IgG Seroconversion and Pathophysiology in Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Henry M Staines, Daniela E Kirwan, David J Clark, Emily R Adams, Yolanda Augustin, Rachel L Byrne, Michael Cocozza, Ana I Cubas-Atienzar, Luis E Cuevas, Martina Cusinato, Benedict M O Davies, Mark Davis, Paul Davis, Annelyse Duvoix, Nicholas M Eckersley, Daniel Forton, Alice J Fraser, Gala Garrod, Linda Hadcocks, Qinxue Hu, Michael Johnson, Grant A Kay, Kesja Klekotko, Zawditu Lewis, Derek C Macallan, Josephine Mensah-Kane, Stefanie Menzies, Irene Monahan, Catherine M Moore, Gerhard Nebe-von-Caron, Sophie I Owen, Chris Sainter, Amadou A Sall, James Schouten, Christopher T Williams, John Wilkins, Kevin Woolston, Joseph R A Fitchett, Sanjeev Krishna, Tim Planche, Henry M Staines, Daniela E Kirwan, David J Clark, Emily R Adams, Yolanda Augustin, Rachel L Byrne, Michael Cocozza, Ana I Cubas-Atienzar, Luis E Cuevas, Martina Cusinato, Benedict M O Davies, Mark Davis, Paul Davis, Annelyse Duvoix, Nicholas M Eckersley, Daniel Forton, Alice J Fraser, Gala Garrod, Linda Hadcocks, Qinxue Hu, Michael Johnson, Grant A Kay, Kesja Klekotko, Zawditu Lewis, Derek C Macallan, Josephine Mensah-Kane, Stefanie Menzies, Irene Monahan, Catherine M Moore, Gerhard Nebe-von-Caron, Sophie I Owen, Chris Sainter, Amadou A Sall, James Schouten, Christopher T Williams, John Wilkins, Kevin Woolston, Joseph R A Fitchett, Sanjeev Krishna, Tim Planche

Abstract

We investigated the dynamics of seroconversion in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. During March 29-May 22, 2020, we collected serum samples and associated clinical data from 177 persons in London, UK, who had SARS-CoV-2 infection. We measured IgG against SARS-CoV-2 and compared antibody levels with patient outcomes, demographic information, and laboratory characteristics. We found that 2.0%-8.5% of persons did not seroconvert 3-6 weeks after infection. Persons who seroconverted were older, were more likely to have concurrent conditions, and had higher levels of inflammatory markers. Non-White persons had higher antibody concentrations than those who identified as White; these concentrations did not decline during follow-up. Serologic assay results correlated with disease outcome, race, and other risk factors for severe SARS-CoV-2 infection. Serologic assays can be used in surveillance to clarify the duration and protective nature of humoral responses to SARS-CoV-2 infection.

Trial registration: ClinicalTrials.gov NCT04351646.

Keywords: 2019 novel coronavirus disease; COVID-19; SARS-CoV-2; United Kingdom; antibodies; antibody responses; coronavirus; coronavirus disease; diagnostics; immunology; respiratory infections; serology; severe acute respiratory syndrome coronavirus 2; viruses; zoonoses.

Figures

Figure 1
Figure 1
Antibody dynamics in patients with severe acute respiratory syndrome coronavirus 2, United Kingdom, 2020. A) NOD by days after first positive PCR result. Blue indicates seroconverting patients; red indicates nonseroconverting patients. B) Mean (± SEM) NODs (>3 samples per time point; n = 48) by days after first positive PCR result for those who seroconverted. A 4-parameter sigmoidal unconstrained model is shown (r2 = 0.45). C) Mean (± SEM) NODs (>3 per time point; n = 45) by days after symptom onset for patients who seroconverted. A 4-parameter sigmoidal unconstrained model is shown (r2 = 0.63). NOD, normalized optical density.
Figure 2
Figure 2
Relationships between CRP levels, symptoms, outcomes, and NODs of patients with severe acute respiratory syndrome coronavirus 2, United Kingdom, 2020. A–C) CRPs at diagnosis for A) 113 symptomatic (open circles) and 21 asymptomatic (closed circles) patients (CRP 97 vs. 56; p

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