Differential DNA methylation 7 months after SARS-CoV-2 infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), and SARS-CoV-2 has been linked to changes in DNA methylation (DNAm) patterns. Studies focused on post-SARS-CoV-2 infection and DNAm have been mainly carried out among severe COVID-19 cases or without distinguishing the severity of cases. However, investigations into mild and asymptomatic cases after SARS-CoV-2 infection are limited. In this study, we analyzed DNAm patterns of mild and asymptomatic cases seven months after SARS-CoV-2 infection in a household setting by conducting epigenome-wide association studies (EWAS).

We identified DNAm changes at 42 CpG sites associated with anti-SARS-CoV-2 antibody levels. We additionally report EWAS between COVID-19 cases and controls, with the case status being confirmed by either an antibody test or a PCR test. The EWAS with an antibody test case definition identified 172 CpG sites to be differentially methylated, while the EWAS with a PCR test case definition identified 502 CpG sites. Two common sites, namely cg17126990 (annotated to AFAP1L2) and cg25483596 (annotated to PC), were identified to be hypermethylated across the three EWAS. Both CpG sites have been reported to be involved in molecular pathways after SARS-CoV-2 infection. While AFAP1L2 has been found to be upregulated after SARS-CoV-2 infection, the pyruvate carboxylase (PC) activity seems to be affected by SARS-CoV-2 infection resulting in changes to the host cell metabolism. Additionally, an EWAS to assess persistent health restrictions among PCR-confirmed cases showed 40 CpG sites to be differentially methylated.

We detected associations between DNAm in individuals who had asymptomatic and mild SARS-CoV-2 infections as compared to their household controls. These findings contribute to our understanding of the molecular consequences of SARS-CoV-2 infection observed months after infection.