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Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection and analysis of IgG non-responders.
PLoS One. 2020; 15(10):e0241104.Plos

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

Authors+Show Affiliations

Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Department of Infectious Diseases, Sahlgrenska University Hospital, Gothenburg, Sweden.Department of Microbiology and Immunology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Department of Clinical Pharmacology, Sahlgrenska University Hospital, Gothenburg, Sweden.Department of Microbiology and Immunology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Department of Clinical Microbiology, Sahlgrenska University Hospital, Gothenburg, Sweden.Department of Microbiology and Immunology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Department of Clinical Immunology and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.Department of Microbiology and Immunology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.Department of Microbiology and Immunology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Department of Clinical Immunology and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.Department of Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden. Department of Laboratory Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Department of Infectious Diseases, Sahlgrenska University Hospital, Gothenburg, Sweden.Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Department of Infectious Diseases, Sahlgrenska University Hospital, Gothenburg, Sweden.Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Department of Clinical Microbiology, Sahlgrenska University Hospital, Gothenburg, Sweden.Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Department of Clinical Microbiology, Sahlgrenska University Hospital, Gothenburg, Sweden.Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Department of Infectious Diseases, Sahlgrenska University Hospital, Gothenburg, Sweden.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33085715

Citation

Marklund, Emelie, et al. "Serum-IgG Responses to SARS-CoV-2 After Mild and Severe COVID-19 Infection and Analysis of IgG Non-responders." PloS One, vol. 15, no. 10, 2020, pp. e0241104.
Marklund E, Leach S, Axelsson H, et al. Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection and analysis of IgG non-responders. PLoS One. 2020;15(10):e0241104.
Marklund, E., Leach, S., Axelsson, H., Nyström, K., Norder, H., Bemark, M., Angeletti, D., Lundgren, A., Nilsson, S., Andersson, L. M., Yilmaz, A., Lindh, M., Liljeqvist, J. Å., & Gisslén, M. (2020). Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection and analysis of IgG non-responders. PloS One, 15(10), e0241104. https://doi.org/10.1371/journal.pone.0241104
Marklund E, et al. Serum-IgG Responses to SARS-CoV-2 After Mild and Severe COVID-19 Infection and Analysis of IgG Non-responders. PLoS One. 2020;15(10):e0241104. PubMed PMID: 33085715.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection and analysis of IgG non-responders. AU - Marklund,Emelie, AU - Leach,Susannah, AU - Axelsson,Hannes, AU - Nyström,Kristina, AU - Norder,Heléne, AU - Bemark,Mats, AU - Angeletti,Davide, AU - Lundgren,Anna, AU - Nilsson,Staffan, AU - Andersson,Lars-Magnus, AU - Yilmaz,Aylin, AU - Lindh,Magnus, AU - Liljeqvist,Jan-Åke, AU - Gisslén,Magnus, Y1 - 2020/10/21/ PY - 2020/07/08/received PY - 2020/10/08/accepted PY - 2020/10/21/entrez PY - 2020/10/22/pubmed PY - 2020/11/3/medline SP - e0241104 EP - e0241104 JF - PloS one JO - PLoS One VL - 15 IS - 10 N2 - BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/33085715/Serum_IgG_responses_to_SARS_CoV_2_after_mild_and_severe_COVID_19_infection_and_analysis_of_IgG_non_responders_ L2 - https://dx.plos.org/10.1371/journal.pone.0241104 DB - PRIME DP - Unbound Medicine ER -