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BackgroundSeroprevalence studies are important tools to estimate the prevalence of prior or recent SARS-CoV-2 infections, identifying hotspots and high-risk groups and informing public health responses to the COVID-19 pandemic. We conducted a city-level seroprevalence study in Holyoke, Massachusetts, USA to estimate the seroprevalence of SARS-CoV-2 antibodies and risk factors for seropositivity. MethodsWe invited inhabitants of 2,000 randomly sampled addresses between November 5 and December 31, 2020. Participants completed questionnaires measuring sociodemographic and health characteristics, and COVID-19 exposure history, and provided dried blood spots for measurement of SARS-CoV-2 IgG and IgM antibodies. We calculate total and subgroup seroprevalence estimates based on presence of IgG antibodies using a Bayesian procedure that incorporates uncertainty in antibody test sensitivity and specificity. We account for clustering by household and weighting based on demographic characteristics to ensure estimates represented the citys population. FindingsWe enrolled 280 households including 472 individuals. 328 underwent antibody testing. The citywide seroprevalence estimate of SARS-CoV-2 IgG was 13.1% (95%CI 6.9-22.3) compared to 9.8% based on publicly reported case counts. Seroprevalence was 16.1% (95%CI 6.2-31.8) among individuals identifying as Hispanic compared to 9.4% (95%CI 4.6-16.4) among those identifying as non-Hispanic white. Seroprevalence was higher among Spanish speaking households (21.9%; 95% CI 8.3-43.9) compared to English speaking households (10.2%; 95% CI 5.2-18.0) and among individuals living in high vulnerability areas (14.4%; 95% CI 7.1-25.5) compared to low vulnerability areas (8.2%; 95% CI 3.1-16.9). InterpretationThe measured SARS-CoV-2 seroprevalence of IgG antibodies in Holyoke was only 13.1% during the second surge of SARS-CoV-2 in this region, far from accepted thresholds for "herd immunity." Already vulnerable communities were at highest risk of prior infection. Implementation of local serosurveys in tandem with proactive public health interventions that address disparities in SARS-CoV-2 exposure are crucial to ensure at-risk communities have appropriate educational materials and access to vaccines, testing, and timely treatment. FundingThe Sullivan Family Foundation, Harvard Data Science Institute Bias2 program, the US Centers for Disease Control and Prevention.
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Early detection of SARS-CoV-2 infection is crucial to prevent the spread of the virus. In this study, we evaluated the performance of a commercial rapid antigen detection test, BD Veritor, and compared this (and another rapid test, Standard Q) against a gold-standard of nasopharyngeal (NP) swab tested by reverse transcription-polymerase chain reaction (RT-PCR) in prospectively-recruited adults in Dhaka, Bangladesh. We compared the sensitivity and specificity of the two rapid antigen tests against RT-PCR results in 130 symptomatic and 130 asymptomatic adults. In addition, we evaluated the suitability and ease-of-use of the BD Veritor test in a subsample of study participants (n=42) and implementers (n=5). The sensitivity of the BD Veritor rapid antigen test was 70% in symptomatic (95% confidence interval [CI]: 51-85%) and 87% (95% CI: 69-96%) in asymptomatic individuals with positive SARSCoV-2 RT-PCR, for overall sensitivity of 78% (95% CI: 66-88%). The sensitivity of the Standard Q rapid antigen test was 63% (95% CI: 44-80%) in symptomatic and 73% (95% CI: 54-87%) in asymptomatic individuals. One false positive in BD Veritor test (specificity 99.5) and no false positive in Standard Q tests were observed (specificity 100%). The BD Veritor rapid antigen test was 78% sensitive when compared with RT-PCR irrespective of the cycle threshold (Ct) levels in this evaluation in Bangladesh. The implementation evaluation data showed good acceptability in the field settings. This warrants large field evaluation as well as use of the rapid antigen test for quick assessment of SARS-CoV-2 for containment of epidemics in the country.
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BackgroundRelatively few COVID-19 cases and deaths have been reported through much of sub-Saharan Africa, including South Sudan, although the extent of SARS-CoV-2 spread remains unclear due to weak surveillance systems and few population-representative serosurveys. MethodsWe conducted a representative household-based cross-sectional serosurvey in Juba, South Sudan. We quantified IgG antibody responses to SARS-CoV-2 spike protein receptor-binding domain and estimated seroprevalence using a Bayesian regression model accounting for test performance. ResultsWe recruited 2,214 participants from August 10 to September 11, 2020 and 22.3% had anti-SARS-CoV-2 IgG titers above levels in pre-pandemic samples. After accounting for waning antibody levels, age, and sex, we estimated that 38.5% (32.1 - 46.8) of the population had been infected with SARS-CoV-2. For each RT-PCR confirmed COVID-19 case, 104 (87-126) infections were unreported. Background antibody reactivity was higher in pre-pandemic samples from Juba compared to Boston, where the serological test was validated. The estimated proportion of the population infected ranged from 30.1% to 60.6% depending on assumptions about test performance and prevalence of clinically severe infections. ConclusionsSARS-CoV-2 has spread extensively within Juba. Validation of serological tests in sub-Saharan African populations is critical to improve our ability to use serosurveillance to understand and mitigate transmission.
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Developing and deploying new diagnostic tests is difficult, but the need to do so in response to a rapidly emerging pandemic such as COVID-19 is crucially important for an effective response. In the early stages of a pandemic, laboratories play a key role in helping health care providers and public health authorities detect active infection, a task most commonly achieved using nucleic acid-based assays. While the landscape of diagnostics is rapidly evolving, polymerase chain reaction (PCR) remains the gold-standard of nucleic acid-based diagnostic assays, in part due to its reliability, flexibility, and wide deployment. To address a critical local shortage of testing capacity persisting during the COVID-19 outbreak, our hospital set up a molecular based laboratory developed test (LDT) to accurately and safely diagnose SARS-CoV-2. We describe here the process of developing an emergency-use LDT, in the hope that our experience will be useful to other laboratories in future outbreaks and will help to lower barriers to fast and accurate diagnostic testing in crisis conditions.
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SARS-CoV-2 has caused a severe, ongoing outbreak of COVID-19 in Massachusetts with 111,070 confirmed cases and 8,433 deaths as of August 1, 2020. To investigate the introduction, spread, and epidemiology of COVID-19 in the Boston area, we sequenced and analyzed 772 complete SARS-CoV-2 genomes from the region, including nearly all confirmed cases within the first week of the epidemic and hundreds of cases from major outbreaks at a conference, a nursing facility, and among homeless shelter guests and staff. The data reveal over 80 introductions into the Boston area, predominantly from elsewhere in the United States and Europe. We studied two superspreading events covered by the data, events that led to very different outcomes because of the timing and populations involved. One produced rapid spread in a vulnerable population but little onward transmission, while the other was a major contributor to sustained community transmission, including outbreaks in homeless populations, and was exported to several other domestic and international sites. The same two events differed significantly in the number of new mutations seen, raising the possibility that SARS-CoV-2 superspreading might encompass disparate transmission dynamics. Our results highlight the failure of measures to prevent importation into MA early in the outbreak, underscore the role of superspreading in amplifying an outbreak in a major urban area, and lay a foundation for contact tracing informed by genetic data.
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BACKGROUNDCharacterizing the humoral immune response to SARS-CoV-2 and developing accurate serologic assays are needed for diagnostic purposes and estimating population-level seroprevalence. METHODSWe measured the kinetics of early antibody responses to the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2 in a cohort of 259 symptomatic North American patients infected with SARS-CoV-2 (up to 75 days after symptom onset) compared to antibody levels in 1548 individuals whose blood samples were obtained prior to the pandemic. RESULTSBetween 14-28 days from onset of symptoms, IgG, IgA, or IgM antibody responses to RBD were all accurate in identifying recently infected individuals, with 100% specificity and a sensitivity of 97%, 91%, and 81% respectively. Although the estimated median time to becoming seropositive was similar across isotypes, IgA and IgM antibodies against RBD were short-lived with most individuals estimated to become seronegative again by 51 and 47 days after symptom onset, respectively. IgG antibodies against RBD lasted longer and persisted through 75 days post-symptoms. IgG antibodies to SARS-CoV-2 RBD were highly correlated with neutralizing antibodies targeting the S protein. No cross-reactivity of the SARS-CoV-2 RBD-targeted antibodies was observed with several known circulating coronaviruses, HKU1, OC 229 E, OC43, and NL63. CONCLUSIONSAmong symptomatic SARS-CoV-2 cases, RBD-targeted antibodies can be indicative of previous and recent infection. IgG antibodies are correlated with neutralizing antibodies and are possibly a correlate of protective immunity.
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IntroductionThe diagnosis of COVID-19 requires integration of clinical and laboratory data. SARS-CoV-2 diagnostic assays play a central role in diagnosis and have fixed technical performance metrics. Interpretation becomes challenging because the clinical sensitivity changes as the virus clears and the immune response emerges. Our goal was to examine the clinical sensitivity of two most common SARS-CoV-2 diagnostic test modalities, polymerase chain reaction (PCR) and serology, over the disease course to provide insight into their clinical interpretation in patients presenting to the hospital. MethodsA single-center, retrospective study. To derive clinical sensitivity of PCR, we identified 209 PCR-positive SARS-CoV-2 patients with multiple PCR test results (624 total PCR tests) and calculated daily sensitivity from date of symptom onset or first positive test. To calculate daily clinical sensitivity by serology, we utilized 157 PCR- positive patients with a total of 197 specimens tested by enzyme-linked immunosorbent assay for IgM, IgG, and IgA anti-SARS-CoV-2 antibodies. ResultsClinical sensitivity of PCR decreased with days post symptom onset with >90% clinical sensitivity during the first 5 days after symptom onset, 70-71% from days 9-11, and 30% at day 21. In contrast, serological sensitivity increased with days post symptom onset with >50% of patients seropositive by at least one antibody isotype after day 7, >80% after day 12, and 100% by day 21. ConclusionPCR and serology are complimentary modalities that require time- dependent interpretation. Superimposition of sensitivities over time indicate that serology can function as a reliable diagnostic aid indicating recent or prior infection.
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Graft-versus-host disease (GVHD) is a serious complication of allogeneic hematopoietic cell transplantation (HCT) and this occurs as donor T lymphocytes, activated by recipient antigen presenting cells (APC), attack the host tissues or organs. This APC activation is a crucial initial step of influencing the outcome of GVHD and is mediated by innate immune signaling. Toll-like receptors (TLRs) and nucleotide binding oligomerization domain (NOD)-like receptors (NLRs) are important components of innate immunity; both families of receptors are known for sensing various microbial ligands or danger signals. Signaling through TLRs/NLRs regulate activities of APCs, through phagocytosis, cytokine and chemokine release, delivery of APCs from peripheral tissues to draining lymph nodes, and antigen presentation. Several TLRs/NLRs have been identified and their ligands and signaling pathways have been described. Recent findings suggest a significant association of TLR/NLR polymorphisms with the increased risk for severe GVHD. Therefore, these TLR/NLR pathways likely contributing to immune response for GVHD may serve as novel therapeutic targets to facilitate allograft tolerance. This review summarizes the role of TLRs/NLRs innate immune receptors and signaling in GVHD pathophysiology.
