Humoral immune responses in hospitalized COVID-19 patients

Abstract

Background: The emerging coronavirus 2019 (COVID-19) disease, caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a worldwide public health crisis. Antibody analysis is an important procedure for the diagnosis of COVID-19 patients. We investigated the IgG, IgM, and IgA responses against the SARS-CoV-2 spike (S) protein among hospitalized COVID-19 patients.

Materials and methods: Hospitalized COVID-19 patients (n = 178) in the Al Madinah region, Saudi Arabia, participated in this study. Of the 178 patients, 72 (40%) were categorized as severe, including 50 (69%) males and 22 (31%) females. The remaining106 (60%) patients were categorized as non-severe, including 85 (80%) males and 21 (20%) females. Qualitative reverse transcription-polymerase chain reaction (RT-PCR) to detect the presence of SARS-CoV-2 RNA was used to confirm the diagnosis of each patient. The specific anti-SARS-CoV-2 S protein IgG, IgM, and IgA antibodies in patients' sera were measured using enzyme-linked immunosorbent assay (ELISA) and compared between case presentations.

Results: The current study showed that all severe hospitalized patients presented significantly (p < 0.0001) increased anti-S IgG and IgM antibody accumulation compared with non-severe patients. Additionally, the results also showed that 50% of severe males were positive to anti-S IgG, IgM, and IgA antibodies, whereas only 40% positivity for all three-antibody isotypes was observed in severe females. The study also showed that 86% of males and 81% of females categorized as severe were positive for both IgG and IgM antibodies but negative for the IgA antibody against the S protein.

Conclusion: The humoral immune response against SARS-CoV-2 proteins commonly results in the production of antibodies against viral proteins. Specific anti-SARS-CoV-2 S protein IgG class antibodies were detected at significantly higher levels than IgM class antibodies, and both IgG and IgM antibodies were detected at significantly higher levels than the IgA antibody among all patients. The variations of the humoral immune responses among hospitalized patients reflect the association between disease presentations and immunity against the virus. Collectively, these findings afford new insights into the different antibody isotypes in responses to COVID-19 hospitalized patients with dissimilar disease severity.

Keywords: Hospitalized; Humoral immunity; Non-severe; SARS-CoV-2; Severe.

Fig. 1

Anti-S IgG, IgM and IgA antibody concentrations in severe (S) and non-severe (NS) patients. The anti-S antibody isotype concentrations in serum of severe (n = 72) and non-severe (n = 106) COVID-19 patients were determined by ELISA and expressed in units of optical density (OD at 405 nm). The p values between the different groups are indicated.

Fig. 2

Correlation between anti-S antibody isotypes in severe and non-severe patients. (a) A strong positive correlation between anti-S IgG and IgM antibodies in severe patients (Spearman’s r = 0.69, p < 0.0001, n = 72). (b) A positive correlation between anti-S IgM and IgA antibodies in severe patients (Spearman’s r = 0.31, p = 0.013, n = 72). (c) A strong positive correlation between anti-S IgG and IgM antibodies in non-severe patients (Spearman’s r = 0.55, p < 0.0001, n = 106). (d) A positive correlation between anti-S IgM and IgA antibodies in non-severe patients (Spearman’s r = 0.24, p = 0.015, n = 106).

Fig. 3

Serum anti-S antibody isotype concentrations in severe and non-severe patients as measured by ELISA. (a) Anti-S IgG, IgM and IgA antibody concentrations of severe male patients (n = 50). (b) Anti-S IgG, IgM and IgA antibody concentrations of severe female patients (n = 22). (c) Anti-S IgG, IgM and IgA antibody concentrations in non-severe male patients (n = 85). (d) Anti-S IgG, IgM and IgA antibody concentrations in non-severe female patients (n = 21). The p values between the different groups are indicated.