Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection and analysis of IgG non-responders

• Published in: PloS one 2020-10, Vol.15 (10), p.e0241104-e0241104
• Main Authors: Marklund, Emelie, Leach, Susannah, Axelsson, Hannes, Nyström, Kristina, Norder, Heléne, Bemark, Mats, Angeletti, Davide, Lundgren, Anna, Nilsson, Staffan, Andersson, Lars-Magnus, Yilmaz, Aylin, Lindh, Magnus, Liljeqvist, Jan-Åke, Gisslén, Magnus
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies; Antibodies, Neutralizing - blood; Antibodies, Viral - blood; Betacoronavirus - genetics; Betacoronavirus - immunology; Biology and life sciences; Causes of; Coronavirus Infections - epidemiology; Coronavirus Infections - immunology; Coronavirus Infections - virology; Coronaviruses; COVID-19; Development and progression; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Health aspects; Hospitals; Humans; IgG antibody; Immune response; Immunoassay; Immunoglobulin G; Immunoglobulin G - blood; Immunologi inom det medicinska området; Immunology; Immunology in the medical area; Infections; Infectious diseases; Infectious Medicine; Infektionsmedicin; Laboratories; Male; Medicine and Health Sciences; Microbiology in the medical area; Middle Aged; Mikrobiologi inom det medicinska området; Neutralizing; Nucleocapsids; Pandemics; Physiological aspects; Pneumonia, Viral - epidemiology; Pneumonia, Viral - immunology; Pneumonia, Viral - virology; Polls & surveys; Proteins; Real-Time Polymerase Chain Reaction; Research and Analysis Methods; SARS-CoV-2; Seroconversion; Seroepidemiologic Studies; Serology; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Severity of Illness Index; Spikes; Sweden - epidemiology; Viral diseases; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0241104

To accurately interpret COVID-19 seroprevalence surveys, knowledge of serum-IgG responses to SARS-CoV-2 with a better understanding of patients who do not seroconvert, is imperative. This study aimed to describe serum-IgG responses to SARS-CoV-2 in a cohort of patients with both severe and mild COVID-19, including extended studies of patients who remained seronegative more than 90 days post symptom onset. SARS-CoV-2-specific IgG antibody levels were quantified using two clinically validated and widely used commercial serological assays (Architect, Abbott Laboratories and iFlash 1800, YHLO), detecting antibodies against the spike and nucleocapsid proteins. Forty-seven patients (mean age 49 years, 38% female) were included. All (15/15) patients with severe symptoms and 29/32 (90.6%) patients with mild symptoms of COVID-19 developed SARS-CoV-2-specific IgG antibodies in serum. Time to seroconversion was significantly shorter (median 11 vs. 22 days, P = 0.04) in patients with severe compared to mild symptoms. Of the three patients without detectable IgG-responses after >90 days, all had detectable virus-neutralizing antibodies and in two, spike-protein receptor binding domain-specific IgG was detected with an in-house assay. Antibody titers were preserved during follow-up and all patients who seroconverted, irrespective of the severity of symptoms, still had detectable IgG levels >75 days post symptom onset. Patients with severe COVID-19 both seroconvert earlier and develop higher concentrations of SARS-CoV-2-specific IgG than patients with mild symptoms. Of those patients who not develop detectable IgG antibodies, all have detectable virus-neutralizing antibodies, suggesting immunity. Our results showing that not all COVID-19 patients develop detectable IgG using two validated commercial clinical methods, even over time, are vital for the interpretation of COVID-19 seroprevalence surveys.