Estimating protection afforded by prior infection in preventing reinfection: Applying the test-negative study design.

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

Covid-19 Vaccine Protection among Children and Adolescents in Qatar.

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

COVID-19 risk score as a public health tool to guide targeted testing: A demonstration study in Qatar.

We developed a Coronavirus Disease 2019 (COVID-19) risk score to guide targeted RT-PCR testing in Qatar. The Qatar national COVID-19 testing database, encompassing a total of 2,688,232 RT-PCR tests conducted between February 5, 2020-January 27, 2021, was analyzed. Logistic regression analyses were implemented to derive the COVID-19 risk score, as a tool to identify those at highest risk of having the infection. Score cut-off was determined using the ROC curve based on maximum sum of sensitivity and specificity. The score's performance diagnostics were assessed. Logistic regression analysis identified age, sex, and nationality as significant predictors of infection and were included in the risk score. The ROC curve was generated and the area under the curve was estimated at 0.63 (95% CI: 0.63-0.63). The score had a sensitivity of 59.4% (95% CI: 59.1%-59.7%), specificity of 61.1% (95% CI: 61.1%-61.2%), a positive predictive value of 10.9% (95% CI: 10.8%-10.9%), and a negative predictive value of 94.9% (94.9%-95.0%). The concept and utility of a COVID-19 risk score were demonstrated in Qatar. Such a public health tool can have considerable utility in optimizing testing and suppressing infection transmission, while maximizing efficiency and use of available resources.

Effects of Previous Infection and Vaccination on Symptomatic Omicron Infections.

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

Characterizing the effective reproduction number during the COVID-19 pandemic: Insights from Qatar's experience.

BACKGROUND: The effective reproduction number, Rt , is a tool to track and understand pandemic dynamics. This investigation of Rt estimations was conducted to guide the national COVID-19 response in Qatar, from the onset of the pandemic until August 18, 2021. METHODS: Real-time "empirical" Rt Empirical was estimated using five methods, including the Robert Koch Institute, Cislaghi, Systrom-Bettencourt and Ribeiro, Wallinga and Teunis, and Cori et al. methods. Rt was also estimated using a transmission dynamics model (Rt Model-based ). Uncertainty and sensitivity analyses were conducted. Correlations between different Rt estimates were assessed by calculating correlation coefficients, and agreements between these estimates were assessed through Bland-Altman plots. RESULTS: Rt Empirical captured the evolution of the pandemic through three waves, public health response landmarks, effects of major social events, transient fluctuations coinciding with significant clusters of infection, and introduction and expansion of the Alpha (B.1.1.7) variant. The various estimation methods produced consistent and overall comparable Rt Empirical estimates with generally large correlation coefficients. The Wallinga and Teunis method was the fastest at detecting changes in pandemic dynamics. Rt Empirical estimates were consistent whether using time series of symptomatic PCR-confirmed cases, all PCR-confirmed cases, acute-care hospital admissions, or ICU-care hospital admissions, to proxy trends in true infection incidence. Rt Model-based correlated strongly with Rt Empirical and provided an average Rt Empirical . CONCLUSIONS: Rt estimations were robust and generated consistent results regardless of the data source or the method of estimation. Findings affirmed an influential role for Rt estimations in guiding national responses to the COVID-19 pandemic, even in resource-limited settings.

Assessing the performance of a serological point-of-care test in measuring detectable antibodies against SARS-CoV-2.

This study investigated the performance of a rapid point-of-care antibody test, the BioMedomics COVID-19 IgM/IgG Rapid Test, in comparison with a high-quality, validated, laboratory-based platform, the Roche Elecsys Anti-SARS-CoV-2 assay. Serological testing was conducted on 709 individuals. Concordance metrics were estimated. Logistic regression was used to assess associations with seropositivity. SARS-CoV-2 seroprevalence was 63.5% (450/709; 95% CI 59.8%-67.0%) using the BioMedomics assay and 71.9% (510/709; 95% CI 68.5%-75.2%) using the Elecsys assay. There were 60 discordant results between the two assays, all of which were seropositive in the Elecsys assay, but seronegative in the BioMedomics assay. Overall, positive, and negative percent agreements between the two assays were 91.5% (95% CI 89.2%-93.5%), 88.2% (95% CI 85.1%-90.9%), and 100% (95% CI 98.2%-100%), respectively, with a Cohen's kappa of 0.81 (95% CI 0.78-0.84). Excluding specimens with lower (Elecsys) antibody titers, the agreement improved with overall, positive, and negative percent concordance of 94.4% (95% CI 92.3%-96.1%), 91.8% (95% CI 88.8%-94.3%), and 100% (95% CI 98.2%-100%), respectively, and a Cohen's kappa of 0.88 (95% CI 0.85-0.90). Logistic regression confirmed better agreement with higher antibody titers. The BioMedomics COVID-19 IgM/IgG Rapid Test demonstrated good performance in measuring detectable antibodies against SARS-CoV-2, supporting the utility of such rapid point-of-care serological testing to guide the public health responses and vaccine prioritization.

The impact of COVID-19 on primary health care services in Qatar: 2 years of response and coping 2020-2021.

Background: Health care systems worldwide have rapidly responded to manage the COVID-19 pandemic by providing screening tests, contact tracing, treatment, and vaccination. However, the long duration of the pandemic has had an enormous load on the health care systems, which disrupted continuity of the essential non-covid services, long waiting time for appointments, and increase in the utilization of telemedicine services. Primary health care was established as an essential foundation for the global response to the COVID-19. In Qatar, Primary Heath Care Corporation (PHCC), the main primary care services provided played a major role in the response to the pandemic. However, its services were affected and disrupted, and new services were added. Hence, the aim of this analysis is to understand the long-term impact of the COVID-19 on the services provided by PHCC in Qatar in terms of PHCC pandemic response, change in utilization of the core, and preventative services, and the introduction of new alternative services. Methods: A retrospective data analysis was conducted for all the appointments and visits for all the PHCC health centers in the years of 2020 and 2021. The study conducted a comparison of the services utilizations using the utilization figures of PHCC services between 1st of January and 31st of December 2019 as a reference year. The differences in the utilization per service were presented in frequencies and percentages. Results: The in-person services dropped drastically in 2020 at 36% reduction in compassion to 2019. However, the newly introduced virtual consultation services in 2020 reached their highest utilization figures in 2021 at 908,965 virtual visits. The COVID-19 specific related services ranging from the COVID-19 drive-through testing to vaccine administration constituted a total number of 2,836,127 visits corresponding to 44% of the total PHCC services utilization visits in 2021. In 2021, PHCC dental services dropped by 25.2%. The most noticeable utilization drops in 2021 were among the preventative services with 53.2% and 78.9% in colorectal screening and non-communicable diseases (NCDs) risk factors annual screening services, respectively. However, mental health services have witnessed a surge in utilization at 134.1% increase in 2021 in comparison to 2019. Conclusion: The COVID-19 pandemic caused a disruption in the PHCC utilization of core services, namely dental services. Additionally, PHCC preventive services utilizations were affected drastically including cancer and NCDs risk factors annual screening. Nevertheless, PHCC managed to provide alternative virtual services and played a vital role in responding to the pandemic by leading the COVID-19 vaccination campaign in Qatar. However, future research is needed to establish which vulnerable patient groups were most affected by the pandemic, to continue to inform strategies and policies directed at mitigating the impact of future potential pandemics.

Waning of BNT162b2 Vaccine Protection against SARS-CoV-2 Infection in Qatar.

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

SARS-CoV-2 infection hospitalization, severity, criticality, and fatality rates in Qatar.

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

Analytic comparison between three high-throughput commercial SARS-CoV-2 antibody assays reveals minor discrepancies in a high-incidence population.

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

Epidemiological impact of prioritising SARS-CoV-2 vaccination by antibody status: mathematical modelling analyses.

BACKGROUND: 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 example. METHODS: 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. RESULTS: 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 individuals 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 amplified 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. CONCLUSIONS: 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.

Testing a multicomponent lifestyle intervention for combatting childhood obesity.

BACKGROUND: Childhood obesity is a major global health concern. Weight-management camps involving delivery of a program of physical activity, health education, and healthy eating are an effective treatment, although post-intervention weight-management is less well understood. Our objective was to assess the effectiveness of a weight-management camp followed by a community intervention in supporting weight-management for overweight children and children with obesity. METHODS: Participants were overweight Qatari schoolchildren or schoolchildren with obesity, ages 8-14 years, (n = 300) recruited over a three-year period across 14 randomly selected schools in the Doha area. They attended a two-week weight management camp, then a 10-week program of weekly lifestyle education and physical activity sessions, which also included behavior change techniques. The programme was cognitive behavioural therapy (CBT)-focused with a strong element of behavioural economics blended in. RESULTS: Participants saw a significant BMI SDS reduction as a result of the entire intervention (camp + education and activity sessions) both at the individual (p < 0.0001) and cluster/school (p = 0.0002) levels, and weight loss occurred during each intervention stage separately for the camp (p < 0.0001 for both the individual and cluster/school levels) and the lifestyle education and activity phase (p < 0.0001 and p = 0.0220 at the individual and cluster/school levels, respectively). CONCLUSIONS: Weekly lifestyle education and activity sessions which include behavior change techniques may be useful in promoting continued weight management in the period following intensive, immersive childhood obesity interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT02972164 , November 23, 2016.

Herd Immunity against Severe Acute Respiratory Syndrome Coronavirus 2 Infection in 10 Communities, Qatar.

We investigated what proportion of the population acquired severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and whether the herd immunity threshold has been reached in 10 communities in Qatar. The study included 4,970 participants during June 21-September 9, 2020. Antibodies against SARS-CoV-2 were detected by using an electrochemiluminescence immunoassay. Seropositivity ranged from 54.9% (95% CI 50.2%-59.4%) to 83.8% (95% CI 79.1%-87.7%) across communities and showed a pooled mean of 66.1% (95% CI 61.5%-70.6%). A range of other epidemiologic measures indicated that active infection is rare, with limited if any sustainable infection transmission for clusters to occur. Only 5 infections were ever severe and 1 was critical in these young communities; infection severity rate of 0.2% (95% CI 0.1%-0.4%). Specific communities in Qatar have or nearly reached herd immunity for SARS-CoV-2 infection: 65%-70% of the population has been infected.

Mathematical modeling of the SARS-CoV-2 epidemic in Qatar and its impact on the national response to COVID-19.

BACKGROUND: 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 epidemic's time-course, forecasted health care needs, predicted the impact of social and physical distancing restrictions, and rationalized and justified easing of restrictions. METHODS: An age-structured deterministic model was constructed to describe SARS-CoV-2 transmission dynamics and disease progression throughout the population. RESULTS: 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 R0 had varied between 1.07-2.78, and 50.8% of the population were estimated to have been infected (1.43 million infections). The proportion of actual infections diagnosed was estimated at 11.6%. Applying the concept of Rt tuning, gradual easing of restrictions was rationalized and justified to start on June 15, 2020, when Rt declined to 0.7, to buffer the increased interpersonal contact with easing of restrictions and to minimize the risk of a second wave. No second wave has materialized as of October 15, 2020, five months after the epidemic peak. CONCLUSIONS: 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 health care system.

Characterizing the Qatar advanced-phase SARS-CoV-2 epidemic.

The overarching objective of this study was to provide the descriptive epidemiology of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in Qatar by addressing specific research questions through a series of national epidemiologic studies. Sources of data were the centralized and standardized national databases for SARS-CoV-2 infection. By July 10, 2020, 397,577 individuals had been tested for SARS-CoV-2 using polymerase-chain-reaction (PCR), of whom 110,986 were positive, a positivity cumulative rate of 27.9% (95% CI 27.8-28.1%). As of July 5, case severity rate, based on World Health Organization (WHO) severity classification, was 3.4% and case fatality rate was 1.4 per 1,000 persons. Age was by far the strongest predictor of severe, critical, or fatal infection. PCR positivity of nasopharyngeal/oropharyngeal 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 testing campaigns in workplaces and residential areas including 26,715 individuals, pooled mean PCR positivity was 15.6% (95% CI 13.7-17.7%). SARS-CoV-2 antibody prevalence was 24.0% (95% CI 23.3-24.6%) in 32,970 residual clinical blood specimens. Antibody prevalence was only 47.3% (95% CI 46.2-48.5%) in those who had at least one PCR positive result, but 91.3% (95% CI 89.5-92.9%) among those who were PCR positive > 3 weeks before serology testing. Qatar has experienced a large SARS-CoV-2 epidemic that is rapidly declining, apparently due to growing immunity levels in the population.