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BackgroundCoronavirus Disease 2019 (COVID-19) vaccine antigen dosage may affect protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but direct evidence to quantify this effect is lacking. MethodsA matched, retrospective, cohort study that emulated a randomized control trial was conducted in Qatar between February 3, 2022 and November 8, 2022, to provide a head-to-head, controlled comparison of protection induced by two antigen dosages of the BNT162b2 vaccine. The study compared incidence of omicron infection in the national cohort of adolescents 12 years of age who received the two-dose primary-series of the 30-{micro}g 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-{micro}g BNT162b2 vaccine. Associations were estimated using Cox proportional-hazard regression models. ResultsAmong adolescents with no record of prior infection, cumulative incidence of infection was 6.0% (95% CI: 4.9-7.3%) for the 30-{micro}g cohort and 7.2% (95% CI: 6.1-8.5%) for the 10-{micro}g 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-{micro}g cohort to the 10-{micro}g cohort was 0.77 (95% CI: 0.60-0.98). Corresponding relative effectiveness was 23.4% (95% CI: 1.6-40.4%). Relative effectiveness was -3.3% (95% CI: -68.0-27.5%) among adolescents with a record of prior infection. ConclusionsThree-fold higher BNT162b2 dosage was associated with [~]25% higher protection against infection in infection-naive adolescents of similar age. These findings may inform design of future COVID-19 vaccines and boosters for persons of different age groups.
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BackgroundSeveral studies reported serological cross-reaction between DENV and SARS-CoV-2 IgG antibodies using rapid point of care (POC) assays. Limited data are available about cross-reactivity when testing is done using advanced chemiluminescence immunoassay (CLIA) and ELISA assays. ObjectiveThis study aims to investigate potential serological cross-reactivity between SARS-CoV-2-IgG and DENV-IgG using CLIA and ELISA assays. Study-designA total of 90 DENV-IgG-ELISA positive and 90 negative pre-pandemic sera were tested for anti-SARS-CoV-2-IgG using the automated CL-900i CLIA assay. Furthermore, a total of 91 SARS-CoV-2-IgG-CLIA positive and 91 negative post-pandemic sera were tested for anti-DENV-IgG using the Novalis ELISA assay. ResultsThe DENV-IgG positive sera had 5 positives and 85 negatives for SARS-CoV-2-IgG. The DENV-IgG negative sera also had 5 positives and 85 negatives for SARS-CoV-2-IgG. No statistically significant difference in specificity between the DENV-IgG positive and DENV-IgG negative sera was found (p-value=1.00). The SARS-CoV-2-IgG positive sera had 43 positives, 47 negatives, and 1 equivocal for DENV-IgG. The SARS-CoV-2-IgG negative sera had 50 positives, 40 negatives, and 1 equivocal for DENV-IgG. No statistically significant difference in the proportion that is DENV-IgG positive between the SARS-CoV-2-IgG positive and SARS-CoV-2-IgG negative sera (p-value=0.58). ConclusionsNo evidence for cross-reactivity between the DENV and SARS-CoV-2 IgG antibodies was found.
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Several studies have investigated the effect of repeated freeze-thaw (F/T) cycles on RNA detection for SARS-CoV-2. However, no data is available regarding the effect of repeated F/T cycles on SARS-CoV-2 antibody detection in serum. We investigated the effect of multiple F/T cycles on anti-SARS-CoV-2 IgG detection using an ELISA test targeting the nucleocapsid antibodies. Ten positive and one negative SARS-CoV-2 IgG sera from 11 participants, in replicates of five were subjected to a total of 16 F/T cycles and stored at 4{degrees}C until tested by ELISA. Statistical analysis was done to test for F/T cycle effect. Non-of the 10 positive sera turned into negative after 16 F/T cycles. There was no significant difference in the OD average reading between the first and last F/T cycles, except for one serum with a minimal decline in the OD. The random-effect linear regression of log (OD) on the number of cycles showed no significant trend with a slope consistent with zero (B=-0.0001; 95% CI -0.0008; 0.0006; p-value=0.781). These results suggest that multiple F/T cycles had no effect on the ability of the ELISA assay to detect the SARS-CoV-2 IgG antibodies.
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The heterogeneity of COVID-19 lies within its diverse symptoms and severity, ranging from mild to lethal. Acute respiratory distress syndrome (ARDS) has been shown to be the leading cause of mortality in COVID-19 patients, characterized by a hyper cytokine storm. Autoimmunity is proposed to occur as a result of COVID-19, given the high similarity of the immune responses observed in COVID-19 and autoimmune diseases. Here, we investigate the level of autoimmune antibodies in COVID-19 patients with different severities. Initial screening for antinuclear antibodies (ANA) IgG revealed that 1.6% (2/126) and 4% (5/126) of ICU COVID-19 cases developed strong and moderate ANA levels, respectively. However, all the non-ICU cases (n=273) were ANA negative. The high ANA level was confirmed by immunofluorescence (IFA) and large-scale autoantibody screening by phage immunoprecipitation-sequencing (PhIP-Seq). Indeed, the majority of the samples showed "speckled" ANA pattern by microscopy, and we demonstrate that samples of ICU patients with strong and moderate ANA levels contain autoantibody specificities that predominantly targeted proteins involved in intracellular signal transduction, metabolism, apoptotic processes, and cell death; further denoting reactivity to nuclear and cytoplasmic antigens. In conclusion, our results further support the notion of routine screening for autoimmune responses in COVID-19 patients, which might help improve disease prognosis and patient management. Further, results provide compelling evidence that ANA-positive individuals should be excluded from being donors for convalescent plasma therapy in the context of Covid-19.
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BackgroundThe objective of this study was to develop a Coronavirus Disease 2019 (COVID-19) risk score to guide targeted RT-PCR testing in Qatar. MethodsThe 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 scores performance diagnostics were assessed. ResultsLogistic regression analysis identified age, sex, and nationality as significant predictors of infection and were included in the risk score. The scores 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. ConclusionsThe 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.
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ObjectiveTo 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. MethodsSerological testing was conducted on 708 individuals. Concordance metrics were estimated. Logistic regression was used to assess associations with seropositivity. ResultsSARS-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 Cohens 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 Cohens kappa of 0.87 (95% CI 0.84-0.89). Logistic regression confirmed better agreement with higher antibody titers. ConclusionThe 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.
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BackgroundReinfection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been documented, raising public health concerns. Risk and incidence rate of SARS-CoV-2 reinfection were assessed in a large cohort of antibody-positive persons in Qatar. MethodsAll SARS-CoV-2 antibody-positive persons with a PCR-positive swab [≥]14 days after the first-positive antibody test were individually investigated for evidence of reinfection. Viral genome sequencing was conducted for paired viral specimens to confirm reinfection. Incidence of reinfection was compared to incidence of infection in the complement cohort of those antibody-negative. ResultsAmong 43,044 anti-SARS-CoV-2 positive persons who were followed for a median of 16.3 weeks (range: 0-34.6), 314 individuals (0.7%) had at least one PCR positive swab [≥]14 days after the first-positive antibody test. Of these individuals, 129 (41.1%) had supporting epidemiological evidence for reinfection. Reinfection was next investigated using viral genome sequencing. Applying the viral-genome-sequencing confirmation rate, the risk of reinfection was estimated at 0.10% (95% CI: 0.08-0.11%). The incidence rate of reinfection was estimated at 0.66 per 10,000 person-weeks (95% CI: 0.56-0.78). Incidence rate of reinfection versus month of follow-up did not show any evidence of waning of immunity for over seven months of follow-up. Meanwhile, in the complement cohort of 149,923 antibody-negative persons followed for a median of 17.0 weeks (range: 0-45.6), risk of infection was estimated at 2.15% (95% CI: 2.08-2.22%) and incidence rate of infection was estimated at 13.69 per 10,000 person-weeks (95% CI: 13.22-14.14). Efficacy of natural infection against reinfection was estimated at 95.2% (95% CI: 94.1-96.0%). Reinfections were less severe than primary infections. Only one reinfection was severe, two were moderate, and none were critical or fatal. Most reinfections (66.7%) were diagnosed incidentally through random or routine testing, or through contact tracing. ConclusionsReinfection is rare. Natural infection appears to elicit strong protection against reinfection with an efficacy [~]95% for at least seven months.
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BackgroundVaccines against SARS-CoV-2 have been developed, but their availability falls far short of global needs. This study aimed to investigate the impact of prioritizing available doses on the basis of recipient antibody status, that is by exposure status, using Qatar as an example. MethodsVaccination impact was assessed under different scale-up scenarios using a deterministic meta-population mathematical model describing SARS-CoV-2 transmission and disease progression in the presence of vaccination. ResultsFor a vaccine that protects against infection with an efficacy of 95%, half as many vaccinations were needed to avert one infection, disease outcome, or death by prioritizing antibody-negative individuals for vaccination. Prioritization by antibody status reduced incidence at a faster rate and led to faster elimination of infection and return to normalcy. Further prioritization by age group amplified the gains of prioritization by antibody status. Gains from prioritization by antibody status were largest in settings where the proportion of the population already infected at the commencement of vaccination was 30-60%, which is perhaps where most countries will be by the time vaccination programs are up and running. For a vaccine that only protects against disease and not infection, vaccine impact was reduced by half, whether this impact was measured in terms of averted infections or disease outcomes, but the relative gains from using antibody status to prioritize vaccination recipients were similar. ConclusionsMajor health, societal, and economic gains can be achieved more quickly by prioritizing those who are antibody-negative while doses of the vaccine remain in short supply.
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BackgroundQatar 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. MethodsResidual blood specimens from individuals 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. ResultsWe tested 112,941 individuals ([~]10% of Qatars 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%). ConclusionsFewer than two in every 10 individuals in Qatars 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.
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BackgroundPerformance 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. MethodsPCR and serological testing was performed on 394 individuals. ResultsSARS-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 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. ConclusionsAll 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.
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BackgroundQatar experienced a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic that disproportionately affected the craft and manual worker (CMW) population who comprise 60% of the total population. This study aimed to assess the proportions of ever and/or current infection in this population. MethodsA cross-sectional population-based survey was conducted during July 26-September 09, 2020 to assess both anti-SARS-CoV-2 positivity through serological testing and polymerase chain reaction (PCR) positivity through PCR testing. Associations with antibody and PCR positivity were identified through regression analyses. ResultsStudy included 2,641 participants, 69.3% of whom were <40 years of age. Anti-SARS-CoV-2 positivity was estimated at 55.3% (95% CI: 53.3-57.3%) and was significantly associated with nationality, geographic location, educational attainment, occupation, presence of symptoms in the two weeks preceding the survey, and previous infection diagnosis. PCR positivity was assessed at 11.3% (95% CI: 9.9-12.8%) and was significantly associated with geographic location, contact with an infected person, and reporting two or more symptoms. Infection positivity (antibody and/or PCR positive) was assessed at 60.6% (95% CI: 9.9-12.8%). The proportion of antibody-positive CMWs that had a prior SARS-CoV-2 diagnosis was 9.3% (95% CI: 7.9-11.0%). Only seven infections were ever severe and one was ever critical--an infection severity rate of 0.5% (95% CI: 0.2-1.0%). ConclusionsSix in every 10 CMWs have been infected, suggestive of reaching the herd immunity threshold. Infection severity was low with only one in every 200 infections progressing to be severe or critical. Only one in every 10 infections had been previously diagnosed suggestive of mostly asymptomatic or minimally mild infections.
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Four endemic human coronaviruses (HCoVs) are commonly associated with acute respiratory infection in humans. B cell responses to these "common cold" viruses remain incompletely understood. Here we report a comprehensive analysis of CoV-specific antibody repertoires in 231 children and 1168 adults using phage-immunoprecipitation sequencing. Seroprevalence of antibodies to endemic HCoVs ranged between ~4 and 27% depending on the species and cohort. We identified at least 136 novel linear B cell epitopes. Antibody repertoires against endemic HCoVs were qualitatively different between children and adults in that anti-HCoV IgG specificities more frequently found among children targeted functionally important and structurally conserved regions of the spike, nucleocapsid and matrix proteins. Moreover, antibody specificities targeting the highly conserved fusion peptide region and S2 cleavage site of the spike protein were broadly cross-reactive with peptides of epidemic human and non-human coronaviruses. In contrast, an acidic tandem repeat in the N-terminal region of the Nsp3 subdomain of the HCoV-HKU1 polyprotein was the predominant target of antibody responses in adult donors. Our findings shed light on the dominant species-specific and pan-CoV target sites of human antibody responses to coronavirus infection, thereby providing important insights for the development of prophylactic or therapeutic monoclonal antibodies and vaccine design.