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1.
IJID Regions ; 2022.
Article in English | ScienceDirect | ID: covidwho-1814553

ABSTRACT

Objectives : SARS-CoV-2 specific antibody responses after Covishield vaccination has been evaluated until 6 months after vaccination. Design : We assessed SARS-CoV-2 specific antibody responses by ELISA to recombinant receptor-binding domain of SARS-CoV-2 in 381 adults given the Covishield vaccine at baseline (n=119), 1 month (n=126) and 2 months (n=75) after the 1st dose, 1 month after the 2nd dose (n=161) and monthly for 3 additional months. Results : Over 51% of the vaccinees were seropositive at baseline before vaccination with Covishield and almost all participants (159/161) became seropositive 1 month after 2nd dose. The levels of antibodies peaked at 1 month after receipt of the second dose and then subsequently decreased by 4 months after the first dose;the lowest responses were found at 6 months after first vaccine dose, although significantly higher antibody responses and responder frequencies remained (P<0.0001) compared to baseline. Compared to younger participants, older participants had lower levels (P<0.05) of antibody responses 6 months after first vaccination. Participants who had previous infection with SARS-CoV-2 showed a robust higher antibody response after vaccination. Conclusions : These findings help elucidate longevity of vaccine-specific antibody responses following Covishield and provide information relevant to planning boosting after initial two dose vaccination.

2.
Microbiol Spectr ; : e0021122, 2022 Mar 21.
Article in English | MEDLINE | ID: covidwho-1752769

ABSTRACT

The use of anti-spike (S) serologic assays as surrogate measurements of SARS-CoV-2 vaccine induced immunity will be an important clinical and epidemiological tool. The characteristics of a commercially available anti-S antibody assay (Roche Elecsys anti-SARS-CoV-2 S) were evaluated in a cohort of vaccine recipients. Levels were correlated with pseudotype neutralizing antibodies (NAb) across SARS-CoV-2 variants. We recruited adults receiving a two-dose series of mRNA-1273 or BNT162b2 and collected serum at scheduled intervals up to 8 months post-first vaccination. Anti-S and NAb levels were measured, and correlation was evaluated by (i) vaccine type and (ii) SARS-CoV-2 variant (wild-type, Alpha, Beta, Gamma, and three constructs Day 146*, Day 152*, and RBM-2). Forty-six mRNA vaccine recipients were enrolled. mRNA-1273 vaccine recipients had higher peak anti-S and NAb levels compared with BNT162b2 (P < 0.001 for anti-S levels; P < 0.05 for NAb levels). When anti-S and NAb levels were compared, there was good correlation (all r values ≥ 0.85) in both BNT162b2 and mRNA-1273 vaccine recipients across all evaluated variants; however, these correlations were nonlinear in nature. Lower correlation was identified between anti-S and NAb for the Beta variant (r = 0.88) compared with the wild-type (WT) strain (r = 0.94). Finally, the degree of neutralizing activity at any given anti-S level was lower for each variant compared with that of the WT strain, (P < 0.001). Although the Roche anti-S assay correlates well with NAb levels, this association is affected by vaccine type and SARS-CoV-2 variant. These variables must be considered when interpreting anti-S levels. IMPORTANCE We evaluated anti-spike antibody concentrations in healthy mRNA vaccinated individuals and compared these concentrations to values obtained from pseudotype neutralization assays targeting SARS-CoV-2 variants of concern to determine how well anti-spike antibodies correlate with neutralizing titers, which have been used as a marker of immunity from COVID-19 infection. We found high peak anti-spike concentrations in these individuals, with significantly higher levels seen in mRNA-1273 vaccine recipients. When we compared anti-spike and pseudotype neuralization titers, we identified good correlation; however, this correlation was affected by both vaccine type and variant, illustrating the difficulty of applying a "one size fits all" approach to anti-spike result interpretation. Our results support CDC recommendations to discourage anti-spike antibody testing to assess for immunity after vaccination and cautions providers in their interpretations of these results as a surrogate of protection in COVID-vaccinated individuals.

3.
IJID Regions ; 2022.
Article in English | ScienceDirect | ID: covidwho-1665003

ABSTRACT

Design A cross-sectional study was conducted in household members in 32 districts of Bangladesh to build knowledge on disease epidemiology and seroepidemiology of COVID-19. Objective We assessed antibody responses to SARS-CoV-2 in people between April-October, 2020. Results Nationally, we estimated a seroprevalence of 30.4% for IgG and 39.7% for IgM. In Dhaka city, seroprevalence for IgG was 35.4% in non-slum areas, while it was 63.5% in slums. In areas outside of Dhaka, the seroprevalence rate for IgG was 37.5 and 28.7%, respectively, in urban and rural areas. Between April and October, 2020, the highest seroprevalence rate (57% for IgG and 64% for IgM) was observed in August. IgM antibody was more prevalent in the younger age participants, while older participants had more frequent IgG seropositivity. Follow-up specimens from COVID-19 patients and their household members suggested that both IgG and IgM seropositivity increased significantly at day 14 and 28 compared to day 1 of enrollment. Conclusions Our findings indicate that there has been an extensive spread of SARS-CoV-2 infection in Bangladesh by October 2020. This highlights the importance of monitoring seroprevalence data, particularly with the emergence of new SARS-CoV-2 variants over time.

4.
Science ; 375(6578): eabl6251, 2022 01 21.
Article in English | MEDLINE | ID: covidwho-1650842

ABSTRACT

Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they have become dominant strains. Here, we evaluate the consequences of further viral evolution. We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. We identify an antibody that binds the RBD core to neutralize pseudotypes for all tested variants but show that the RBD can acquire an N-linked glycan to escape neutralization. Our findings portend continued emergence of escape variants as SARS-CoV-2 adapts to humans.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Immune Evasion , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/metabolism , Betacoronavirus/immunology , COVID-19/immunology , COVID-19/virology , Cross Reactions , Cryoelectron Microscopy , Crystallography, X-Ray , Epitopes , Evolution, Molecular , Humans , Models, Molecular , Mutation , Polysaccharides/analysis , Protein Binding , Protein Domains , Receptors, Coronavirus/chemistry , Receptors, Coronavirus/metabolism , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
5.
PLoS Negl Trop Dis ; 16(1): e0010102, 2022 01.
Article in English | MEDLINE | ID: covidwho-1603353

ABSTRACT

BACKGROUND: COVID-19 caused by SARS-CoV-2 ranges from asymptomatic to severe disease and can cause fatal and devastating outcome in many cases. In this study, we have compared the clinical, biochemical and immunological parameters across the different disease spectrum of COVID-19 in Bangladeshi patients. METHODOLOGY/PRINCIPAL FINDINGS: This longitudinal study was conducted in two COVID-19 hospitals and also around the community in Dhaka city in Bangladesh between November 2020 to March 2021. A total of 100 patients with COVID-19 infection were enrolled and classified into asymptomatic, mild, moderate and severe cases (n = 25/group). In addition, thirty age and sex matched healthy participants were enrolled and 21 were analyzed as controls based on exclusion criteria. After enrollment (study day1), follow-up visits were conducted on day 7, 14 and 28 for the cases. Older age, male gender and co-morbid conditions were the risk factors for severe COVID-19 disease. Those with moderate and severe cases of infection had low lymphocyte counts, high neutrophil counts along with a higher neutrophil-lymphocyte ratio (NLR) at enrollment; this decreased to normal range within 42 days after the onset of symptom. At enrollment, D-dimer, CRP and ferritin levels were elevated among moderate and severe cases. The mild, moderate, and severe cases were seropositive for IgG antibody by day 14 after enrollment. Moderate and severe cases showed significantly higher IgM and IgG levels of antibodies to SARS-CoV-2 compared to mild and asymptomatic cases. CONCLUSION/SIGNIFICANCE: We report on the clinical, biochemical, and hematological parameters associated with the different severity of COVID-19 infection. We also show different profile of antibody response against SARS-CoV-2 in relation to disease severity, especially in those with moderate and severe disease manifestations compared to the mild and asymptomatic infection.


Subject(s)
Antibodies, Viral/immunology , COVID-19/diagnosis , COVID-19/immunology , Severity of Illness Index , Adult , Antibody Formation , Bangladesh , COVID-19 Testing , Cohort Studies , Female , Fibrin Fibrinogen Degradation Products , Humans , Immunoglobulin G , Longitudinal Studies , Lymphocytes , Male , Middle Aged , Neutrophils , Risk Factors , SARS-CoV-2 , Viral Load
6.
Clin Infect Dis ; 73(12): 2248-2256, 2021 12 16.
Article in English | MEDLINE | ID: covidwho-1592977

ABSTRACT

BACKGROUND: Isolation of hospitalized persons under investigation (PUIs) for coronavirus disease 2019 (COVID-19) reduces nosocomial transmission risk. Efficient evaluation of PUIs is needed to preserve scarce healthcare resources. We describe the development, implementation, and outcomes of an inpatient diagnostic algorithm and clinical decision support system (CDSS) to evaluate PUIs. METHODS: We conducted a pre-post study of CORAL (COvid Risk cALculator), a CDSS that guides frontline clinicians through a risk-stratified COVID-19 diagnostic workup, removes transmission-based precautions when workup is complete and negative, and triages complex cases to infectious diseases (ID) physician review. Before CORAL, ID physicians reviewed all PUI records to guide workup and precautions. After CORAL, frontline clinicians evaluated PUIs directly using CORAL. We compared pre- and post-CORAL frequency of repeated severe acute respiratory syndrome coronavirus 2 nucleic acid amplification tests (NAATs), time from NAAT result to PUI status discontinuation, total duration of PUI status, and ID physician work hours, using linear and logistic regression, adjusted for COVID-19 incidence. RESULTS: Fewer PUIs underwent repeated testing after an initial negative NAAT after CORAL than before CORAL (54% vs 67%, respectively; adjusted odd ratio, 0.53 [95% confidence interval, .44-.63]; P < .01). CORAL significantly reduced average time to PUI status discontinuation (adjusted difference [standard error], -7.4 [0.8] hours per patient), total duration of PUI status (-19.5 [1.9] hours per patient), and average ID physician work-hours (-57.4 [2.0] hours per day) (all P < .01). No patients had a positive NAAT result within 7 days after discontinuation of precautions via CORAL. CONCLUSIONS: CORAL is an efficient and effective CDSS to guide frontline clinicians through the diagnostic evaluation of PUIs and safe discontinuation of precautions.


Subject(s)
Anthozoa , COVID-19 , Animals , Humans , Nucleic Acid Amplification Techniques , Odds Ratio , SARS-CoV-2
8.
Open forum infectious diseases ; 8(Suppl 1):S467-S467, 2021.
Article in English | EuropePMC | ID: covidwho-1564394

ABSTRACT

Background In January–March 2020, the Centers for Disease Control and Prevention (CDC) issued multiple warnings regarding COVID-19 travel-associated risks. We sought to describe US travelers seeking pretravel consultation regarding international travel at US Global TravEpiNet (GTEN) sites before and after the initial COVID-19 travel warnings. Methods We prospectively collected data at 22 GTEN sites pre-COVID-19 (January–December 2019) and 18 GTEN sites during the COVID-19 pandemic (April 2020–March 2021). We excluded travelers evaluated during January–March 2020, when CDC travel guidance was evolving rapidly. Travelers used standardized questionnaires to self-report data regarding demographics and travel-related characteristics. Providers confirmed these data and documented their recommendations during pretravel consultation, which could be performed virtually. We conducted descriptive analyses of differences in demographics, travel-related characteristics, vaccinations, and medications (SAS v9.4;Cary, NC). Results Compared with 16,903 pre-COVID-19 consultations, only 1,564 consultations occurred during the COVID-19 pandemic, a 90% reduction (Table). During COVID-19, a greater proportion of travelers were children aged 1–5 years, visiting friends and relatives (VFR), with itineraries ≥ 30 days, and going to Africa;a smaller proportion of travelers were aged > 55 years, or traveling to Southeast Asia or the Western Pacific. During COVID-19, fewer vaccine-eligible travelers received vaccines at the pretravel consultation except for yellow fever, and a greater proportion were referred to another provider for vaccination (Figure). Table. Demographics and travel-related characteristics of international travelers seeking pretravel consultation at Global TravEpiNet sites before and during the COVID-19 pandemic Table continued. Demographics and travel-related characteristics of international travelers seeking pretravel consultation at Global TravEpiNet sites before and during the COVID-19 pandemic Figure. Vaccinations and reasons for nonvaccination among vaccine-eligible international travelers at pretravel consultations at Global TravEpiNet (GTEN) sites before and during the COVID-19 pandemic. Among vaccine-eligible travelers, we summarized those who were vaccinated at the visit (blue) and not vaccinated (orange). We then categorized reasons for nonvaccination into: provider decision (solid), referral to another provider (dots), traveler refusal (striped), or other (hatched). COVID-19 vaccination was not available at GTEN sites during the analysis period;although COVID-19 vaccinations outside of GTEN sites might have affected vaccination recommendations, they were unlikely to have had a large effect given their limited availability in January-March 2021. Conclusion Compared with pre-COVID-19, US travelers seeking pretravel consultations at GTEN sites during the pandemic might be at higher risk for travel-related infections given VFR status, traveling for ≥ 30 days, and going to Africa. Fewer vaccine-eligible travelers were vaccinated at pretravel consultations, which could reflect more virtual pretravel consultations. Counseling and vaccination for international travelers continue to be priorities during the COVID-19 pandemic. Disclosures All Authors: No reported disclosures

9.
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
10.
Cell Host Microbe ; 29(9): 1437-1453.e8, 2021 09 08.
Article in English | MEDLINE | ID: covidwho-1347535

ABSTRACT

The SARS-CoV-2 pandemic has affected more than 185 million people worldwide resulting in over 4 million deaths. To contain the pandemic, there is a continued need for safe vaccines that provide durable protection at low and scalable doses and can be deployed easily. Here, AAVCOVID-1, an adeno-associated viral (AAV), spike-gene-based vaccine candidate demonstrates potent immunogenicity in mouse and non-human primates following a single injection and confers complete protection from SARS-CoV-2 challenge in macaques. Peak neutralizing antibody titers are sustained at 1 year and complemented by functional memory T cell responses. The AAVCOVID vector has no relevant pre-existing immunity in humans and does not elicit cross-reactivity to common AAVs used in gene therapy. Vector genome persistence and expression wanes following injection. The single low-dose requirement, high-yield manufacturability, and 1-month stability for storage at room temperature may make this technology well suited to support effective immunization campaigns for emerging pathogens on a global scale.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 Vaccines/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/genetics , Dependovirus/genetics , Dependovirus/metabolism , Female , Humans , Immunogenicity, Vaccine/immunology , Immunologic Memory/immunology , Macaca fascicularis , Macaca mulatta , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , T-Lymphocytes/immunology , Transgenes/genetics , Vaccination/methods , Viral Load/immunology
11.
Nat Med ; 27(3): 454-462, 2021 03.
Article in English | MEDLINE | ID: covidwho-1319036

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to spread relentlessly, associated with a high frequency of respiratory failure and mortality. Children experience largely asymptomatic disease, with rare reports of multisystem inflammatory syndrome in children (MIS-C). Identifying immune mechanisms that result in these disparate clinical phenotypes in children could provide critical insights into coronavirus disease 2019 (COVID-19) pathogenesis. Using systems serology, in this study we observed in 25 children with acute mild COVID-19 a functional phagocyte and complement-activating IgG response to SARS-CoV-2, similar to the acute responses generated in adults with mild disease. Conversely, IgA and neutrophil responses were significantly expanded in adults with severe disease. Moreover, weeks after the resolution of SARS-CoV-2 infection, children who develop MIS-C maintained highly inflammatory monocyte-activating SARS-CoV-2 IgG antibodies, distinguishable from acute disease in children but with antibody levels similar to those in convalescent adults. Collectively, these data provide unique insights into the potential mechanisms of IgG and IgA that might underlie differential disease severity as well as unexpected complications in children infected with SARS-CoV-2.


Subject(s)
Antibodies, Viral/blood , COVID-19/epidemiology , SARS-CoV-2/immunology , Adolescent , Adult , Age of Onset , Aged , Antibodies, Neutralizing/analysis , Antibodies, Neutralizing/blood , Antibodies, Viral/analysis , Asymptomatic Infections , COVID-19/blood , COVID-19/pathology , Carrier State/blood , Carrier State/epidemiology , Child , Child, Preschool , Cohort Studies , Female , Humans , Immunity/physiology , Immunoglobulin A/blood , Immunoglobulin G/blood , Infant , Infant, Newborn , Male , Middle Aged , Pandemics , Severity of Illness Index , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/epidemiology , Young Adult
12.
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
13.
Clin Infect Dis ; 73(12): 2248-2256, 2021 12 16.
Article in English | MEDLINE | ID: covidwho-1075482

ABSTRACT

BACKGROUND: Isolation of hospitalized persons under investigation (PUIs) for coronavirus disease 2019 (COVID-19) reduces nosocomial transmission risk. Efficient evaluation of PUIs is needed to preserve scarce healthcare resources. We describe the development, implementation, and outcomes of an inpatient diagnostic algorithm and clinical decision support system (CDSS) to evaluate PUIs. METHODS: We conducted a pre-post study of CORAL (COvid Risk cALculator), a CDSS that guides frontline clinicians through a risk-stratified COVID-19 diagnostic workup, removes transmission-based precautions when workup is complete and negative, and triages complex cases to infectious diseases (ID) physician review. Before CORAL, ID physicians reviewed all PUI records to guide workup and precautions. After CORAL, frontline clinicians evaluated PUIs directly using CORAL. We compared pre- and post-CORAL frequency of repeated severe acute respiratory syndrome coronavirus 2 nucleic acid amplification tests (NAATs), time from NAAT result to PUI status discontinuation, total duration of PUI status, and ID physician work hours, using linear and logistic regression, adjusted for COVID-19 incidence. RESULTS: Fewer PUIs underwent repeated testing after an initial negative NAAT after CORAL than before CORAL (54% vs 67%, respectively; adjusted odd ratio, 0.53 [95% confidence interval, .44-.63]; P < .01). CORAL significantly reduced average time to PUI status discontinuation (adjusted difference [standard error], -7.4 [0.8] hours per patient), total duration of PUI status (-19.5 [1.9] hours per patient), and average ID physician work-hours (-57.4 [2.0] hours per day) (all P < .01). No patients had a positive NAAT result within 7 days after discontinuation of precautions via CORAL. CONCLUSIONS: CORAL is an efficient and effective CDSS to guide frontline clinicians through the diagnostic evaluation of PUIs and safe discontinuation of precautions.


Subject(s)
Anthozoa , COVID-19 , Animals , Humans , Nucleic Acid Amplification Techniques , Odds Ratio , SARS-CoV-2
16.
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.

17.
medRxiv ; 2020 May 02.
Article in English | MEDLINE | ID: covidwho-900732

ABSTRACT

The COVID-19 pandemic continues to infect millions of people worldwide. In order to curb its spread and reduce morbidity and mortality, it is essential to develop sensitive and quantitative methods that identify infected individuals and enable accurate population-wide screening of both past and present infection. Here we show that Single Molecule Array assays detect seroconversion in COVID-19 patients as soon as one day after symptom onset using less than a microliter of blood. This multiplexed assay format allows us to quantitate IgG, IgM and IgA immunoglobulins against four SARS-CoV-2 targets, thereby interrogating 12 antibody isotype-viral protein interactions to give a high resolution profile of the immune response. Using a cohort of samples collected prior to the outbreak as well as samples collected during the pandemic, we demonstrate a sensitivity of 86% and a specificity of 100% during the first week of infection, and 100% sensitivity and specificity thereafter. This assay should become the gold standard for COVID19 serological profiling and will be a valuable tool for answering important questions about the heterogeneity of clinical presentation seen in the ongoing pandemic.

18.
Cell ; 183(6): 1508-1519.e12, 2020 12 10.
Article in English | MEDLINE | ID: covidwho-898562

ABSTRACT

The urgent need for an effective SARS-CoV-2 vaccine has forced development to progress in the absence of well-defined correlates of immunity. While neutralization has been linked to protection against other pathogens, whether neutralization alone will be sufficient to drive protection against SARS-CoV-2 in the broader population remains unclear. Therefore, to fully define protective humoral immunity, we dissected the early evolution of the humoral response in 193 hospitalized individuals ranging from moderate to severe. Although robust IgM and IgA responses evolved in both survivors and non-survivors with severe disease, non-survivors showed attenuated IgG responses, accompanied by compromised Fcɣ receptor binding and Fc effector activity, pointing to deficient humoral development rather than disease-enhancing humoral immunity. In contrast, individuals with moderate disease exhibited delayed responses that ultimately matured. These data highlight distinct humoral trajectories associated with resolution of SARS-CoV-2 infection and the need for early functional humoral immunity.


Subject(s)
COVID-19 , Immunity, Humoral , Immunoglobulin A/immunology , Immunoglobulin M/immunology , Receptors, IgG/immunology , SARS-CoV-2/immunology , COVID-19/immunology , COVID-19/mortality , Female , HL-60 Cells , Humans , Male
19.
Nat Commun ; 11(1): 5493, 2020 10 30.
Article in English | MEDLINE | ID: covidwho-894389

ABSTRACT

The relationship between SARS-CoV-2 viral load and risk of disease progression remains largely undefined in coronavirus disease 2019 (COVID-19). Here, we quantify SARS-CoV-2 viral load from participants with a diverse range of COVID-19 disease severity, including those requiring hospitalization, outpatients with mild disease, and individuals with resolved infection. We detected SARS-CoV-2 plasma RNA in 27% of hospitalized participants, and 13% of outpatients diagnosed with COVID-19. Amongst the participants hospitalized with COVID-19, we report that a higher prevalence of detectable SARS-CoV-2 plasma viral load is associated with worse respiratory disease severity, lower absolute lymphocyte counts, and increased markers of inflammation, including C-reactive protein and IL-6. SARS-CoV-2 viral loads, especially plasma viremia, are associated with increased risk of mortality. Our data show that SARS-CoV-2 viral loads may aid in the risk stratification of patients with COVID-19, and therefore its role in disease pathogenesis should be further explored.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/virology , Pneumonia, Viral/virology , Adult , Aged , Antibodies, Viral/blood , Betacoronavirus/genetics , Betacoronavirus/growth & development , Biomarkers/blood , C-Reactive Protein , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/mortality , Coronavirus Infections/pathology , Female , Hospitalization , Humans , Inflammation/blood , Inflammation/virology , Interleukin-6/blood , Longitudinal Studies , Massachusetts/epidemiology , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/mortality , Pneumonia, Viral/pathology , RNA, Viral/blood , SARS-CoV-2 , Severity of Illness Index , Viral Load , Viremia/blood , Viremia/virology
20.
J Pediatr ; 227: 45-52.e5, 2020 12.
Article in English | MEDLINE | ID: covidwho-872293

ABSTRACT

OBJECTIVES: As schools plan for re-opening, understanding the potential role children play in the coronavirus infectious disease 2019 (COVID-19) pandemic and the factors that drive severe illness in children is critical. STUDY DESIGN: Children ages 0-22 years with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection presenting to urgent care clinics or being hospitalized for confirmed/suspected SARS-CoV-2 infection or multisystem inflammatory syndrome in children (MIS-C) at Massachusetts General Hospital were offered enrollment in the Massachusetts General Hospital Pediatric COVID-19 Biorepository. Enrolled children provided nasopharyngeal, oropharyngeal, and/or blood specimens. SARS-CoV-2 viral load, ACE2 RNA levels, and serology for SARS-CoV-2 were quantified. RESULTS: A total of 192 children (mean age, 10.2 ± 7.0 years) were enrolled. Forty-nine children (26%) were diagnosed with acute SARS-CoV-2 infection; an additional 18 children (9%) met the criteria for MIS-C. Only 25 children (51%) with acute SARS-CoV-2 infection presented with fever; symptoms of SARS-CoV-2 infection, if present, were nonspecific. Nasopharyngeal viral load was highest in children in the first 2 days of symptoms, significantly higher than hospitalized adults with severe disease (P = .002). Age did not impact viral load, but younger children had lower angiotensin-converting enzyme 2 expression (P = .004). Immunoglobulin M (IgM) and Immunoglobulin G (IgG) to the receptor binding domain of the SARS-CoV-2 spike protein were increased in severe MIS-C (P < .001), with dysregulated humoral responses observed. CONCLUSIONS: This study reveals that children may be a potential source of contagion in the SARS-CoV-2 pandemic despite having milder disease or a lack of symptoms; immune dysregulation is implicated in severe postinfectious MIS-C.


Subject(s)
COVID-19 , Adolescent , Age Factors , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/immunology , COVID-19/transmission , COVID-19 Testing , Child , Child, Preschool , Comorbidity , Female , Humans , Infant , Infant, Newborn , Male , Massachusetts/epidemiology , Pandemics , Severity of Illness Index , Viral Load , Young Adult
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