Antigen Coverage Presented by MHC Class I Has a Negative Correlation with SARS-CoV-2-Induced Mortality

Area of Science:

• Immunology
• Epidemiology
• Virology

Background:

• The COVID-19 pandemic necessitates understanding factors influencing patient prognosis.
• Adaptive immune responses, involving SARS-CoV-2 antigens and MHC class I, are crucial in disease outcomes.

Purpose of the Study:

• To investigate the correlation between SARS-CoV-2 antigen coverage presented by MHC class I and COVID-19 mortality rates.
• To determine if specific antigen domains, like the spike protein, influence this correlation.

Main Methods:

• Inferred national-level antigen coverage using country-specific HLA allele frequencies and predicted antigen binding.
• Performed regression analyses to assess the relationship between antigen coverage and COVID-19 death rates.
• Incorporated known risk factors, such as underlying disease prevalence, into multiple regression models.

Main Results:

• A significant negative correlation was observed between overall antigen coverage and COVID-19 mortality, particularly when presented by HLA-B.
• This negative correlation persisted after accounting for confounding factors like underlying disease prevalence.
• Antigen coverage derived from the SARS-CoV-2 spike domain showed a significant negative correlation with mortality.

Conclusions:

• HLA-B-presented SARS-CoV-2 antigen coverage may be a favorable prognostic factor for COVID-19.
• Spike protein-derived antigen coverage appears particularly beneficial for COVID-19 prognosis.