An assessment of alterations to human sperm methylation patterns in coronavirus disease 2019 infected and healthy control males.

Objective: To determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection affects male reproductive health, considering the many potential factors that contribute to declines in male fertility on a semiglobal scale.

Design: In total, 64 human semen samples-32 treatment and 32 control-were laboratory processed and bioinformatically analyzed to assess differences in DNA methylation patterns. Implementing multiple bioinformatic tools, the analyses conducted will elicit between-group differences with respect to epigenetic age, epigenetic instability, semiglobal, and regional methylation, in addition to methylation patterns as a function of time since infection.

Setting: University hospital.

Patients: The study cohort of 64 individuals was drawn from a larger population of 94 volunteer participants recruited at the Human Reproduction Center at the Clinical Hospital of the Ribeirao Preto Medical School-University of São Paulo between June 2021 and January 2022 as well as in accordance with the ethical guidelines established by the Declaration of Helsinki.

Intervention: Exposure to SARS-CoV-2.

Main Outcome Measure(s): Effects on male reproductive health were reported as differences in DNA methylation measured using an array. Mean β values at key regulatory loci for human spermatocytes were analyzed and compared between groups. Further analysis of β values using epigenetic age, instability, semiglobal, and regional methylation tools provided an analysis with substantial breadth and depth.

Results: In all analyses, there were no differences between groups. Considering these results, it can be inferred that infection with SARS-CoV-2 does not alter the epigenome of human spermatocytes in significant and/or persistent ways. Tangentially, these data also suggest that human male reproductive health is minimally altered by the virus, or that it is altered in a way that is independent of epigenetic programming.

Conclusion: Infection with SARS-CoV-2 has been reportedly associated with alterations in male fertility. This study asserts that such alterations do not have an epigenetic basis but are likely a result of concomitant symptomatology, i.e., fever and inflammation. Across the multiple bioinformatic analyses conducted, the results of this test did not detect any differences in DNA methylation patterns between coronavirus disease 2019 and noncoronavirus disease semen donor groups.