BackgroundThe 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 methodsHospitalized 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.ResultsThe 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.ConclusionThe 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.