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1.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-321423

ABSTRACT

Studies on serologic responses following COVID-19 have been published primarily in individuals who are moderately or severely symptomatic, but there are few data from individuals who are only mildly symptomatic or asymptomatic. To generate such data, we used World Health Organization disease severity categorization, and measured IgG, IgM, and IgA antibodies to the receptor binding domain (RBD) of spike protein of SARS-CoV-2 by ELISA in infected individuals, both mildly symptomatic (n=108) and asymptomatic (n=63) on days 1, 7, 14, and 30 following RT-PCR-based confirmation of infection in Bangladesh, and compared these results to those detected in pre-pandemic samples, including healthy controls (n=73) and individuals infected with other viruses commonly seen in this area (n = 79). Mildly symptomatic individuals developed IgM and IgA antibody responses by day 14 after detection of infection in 72% and 83% of individuals, respectively, while 95% of these individuals developed an IgG antibody response by day 14, and rose to 100% by day 30. In contrast, individuals infected with SARS-CoV-2 but who remained asymptomatic developed antibody responses significantly less frequently, with only 20% positive for IgA by day 14, 22% positive for IgM by day 14, and 45% positive for IgG by day 30 after detection of infection. These results confirm that immune responses are generated following COVID in individuals who develop mildly symptomatic illness. However, those with asymptomatic infection do not respond or have lower antibody levels. These results will impact modelling needed for determining herd immunity generated by natural infection or vaccination.Funding Statement: World Health Organization, Fogarty International Center TW005572 and Emerging Global Leader Award;K43 TW010362, the Fondation Merieux and the Bill and Melinda Gates Foundation (BMGF). This study was carried out with the support of the United States Agency for International Development (USAID) under the terms of USAID’s Alliance for Combating TB in Bangladesh activity cooperative agreement no. CA # 72038820CA00002.Declaration of Interests: The authors declare no conflict of interest.Ethics Approval Statement: The study was also approved by the IRB of the IEDCR and icddr,b.

3.
Open forum infectious diseases ; 8(Suppl 1):S299-S300, 2021.
Article in English | EuropePMC | ID: covidwho-1564497

ABSTRACT

Background Seroprevalence studies are important tools to estimate the prevalence of prior or recent SARS-CoV-2 infections. This information is critical for 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 to estimate the seroprevalence of SARS-CoV-2 antibodies and risk factors for seropositivity. Methods We invited inhabitants of 2,000 randomly sampled addresses to participate 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. To calculate total and group seroprevalence estimates, inverse probability of response weights were constructed based on age, gender, race/ethnicity and census tract to ensure estimates represented the city’s population. Results We enrolled 280 households including 472 individuals. 328 underwent antibody testing. The citywide weighted seroprevalence of SARS-CoV-2 IgG or IgM was 13.9% (95%CI 7.8 - 21.8) compared to 9.8% based on publicly reported case counts. Seroprevalence was 16.8% (95%CI 5.7 – 28.0) among individuals identifying as Hispanic compared to 8.9% (95%CI 3.0 - 14.7) among those identifying as White. Seroprevalence was 20.7% (95%CI 2.2 – 39.2) for ages 0-19;13.8% (95%CI 5.6 – 22) for ages 20 – 44;9.6% (95%CI 0 – 20.5) for ages 45 – 59;4.8% (95%CI 0 – 10.2) for ages 60 – 84;and 42.9% (95%CI 0 – 100) for ages >85. Table 1. Seroprevalence by antibody positivity profile Table 2. Unweighted and weighted seroprevalence by sociodemographic characteristics Figure 1. Seroprevalence by Medical, Symptom, Testing and Exposure History. Conclusion The measured SARS-CoV-2 seroprevalence in Holyoke was only 13.9% during the second surge of SARS-CoV-2 in this region, far from accepted thresholds for “herd immunity” and highlighting the need for expanding vaccination. Individuals identifying as Hispanic were at high risk of prior infection. Subsequent community-level serosurveys are necessary to guide local responses to the SARS-CoV-2 pandemic. Disclosures All Authors: No reported disclosures

4.
Science ; 371(6529)2021 02 05.
Article in English | MEDLINE | ID: covidwho-1388436

ABSTRACT

Analysis of 772 complete severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from early in the Boston-area epidemic revealed numerous introductions of the virus, a small number of which led to most cases. The data revealed two superspreading events. One, in a skilled nursing facility, led to rapid transmission and significant mortality in this vulnerable population but little broader spread, whereas other introductions into the facility had little effect. The second, at an international business conference, produced sustained community transmission and was exported, resulting in extensive regional, national, and international spread. The two events also differed substantially in the genetic variation they generated, suggesting varying transmission dynamics in superspreading events. Our results show how genomic epidemiology can help to understand the link between individual clusters and wider community spread.


Subject(s)
COVID-19/epidemiology , Genome, Viral , Phylogeny , SARS-CoV-2/genetics , Boston/epidemiology , COVID-19/transmission , Disease Outbreaks , Epidemiological Monitoring , Humans
5.
J Clin Pathol ; 74(8): 496-503, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1247388

ABSTRACT

Developing and deploying new diagnostic tests are difficult, but the need to do so in response to a rapidly emerging pandemic such as COVID-19 is crucially important. During a pandemic, laboratories play a key role in helping healthcare 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, 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 establishing fast and accurate diagnostic testing in crisis conditions.


Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19/diagnosis , Emergency Service, Hospital , Laboratories, Hospital , Real-Time Polymerase Chain Reaction , SARS-CoV-2/genetics , COVID-19/virology , Humans , Predictive Value of Tests , Reproducibility of Results
6.
Emerg Infect Dis ; 27(6): 1598-1606, 2021 06.
Article in English | MEDLINE | ID: covidwho-1236654

ABSTRACT

Relatively few coronavirus disease cases and deaths have been reported from sub-Saharan Africa, although the extent of its spread remains unclear. During August 10-September 11, 2020, we recruited 2,214 participants for a representative household-based cross-sectional serosurvey in Juba, South Sudan. We found 22.3% of participants had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor binding domain IgG titers above prepandemic levels. After accounting for waning antibody levels, age, and sex, we estimated that 38.3% (95% credible interval 31.8%-46.5%) of the population had been infected with SARS-CoV-2. At this rate, for each PCR-confirmed SARS-CoV-2 infection reported by the Ministry of Health, 103 (95% credible interval 86-126) infections would have been unreported, meaning SARS-CoV-2 has likely spread extensively within Juba. We also found differences in background reactivity in Juba compared with Boston, Massachusetts, USA, where the immunoassay was validated. Our findings underscore the need to validate serologic tests in sub-Saharan Africa populations.


Subject(s)
COVID-19 , SARS-CoV-2 , Africa South of the Sahara , Antibodies, Viral , Boston , Cross-Sectional Studies , Humans , Immunoglobulin G , Massachusetts , Seroepidemiologic Studies , South Sudan
7.
medRxiv ; 2020 Jul 20.
Article in English | MEDLINE | ID: covidwho-915962

ABSTRACT

BACKGROUND: Characterizing the humoral immune response to SARS-CoV-2 and developing accurate serologic assays are needed for diagnostic purposes and estimating population-level seroprevalence. METHODS: We 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. RESULTS: Between 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. CONCLUSIONS: Among 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.

8.
Sci Immunol ; 5(52)2020 10 08.
Article in English | MEDLINE | ID: covidwho-842518

ABSTRACT

We measured plasma and/or serum antibody responses to the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2 in 343 North American patients infected with SARS-CoV-2 (of which 93% required hospitalization) up to 122 days after symptom onset and compared them to responses in 1548 individuals whose blood samples were obtained prior to the pandemic. After setting seropositivity thresholds for perfect specificity (100%), we estimated sensitivities of 95% for IgG, 90% for IgA, and 81% for IgM for detecting infected individuals between 15 and 28 days after symptom onset. While the median time to seroconversion was nearly 12 days across all three isotypes tested, IgA and IgM antibodies against RBD were short-lived with median times to seroreversion of 71 and 49 days after symptom onset. In contrast, anti-RBD IgG responses decayed slowly through 90 days with only 3 seropositive individuals seroreverting within this time period. IgG antibodies to SARS-CoV-2 RBD were strongly correlated with anti-S neutralizing antibody titers, which demonstrated little to no decrease over 75 days since symptom onset. We observed no cross-reactivity of the SARS-CoV-2 RBD-targeted antibodies with other widely circulating coronaviruses (HKU1, 229 E, OC43, NL63). These data suggest that RBD-targeted antibodies are excellent markers of previous and recent infection, that differential isotype measurements can help distinguish between recent and older infections, and that IgG responses persist over the first few months after infection and are highly correlated with neutralizing antibodies.


Subject(s)
Antibodies, Viral/immunology , Betacoronavirus/immunology , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Protein Domains/immunology , Spike Glycoprotein, Coronavirus/immunology , Adult , Aged , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Betacoronavirus/genetics , Biomarkers/blood , COVID-19 , Cohort Studies , Coronavirus Infections/virology , Cross Reactions , Dried Blood Spot Testing , Female , Humans , Immunoglobulin A/blood , Immunoglobulin A/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Male , Middle Aged , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/chemistry
9.
Int J Infect Dis ; 101: 220-225, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-813629

ABSTRACT

OBJECTIVES: Studies on serological responses following coronavirus disease-2019 (COVID-19) have been published primarily in individuals who are moderately or severely symptomatic, but there are few data from individuals who are mildly symptomatic or asymptomatic. METHODS: We measured IgG, IgM, and IgA to the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by using enzyme-linked immunosorbent assay in mildly symptomatic (n = 108) and asymptomatic (n = 63) on days 1, 7, 14, and 30 following RT-PCR confirmation in Bangladesh and when compared with pre-pandemic samples, including healthy controls (n = 73) and individuals infected with other viruses (n = 79). RESULTS: Mildly symptomatic individuals developed IgM and IgA responses by day 14 in 72% and 83% of individuals, respectively, while 95% of individuals developed IgG response, and rose to 100% by day 30. In contrast, individuals infected with SARS-CoV-2 but who remained asymptomatic developed antibody responses significantly less frequently, with only 20% positive for IgA and 22% positive for IgM by day 14, and 45% positive for IgG by day 30 after infection. CONCLUSIONS: These results confirm immune responses are generated following COVID-19 who develop mildly symptomatic illness. However, those with asymptomatic infection do not respond or have lower antibody levels. These results will impact modeling needed for determining herd immunity generated by natural infection or vaccination.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , Carrier State/immunology , SARS-CoV-2/immunology , Adult , Antibodies, Viral/blood , Antibody Formation , Bangladesh/epidemiology , COVID-19/blood , COVID-19/epidemiology , COVID-19/virology , Carrier State/blood , Carrier State/epidemiology , Carrier State/virology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Male , Middle Aged , Pandemics , SARS-CoV-2/genetics
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