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BackgroundThere is limited seroepidemiological evidence on the magnitude and long-term durability of antibody titers of mRNA and non-mRNA vaccines in the Qatari population. This study was conducted to generate evidence on long-term anti-S IgG antibodies titers and their dynamics in individuals who have completed a primary COVID-19 vaccination schedule. MethodsA total of 300 participants who received any of the following vaccines BNT162b2/Comirnaty or mRNA-1273 or ChAdOx1-S/Covishield or COVID-19 Vaccine Janssen/Johnson or BBIBP-CorV or Covaxin were enrolled in our study. All sera samples were tested by chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of IgG antibodies to SARS-CoV-2, receptor-binding domain (RBD) of the S1 subunit of the spike protein of SARS-CoV-2. Antibodies against SARS-CoV-2 nucleocapsid (SARS-CoV-2 N-protein IgG) were also determined. Kaplan-Meier survival curves were used to compare the time from the last dose of the primary vaccination schedule to the time by which anti-S IgG antibodies titers fell into the lowest quartile (range of values collected) for the mRNA and non-mRNA vaccines. ResultsParticipants vaccinated with mRNA vaccines had higher median anti-S IgG antibody titers. Participants vaccinated with the mRNA-1273 vaccine had the highest median anti-S-antibody level of 13720.9 AU/mL (IQR 6426.5 to 30185.6 AU/mL) followed by BNT162b2 (median, 7570.9 AU/ml; IQR, 3757.9 to 16577.4 AU/mL); while the median anti-S antibody titer for non-mRNA vaccinated participants was 3759.7 AU/mL (IQR, 2059.7-5693.5 AU/mL). The median time to reach the lowest quartile was 3.53 months (IQR, 2.2-4.5 months) and 7.63 months (IQR, 6.3-8.4 months) for the non-mRNA vaccine recipients and Pfizer vaccine recipients, respectively. However, more than 50% of the Moderna vaccine recipients did not reach the lowest quartile by the end of the follow-up period. ConclusionsThis evidence on anti-S IgG antibody titers, their durability and decay over time should be considered for the utility of these assays in transmission dynamics after the full course of primary vaccination.
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BackgroundWaning immunity following administration of mRNA based COVID-19 vaccines remains a concern for many health systems. We undertook a study of SARS-CoV-2 infections, with and without requirement for intensive care to shed more light on the duration of vaccine effectiveness for protection against the need for intensive care. MethodsWe used a matched case-control study design with the study base being all individuals with first infection with SARS-CoV-2 reported in the State of Qatar between 1 Jan 2021 and 20 Feb 2022. Cases were those requiring intensive care while controls were those who recovered without need for intensive care. Vaccine effectiveness against requiring intensive care and number needed to vaccinate (NNV) to prevent one more case of COVID-19 requiring intensive care were computed for the mRNA (BNT162b2 / mRNA-1273) vaccines. ResultsVaccine effectiveness against requiring intensive care was 59% (95% confidence interval [CI], 50 to 76) between the first and second dose and strengthened to 89% (95% CI, 85 to 92) between the second dose and 4 months post the second dose in persons who received a primary course of the vaccine. There was no waning of vaccine effectiveness in the period from 4 to 12 months after the second dose. ConclusionsThis study demonstrates that vaccine effectiveness against requiring intensive care remains robust till at least 12 months after the second dose of mRNA based vaccines.
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BackgroundSeveral studies have compared the performance of reverse transcription-polymerase chain reaction (RT-PCR) and antigen rapid diagnostic tests (Ag-RDTs) as tools to diagnose SARS-CoV-2 disease (COVID-19). As the performance of Ag-RDT may vary among different products and viral load scenarios, the clinical utility of the Ag-RDT remains unclear. Our aim is to assess the diagnostic agreement between Ag-RDTs and RT-PCR in testing for COVID-19 across different products and cycle threshold (Ct) values. MethodsAn evidence synthesis and meta-analysis of Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) was conducted after an exhaustive search of five databases to locate published studies that compared Ag-RDT to RT-PCR and reported quantitative comparison results. After the screening, quality assessment, and data extraction, the synthesis of pooled estimates was carried out utilizing the quality-effects (QE) model and Freeman-Tukey double arcsine transformation (FTT) for variance stabilization. Subgroup analysis was also conducted to evaluate the tests diagnostic agreement across distinctive products and Ct-value thresholds. FindingsA total of 420 studies were screened by title and abstract, of which 39 were eventually included in the analysis. The overall NPA was 99.4% (95%CI 98.8-99.8, I2=91.40%). The PPA was higher in lower Ct groups such as groups with Ct <20 and Ct <25, which had an overall PPA of 95.9% (95%CI 92.7-98.2, I2=0%) and 96.8% (95%CI 95.2-98.0, I2=50.1%) respectively. This is in contrast to groups with higher Ct values, which had relatively lower PPA. Panbio and Roche Ag-RDTs had the best consistent overall PPA across different Ct groups especially in groups with Ct <20 and Ct <25. InterpretationThe findings of our meta-analysis support the use of Ag-RDTs in lieu of RT-PCR for decision making regarding COVID-19 control measures, since the enhanced capacity of RT-PCR to detect disease in those that are Ag-RDT negative will be unlikely to have much public health utility. This step will drastically reduce the cost and time in testing for COVID-19. FundingThis research did not receive any specific funding.
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ObjectivesThis study aims to estimate the prevalence and longevity of detectable SARS-CoV-2 antibodies as well as memory cells T and B after recovery. In addition, the prevalence of COVID-19 reinfection, and the preventive efficacy of previous infection with SARS-CoV-2 were investigated. Methods and analysesA synthesis of existing research was conducted. The Cochrane Library for COVID-19 resources, the China Academic Journals Full Text Database, PubMed, and Scopus as well as preprint servers were searched for studies conducted between 1 January 2020 to 1 April 2021. We included studies with the relevant outcomes of interest. All included studies were assessed for methodological quality and pooled estimates of relevant outcomes were obtained in a meta-analysis using a bias adjusted synthesis method. Proportions were synthesized with the Freeman-Tukey double arcsine transformation and binary outcomes using the odds ratio (OR). Heterogeneity between included studies was assessed using the I2 and Cochrans Q statistics and publication bias was assessed using Doi plots. ResultsFifty-four studies, from 18 countries, with around 12 000 000 individuals, followed up to 8 months after recovery were included. At 6-8 months after recovery, the prevalence of SARS-CoV-2 specific immunological memory remained high; IgG - 90.4% (95%CI 72.2-99.9, I2=89.0%, 5 studies), CD4+ - 91.7% (95%CI 78.2 - 97.1, one study), and memory B cells 80.6% (95%CI 65.0-90.2, one study) and the pooled prevalence of reinfection was 0.2% (95%CI 0.0 - 0.7, I2 = 98.8, 9 studies). Individuals previously infected with SARS-CoV-2 had an 81% reduction in odds of a reinfection (OR 0.19, 95% CI 0.1 - 0.3, I2 = 90.5%, 5 studies). ConclusionAround 90% of people previously infected with SARS-CoV-2 had evidence of immunological memory to SARS-CoV-2, which was sustained for at least 6-8 months after recovery, and had a low risk of reinfection. RegistrationPROSPERO: CRD42020201234 What is already known on this topicIndividuals who recover from COVID-19 may have immunity against future infection but the proportion who develop immunity is uncertain. Further, there is uncertainty about the proportion of individuals who get reinfected with COVID-19. What this study addsUsing data from 54 studies with follow up time up to 8 months after recovery, during the period February 2020-February 2021, we found that, post-COVID-19, up to 90% of individuals had antibodies and memory T and B cells against SARS-CoV-2. We also found a pooled prevalence of reinfection of 0.2%, and that infection conferred an 81% decrease in odds of reinfection with SARS-CoV-2, compared to unimmunized individuals without previous COVID-19. This review of 12 million individuals presents evidence that most individuals who recover from COVID-19 develop immunological memory to SARS-CoV-2, which was still detectable for up to 8 months. Further, reinfection after recovery from COVID-19 was rare during the first 8 months after recovery, with a prevalence below 1%, while prior infection confers protection with an odds ratio of 0.19 and a preventive efficacy of 80% at a baseline prevalence of 5% for COVID-19 in a community. Implications of all the available evidenceIndividuals with a history of COVID-19 infection have immunity against the disease for up to 8 months, although this period could be longer. These individuals could be prioritized last for COVID-19 vaccinations or considered for single dose vaccinations. StrengthsThis comprehensive review addresses key questions on prevalent immunological memory and risk of reinfection in individuals with prior confirmed COVID-19 using robust systematic review methods. LimitationsSome of the included studies which examined prevalent immunological memory were small studies which were affected by loss to follow up. The review did not examine evidence for immunity against the new divergent variants, which may be more likely to have immune evasion behaviour and may present a higher risk of reinfection. Lastly, the review did not examine the effect of the severity of COVID-19 on both immunological memory and the risk of reinfection.
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BackgroundThere is conflicting evidence about the risk of mortality and severe disease due to COVID-19 in people living with HIV (PLHIV). ObjectivesTo compare mortality, hospitalization, and the need for intensive care services due to COVID-19 between PLHIV and individuals without HIV based on data from the existing literature. MethodsA comprehensive search in PubMed, Cochrane Library, Scopus, China Academic Journals Full Text Database, the Database of Abstracts of Reviews of Effectiveness (DARE) and and the medRXIV and bioRxiv databases of preprints was carried out. Each data source was searched from 1 January 2020 to 20th of February 2021. Eligible studies were case control, cross-sectional and cohort studies where participants had confirmed COVID-19. From each study, data on numbers of PLHIV and individuals without HIV for each outcome were extracted. Study quality was assessed using the MethodologicAl STandard for Epidemiological Research (MASTER) scale. Data synthesis used a bias adjusted model and predefined age and geographical subgroups were analysed. ResultsOf a total of 2757 records identified, 11 studies, from 4 countries, the United Kingdom, Spain, the United States of America and South Africa, were included. The total participants assessed for the outcomes in this meta-analysis were 1 268 676 of which 13 886 were PLHIV. Overall, the estimated effect of HIV on mortality suggested some worsening (OR 1.3, 95% CI: 0.9 - 2.0, I2 = 78.6%) with very weak evidence against the model hypothesis at this sample size. However, in individuals aged <60 years, the estimated effect on mortality suggested more worsening in PLHIV (OR 2.7, 95% CI: 1.1 - 6.5, I2 = 95.7%) with strong evidence against the model hypothesis at this sample size. HIV was also associated with an estimated effect on hospitalization for COVID-19 that suggested worsening (OR 1.6, 95% CI: 1.3-2.1, I2 = 96.0%) also with strong evidence against the model hypothesis at this sample size. A secondary analysis of the included studies suggested no difference, by HIV status, in the prevalence of pre-existing conditions. ConclusionPeople living with HIV have higher risk of death and hospitalisation from COVID-19, compared to individuals without HIV. A secondary analysis suggests this is not due to associated comorbid conditions. The difference in mortality is exaggerated in those younger than 60 years of age. RegistrationPROSPERO: CRD42020221311 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=221311) Evidence before this studyFindings from existing studies have shown conflicting evidence concerning the risk of severe COVID-19 and death from COVID-19 in people living with HIV (PLHIV) compared to people without HIV. Evidence from three existing systematic reviews suggests that the risk of severe COVID-19 and death from COVID-19 in PLHIV may be similar to that in individuals without HIV. However, findings from three large cohort studies and one meta-analysis of four studies suggest that the risk of death from COVID-19 in PLHIV may be higher than that in individuals without HIV. One of the large cohort studies, which is also included in the previous meta-analysis, consisted of individuals with unknown COVID-19 status, and therefore there is still debate concerning the risk of severe COVID-19 outcomes in PLHIV. Added value of this studyIn this meta-analysis of 11 studies with 1 268 676 individuals with confirmed COVID-19, we found a stronger difference in mortality by HIV status for those individuals below the age of 60 years, and over this age, HIV had an attenuated effect on mortality, suggesting that age-related mortality overshadows PLHIV related mortality. Further, PLHIV had increased odds of being hospitalized and needing intensive cares services, probably related to increased COVID-19 severity in PLHIV. A secondary analysis of the included studies suggested no difference in the prevalence of pre-existing conditions. Implications of all the available evidenceOur findings suggest that PLHIV are at higher risk than the general population and should be prioritized for vaccine coverage and monitoring if diagnosed with COVID-19. This is especially important for countries in Sub-Saharan Africa that have a high burden of HIV in the younger populations who are more vulnerable. StrengthsThis study was carried out rigorously following the PRISMA guidelines for systematic reviews and meta-analyses. We used a comprehensive search strategy across most of the main citation databases to ensure that no relevant studies were missed. We included studies where participants had confirmed COVID-19 only and we synthesized the findings from studies using a bias adjustment model that took into consideration the quality of included studies. LimitationsAll studies included in this review are observational studies and conclusions about causality require cautious interpretation. Due to a lack of data from included studies, we were not able to analyse the effect of being on treatment for HIV, and HIV control variables such as viral load and CD4 counts on COVID-19 hospitalization, intensive care services and mortality. Lastly most of the included studies had small samples overall or for PLHIV and this may affect the effect estimates in this analysis. Future research is therefore indicated to confirm these findings.