Abstract

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global concern. Immunoglobin A (IgA) contributes to virus neutralization at the early stage of infection. Longitudinal studies are needed to assess whether SARS-CoV-2-specific IgA production persists for a longer time in patients recovered from severe COVID-19 and its lasting symptoms that can have disabling consequences should also be alerted to susceptible hosts. Here, we tracked the anti-SARS-CoV-2 spike protein receptor-binding domain (RBD) antibody levels in a cohort of 88 COVID-19 patients. We found that 52.3% of the patients produced more anti-SARS-CoV-2 RBD IgA than IgG or IgM, and the levels of IgA remained stable during 4–41 days of infection. One of these IgA-dominant COVID-19 patients, concurrently with IgA nephropathy (IgAN), presented with elevated serum creatinine and worse proteinuria during the infection, which continued until seven months post-infection. The serum levels of anti-SARS-CoV-2 RBD and total IgA were higher in this patient than in healthy controls. Changes in the composition of the intestinal microbiota, increased IgA highly coated bacteria, and elevated concentration of the proinflammatory cytokine IL-18 were indicative of potential involvement of intestinal dysbiosis and inflammation to the systemic IgA level and, consequently, the disease progression. Collectively, our work highlighted the potential adverse effect of the mucosal immune response to SARS-CoV-2 infection, and that additional care should be taken with COVID-19 patients presenting with chronic diseases such as IgAN.

Highlights

  • Analysis of the anti-SARS-CoV-2 receptor-binding domain (RBD) antibodies in the sera of the 88 COVID-19 patients showed that 46 (52.3%) had Immunoglobin A (IgA) as the dominant isotype during the infection (Figure 1a)

  • We observed that SARS-CoV-2 infection activated aberrant mucosal humoral responses in both the lung and the intestine, which may have resulted in long-term side effects on the renal function of an IgA nephropathy (IgAN) patient who had recovered from COVID-19

  • Focusing on the humoral response to SARS-CoV-2 infection in a cohort of 88 COVID19 patients, we found that anti-SARS-CoV-2 RBD IgA was the dominant isotype in the serum of these patients during the infection, with 52.3% showing IgA-dominant COVID-19

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Summary

Introduction

Pneumonia is the most common symptom in patients with moderate-to-severe illness [5,6,7,8,9,10], 17.6% of COVID-19 patients develop gastrointestinal symptoms, including diarrhea, anorexia, and nausea [11,12,13,14]. SARS-CoV-2 RNA was reported to be re-detectable in 12 out of 173 patients who had recovered from COVID-19, which was associated with potential SARS-CoV-2 intestinal infection [15,16,17,18]. Recent studies have indicated that SARS-CoV-2 infection leads to intestinal dysbiosis, along with an increase in the numbers of opportunistic pathogens in the intestine [19,20,21]

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