ORCID Profile
0000-0003-0790-0506
Current Organisations
Hamad bin Khalifa University
,
Weill Cornell Medical College in Qatar
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Publisher: Cold Spring Harbor Laboratory
Date: 27-08-2021
DOI: 10.1101/2021.08.25.21262584
Abstract: Waning 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. A 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. Estimated 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 20 th week. 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. BNT162b2-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.
Publisher: Cold Spring Harbor Laboratory
Date: 19-04-2023
DOI: 10.1101/2023.04.15.23288612
Abstract: 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.
Publisher: Cold Spring Harbor Laboratory
Date: 14-12-2020
DOI: 10.1101/2020.12.14.20248163
Abstract: 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 s le in a high exposure setting. PCR and serological testing was performed on 394 in iduals. 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 kappa statistic ranged from 0.86-0.91 and 35 specimens (8.9%) showed discordant results. Among all in iduals, 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 in iduals (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 in iduals with past or current infection. Commercial antibody assays can substantially underestimate ever infection, more so when infection rates are high.
Publisher: Massachusetts Medical Society
Date: 31-03-2022
DOI: 10.1056/NEJMC2200133
Publisher: Springer Science and Business Media LLC
Date: 03-11-2022
DOI: 10.1038/S41586-022-05398-2
Abstract: Despite notable scientific and medical advances, broader political, socioeconomic and behavioural factors continue to undercut the response to the COVID-19 pandemic 1,2 . Here we convened, as part of this Delphi study, a erse, multidisciplinary panel of 386 academic, health, non-governmental organization, government and other experts in COVID-19 response from 112 countries and territories to recommend specific actions to end this persistent global threat to public health. The panel developed a set of 41 consensus statements and 57 recommendations to governments, health systems, industry and other key stakeholders across six domains: communication health systems vaccination prevention treatment and care and inequities. In the wake of nearly three years of fragmented global and national responses, it is instructive to note that three of the highest-ranked recommendations call for the adoption of whole-of-society and whole-of-government approaches 1 , while maintaining proven prevention measures using a vaccines-plus approach 2 that employs a range of public health and financial support measures to complement vaccination. Other recommendations with at least 99% combined agreement advise governments and other stakeholders to improve communication, rebuild public trust and engage communities 3 in the management of pandemic responses. The findings of the study, which have been further endorsed by 184 organizations globally, include points of unanimous agreement, as well as six recommendations with % disagreement, that provide health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.
Publisher: Elsevier BV
Date: 06-2020
Publisher: Cold Spring Harbor Laboratory
Date: 26-07-2021
DOI: 10.1101/2021.07.25.21261093
Abstract: 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.
Publisher: Microbiology Society
Date: 16-05-2022
DOI: 10.1099/JMM.0.001499
Abstract: Introduction. The cycle threshold (Ct) value in real-time PCR (RT-PCR) is where a target-specific lification 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 .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.
Publisher: Cold Spring Harbor Laboratory
Date: 09-03-2021
DOI: 10.1101/2021.03.06.21252601
Abstract: The objective of this study was to develop a Coronavirus Disease 2019 (COVID-19) risk score to guide targeted RT-PCR testing in Qatar. The Qatar national COVID-19 testing database was analyzed. This database includes a total of 2,688,232 RT-PCR tests conducted between February 5, 2020-January 27, 2021. Logistic regression analyses were implemented to identify predictors of infection and 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 receiving operating characteristic (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 score’s scoring points were lower for females compared to males and higher for specific nationalities. 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 risk score derived early in the epidemic, based on data until only April 21, 2020, had a performance comparable to that of a score based on a year-long testing. The concept and utility of a COVID-19 risk score were demonstrated in Qatar. Such a public health tool, based on a set of non-invasive and easily captured variables can have considerable utility in optimizing testing and suppressing infection transmission, while maximizing efficiency and use of available resources.
Publisher: Cold Spring Harbor Laboratory
Date: 12-07-2022
DOI: 10.1101/2022.07.11.22277448
Abstract: This study estimates the effectiveness of previous infection with SARS-CoV-2 in preventing reinfection with Omicron BA.4/BA.5 subvariants using a test-negative, case–control study design. Cases (SARS-CoV-2-positive test results) and controls (SARS-CoV-2-negative test results) were matched according to sex, 10-year age group, nationality, comorbid condition count, calendar week of testing, method of testing, and reason for testing. Effectiveness was estimated using the S-gene “target failure” (SGTF) infections between May 7, 2022-July 4, 2022. SGTF status provides a proxy for BA.4/BA.5 infections, considering the negligible incidence of other SGTF variants during the study. Effectiveness was also estimated using all diagnosed infections between June 8, 2022-July 4, 2022, when BA.4/BA.5 dominated incidence. Effectiveness of a previous pre-Omicron infection against symptomatic BA.4/BA.5 reinfection was 15.1% (95% CI: -47.1-50.9%), and against any BA.4/BA.5 reinfection irrespective of symptoms was 28.3% (95% CI: 11.4-41.9%). Effectiveness of a previous Omicron infection against symptomatic BA.4/BA.5 reinfection was 76.1% (95% CI: 54.9-87.3%), and against any BA.4/BA.5 reinfection was 79.7% (95% CI: 74.3-83.9%). Results using all diagnosed infections when BA.4/BA.5 dominated incidence confirmed the same findings. Sensitivity analyses adjusting for vaccination status confirmed study results. Protection of a previous infection against BA.4/BA.5 reinfection was modest when the previous infection involved a pre-Omicron variant, but strong when the previous infection involved the Omicron BA.1 or BA.2 subvariants. Protection of a previous infection against BA.4/BA.5 was lower than that against BA.1/BA.2, consistent with BA.4/BA.5’s greater capacity for immune-system evasion than that of BA.1/BA.2.
Publisher: Cold Spring Harbor Laboratory
Date: 26-08-2020
DOI: 10.1101/2020.08.24.20179457
Abstract: Reinfection 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. All SARS-CoV-2 laboratory-confirmed cases with at least one PCR positive swab that is ≥45 days after a first-positive swab were in idually 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. Out 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 c aigns/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. SARS-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.
Publisher: Cold Spring Harbor Laboratory
Date: 24-08-2022
DOI: 10.1101/2022.08.23.22279026
Abstract: We investigated epidemiological evidence for immune imprinting by comparing incidence of re-reinfection in the national cohort of in iduals 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 in iduals 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 in iduals 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 erged 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.
Publisher: Massachusetts Medical Society
Date: 27-10-2022
DOI: 10.1056/NEJMC2209306
Publisher: Springer Science and Business Media LLC
Date: 27-01-2022
DOI: 10.1038/S41467-022-28199-7
Abstract: SARS-CoV-2 breakthrough infections in vaccinated in iduals 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 in iduals. 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 in iduals. 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 in iduals. 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.
Publisher: Cold Spring Harbor Laboratory
Date: 25-09-2020
DOI: 10.1101/2020.09.24.20200543
Abstract: Qatar experienced a large severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic that disproportionately affected the craft and manual workers (CMWs) who constitute 60% of the population. This study aimed to investigate level of immunity in communities within this population as well as infection exposure required to achieve herd immunity. Anti - SARS-CoV-2 seropositivity was assessed in ten CMW communities between June 21 and September 9, 2020. PCR positivity, infection positivity (antibody and/or PCR positive), and infection severity rate were also estimated. Associations with anti-SARS-CoV-2 positivity were investigated using regression analyses. Study included 4,970 CMWs who were mostly men (95.0%) and years of age (71.5%). Seropositivity ranged from 54.9% (95% CI: 50.2-59.4%) to 83.8% (95% CI: 79.1-87.7%) in the different CMW communities. Pooled mean seropositivity across all communities was 66.1% (95% CI: 61.5-70.6%). PCR positivity ranged from 0.0% to 10.5% (95% CI: 7.4-14.8%) in the different CMW communities. Pooled mean PCR positivity was 3.9% (95% CI: 1.6-6.9%). Median cycle threshold (Ct) value was 34.0 (range: 15.8-37.4)—majority (79.5%) of PCR-positive in iduals had Ct value indicative of earlier rather than recent infection. Infection positivity (antibody and/or PCR positive) ranged from 62.5% (95% CI: 58.3-66.7%) to 83.8% (95% CI: 79.1-87.7%) in the different CMW communities. Pooled mean infection positivity was 69.5% (95% CI: 62.8-75.9%). Only five infections were ever severe and one was ever critical—an infection severity rate of 0.2% (95% CI: 0.1-0.4%). Based on an extended range of epidemiological measures, active infection is rare in these communities with limited if any sustainable infection transmission for clusters to occur. At least some CMW communities in Qatar have reached or nearly reached herd immunity for SARS-CoV-2 infection at a proportion of ever infection of 65-70%.
Publisher: Cold Spring Harbor Laboratory
Date: 07-10-2021
DOI: 10.1101/2021.10.07.21264599
Abstract: The effective reproduction number, R t , is a tool to track and understand epidemic dynamics. This investigation of R t estimations was conducted to guide the national COVID-19 response in Qatar, from the onset of the epidemic until August 18, 2021. Real-time “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 was also estimated using a transmission dynamics model . Uncertainty and sensitivity analyses were conducted. Agreements between different R t estimates were assessed by calculating correlation coefficients. captured the evolution of the epidemic 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 B.1.1.7 variant. The various estimation methods produced consistent and overall comparable estimates with generally large correlation coefficients. The Wallinga and Teunis method was the fastest at detecting changes in epidemic dynamics. 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. correlated strongly with and provided an average . 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.
Publisher: Public Library of Science (PLoS)
Date: 31-01-2022
DOI: 10.1371/JOURNAL.PONE.0262897
Abstract: 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 in iduals. 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.
Publisher: Cold Spring Harbor Laboratory
Date: 10-11-2020
DOI: 10.1101/2020.11.08.20184663
Abstract: Mathematical 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. An age-structured deterministic model was constructed to describe SARS-CoV-2 transmission dynamics and disease progression throughout the population. The 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 R 0 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 R t tuning, gradual easing of restrictions was rationalized and justified to start on June 15, 2020, when R t 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. Use 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.
Publisher: Cold Spring Harbor Laboratory
Date: 22-03-2022
DOI: 10.1101/2022.03.22.22272745
Abstract: BACKGROUND: Protection offered by five different forms of immunity, combining natural and vaccine immunity, was investigated against SARS-CoV-2 Omicron symptomatic BA.1 infection, symptomatic BA.2 infection, BA.1 hospitalization and death, and BA.2 hospitalization and death, in Qatar, between December 23, 2021 and February 21, 2022. METHODS: Six national, matched, test-negative case-control studies were conducted to estimate effectiveness of BNT162b2 (Pfizer-BioNTech) vaccine, mRNA-1273 (Moderna) vaccine, natural immunity due to prior infection with pre-Omicron variants, and hybrid immunity from prior infection and vaccination. RESULTS: Effectiveness of only prior infection against symptomatic BA.2 infection was 46.1% (95% CI: 39.5-51.9%). Effectiveness of only two-dose BNT162b2 vaccination was negligible at -1.1% (95% CI: -7.1-4.6), but nearly all in iduals had received their second dose several months earlier. Effectiveness of only three-dose BNT162b2 vaccination was 52.2% (95% CI: 48.1-55.9%). Effectiveness of hybrid immunity of prior infection and two-dose BNT162b2 vaccination was 55.1% (95% CI: 50.9-58.9%). Effectiveness of hybrid immunity of prior infection and three-dose BNT162b2 vaccination was 77.3% (95% CI: 72.4-81.4%). Meanwhile, prior infection, BNT162b2 vaccination, and hybrid immunity all showed strong effectiveness % against any severe, critical, or fatal COVID-19 due to BA.2 infection. Similar levels and patterns of effectiveness were observed for BA.1 and for the mRNA-1273 vaccine. CONCLUSIONS: There are no discernable differences in the effects of prior infection, vaccination, and hybrid immunity against BA.1 versus BA.2. Hybrid immunity resulting from prior infection and recent booster vaccination confers the strongest protection against either subvariant. Vaccination enhances protection of those with a prior infection.
Publisher: Massachusetts Medical Society
Date: 12-05-2022
Publisher: Cold Spring Harbor Laboratory
Date: 11-2022
DOI: 10.1101/2022.10.31.22281756
Abstract: Laboratory science evidence suggests possibility of immune imprinting, a negative impact for vaccination on subsequent protective immunity against SARS-CoV-2 infection. We investigated differences in incidence of SARS-CoV-2 reinfection in the cohort of persons who had a primary omicron infection, but different vaccination histories using matched, national, retrospective, cohort studies. Adjusted hazard ratio (AHR) for incidence of reinfection, factoring also adjustment for differences in testing rate, was 0.43 (95% CI: 0.39-0.49) comparing history of two-dose vaccination to no vaccination, 1.47 (95% CI: 1.23-1.76) comparing history of three-dose vaccination to two-dose vaccination, and 0.57 (95% CI: 0.48-0.68) comparing history of three-dose vaccination to no vaccination. Divergence in cumulative incidence curves increased markedly when incidence was dominated by BA.4/BA.5 and BA.2.75* omicron subvariant. 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 short-term public health utility of booster vaccination. History of booster vaccination showed lower protection against omicron reinfection than history of two-dose vaccination.
Publisher: Springer Science and Business Media LLC
Date: 09-08-2022
DOI: 10.1038/S41467-022-32363-4
Abstract: 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.
Publisher: Cold Spring Harbor Laboratory
Date: 12-02-2021
DOI: 10.1101/2021.02.11.21251557
Abstract: The Cycle Threshold (CT) value in Real-time Polymerase Chain Reaction (RT-PCR) is where a target specific lification signal becomes detectable and can infer viral load, risk of transmission and recovery in SARS-CoV-2 infections. Adoption into routine practice is however uncommon. The lack of inclusion of CT values when reporting SARS-CoV-2 RT-PCR results in routine practice. To use CT values when reporting SARS-CoV-2 RT-PCR results in Qatar to aid clinical interpretation and patient management. Routine CT values across 3 different RT-PCR platforms were reviewed for concordance at presentation and clearance in patients with COVID-19. An Indicative Threshold of CT 30 based on viral clearance kinetics categorized low and high CT values. There was very high Correlation and Kappa Score agreement between the different gene targets in each platform (p .001). Using the Indicative Threshold it was possible to autoverify and add average CT values and append Interpretive Comments to all RT-PCR reports. The new reporting algorithm impacted immediately and safely on: physician interpretation of SARS-CoV-2 results patient management staff surveillance protocols length of stay in quarantine a redefinition of patient recovery. 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 Indicative Threshold and interpretive comments improves clinical interpretation of the result and could be a model for reporting other respiratory infections. The current accepted practice of withholding CT values should be reviewed by the profession, accreditation bodies and regulators.
Publisher: Massachusetts Medical Society
Date: 08-07-2021
DOI: 10.1056/NEJMC2104974
Publisher: Elsevier BV
Date: 09-2014
Publisher: Cold Spring Harbor Laboratory
Date: 07-2023
DOI: 10.1101/2023.06.29.23292041
Abstract: Our understanding of SARS-CoV-2 reinfection patterns remains limited. We conducted a longitudinal study using Qatar’s national SARS-CoV-2 data from February 28, 2020 to June 11, 2023 to investigate incidence of reinfections both prior to and after omicron emergence. The latter analysis excluded in iduals with pre-omicron infections. Before omicron introduction, the proportion of incident infections classified as reinfections gradually increased but remained minimal, reaching 1.8% just before omicron emerged. During the first omicron wave, this proportion reached 9.0%, a 5-fold increase. After the conclusion of the first omicron wave, the proportion of incident infections identified as reinfections rapidly increased, reaching 43.3% towards the end of the study. In the pre-omicron era, a total of 3,131 reinfections were documented, of which 99.6% were first reinfections and 0.4% were second reinfections. Meanwhile, a total of 20,962 reinfections were documented after an omicron primary infection of which 99.0% were first reinfections, 1.0% were second reinfections, and 0.01% were third reinfections. Reinfections were rare before omicron’s emergence but became widespread during the omicron era, including among in iduals previously infected with omicron. Our findings may indicate accelerated viral evolution in the omicron era aimed at evading population immunity, but with minimal impact on COVID-19 severity, or potentially suggest immune imprinting effects that require further investigation.
Publisher: American Medical Association (AMA)
Date: 03-2016
Publisher: American Association for the Advancement of Science (AAAS)
Date: 06-10-2023
Publisher: Cold Spring Harbor Laboratory
Date: 18-03-2022
DOI: 10.1101/2022.03.17.22272529
Abstract: Protection 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. Two 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. The 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. Natural 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.
Publisher: Cold Spring Harbor Laboratory
Date: 30-11-2020
DOI: 10.1101/2020.11.29.20240416
Abstract: This 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 % of the population being ≥50 years of age. Infection 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. All outcomes showed very strong age dependence, with low values for those years of age, but rapidly growing rates for those ≥50 years of age. The strong age dependence was particularly pronounced for infection criticality rate and infection fatality rate. Infection acute-care and intensive-care-unit bed hospitalization rates were estimated at 13.10 (95% CI: 12.82-13.24) and 1.60 (95% CI: 1.58-1.61) per 1,000 infections, respectively. Infection severity and criticality rates were estimated at 3.06 (95% CI: 3.01-3.10) and 0.68 (95% CI: 0.67-0.68) per 1,000 infections, respectively. Infection fatality rate was estimated at 1.85 (95% CI: 1.74-1.95) per 10,000 infections. SARS-CoV-2 severity and fatality in Qatar was not high and demonstrated a very strong age dependence with infections in every 1,000 being severe or critical and in every 10,000 being fatal. Epidemic expansion in nations with young populations may lead to lower disease burden than previously thought.
Publisher: Cold Spring Harbor Laboratory
Date: 13-11-2021
DOI: 10.1101/2021.11.12.21266250
Abstract: Growing 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. In 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. After dose 1, cumulative incidence of breakthrough infection was 0.79% (95% CI: 0.75-0.83%) for mRNA-1273-vaccinated in iduals and 0.86% (95% CI: 0.82-0.90%) for BNT162b2-vaccinated in iduals, 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 p .001) in the third week after dose 1. AHR for any severe, critical, or fatal COVID-19 was 0.71 (95% CI: 0.53-0.95 p=0.020). After dose 2, cumulative incidence was 0.59% (95% CI: 0.55-0.64%) for mRNA-1273-vaccinated in iduals and 0.84% (95% CI: 0.79-0.89%) for BNT162b2-vaccinated in iduals, 180 days post-injection. AHR for breakthrough infection was 0.69 (95% CI: 0.63-0.75 p .001) and was largely constant over time after dose 2. AHR for any severe, critical, or fatal COVID-19 was 0.37 (95% CI: 0.10-1.41 p=0.147). mRNA-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.
Publisher: Cold Spring Harbor Laboratory
Date: 06-01-2021
DOI: 10.1101/2021.01.05.21249247
Abstract: Qatar has experienced a large SARS-CoV-2 epidemic. Our first objective was to assess the proportion of the urban population that has been infected with SARS-CoV-2, by measuring the prevalence of detectable antibodies. Our second objective was to identify predictors for infection and for having higher antibody titers. Residual blood specimens from in iduals receiving routine and other clinical care between May 12-September 9, 2020 were tested for anti-SARS-CoV-2 antibodies. Associations with seropositivity and higher antibody titers were identified through regression analyses. Probability weights were applied in deriving the epidemiological measures. We tested 112,941 in iduals (∼10% of Qatar’s urban population), of whom 51.6% were men and 66.0% were 20-49 years of age. Seropositivity was 13.3% (95% CI: 13.1-13.6%) and was significantly associated with sex, age, nationality, clinical-care type, and testing date. The proportion with higher antibody titers varied by age, nationality, clinical-care type, and testing date. There was a strong correlation between higher antibody titers and seroprevalence in each nationality, with a Pearson correlation coefficient of 0.85 (95% CI: 0.47-0.96), suggesting that higher antibody titers may indicate repeated exposure to the virus. The percentage of antibody-positive persons with prior PCR-confirmed diagnosis was 47.1% (95% CI: 46.1-48.2%), severity rate was 3.9% (95% CI: 3.7-4.2%), criticality rate was 1.3% (95% CI: 1.1-1.4%), and fatality rate was 0.3% (95% CI: 0.2-0.3%). Fewer than two in every 10 in iduals in Qatar’s urban population had detectable antibodies against SARS-CoV-2 between May 12-September 9, 2020, suggesting that this population is still far from the herd immunity threshold and at risk from a subsequent epidemic wave.
Publisher: Cold Spring Harbor Laboratory
Date: 15-01-2021
DOI: 10.1101/2021.01.15.21249731
Abstract: Reinfection 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. All SARS-CoV-2 antibody-positive persons with a PCR-positive swab ≥14 days after the first-positive antibody test were in idually 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. Among 43,044 anti-SARS-CoV-2 positive persons who were followed for a median of 16.3 weeks (range: 0-34.6), 314 in iduals (0.7%) had at least one PCR positive swab ≥14 days after the first-positive antibody test. Of these in iduals, 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. Reinfection is rare. Natural infection appears to elicit strong protection against reinfection with an efficacy ∼95% for at least seven months.
Publisher: Elsevier BV
Date: 06-2021
Publisher: Cold Spring Harbor Laboratory
Date: 03-01-2022
DOI: 10.1101/2022.01.02.22268622
Abstract: The 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 ( PE S ) by novel variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Mathematical modeling was used to demonstrate the applicability of the test-negative, case-control study design to derive PE S . Modeling was also used to investigate effects of bias in PE S estimation. The test-negative design was applied to national-level testing data in Qatar to estimate PE S for SARS-CoV-2 infection and to validate this design. Apart from the very early phase of an epidemic, the difference between the test-negative estimate for PE S and the true value of PE S was minimal and became negligible as the epidemic progressed. The test-negative design provided robust estimation of PE S even when PE S began to wane after prior infection. Assuming that only 25% of prior infections are documented, misclassification of prior infection status underestimated PE S , but the underestimate was considerable only when % 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 PE S . PE 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.
Publisher: Cold Spring Harbor Laboratory
Date: 08-12-2022
DOI: 10.1101/2022.11.29.22282864
Abstract: Coronavirus 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. A 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. Among 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. Three-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.
Publisher: Cold Spring Harbor Laboratory
Date: 11-08-2021
DOI: 10.1101/2021.08.11.21261885
Abstract: The SARS-CoV-2 Delta (B.1.617.2) variant of concern is expanding globally. Here, we assess real-world effectiveness of the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines against this variant in the population of Qatar, using a matched test-negative, case- control study design. BNT162b2 effectiveness against any Delta infection, symptomatic or asymptomatic, was 64.2% (95% CI: 38.1-80.1%) ≥14 days after the first dose and before the second dose, but was only 53.5% (95% CI: 43.9-61.4%) ≥14 days after the second dose, in a population in which a large proportion of fully vaccinated persons received their second dose several months earlier. Corresponding effectiveness measures for mRNA-1273 were 79.0% (95% CI: 58.9-90.1%) and 84.8% (95% CI: 75.9-90.8%), respectively. Effectiveness against any severe, critical, or fatal COVID-19 disease due to Delta was 89.7% (95% CI: 61.0-98.1%) for BNT162b2 and 100.0% (95% CI: 41.2-100.0%) for mRNA-1273, ≥14 days after the second dose. Both BNT162b2 and mRNA-1273 are highly effective in preventing Delta hospitalization and death, but less so in preventing infection, particularly for BNT162b2.
Publisher: Massachusetts Medical Society
Date: 16-02-2023
DOI: 10.1056/NEJMC2214114
Publisher: Springer Science and Business Media LLC
Date: 30-05-2022
Publisher: Cold Spring Harbor Laboratory
Date: 04-10-2022
DOI: 10.1101/2022.10.02.22280610
Abstract: We aimed to systematically review the magnitude and duration of the protective effectiveness of prior infection (PE) and hybrid immunity (HE) against Omicron infection and severe disease. We searched pre-print and peer-reviewed electronic databases for controlled studies from January 1, 2020, to June 1, 2022. Risk of bias (RoB) was assessed using the Risk of Bias In Non-Randomized Studies of Interventions (ROBINS-I)-Tool. We used random-effects meta-regression to estimate the magnitude of protection at 1-month intervals and the average change in protection since the last vaccine dose or infection from 3 months to 6 or 12 months. We compared our estimates of PE and HE to previously published estimates of the magnitude and durability of vaccine effectiveness (VE) against Omicron. Eleven studies of prior infection and 15 studies of hybrid immunity were included. For prior infection, there were 97 estimates (27 at moderate RoB and 70 at serious RoB), with the longest follow up at 15 months. PE against hospitalization or severe disease was 82·5% [71·8-89·7%] at 3 months, and 74·6% [63·1-83·5%] at 12 months. PE against reinfection was 65·2% [52·9-75·9%] at 3 months, and 24·7% [16·4-35·5%] at 12 months. For HE, there were 153 estimates (78 at moderate RoB and 75 at serious RoB), with the longest follow up at 11 months for primary series vaccination and 4 months for first booster vaccination. Against hospitalization or severe disease, HE involving either primary series vaccination or first booster vaccination was consistently % for the available follow up. Against reinfection, HE involving primary series vaccination was 69·0% [58·9-77·5%] at 3 months after the most recent infection or vaccination, and 41·8% [31·5-52·8%] at 12 months, while HE involving first booster vaccination was 68·6% [58·8-76·9%] at 3 months, and 46·5% [36·0-57·3%] at 6 months. Against hospitalization or severe disease at 6 months, hybrid immunity with first booster vaccination (effectiveness 95·3% [81·9-98·9%]) or with primary series alone (96·5% [90·2-98·8%]) provided significantly greater protection than prior infection alone (80·1% [70·3-87·2%]), first booster vaccination alone (76·7% [72·5-80·4%]), or primary series alone (64·6% [54·5-73·6%]). Results for protection against reinfection were similar. Prior infection and hybrid immunity both provided greater and more sustained protection against Omicron than vaccination alone. All protection estimates waned quickly against infection but remained high for hospitalisation or severe disease. In iduals with hybrid immunity had the highest magnitude and durability of protection against all outcomes, reinforcing the global imperative for vaccination. WHO COVID-19 Solidarity Response Fund and the Coalition for Epidemic Preparedness Innovations. The global emergence and rapid spread of Omicron (B.1.1.529) variant of concern, characterized by their ability to escape immunity, has required scientists and policymakers to reassess the population protection against Omicron infection and severe disease. So far, few systematic reviews have incorporated data on Omicron, and none have examined the protection against Omicron conferred by hybrid immunity (i.e. the immunity gained from the combination of vaccination and prior infection) which is now widespread globally. While one preprint has recently reported protection from prior infection over time, no systematic review has systematically compared the magnitude and duration of vaccination, prior infection, and hybrid immunity. A large single-country study has reported that protection from either infection or hybrid immunity against Omicron infection wanes to low levels at 15 months, but is relatively stable against severe disease. Prior infection and hybrid immunity both provided greater and more sustained protection against Omicron than vaccination alone. In iduals with hybrid immunity had the highest magnitude and durability of protection against all outcomes protection against severe disease remained above 95% until the end of available follow-up at 11 months after hybrid immunity with primary series and 4 months after hybrid immunity with booster vaccination, and was sustained at these high levels of protection in projections to 12 months and 6 months, respectively. These results may serve to tailor guidance on the optimal number and timing of vaccinations. At the public health level, these findings can be combined with data on local infection prevalence, vaccination rates, and their timing. In settings with high seroprevalence, limited resources, and competing health priorities, it may be reasonable to focus on achieving high coverage rates with primary series among in iduals who are at higher risk of poor outcome, as this will provide a high level of protection against severe disease for at least one year among those with prior infection. Furthermore, given the waning protection for both infection-and vaccine induced immunity against infection or reinfection, mass vaccination could be timed for roll-out prior to periods of expected increased incidence, such as the winter season. At the in idual level, these results can be combined with knowledge of a person’s infection and vaccination history. A six-month delay in booster may be justified after the last infection or vaccination for in iduals with a known prior infection and full primary series vaccination. Further follow-up of the protective effectiveness of hybrid immunity against hospitalization or severe disease for all vaccines is needed to clarify how much waning of protection might occur with longer duration since the last infection or vaccination. Producing estimates of protection for new variant-containing vaccines will be crucial for COVID-19 vaccine policy and decision-making bodies. Policy makers considering the use and timing of vaccinations should include the local extent of past infection, the protection conferred by prior infection or hybrid immunity, and the duration of this protection as key considerations to inform their decision-making.
Publisher: Cold Spring Harbor Laboratory
Date: 29-04-2023
DOI: 10.1101/2023.04.28.23289254
Abstract: 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. 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. 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 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 % throughout the study duration. High 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. 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. SARS-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 of population immunity to 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. This 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. Both 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.
Publisher: Springer Science and Business Media LLC
Date: 02-11-2021
DOI: 10.1038/S41591-021-01583-4
Abstract: 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 in iduals 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.
Publisher: Cold Spring Harbor Laboratory
Date: 13-03-2022
DOI: 10.1101/2022.03.13.22272308
Abstract: The SARS-CoV-2 Omicron (B.1.1.529) variant has two subvariants, BA.1 and BA.2, that are genetically quite ergent. We conducted a matched, test-negative, case-control study to estimate duration of protection of mRNA COVID-19 vaccines, after the second dose and after a third/booster dose, against BA.1 and BA.2 infections in Qatar’s population. BNT162b2 effectiveness against symptomatic BA.1 infection was highest at 46.6% (95% CI: 33.4-57.2%) in the first three months after the second dose, but then declined to ∼10% or below thereafter. Effectiveness rapidly rebounded to 59.9% (95% CI: 51.2-67.0%) in the first month after the booster dose, but then started to decline again. BNT162b2 effectiveness against symptomatic BA.2 infection was highest at 51.7% (95% CI: 43.2-58.9%) in the first three months after the second dose, but then declined to ∼10% or below thereafter. Effectiveness rapidly rebounded to 43.7% (95% CI: 36.5-50.0%) in the first month after the booster dose, but then declined again. Effectiveness against COVID-19 hospitalization and death was in the range of 70-80% any time after the second dose, and was greater than 90% after the booster dose. Similar patterns of protection were observed for the mRNA-1273 vaccine. mRNA vaccines provide only moderate and short-lived protection against symptomatic Omicron infections, with no discernable differences in protection against either the BA.1 or BA.2 subvariants. Vaccine protection against COVID-19 hospitalization and death is strong and durable after the second dose, but is more robust after a booster dose.
Publisher: Public Library of Science (PLoS)
Date: 16-12-2021
DOI: 10.1371/JOURNAL.PMED.1003879
Abstract: 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. Reinfections with the B.1.1.7 variant and variants of unknown status were investigated in a national cohort of 158,608 in iduals with prior PCR-confirmed infections and a national cohort of 42,848 antibody-positive in iduals. Infections with B.1.1.7 and variants of unknown status were also investigated in a national comparator cohort of 132,701 antibody-negative in iduals. 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. 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.
Publisher: BMJ
Date: 31-03-2021
DOI: 10.1136/BMJINNOV-2021-000677
Abstract: Vaccines against SARS-CoV-2 have been developed, but their availability falls far short of global needs. This study aimed to investigate the impact of prioritising available doses on the basis of recipient antibody status, that is by exposure status, using Qatar as an ex le. Vaccination impact (defined as the reduction in infection incidence and the number of vaccinations needed to avert one infection or one adverse disease outcome) 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. For 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 prioritising antibody-negative in iduals for vaccination. Prioritisation by antibody status reduced incidence at a faster rate and led to faster elimination of infection and return to normalcy. Further prioritisation by age group lified the gains of prioritisation by antibody status. Gains from prioritisation by antibody status were largest in settings where the proportion of the population already infected at the commencement of vaccination was 30%–60%. 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 prioritise vaccination recipients were similar. Major health and economic gains can be achieved more quickly by prioritizing those who are antibody-negative while doses of the vaccine remain in short supply.
Publisher: Cold Spring Harbor Laboratory
Date: 12-01-2021
DOI: 10.1101/2021.01.10.21249382
Abstract: Vaccines 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 ex le. Vaccination 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. For 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 in iduals 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 lified 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. Major 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.
Publisher: Cold Spring Harbor Laboratory
Date: 06-01-2022
DOI: 10.1101/2022.01.05.22268782
Abstract: Natural 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. PES 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. PES 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. Protection 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.
Publisher: Cold Spring Harbor Laboratory
Date: 07-07-2022
DOI: 10.1101/2022.07.05.22277257
Abstract: 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 s le 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 years of age, signifying lower infectiousness of small children. Children 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 in iduals, the Ct value was higher among in iduals 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 in iduals tested because of symptoms and was highest among in iduals 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.
Publisher: Cold Spring Harbor Laboratory
Date: 30-10-2022
Publisher: Cold Spring Harbor Laboratory
Date: 30-07-2021
DOI: 10.1101/2021.07.28.21261086
Abstract: SARS-CoV-2 breakthrough infections in vaccinated in iduals 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 in iduals. 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 in iduals. 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 in iduals. 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.
Publisher: Massachusetts Medical Society
Date: 24-02-2022
DOI: 10.1056/NEJMC2117933
Publisher: Massachusetts Medical Society
Date: 09-12-2021
Publisher: Elsevier BV
Date: 11-2023
Publisher: Cold Spring Harbor Laboratory
Date: 07-07-2022
DOI: 10.1101/2022.07.06.22277306
Abstract: The 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. Three 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. Effectiveness 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 7 th month after the primary infection, but waned to ∼70% by the 16 th month. Extrapolating this waning trend using a Gompertz curve suggested an effectiveness of 50% in the 22 nd month and % by the 32 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 % by the 15 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. 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.
Publisher: Springer Science and Business Media LLC
Date: 02-06-2022
DOI: 10.1038/S41467-022-30895-3
Abstract: SARS-CoV-2 Omicron BA.1 and BA.2 subvariants are genetically ergent. 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 % 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.
Publisher: Massachusetts Medical Society
Date: 30-12-2021
DOI: 10.1056/NEJMC2110300
Publisher: Massachusetts Medical Society
Date: 17-03-2022
DOI: 10.1056/NEJMC2119432
Publisher: Springer Science and Business Media LLC
Date: 09-07-2021
Publisher: Cold Spring Harbor Laboratory
Date: 08-02-2022
DOI: 10.1101/2022.02.07.22270568
Abstract: Qatar 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. Vaccine 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. BNT162b2 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 5 th 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 % after the second dose and at % 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 % after the second dose and at % after the booster, but the confidence intervals were wide owing to the small number of cases. BNT162b2 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.
Publisher: Massachusetts Medical Society
Date: 07-07-2022
Publisher: Cold Spring Harbor Laboratory
Date: 04-08-2021
DOI: 10.1101/2021.08.02.21261465
Abstract: 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.
Publisher: Cold Spring Harbor Laboratory
Date: 15-11-2022
DOI: 10.1101/2022.11.14.22282103
Abstract: Long-term effectiveness of COVID-19 mRNA boosters in populations with different prior infection histories and clinical vulnerability profiles is inadequately understood. A 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. Booster 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). Boosters 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.
Publisher: Cold Spring Harbor Laboratory
Date: 21-01-2022
DOI: 10.1101/2022.01.18.22269452
Abstract: Waning 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. In 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. For 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. mRNA 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.
Publisher: Cold Spring Harbor Laboratory
Date: 06-02-2021
DOI: 10.1101/2021.02.04.21251126
Abstract: To investigate 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 708 in iduals. Concordance metrics were estimated. Logistic regression was used to assess associations with seropositivity. SARS-CoV-2 seroprevalence was 63.4% (449/708 95% CI 59.8%-66.9%) using the BioMedomics assay and 71.9% (509/708 95% CI 68.5%-75.1%) using the Elecsys assay. There were 62 discordant results between the two assays. One specimen was seropositive in the BioMedomics assay, but seronegative in the Elecsys assay, while 61 specimens were seropositive in the Elecsys assay, but seronegative in the BioMedomics assay. Positive, negative, and overall percent agreements between the two assays were 88.0% (95% CI 84.9%-90.6%), 99.5% (95% CI 97.2%-99.9%), and 91.2% (95% CI 88.9%-93.1%), respectively, with a Cohen’s kappa of 0.80 (95% CI 0.77-0.83), indicating excellent agreement. Excluding specimens with lower antibody titers, the agreement improved with positive, negative, and overall percent concordance of 91.2% (95% CI 88.2%-93.6%), 99.5% (95% CI 97.2%-99.9%), and 93.9% (95% CI 91.7%-95.5%), respectively, and a Cohen’s kappa of 0.87 (95% CI 0.84-0.89). Logistic regression confirmed better agreement with higher antibody titers. The BioMedomics COVID-19 IgM/IgG Rapid Test demonstrated excellent 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 possible vaccine prioritization.
Publisher: Cold Spring Harbor Laboratory
Date: 22-04-2023
DOI: 10.1101/2023.04.21.23288917
Abstract: 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. Six national, matched, test-negative, case-control studies were conducted between January 18-December 18, 2021 on a s le of 239,120 PCR-positive tests and 6,103,365 PCR-negative tests. 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 % protection against severe, critical, or fatal COVID-19 regardless of variant. Similar effectiveness estimates were observed for mRNA-1273. All 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.
Publisher: Cold Spring Harbor Laboratory
Date: 25-02-2022
DOI: 10.1101/2022.02.24.22271440
Abstract: The SARS-CoV-2 Omicron (B.1.1.529) variant has two main sub-lineages, BA.1 and BA.2 with significant genetic distance between them. This study investigated 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 February 21, 2022. Two national matched, retrospective cohort studies were conducted to estimate effectiveness of BA.1 infection against reinfection with BA.2 (N=20,197 BA.1-against-BA.2 study), and effectiveness of BA.2 infection against reinfection with BA.1 (N=100,925 BA.2-against-BA.1 study). Associations were estimated using Cox proportional-hazards regression models. In the BA.1-against-BA.2 study, cumulative incidence of infection was estimated at 0.03% (95% CI: 0.01-0.07%) for the BA.1-infected cohort and at 0.62% (95% CI: 0.51-0.75%) for the uninfected-control cohort, 15 days after the start of follow-up. Effectiveness of BA.1 infection against reinfection with BA.2 was estimated at 94.9% (95% CI: 88.4-97.8%). In the BA.2-against-BA.1 study, cumulative incidence of infection was estimated at 0.03% (95% CI: 0.02-0.04%) for the BA.2-infected cohort and at 0.17% (95% CI: 0.15-0.21%) for the uninfected-control cohort, 15 days after the start of follow-up. Effectiveness of BA.2 infection against reinfection with BA.1 was estimated at 85.6% (95% CI: 77.4-90.9%). Infection with an Omicron sub-lineage appears to induce strong, but not full protection against reinfection with the other sub-lineage, for at least several weeks after the initial infection.
Publisher: Elsevier BV
Date: 11-2021
DOI: 10.1016/J.IJID.2021.09.006
Abstract: Complementing whole genome sequencing strategies with high-throughput multiplex RT-qPCR genotyping allows for more comprehensive and real-time tracking of SARS-CoV-2 variants of concern. During the second and third waves of COVID-19 in Qatar, PCR genotyping, combined with Sanger sequencing of un-typeable s les, was employed to describe the epidemiology of the Alpha, Beta and Delta variants. A total of 9792 nasopharyngeal PCR-positive s les collected between April-June 2021 were successfully genotyped, revealing the importation and transmission dynamics of these three variants in Qatar.
Publisher: Elsevier BV
Date: 05-2021
Publisher: Cold Spring Harbor Laboratory
Date: 09-08-2021
DOI: 10.1101/2021.08.07.21261578
Abstract: 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 c aign. 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.
Publisher: Cold Spring Harbor Laboratory
Date: 19-07-2020
DOI: 10.1101/2020.07.16.20155317
Abstract: Qatar 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. A 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 c aigns 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. By July 10, 397,577 in iduals 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 c aigns in workplaces and residential areas including 26,715 in iduals, 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 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. R 0 ranged between 1.45-1.68 throughout the epidemic. R t 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. Qatar 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 R 0 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.
Publisher: Cold Spring Harbor Laboratory
Date: 26-07-2022
DOI: 10.1101/2022.07.26.22278045
Abstract: The 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. Three matched, retrospective, target-trial, cohort studies were conducted to compare incidence of SARS-CoV-2 infection in the national cohort of vaccinated in iduals to incidence in the national cohort of unvaccinated in iduals. Associations were estimated using Cox proportional-hazards regression models. Effectiveness 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. Pediatric 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.
Publisher: Massachusetts Medical Society
Date: 17-11-2022
Publisher: American Association for the Advancement of Science (AAAS)
Date: 30-03-2007
Publisher: Cold Spring Harbor Laboratory
Date: 28-05-2023
DOI: 10.1101/2023.05.28.23290641
Abstract: This 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. A 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. The 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. The 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.
Publisher: Massachusetts Medical Society
Date: 03-11-2022
DOI: 10.1056/NEJMC2211055
Publisher: Cold Spring Harbor Laboratory
Date: 04-03-2022
DOI: 10.1101/2022.03.02.22271771
Abstract: Qatar experienced a large SARS-CoV-2 Omicron (B.1.1.529) wave that started on December 19, 2021 and peaked in mid-January, 2022. We investigated effects of Omicron subvariant (BA.1 and BA.2), previous vaccination, and prior infection on infectiousness of Omicron infections, between December 23, 2021 and February 20, 2022. Univariable and multivariable regression analyses were conducted to estimate the association between the RT-qPCR cycle threshold (Ct) value of PCR tests (a proxy for SARS-CoV-2 infectiousness) and each of the Omicron subvariants, mRNA vaccination, prior infection, reason for RT-qPCR testing, calendar week of RT-qPCR testing (to account for phases of the rapidly evolving Omicron wave), and demographic factors. Compared to BA.1, BA.2 was associated with 3.53 fewer cycles (95% CI: 3.46-3.60), signifying higher infectiousness. Ct value decreased with time since second and third vaccinations. Ct values were highest for those who received their boosters in the month preceding the RT-qPCR test—0.86 cycles (95% CI: 0.72-1.00) higher than for unvaccinated persons. Ct value was 1.30 (95% CI: 1.20-1.39) cycles higher for those with a prior infection compared to those without prior infection, signifying lower infectiousness. Ct value declined gradually with age. Ct value was lowest for those who were tested because of symptoms and was highest for those who were tested for travel-related purposes. Ct value was lowest during the exponential-growth phase of the Omicron wave and was highest after the wave peaked and was declining. The BA.2 subvariant appears substantially more infectious than the BA.1 subvariant. This may reflect higher viral load and/or longer duration of infection, thereby explaining the rapid expansion of this subvariant in Qatar.
Publisher: Cold Spring Harbor Laboratory
Date: 30-01-2023
DOI: 10.1101/2023.01.29.23285152
Abstract: Risk of short- and long-term all-cause mortality after a primary SARS-CoV-2 infection is inadequately understood. A 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. Among 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. COVID-19 mortality in Qatar appears primarily driven by forward displacement of deaths of in iduals with relatively short life expectancy and more clinically vulnerable to severe COVID-19. Vaccination negated the mortality displacement by preventing early deaths.
Publisher: Cold Spring Harbor Laboratory
Date: 16-12-2021
DOI: 10.1101/2021.12.16.21267902
Abstract: In early 2021, Qatar launched a mass immunization c aign 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. Effectiveness 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. By 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 7 th 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. mRNA-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.
Location: United States of America
No related grants have been discovered for Laith Abu-Raddad.