IgA2 Antibodies against SARS-CoV-2 Correlate with NET Formation and Fatal Outcome in Severely Diseased COVID-19 Patients.

Léonie A N Staats,Holger Hackstein,Ulrike Steffen,Hella Pfeiffer,Aylin Lindemann,Moritz Leppkes,Martin Herrmann,Jasmin Knopf,Susanne Achenbach,Julia Fürst,Georg Schett,Markus F Neurath,Luis E Muñoz,Andreas E Kremer

doi:10.3390/cells9122676

Abstract

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to an adaptive immune response in the host and the formation of anti-SARS-CoV-2 specific antibodies. While IgG responses against SARS-CoV-2 have been characterized quite well, less is known about IgA. IgA2 activates immune cells and induces inflammation and neutrophil extracellular trap (NET) formation which may contribute to organ injury and fatal outcome in SARS-CoV-2-infected patients. SARS-CoV-2 spike protein specific antibody levels were measured in plasma samples of 15 noninfected controls and 82 SARS-CoV-2-infected patients with no or mild symptoms, moderate symptoms (hospitalization) or severe disease (intensive care unit, ICU). Antibody levels were compared to levels of C-reactive protein (CRP) and circulating extracellular DNA (ecDNA) as markers for general inflammation and NET formation, respectively. While levels of SARS-CoV-2-specific IgG were similar in all patient groups, IgA2 antibodies were restricted to severe disease and showed the strongest discrimination between nonfatal and fatal outcome in patients with severe SARS-CoV-2 infection. While anti-SARS-CoV-2 IgG and IgA2 levels correlated with CRP levels in severely diseased patients, only anti-SARS-CoV-2 IgA2 correlated with ecDNA. These data suggest that the formation of anti-SARS-CoV-2 IgA2 during SARS-CoV-2 infection is a marker for more severe disease related to NET formation and poor outcome.

Highlights

In 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has induced a pandemic disease (coronavirus disease of 2019 (COVID-19)) with more than 37 million people infected andCells 2020, 9, 2676; doi:10.3390/cells9122676 www.mdpi.com/journal/cellsCells 2020, 9, 2676 over 1 million deaths worldwide [1]
When analyzing antibody levels directed against the S1+S2 spike protein of SARS-CoV-2 in plasma of these subjects, we found that IgG levels were profoundly increased in all patient groups the plasma of these subjects, we found that IgG levels were profoundly increased in all patient compared to healthy controls (Figure 1a)
There is evidence that the immune system might worsen the disease at later stages

Summary

Introduction

In 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has induced a pandemic disease (coronavirus disease of 2019 (COVID-19)) with more than 37 million people infected andCells 2020, 9, 2676; doi:10.3390/cells9122676 www.mdpi.com/journal/cellsCells 2020, 9, 2676 over 1 million deaths worldwide (status from 11 October 2020) [1]. In 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has induced a pandemic disease (coronavirus disease of 2019 (COVID-19)) with more than 37 million people infected and. It is assumed that in the early phase of the disease, antibodies help to clear the virus and contribute to controlling the infection. Increased antibody levels at early stages of COVID-19 were found to correlate with a decreased viral load and better survival of the patients [5]. SARS-CoV-2-specific antibodies likely form immune complexes together with their viral antigens. Immune complexes activate the complement system and innate immune cells, such as macrophages or neutrophils. There is evidence that SARS-CoV-2 infection can cause alveolar epithelial cell damage due to the viral activity and lead to a cytokine-storm-like hyperinflammation that provokes further injury [8,9]

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