recent-vaccination cohort. During follow-up, 65 infections were recorded in the bivalent cohort and 406 were recorded in the no-recent-vaccination cohort. None progressed to severe, critical, or fatal COVID-19. Cumulative incidence of infection was 0.80% (95% CI: 0.61-1.07%) in the bivalent cohort and 1.00% (95% CI: 0.89-1.11%) in the no-recent-vaccination cohort, 150 days after the start of follow-up. Incidence during follow-up was dominated by omicron XBB* subvariants including XBB, XBB.1, XBB.1.5, XBB.1.9.1, XBB.1.9.2, XBB.1.16, and XBB.2.3. The adjusted hazard ratio comparing incidence of infection in the bivalent cohort to that in the no-recent-vaccination cohort was 0.75 (95% CI: 0.57-0.97). Bivalent vaccine effectiveness against infection was 25.2% (95% CI: 2.6-42.6%). Effectiveness was 21.5% (95% CI: -8.2-43.5%) among persons with no prior infection and 33.3% (95% CI: -4.6-57.6%) among persons with prior infection. mRNA-1273.214 reduced incidence of SARS-CoV-2 infection, but the protection was modest at only 25%. The modest protection may have risen because of XBB* immune evasion or immune imprinting effects, or combination of both.

BackgroundRisk of short- and long-term all-cause mortality after a primary SARS-CoV-2 infection is inadequately understood.MethodsA national, matched, retrospective cohort study was conducted in Qatar to assess the risk of all-cause mortality in the national cohort of people infected with SARS-CoV-2 compared with a reference national control cohort of uninfected persons. Associations were estimated using Cox proportional-hazards regression models.ResultsAmong unvaccinated persons, within 90 days after primary infection, adjusted hazard ratio (aHR) comparing incidence of death in the primary-infection cohort with the infection-naïve cohort was 1.19 (95% CI: 1.02-1.39). The aHR was 1.34 (95% CI: 1.11-1.63) in persons more clinically vulnerable to severe COVID-19 and 0.94 (95% CI: 0.72-1.24) in those less clinically vulnerable to severe COVID-19. In subsequent follow-up, the aHR was 0.50 (95% CI: 0.37-0.68). The aHR was 0.41 (95% CI: 0.28-0.58) in months 3-7 after the primary infection and 0.76 (95% CI: 0.46-1.26) in subsequent months. The aHR was 0.37 (95% CI: 0.25-0.54) in persons more clinically vulnerable to severe COVID-19 and 0.77 (95% CI: 0.48-1.24) in those less clinically vulnerable to severe COVID-19. Among vaccinated persons, no evidence was found for differences in incidence of death in the primary-infection versus infection-naïve cohorts, even among persons more clinically vulnerable to severe COVID-19.ConclusionsCOVID-19 mortality in Qatar appears primarily driven by forward displacement of deaths of individuals with relatively short life expectancy and more clinically vulnerable to severe COVID-19. Vaccination negated the mortality displacement by preventing early deaths.

BackgroundCoronavirus Disease 2019 (COVID-19) vaccine antigen dosage may affect protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but direct evidence to quantify this effect is lacking.MethodsA matched, retrospective, cohort study that emulated a randomized control trial was conducted in Qatar between February 3, 2022 and November 8, 2022, to provide a head-to-head, controlled comparison of protection induced by two antigen dosages of the BNT162b2 vaccine. The study compared incidence of omicron infection in the national cohort of adolescents 12 years of age who received the two-dose primary-series of the 30-µg BNT162b2 vaccine to that in the national cohort of adolescents 11 years of age who received the two-dose primary-series of the pediatric 10-µg BNT162b2 vaccine. Associations were estimated using Cox proportional-hazard regression models.ResultsAmong adolescents with no record of prior infection, cumulative incidence of infection was 6.0% (95% CI: 4.9-7.3%) for the 30-µg cohort and 7.2% (95% CI: 6.1-8.5%) for the 10-µg cohort, 210 days after the start of follow-up. Incidence during follow-up was dominated by omicron subvariants including, consecutively, BA.1/BA.2, BA.4/BA.5, BA.2.75*, and XBB. The adjusted hazard ratio comparing incidence of infection in the 30-µg cohort to the 10-µg cohort was 0.77 (95% CI: 0.60-0.98). Corresponding relative effectiveness was 23.4% (95% CI: 1.6-40.4%). Relative effectiveness was -3.3% (95% CI: -68.0-27.5%) among adolescents with a record of prior infection.ConclusionsThree-fold higher BNT162b2 dosage was associated with ∼25% higher protection against infection in infection-naïve adolescents of similar age. These findings may inform design of future COVID-19 vaccines and boosters for persons of different age groups.

BackgroundLong-term effectiveness of COVID-19 mRNA boosters in populations with different prior infection histories and clinical vulnerability profiles is inadequately understood.MethodsA national, matched, retrospective, target trial cohort study was conducted in Qatar to investigate effectiveness of a third mRNA (booster) dose, relative to a primary series of two doses, against SARS-CoV-2 omicron infection and against severe COVID-19. Associations were estimated using Cox proportional-hazards regression models.ResultsBooster effectiveness relative to primary series was 41.1% (95% CI: 40.0-42.1%) against infection and 80.5% (95% CI: 55.7-91.4%) against severe, critical, or fatal COVID-19, over one-year follow-up after the booster. Among persons clinically vulnerable to severe COVID-19, effectiveness was 49.7% (95% CI: 47.8-51.6%) against infection and 84.2% (95% CI: 58.8-93.9%) against severe, critical, or fatal COVID-19. Effectiveness against infection was highest at 57.1% (95% CI: 55.9-58.3%) in the first month after the booster but waned thereafter and was modest at only 14.4% (95% CI: 7.3-20.9%) 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 reaching -20.3% (95% CI: -55.0-29.0%) after one year of follow-up. Similar levels and patterns of protection were observed irrespective of prior infection status, clinical vulnerability, or type of vaccine (BNT162b2 versus mRNA-1273).ConclusionsBoosters reduced infection and severe COVID-19, particularly among those clinically vulnerable to severe COVID-19. However, protection against infection waned after the booster, and eventually suggested an imprinting effect of compromised protection relative to the primary series. However, imprinting effects are unlikely to negate the overall public health value of booster vaccinations.

We investigated epidemiological evidence for immune imprinting by comparing incidence of re-reinfection in the national cohort of individuals with a documented Omicron (BA.1/BA.2) reinfection after a pre-Omicron primary infection (designated as the reinfection cohort), to incidence of reinfection in the national cohort of individuals with a documented Omicron (BA.1/BA.2) primary infection (designated as the primary-infection cohort). This was done using a matched, retrospective cohort study that emulated a randomized “target trial”. Vaccinated individuals were excluded. Associations were estimated using Cox proportional-hazard regression models. Cumulative incidence of infection was 1.1% (95% CI: 0.8-1.4%) for the reinfection cohort and 2.1% (95% CI: 1.8-2.3%) for the primary-infection cohort, 135 days after the start of follow-up. The adjusted hazard ratio (aHR) for infection was 0.52 (95% CI: 0.40-0.68), comparing incidence in the reinfection cohort to that in the primary-infection cohort. The aHR was 0.59 (95% CI: 0.40-0.85) in a subgroup analysis in which primary infection in the reinfection cohort was restricted to only the index virus or Alpha variant. In the first 70 days of follow-up, when incidence was dominated by BA.2, the aHR was 0.92 (95% CI: 0.51-1.65). However, cumulative incidence curves diverged when BA.4/BA.5 subvariants dominated incidence (aHR, 0.46 (95% CI: 0.34-0.62)). There was no evidence that immune imprinting compromises protection against Omicron subvariants. However, there was evidence that having two infections, one with a pre-Omicron variant followed by one with an Omicron subvariant, elicits stronger protection against future Omicron-subvariant reinfection than having had only one infection with an Omicron subvariant.

BackgroundThe BNT162b2 COVID-19 vaccine is authorized for children 5-11 years of age and adolescents 12-17 years of age, but in different dose sizes. We assessed BNT162b2 real-world effectiveness against SARS-CoV-2 infection among children and adolescents in Qatar.MethodsThree matched, retrospective, target-trial, cohort studies were conducted to compare incidence of SARS-CoV-2 infection in the national cohort of vaccinated individuals to incidence in the national cohort of unvaccinated individuals. Associations were estimated using Cox proportional-hazards regression models.ResultsEffectiveness of the 10 µg dose for children against Omicron infection was 25.7% (95% CI: 10.0-38.6%). It was highest at 49.6% (95% CI: 28.5-64.5%) right after the second dose, but waned rapidly thereafter and was negligible after 3 months. Effectiveness was 46.3% (95% CI: 21.5-63.3%) among those aged 5-7 years and 16.6% (−4.2-33.2%) among those aged 8-11 years. Effectiveness of the 30 µg dose for adolescents against Omicron infection was 30.6% (95% CI: 26.9-34.1%), but many adolescents were vaccinated months earlier. Effectiveness waned with time after the second dose. Effectiveness was 35.6% (95% CI: 31.2-39.6%) among those aged 12-14 years and 20.9% (13.8-27.4%) among those aged 15-17 years. Effectiveness of the 30 µg dose for adolescents against pre-Omicron infection was 87.6% (95% CI: 84.0-90.4%) and waned relatively slowly after the second dose.ConclusionsPediatric vaccination is associated with modest and rapidly waning protection against Omicron infection. Adolescent vaccination is associated with stronger and more durable protection, perhaps because of the larger dose size. Age at such young age appears to play a role in determining vaccine protection, with greater protection observed in younger than older children or adolescents.

BACKGROUNDThe future of the SARS-CoV-2 pandemic hinges on virus evolution and duration of immune protection of natural infection against reinfection. We investigated 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 February 28, 2020 and June 5, 2022.METHODSThree national, matched, retrospective cohort studies were conducted to compare incidence of SARS-CoV-2 infection and 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.RESULTSEffectiveness of pre-Omicron primary infection against pre-Omicron reinfection was 85.5% (95% 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 nd 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 th 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.CONCLUSIONSProtection 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.

BACKGROUNDProtection conferred by natural SARS-CoV-2 infection versus COVID-19 vaccination has not been investigated in rigorously controlled studies. We compared head-to-head protection conferred by natural infection to that from the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines in Qatar, between February 28, 2020 and March 6, 2022.METHODSTwo national matched retrospective target-trial cohort studies were conducted to compare incidence of SARS-CoV-2 infection and COVID-19 hospitalization and death among those with a documented primary infection to incidence among those with a two-dose primary-series vaccination. Associations were estimated using Cox proportional-hazards regression models.RESULTSThe overall adjusted hazard ratio (AHR) for infection was 0.46 (95% CI: 0.45-0.48) comparing those with a prior infection to those vaccinated with BNT162b2, and 0.51 (95% CI: 0.48-0.53) comparing those with a prior infection to those vaccinated with mRNA-1273. For BNT162b2, the AHR decreased gradually from 0.55 (95% CI: 0.46-0.65) in the fourth month after primary infection/vaccination to 0.31 (95% CI: 0.27-0.37) in the eighth month, while for mRNA-1273, it decreased from 0.80 (95% CI: 0.59-1.07) to 0.35 (95% CI: 0.29-0.41) over the same time period. During the Omicron wave, the AHR was ∼0.50 for BNT162b2 and ∼0.60 for mRNA-1273. The overall AHR for any severe, critical, or fatal COVID-19 (against all variants) was 0.32 (95% CI: 0.10-1.00) for BNT162b2, and 0.58 (95% CI: 0.14-2.43) for mRNA-1273.CONCLUSIONSNatural infection was associated with stronger and more durable protection against infection, regardless of the variant, than mRNA primary-series vaccination. Nonetheless, vaccination remains the safest and optimal tool of protection against infection and COVID-19 hospitalization and death.

BACKGROUNDQatar has been experiencing a large SARS-CoV-2 Omicron (B.1.1.529) wave that started on December 19, 2021. We assessed duration of protection of BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccines after second dose and after third/booster dose against symptomatic Omicron infection and against COVID-19 hospitalization and death, between December 23, 2021 and February 2, 2022.METHODSVaccine effectiveness was estimated using the test-negative, case-control study design, applying the same methodology used earlier to assess waning of BNT162b2 and mRNA-1273 effectiveness in the same population during earlier infection waves.RESULTSBNT162b2 effectiveness against symptomatic Omicron infection was highest at 61.9% (95% CI: 49.9-71.1%) in the first month after the second dose, but then gradually declined and was at 10% or less starting from the 5th month after the second dose. After the booster, effectiveness rapidly rebounded to peak at about 55% between 2-5 weeks after the booster, but then started to decline again thereafter. Effectiveness against severe, critical, or fatal COVID-19 was maintained at >70% after the second dose and at >90% after the booster with no evidence for declining effectiveness over time. mRNA-1273 effectiveness against symptomatic Omicron infection was highest at 44.8% (95% CI: 16.0-63.8%) in the first three months after the second dose, before gradually declining to negligible levels thereafter. After the booster, effectiveness rapidly rebounded to peak at about 55% between 2-5 weeks after the booster, but then declined again thereafter. Effectiveness against severe, critical, or fatal COVID-19 was high at >60% after the second dose and at >80% after the booster, but the confidence intervals were wide owing to the small number of cases.CONCLUSIONSBNT162b2 and mRNA-1273 vaccines show a similar level and pattern of protection against symptomatic Omicron infection. Protection against Omicron is lower than that against Alpha, Beta, and Delta variants, and wanes more rapidly than against earlier variants after the second and booster doses. Meanwhile, protection against hospitalization and death appears robust and durable after both the second and booster doses.

BACKGROUNDWaning of COVID-19 vaccine protection and emergence of SARS-CoV-2 Omicron (B.1.1.529) variant have expedited efforts to scale up booster vaccination. This study compared protection afforded by booster doses of the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines, compared to the primary series of only two doses in Qatar, during a large, rapidly growing Omicron wave.METHODSIn a population of 2,232,224 vaccinated persons with at least two doses, two matched, retrospective cohort studies were implemented to investigate effectiveness of booster vaccination against symptomatic SARS-CoV-2 infection and against COVID-19 hospitalization and death, up to January 9, 2022. Association of booster status with infection was estimated using Cox proportional-hazards regression models.RESULTSFor BNT162b2, cumulative symptomatic infection incidence was 2.9% (95% CI: 2.8-3.1%) in the booster-dose cohort and 5.5% (95% CI: 5.3-5.7%) in the primary-series cohort, after 49 days of follow-up. Adjusted hazard ratio for symptomatic infection was 0.50 (95% CI: 0.47-0.53). Booster effectiveness relative to primary series was 50.1% (95% CI: 47.3-52.8%). For mRNA-1273, cumulative symptomatic infection incidence was 1.9% (95% CI: 1.7-2.2%) in the booster-dose cohort and 3.5% (95% CI: 3.2-3.9%) in the primary-series cohort, after 35 days of follow-up. The adjusted hazard ratio for symptomatic infection was 0.49 (95% CI: 0.43-0.57). Booster effectiveness relative to primary series was 50.8% (95% CI: 43.4-57.3%). There were fewer cases of severe COVID-19 in booster-dose cohorts than in primary-series cohorts, but cases of severe COVID-19 were rare in all cohorts.CONCLUSIONSmRNA booster vaccination is associated with modest effectiveness against symptomatic infection with Omicron. The development of a new generation of vaccines targeting a broad range of variants may be warranted.

BACKGROUNDNatural SARS-CoV-2 infection elicits strong protection against reinfection with the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2) variants. However, the Omicron (B.1.1.529) variant harbors multiple mutations that can mediate immune evasion. We estimated effectiveness of prior infection in preventing reinfection (PES) with Omicron and other SARS-CoV-2 variants in Qatar.METHODSPES was estimated using the test-negative, case-control study design, employing a methodology that was recently investigated and validated for derivation of robust estimates for PES. Cases (PCR-positive persons with a variant infection) and controls (PCR-negative persons) were exact-matched by sex, 10-year age group, nationality, and calendar time of PCR test, to control for known differences in the risk of exposure to SARS-CoV-2 infection in Qatar.RESULTSPES against symptomatic reinfection was estimated at 90.2% (95% CI: 60.2-97.6) for Alpha, 84.8% (95% CI: 74.5-91.0) for Beta, 92.0% (95% CI: 87.9-94.7) for Delta, and 56.0% (95% CI: 50.6-60.9) for Omicron. Only 1 Alpha, 2 Beta, 0 Delta, and 2 Omicron reinfections progressed to severe COVID-19. None progressed to critical or fatal COVID-19. PES against hospitalization or death due to reinfection was estimated at 69.4% (95% CI: −143.6-96.2) for Alpha, 88.0% (95% CI: 50.7-97.1) for Beta, 100% (95% CI: 43.3-99.8) for Delta, and 87.8% (95% CI: 47.5-97.1) for Omicron.CONCLUSIONSProtection afforded by prior infection in preventing symptomatic reinfection with Alpha, Beta, or Delta is robust, at about 90%. While such protection against reinfection with Omicron is lower, it is still considerable at nearly 60%. Prior-infection protection against hospitalization or death at reinfection appears robust, regardless of variant.

BackgroundThe Coronavirus Disease 2019 (COVID-19) pandemic has highlighted an urgent need to use infection testing databases to rapidly estimate effectiveness of prior infection in preventing reinfection (PES) by novel variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).MethodsMathematical modeling was used to demonstrate the applicability of the test-negative, case-control study design to derive PES. Modeling was also used to investigate effects of bias in PES estimation. The test-negative design was applied to national-level testing data in Qatar to estimate PES for SARS-CoV-2 infection and to validate this design.ResultsApart from the very early phase of an epidemic, the difference between the test-negative estimate for PES and the true value of PES was minimal and became negligible as the epidemic progressed. The test-negative design provided robust estimation of PES even when PES began to wane after prior infection. Assuming that only 25% of prior infections are documented, misclassification of prior infection status underestimated PES, 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 PES. PES 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.ConclusionsThe test-negative design offers a feasible, robust method to estimate protection from prior infection in preventing reinfection.

BACKGROUNDIn early 2021, Qatar launched a mass immunization campaign with Moderna’s mRNA-1273 COVID-19 vaccine. We assessed persistence of real-world mRNA-1273 effectiveness against SARS-CoV-2 infection and against COVID-19 hospitalization and death.METHODSEffectiveness was estimated using test-negative, case-control study design, between January 1 and December 5, 2021. Effectiveness was estimated against documented infection (a PCR-positive swab, regardless symptoms), and against any severe (acute-care hospitalization), critical (ICU hospitalization), or fatal COVID-19.RESULTSBy December 5, 2021, 2,962 breakthrough infections had been recorded among those who received two mRNA-1273 doses. Of these infections, 19 progressed to severe COVID-19 and 4 to critical, but none to fatal disease. mRNA-1273 effectiveness against infection was negligible for the first two weeks after the first dose, increased to 65.5% (95% CI: 62.7-68.0%) 14 or more days after the first dose, and reached its peak at about 90% in the first three months after the second dose. Effectiveness declined gradually starting from the fourth month after the second dose and was below 50% by the 7th month after the second dose. Effectiveness against severe, critical, or fatal COVID-19 reached its peak at essentially 100% right after the second dose, and there was no evidence for declining effectiveness over time. Effectiveness against symptomatic versus asymptomatic infection demonstrated the same pattern of waning, but effectiveness against symptomatic infection was consistently higher than that against asymptomatic infection and waned more slowly.CONCLUSIONSmRNA-1273-induced protection against infection appears to wane month by month after the second dose. Meanwhile, protection against hospitalization and death appears robust with no evidence for waning for several months after the second dose.

BACKGROUNDGrowing evidence suggests that COVID-19 vaccines differ in effectiveness against breakthrough infection or severe COVID-19, but vaccines have yet to be investigated in controlled studies that head-to-head compare immunity of one to another. This study compared protection offered by the mRNA-1273 (Moderna) vaccine with that of the BNT162b2 (Pfizer-BioNTech) vaccine in Qatar.METHODSIn a population of 1,531,736 vaccinated persons, two matched retrospective cohort studies were designed and used to investigate differences in mRNA-1273 and BNT162b2 vaccine protection, after the first and second doses, from December 21, 2020 to October 20, 2021.RESULTSAfter dose 1, cumulative incidence of breakthrough infection was 0.79% (95% CI: 0.75-0.83%) for mRNA-1273-vaccinated individuals and 0.86% (95% CI: 0.82-0.90%) for BNT162b2-vaccinated individuals, 21 days post-injection. Adjusted hazard ratio (AHR) for breakthrough infection was 0.89 (95% CI: 0.83-0.95; p=0.001). AHR was constant in the first two weeks at 1, but it declined to 0.67 (95% CI: 0.57-0.77; pCONCLUSIONSmRNA-1273 vaccination is associated with lower SARS-CoV-2 breakthrough infection and COVID-19 hospitalization and death than BNT162b2 vaccination, but the number of hospitalizations and deaths was exceedingly small for both vaccines. Both vaccines demonstrated strikingly similar patterns of build-up of protection after the first dose and waning of protection after the second dose.

BACKGROUNDWaning of vaccine protection against SARS-CoV-2 infection or COVID-19 disease is a concern. This study investigated persistence of BNT162b2 (Pfizer-BioNTech) vaccine effectiveness against infection and disease in Qatar, where the Beta and Delta variants have dominated incidence and PCR testing is done at a mass scale.METHODSA matched test-negative, case-control study design was used to estimate vaccine effectiveness against SARS-CoV-2 infection and against any severe, critical, or fatal COVID-19 disease, between January 1, 2021 to August 15, 2021.RESULTSEstimated BNT162b2 effectiveness against any infection, asymptomatic or symptomatic, was negligible for the first two weeks after the first dose, increased to 36.5% (95% CI: 33.1-39.8) in the third week after the first dose, and reached its peak at 72.1% (95% CI: 70.9-73.2) in the first five weeks after the second dose. Effectiveness declined gradually thereafter, with the decline accelerating ≥15 weeks after the second dose, reaching diminished levels of protection by the 20thweek. Effectiveness against symptomatic infection was higher than against asymptomatic infection, but still waned in the same fashion. Effectiveness against any severe, critical, or fatal disease increased rapidly to 67.7% (95% CI: 59.1-74.7) by the third week after the first dose, and reached 95.4% (95% CI: 93.4-96.9) in the first five weeks after the second dose, where it persisted at about this level for six months.CONCLUSIONSBNT162b2-induced protection against infection appears to wane rapidly after its peak right after the second dose, but it persists at a robust level against hospitalization and death for at least six months following the second dose.

COVID-19 vaccine protection against infection in immunosuppressed solid organ transplant recipients is unknown but possibly weak with the low proportion of these patients mounting a robust humoral and cellular immune response after vaccination. Using a retrospective cohort study design with cross-over, we assessed vaccine effectiveness among 782 kidney transplant recipients registered at Hamad Medical Corporation, the national public healthcare provider in Qatar, where the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines have been used in the national immunization campaign. Vaccine effectiveness against any SARS-CoV-2 infection was estimated at 46.6% (95% CI: 0.0-73.7%) ≥14 days after the second dose, 66.0% (95% CI: 21.3-85.3%) ≥42 days after the second dose, and 73.9% (95% CI: 33.0-89.9%) ≥56 days after the second dose. Vaccine effectiveness against any severe, critical, or fatal COVID-19 disease was estimated at 72.3% (95% CI: 0.0-90.9%) ≥14 days after the second dose, 85.0% (95% CI: 35.7-96.5%) ≥42 days after the second dose, and 83.8% (95% CI: 31.3-96.2%) ≥56 days after the second dose. Most vaccine breakthrough infections occurred in the first few weeks after receiving the first and/or second dose. Vaccine effectiveness reached considerable levels in kidney transplant recipients, but vaccine protection mounted slowly and did not reach a high level until several weeks after the second dose.

Severity (acute-care hospitalization), criticality (ICU hospitalization), and fatality of SARS-CoV-2 Beta (B.1.351) variant was investigated through case-control studies applied to complete national cohorts of infection, disease, and death cases in Qatar. Compared to Alpha (B.1.1.7) variant, odds of progressing to severe disease were 1.24-fold (95% CI: 1.11-1.39) higher for Beta. Odds of progressing to critical disease were 1.49-fold (95% CI: 1.13-1.97) higher. Odds of COVID-19 death were 1.57-fold (95% CI: 1.03-2.43) higher. Findings highlight risks to healthcare systems, particularly to intensive care facilities and resources, with increased circulation of Beta.

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 investigated 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. Through matched-cohort analyses of the randomly diagnosed infections, the mean Ct value was higher in all cohorts of breakthrough infections compared to the cohort of primary infections in unvaccinated individuals. The Ct value was 1.3 (95% CI: 0.9-1.8) cycles higher for BNT162b2 breakthrough infections, 3.2 (95% CI: 1.8-4.5) cycles higher for mRNA-1273 breakthrough infections, and 4.0 (95% CI: 3.4-4.6) cycles higher for reinfections in unvaccinated individuals. Assuming a linear relationship between viral load and infectiousness, these differences imply that breakthrough infections are at least 50% 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.

Effect of prior SARS-CoV-2 infection on vaccine protection remains poorly understood. Here, we investigated whether persons vaccinated after a prior infection have better protection against future infection than those vaccinated without prior infection. Effect of prior infection was assessed in Qatar’s population, where the Alpha (B.1.1.7) and Beta (B.1.351) variants dominate incidence, using two national retrospective, matched-cohort studies, one for the BNT162b2 (Pfizer-BioNTech) vaccine, and one for the mRNA-1273 (Moderna) vaccine. Incidence rates of infection among BNT162b2-vaccinated persons, with and without prior infection, were estimated, respectively, at 1.66 (95% CI: 1.26-2.18) and 11.02 (95% CI: 9.90-12.26) per 10,000 person-weeks. The incidence rate ratio was 0.15 (95% CI: 0.11-0.20). Analogous incidence rates among mRNA-1273-vaccinated persons were estimated at 1.55 (95% CI: 0.86-2.80) and 1.83 (95% CI: 1.07-3.16) per 10,000 person-weeks. The incidence rate ratio was 0.85 (95% CI: 0.34-2.05). Prior infection enhanced protection of those BNT162b2-vaccinated, but not those mRNA-1273-vaccinated. These findings may have implications for dosing, interval between doses, and potential need for booster vaccination.

We aimed to estimate, albeit crudely and provisionally, national, regional, and global proportions of respective populations that have been infected with SARS-CoV-2, and to assess infection morbidity and mortality rates, factoring both documented and undocumented infections. The estimates were generated by applying mathematical models to 159 countries and territories. The percentage of the world’s population that has been infected as of 31 December 2020 was estimated at 12.56% (95% CI: 11.17-14.05%). It was lowest in the Western Pacific Region at 0.66% (95% CI: 0.59-0.75%) and highest in the Americas at 41.92% (95% CI: 37.95-46.09%). The global infection fatality rate was 10.73 (95% CI: 10.21-11.29) per 10,000 infections. Globally per 1,000 infections, the infection acute-care bed hospitalization rate was 19.22 (95% CI: 18.73-19.51), the infection ICU bed hospitalization rate was 4.14 (95% CI: 4.10-4.18), the infection severity rate was 6.27 (95% CI: 6.18-6.37), and the infection criticality rate was 2.26 (95% CI: 2.24-2.28). If left unchecked with no interventions, the pandemic would eventually cause 8.18 million (95% CI: 7.30-9.18) deaths, 163.67 million (95% CI: 148.12-179.51) acute-care hospitalizations, 33.01 million (95% CI: 30.52-35.70) ICU hospitalizations, 50.23 million (95% CI: 46.24-54.67) severe cases, and 17.62 million (95% CI: 16.36-18.97) critical cases. The global population remains far below the herd immunity threshold and at risk of repeated waves of infection. Global epidemiology reveals immense regional variation in infection exposure and morbidity and mortality rates.

BackgroundReinfection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been documented, raising public health concerns. Risk and incidence rate of SARS-CoV-2 reinfection were assessed in a large cohort of antibody-positive persons in Qatar.MethodsAll SARS-CoV-2 antibody-positive persons with a PCR-positive swab ≥14 days after the first-positive antibody test were individually investigated for evidence of reinfection. Viral genome sequencing was conducted for paired viral specimens to confirm reinfection. Incidence of reinfection was compared to incidence of infection in the complement cohort of those antibody-negative.ResultsAmong 43,044 anti-SARS-CoV-2 positive persons who were followed for a median of 16.3 weeks (range: 0-34.6), 314 individuals (0.7%) had at least one PCR positive swab ≥14 days after the first-positive antibody test. Of these individuals, 129 (41.1%) had supporting epidemiological evidence for reinfection. Reinfection was next investigated using viral genome sequencing. Applying the viral-genome-sequencing confirmation rate, the risk of reinfection was estimated at 0.10% (95% CI: 0.08-0.11%). The incidence rate of reinfection was estimated at 0.66 per 10,000 person-weeks (95% CI: 0.56-0.78). Incidence rate of reinfection versus month of follow-up did not show any evidence of waning of immunity for over seven months of follow-up. Meanwhile, in the complement cohort of 149,923 antibody-negative persons followed for a median of 17.0 weeks (range: 0-45.6), risk of infection was estimated at 2.15% (95% CI: 2.08-2.22%) and incidence rate of infection was estimated at 13.69 per 10,000 person-weeks (95% CI: 13.22-14.14). Efficacy of natural infection against reinfection was estimated at 95.2% (95% CI: 94.1-96.0%). Reinfections were less severe than primary infections. Only one reinfection was severe, two were moderate, and none were critical or fatal. Most reinfections (66.7%) were diagnosed incidentally through random or routine testing, or through contact tracing.ConclusionsReinfection is rare. Natural infection appears to elicit strong protection against reinfection with an efficacy ∼95% for at least seven months.

BackgroundVaccines against SARS-CoV-2 have been developed, but their availability falls far short of global needs. This study aimed to investigate the impact of prioritizing available doses on the basis of recipient antibody status, that is by exposure status, using Qatar as an example.MethodsVaccination impact was assessed under different scale-up scenarios using a deterministic meta-population mathematical model describing SARS-CoV-2 transmission and disease progression in the presence of vaccination.ResultsFor a vaccine that protects against infection with an efficacy of 95%, half as many vaccinations were needed to avert one infection, disease outcome, or death by prioritizing antibody-negative individuals for vaccination. Prioritization by antibody status reduced incidence at a faster rate and led to faster elimination of infection and return to normalcy. Further prioritization by age group amplified the gains of prioritization by antibody status. Gains from prioritization by antibody status were largest in settings where the proportion of the population already infected at the commencement of vaccination was 30-60%, which is perhaps where most countries will be by the time vaccination programs are up and running. For a vaccine that only protects against disease and not infection, vaccine impact was reduced by half, whether this impact was measured in terms of averted infections or disease outcomes, but the relative gains from using antibody status to prioritize vaccination recipients were similar.ConclusionsMajor health, societal, and economic gains can be achieved more quickly by prioritizing those who are antibody-negative while doses of the vaccine remain in short supply.

BackgroundThe objective of this study was to forecast the impact of COVID-19 vaccination in the United States (US) and China, two countries at different epidemic phases.MethodsA mathematical model describing SARS-CoV-2 transmission and disease progression was used to investigate vaccine impact. Impact was assessed both for a vaccine that prevents infection (VES = 95%) and a vaccine that prevents only disease (VEP = 95%).ResultsFor VES = 95% and gradual easing of restrictions, vaccination in the US reduced the peak incidence of infection, disease, and death by >55% and cumulative incidence by >32%, and in China by >77% and >65%, respectively. Nearly three vaccinations were needed to avert one infection in the US, but only one was needed in China. For VEP = 95%, benefits of vaccination were half those for VES = 95%. In both countries, the impact of vaccination was substantially enhanced with rapid scale-up, vaccine coverage >50%, and slower or no easing of restrictions, particularly in the US.ConclusionsCOVID-19 vaccination can flatten, delay, and/or prevent future epidemic waves. However, vaccine impact is destined to be heterogeneous across countries because of an underlying “epidemiologic inequity” that reduces benefits for countries already at high incidence, such as the US. Despite 95% efficacy, actual vaccine impact could be meager in such countries, if vaccine scale-up is slow, acceptance of the vaccine is poor, or restrictions are eased prematurely.One Sentence SummaryVaccine impact will be heterogeneous across countries disadvantaging countries at high incidence. This heterogeneity can be alleviated with rapid vaccination scale-up and limited easing of restrictions.

BackgroundThis study aimed to estimate the age-stratified and overall morbidity and mortality rates of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection based on an analysis of the pervasive SARS-CoV-2 epidemic in Qatar, a country with MethodsInfection disease outcomes were investigated using a Bayesian approach applied to an age-structured mathematical model describing SARS-CoV-2 transmission and disease progression in the population. The model was fitted to infection and disease time-series and age-stratified data. Two separate criteria for classifying morbidity were used: one based on actual recorded hospital admission (acute-care or intensive-care-unit hospitalization) and one based on clinical presentation as per World Health Organization classification of disease severity or criticality.ResultsAll outcomes showed very strong age dependence, with low values for those ConclusionsSARS-CoV-2 severity and fatality in Qatar was not high and demonstrated a very strong age dependence with

BackgroundMathematical modeling constitutes an important tool for planning robust responses to epidemics. This study was conducted to guide the Qatari national response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic. The study investigated the time course of the epidemic, forecasted healthcare needs, predicted the impact of social and physical distancing restrictions, and rationalized and justified easing of restrictions.MethodsAn age-structured deterministic model was constructed to describe SARS-CoV-2 transmission dynamics and disease progression throughout the population.ResultsThe enforced social and physical distancing interventions flattened the epidemic curve, reducing the peaks for incidence, prevalence, acute-care hospitalization, and intensive care unit (ICU) hospitalizations by 87%, 86%, 76%, and 78%, respectively. The daily number of new infections was predicted to peak at 12,750 on May 23, and active-infection prevalence was predicted to peak at 3.2% on May 25. Daily acute-care and ICU-care hospital admissions and occupancy were forecast accurately and precisely. By October 15, 2020, the basic reproduction number R0 had varied between 1.07-2.78, and 50.8% of the population were estimated to have been infected (1.43 million infections). The proportion of actual infections diagnosed was estimated at 11.6%. Applying the concept of Rt tuning, gradual easing of restrictions was rationalized and justified to start on June 15, 2020, when Rt declined to 0.7, to buffer the increased interpersonal contact with easing of restrictions and to minimize the risk of a second wave. No second wave has materialized as of October 15, 2020, five months after the epidemic peak.ConclusionsUse of modeling and forecasting to guide the national response proved to be a successful strategy, reducing the toll of the epidemic to a manageable level for the healthcare system.

BackgroundReinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is debated. We assessed risk and incidence rate of documented SARS-CoV-2 reinfection in a large cohort of laboratory-confirmed cases in Qatar.MethodsAll SARS-CoV-2 laboratory-confirmed cases with at least one PCR positive swab that is ≥45 days after a first-positive swab were individually investigated for evidence of reinfection, and classified as showing strong, good, some, or weak/no evidence for reinfection. Viral genome sequencing of the paired first-positive and reinfection viral specimens was conducted to confirm reinfection. Risk and incidence rate of reinfection were estimated.ResultsOut of 133,266 laboratory-confirmed SARS-CoV-2 cases, 243 persons (0.18%) had at least one 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 first 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 one person was hospitalized at time of reinfection, but still with mild infection. No deaths were recorded. Viral genome sequencing confirmed four out of 12 cases with available genetic evidence. Risk of reinfection was estimated at 0.01% (95% CI: 0.01-0.02%) and incidence rate of reinfection was estimated at 0.36 (95% CI: 0.28-0.47) per 10,000 person-weeks.ConclusionsSARS-CoV-2 reinfection can occur but is a rare phenomenon suggestive of a strong protective immunity against reinfection that lasts for at least a few months post primary infection.

BackgroundQatar has a population of 2.8 million, over half of whom are expatriate craft and manual workers (CMW). We aimed to characterize the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in Qatar.MethodsA series of epidemiologic studies were conducted including analysis of the national SARS-CoV-2 PCR testing and hospitalization database, community surveys assessing current infection, ad-hoc PCR testing campaigns in workplaces and residential areas, serological testing for antibody on blood specimens collected for routine clinical screening/management, national Coronavirus Diseases 2019 (COVID-19) death registry, and a mathematical model.ResultsBy July 10, 397,577 individuals had been PCR tested for SARS-CoV-2, of whom 110,986 were positive, a positivity cumulative rate of 27.9% (95% CI: 27.8-28.1%). PCR positivity of nasopharyngeal swabs in a national community survey (May 6-7) including 1,307 participants was 14.9% (95% CI: 11.5-19.0%); 58.5% of those testing positive were asymptomatic. Across 448 ad-hoc PCR testing campaigns in workplaces and residential areas including 26,715 individuals, pooled mean PCR positivity was 15.6% (95% CI: 13.7-17.7%). SARS-CoV-2 antibody prevalence was 24.0% (95% CI: 23.3-24.6%) in 32,970 residual clinical blood specimens. Antibody prevalence was only 47.3% (95% CI: 46.2-48.5%) in those who had at least one PCR positive result, but it was 91.3% (95% CI: 89.5-92.9%) among those who were PCR positive >3 weeks before serology testing. There were substantial differences in exposure to infection by nationality and sex, reflecting risk differentials between the craft/manual workers and urban populations. As of July 5, case severity rate, based on the WHO severity classification, was 3.4% and case fatality rate was 1.4 per 1,000 persons. Model-estimated daily number of infections and active-infection prevalence peaked at 22,630 and 5.7%, respectively, on May 21 and May 23. Attack rate (ever infection) was estimated at 53.5% on July 12. R0 ranged between 1.45-1.68 throughout the epidemic. Rt was estimated at 0.70 on June 15, which was hence set as onset date for easing of restrictions. Age was by far the strongest predictor of severe, critical, or fatal infection.ConclusionsQatar has experienced a large SARS-CoV-2 epidemic that is rapidly declining, apparently due to exhaustion of susceptibles. The epidemic demonstrated a classic susceptible-infected-recovered “SIR” dynamics with a rather stable R0 of about 1.6. The young demographic structure of the population, in addition to a resourced public health response, yielded a milder disease burden and lower mortality than elsewhere.

This study aims to inform SARS-CoV-2 vaccine development/licensure/decision-making/implementation, using mathematical modeling, by determining key preferred vaccine product characteristics and associated population-level impacts of a vaccine eliciting long-term protection. A prophylactic vaccine with efficacy against acquisition (VES) &ge, 70% can eliminate the infection. A vaccine with VES &lt, 70% may still control the infection if it reduces infectiousness or infection duration among those vaccinated who acquire the infection, if it is supplemented with &lt, 20% reduction in contact rate, or if it is complemented with herd-immunity. At VES of 50%, the number of vaccinated persons needed to avert one infection is 2.4, and the number is 25.5 to avert one severe disease case, 33.2 to avert one critical disease case, and 65.1 to avert one death. The probability of a major outbreak is zero at VES &ge, 70% regardless of the number of virus introductions. However, an increase in social contact rate among those vaccinated (behavior compensation) can undermine vaccine impact. In addition to the reduction in infection acquisition, developers should assess the natural history and disease progression outcomes when evaluating vaccine impact.

BackgroundCurrent geographic spread of documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections shows heterogeneity. This study explores the role of age in potentially driving differentials in infection spread, epidemic potential, and rates of disease severity and mortality across countries.MethodsAn age-stratified deterministic mathematical model that describes SARS-CoV-2 transmission dynamics was applied to 159 countries and territories with a population ≥1 million.ResultsAssuming worst-case scenario for the pandemic, the results indicate that there could be stark regional differences in epidemic trajectories driven by differences in the distribution of the population by age. In the African Region (median age: 18.9 years), the median R0 was 1.05 versus 2.05 in the European Region (median age: 41.7 years), and the median (per 100 persons) for the infections rate was 22.5 (versus 69.0), for severe and/or critical disease cases rate was 3.3 (versus 13.0), and for death rate was 0.5 (versus 3.9).ConclusionsAge could be a driver of variable SARS-CoV-2 epidemic trajectories worldwide. Countries with sizable adult and/or elderly populations and smaller children populations may experience large and rapid epidemics in absence of interventions. Meanwhile, countries with predominantly younger age cohorts may experience smaller and slower epidemics. These predictions, however, should not lead to complacency, as the pandemic could still have a heavy toll nearly everywhere.

BackgroundA novel coronavirus strain, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China in late 2019. The resulting disease, Coronavirus Disease 2019 (COVID-2019), soon became a pandemic. This study aims to characterize key attributes of the epidemiology of this infection in China.MethodsAn age-stratified mathematical model was constructed to describe the transmission dynamics and estimate the age-specific differences in the biological susceptibility to the infection, age-assortativeness in transmission mixing, case fatality rate (CFR), and transition in rate of infectious contacts (and reproduction number R0) following introduction of mass interventions.ResultsThe model estimated the infectious contact rate in early epidemic at 0.59 contacts per day (95% uncertainty interval (UI)=0.48-0.71). Relative to those 60-69 years of age, susceptibility to the infection was only 0.06 in those ≤19 years, 0.34 in 20-29 years, 0.57 in 30-39 years, 0.69 in 40-49 years, 0.79 in 50-59 years, 0.94 in 70-79 years, and 0.88 in ≥80 years. The assortativeness in transmission mixing by age was very limited at 0.004 (95% UI=0.002-0.008). Final CFR was 5.1% (95% UI=4.8-5.4%). R0 rapidly declined from 2.1 (95% UI=1.8-2.4) to 0.06 (95% UI=0.05-0.07) following onset of interventions.ConclusionAge appears to be a principal factor in explaining the patterns of COVID-19 transmission dynamics in China. The biological susceptibility to the infection seems limited among children, intermediate among young to mid-age adults, but high among those >50 years of age. There was no evidence for differential contact mixing by age, consistent with most transmission occurring in households rather than in schools or workplaces.