Antibody responses to SARS-CoV-2 in patients with COVID-19.
TL;DR: It is suggested that SARS-CoV2-specific IgG or IgM seroconversion occurs within 20 days post symptom onset and may be helpful for the diagnosis of suspected patients with negative RT–PCR results and for the identification of asymptomatic infections.
Abstract: We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections.
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TL;DR: A cohort of asymptomatic patients infected with SARS-CoV-2 had significantly lower levels of virus-specific IgG antibodies compared to a cohort of age- and sex-matched symptomatic infected patients.
Abstract: The clinical features and immune responses of asymptomatic individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been well described We studied 37 asymptomatic individuals in the Wanzhou District who were diagnosed with RT-PCR-confirmed SARS-CoV-2 infections but without any relevant clinical symptoms in the preceding 14 d and during hospitalization Asymptomatic individuals were admitted to the government-designated Wanzhou People's Hospital for centralized isolation in accordance with policy1 The median duration of viral shedding in the asymptomatic group was 19 d (interquartile range (IQR), 15-26 d) The asymptomatic group had a significantly longer duration of viral shedding than the symptomatic group (log-rank P = 0028) The virus-specific IgG levels in the asymptomatic group (median S/CO, 34; IQR, 16-107) were significantly lower (P = 0005) relative to the symptomatic group (median S/CO, 205; IQR, 58-382) in the acute phase Of asymptomatic individuals, 933% (28/30) and 811% (30/37) had reduction in IgG and neutralizing antibody levels, respectively, during the early convalescent phase, as compared to 968% (30/31) and 622% (23/37) of symptomatic patients Forty percent of asymptomatic individuals became seronegative and 129% of the symptomatic group became negative for IgG in the early convalescent phase In addition, asymptomatic individuals exhibited lower levels of 18 pro- and anti-inflammatory cytokines These data suggest that asymptomatic individuals had a weaker immune response to SARS-CoV-2 infection The reduction in IgG and neutralizing antibody levels in the early convalescent phase might have implications for immunity strategy and serological surveys
2,463 citations
Emory University1, United States Public Health Service2, Rutgers University3, Harvard University4, Central Michigan University5, Westchester Medical Center6, Icahn School of Medicine at Mount Sinai7, New York University8, Saint Barnabas Medical Center9, University of Pennsylvania10, SUNY Downstate Medical Center11, Yale University12, University of Colorado Denver13, Boston Children's Hospital14, Case Western Reserve University15, Louisiana State University16, University of Washington17, Johns Hopkins University18, University of Texas Health Science Center at Houston19, University of Mississippi20, Tufts University21, Vanderbilt University22
TL;DR: Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents.
Abstract: Background Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19)...
1,887 citations
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TL;DR: In this article, a picture has begun to emerge that reveals that CD4+ T cells, CD8+ Tcells, and neutralizing antibodies all contribute to control SARS-CoV-2 in both non-hospitalized and hospitalized cases of COVID-19.
1,092 citations
TL;DR: The present study has important implications when considering widespread serological testing and antibody protection against reinfection with SARS-CoV-2, and may suggest that vaccine boosters are required to provide long-lasting protection.
Abstract: Antibody responses to SARS-CoV-2 can be detected in most infected individuals 10-15 d after the onset of COVID-19 symptoms. However, due to the recent emergence of SARS-CoV-2 in the human population, it is not known how long antibody responses will be maintained or whether they will provide protection from reinfection. Using sequential serum samples collected up to 94 d post onset of symptoms (POS) from 65 individuals with real-time quantitative PCR-confirmed SARS-CoV-2 infection, we show seroconversion (immunoglobulin (Ig)M, IgA, IgG) in >95% of cases and neutralizing antibody responses when sampled beyond 8 d POS. We show that the kinetics of the neutralizing antibody response is typical of an acute viral infection, with declining neutralizing antibody titres observed after an initial peak, and that the magnitude of this peak is dependent on disease severity. Although some individuals with high peak infective dose (ID50 > 10,000) maintained neutralizing antibody titres >1,000 at >60 d POS, some with lower peak ID50 had neutralizing antibody titres approaching baseline within the follow-up period. A similar decline in neutralizing antibody titres was observed in a cohort of 31 seropositive healthcare workers. The present study has important implications when considering widespread serological testing and antibody protection against reinfection with SARS-CoV-2, and may suggest that vaccine boosters are required to provide long-lasting protection.
1,052 citations
University of Bonn1, Charité2, Hannover Medical School3, University Hospital Bonn4, German Center for Neurodegenerative Diseases5, Leibniz Association6, Radboud University Nijmegen7, Max Delbrück Center for Molecular Medicine8, Bernhard Nocht Institute for Tropical Medicine9, University of Hamburg10
TL;DR: This study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and it reveals profound alterations in the myeloid cell compartment associated with severe COVID-19.
1,042 citations
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TL;DR: Results of an analysis of nasal and throat swabs from 17 patients in Zhuhai, China, who had received a diagnosis of Covid-19 and found SARS-CoV-2 Viral Load in Upper Respiratory Specimens positive.
Abstract: SARS-CoV-2 Viral Load in Upper Respiratory Specimens The authors report results of an analysis of nasal and throat swabs from 17 patients in Zhuhai, China, who had received a diagnosis of Covid-19....
4,236 citations
TL;DR: In the preanalytical stage, collecting the proper respiratory tract specimen at the right time from the right anatomic site is essential for a prompt and accurate molecular diagnosis of COVID-19, and real-time reverse transcription-PCR assays remain the molecular test of choice for the etiologic diagnosis of SARS-CoV-2 infection while antibody-based techniques are being introduced as supplemental tools.
Abstract: The COVID-19 outbreak has had a major impact on clinical microbiology laboratories in the past several months. This commentary covers current issues and challenges for the laboratory diagnosis of infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the preanalytical stage, collecting the proper respiratory tract specimen at the right time from the right anatomic site is essential for a prompt and accurate molecular diagnosis of COVID-19. Appropriate measures are required to keep laboratory staff safe while producing reliable test results. In the analytic stage, real-time reverse transcription-PCR (RT-PCR) assays remain the molecular test of choice for the etiologic diagnosis of SARS-CoV-2 infection while antibody-based techniques are being introduced as supplemental tools. In the postanalytical stage, testing results should be carefully interpreted using both molecular and serological findings. Finally, random-access, integrated devices available at the point of care with scalable capacities will facilitate the rapid and accurate diagnosis and monitoring of SARS-CoV-2 infections and greatly assist in the control of this outbreak.
955 citations
TL;DR: The rate of secondary transmission among household contacts of patients with MERS-CoV infection has been approximately 5%, and the data provide insight into the rate of subclinical transmission of MSPS coronavirus in the home.
Abstract: BACKGROUND: Strategies to contain the Middle East respiratory syndrome coronavirus (MERS-CoV) depend on knowledge of the rate of human-to-human transmission, including subclinical infections. A lack of serologic tools has hindered targeted studies of transmission. METHODS: We studied 26 index patients with MERS-CoV infection and their 280 household contacts. The median time from the onset of symptoms in index patients to the latest blood sampling in contact patients was 17.5 days (range, 5 to 216; mean, 34.4). Probable cases of secondary transmission were identified on the basis of reactivity in two reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays with independent RNA extraction from throat swabs or reactivity on enzyme-linked immunosorbent assay against MERS-CoV S1 antigen, supported by reactivity on recombinant S-protein immunofluorescence and demonstration of neutralization of more than 50% of the infectious virus seed dose on plaque-reduction neutralization testing. RESULTS: Among the 280 household contacts of the 26 index patients, there were 12 probable cases of secondary transmission (4%; 95% confidence interval, 2 to 7). Of these cases, 7 were identified by means of RT-PCR, all in samples obtained within 14 days after the onset of symptoms in index patients, and 5 were identified by means of serologic analysis, all in samples obtained 13 days or more after symptom onset in index patients. Probable cases of secondary transmission occurred in 6 of 26 clusters (23%). Serologic results in contacts who were sampled 13 days or more after exposure were similar to overall study results for combined RT-PCR and serologic testing. CONCLUSIONS: The rate of secondary transmission among household contacts of patients with MERS-CoV infection has been approximately 5%. Our data provide insight into the rate of subclinical transmission of MERS-CoV in the home.
351 citations
TL;DR: In a study of viral load, shedding, and immune response in 37 cases of Middle East respiratory syndrome coronavirus infection, virus was not eliminated upon development of neutralizing serum antibodies.
Abstract: Background. The Middle East respiratory syndrome (MERS) coronavirus causes isolated cases and outbreaks of severe respiratory disease. Essential features of the natural history of disease are poorly understood.
Methods. We studied 37 adult patients infected with MERS coronavirus for viral load in the lower and upper respiratory tracts (LRT and URT, respectively), blood, stool, and urine. Antibodies and serum neutralizing activities were determined over the course of disease.
Results. One hundred ninety-nine LRT samples collected during the 3 weeks following diagnosis yielded virus RNA in 93% of tests. Average (maximum) viral loads were 5 × 106 (6 × 1010) copies/mL. Viral loads (positive detection frequencies) in 84 URT samples were 1.9 × 104 copies/mL (47.6%). Thirty-three percent of all 108 serum samples tested yielded viral RNA. Only 14.6% of stool and 2.4% of urine samples yielded viral RNA. All seroconversions occurred during the first 2 weeks after diagnosis, which corresponds to the second and third week after symptom onset. Immunoglobulin M detection provided no advantage in sensitivity over immunoglobulin G (IgG) detection. All surviving patients, but only slightly more than half of all fatal cases, produced IgG and neutralizing antibodies. The levels of IgG and neutralizing antibodies were weakly and inversely correlated with LRT viral loads. Presence of antibodies did not lead to the elimination of virus from LRT.
Conclusions. The timing and intensity of respiratory viral shedding in patients with MERS closely matches that of those with severe acute respiratory syndrome. Blood viral RNA does not seem to be infectious. Extrapulmonary loci of virus replication seem possible. Neutralizing antibodies do not suffice to clear the infection.
350 citations
"Antibody responses to SARS-CoV-2 in..." refers background or methods in this paper
...Our data indicate that virus-specific antibody detection for COVID-19 could be important (1) Patient...
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...recommended by WHO, including (1) seroconversion or (2) a fourfold increase in IgG-specific antibody titers, are suitable for the diagnosis of COVID-19 (using paired samples from 41 patients)....
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TL;DR: The performance of different serological assays as well as the applicability of the two main applied antigens used during the SARS-CoV outbreak are summarized and a recommendation for a serological testing scheme is given and necessary improvements are outlined for a better preparedness.
327 citations