Experiments in mice have shown that infecting male mice with SARS-CoV-2 alters the composition of their sperm and causes behavioral changes in their offspring. The work raises concerns about the possible long-term effects of COVID-19 on generations, but so far all findings only apply to rodent models.
The team, led by Professor Anthony Hannan, infected male mice with a rodent-adapted version of SARS-CoV-2 at doses that were moderate to high infectivity. Four weeks after recovery — when the virus was no longer detectable — these males were mated with uninfected females. The researchers then performed a series of behavioral tests on the adult offspring, measuring anxiety, depressive-like reactions, learning, and memory. Offspring of parents who had been infected showed increased anxiety-like behavior compared to controls; females also showed changes in gene expression in the hippocampus, a region of the brain important for memory and emotion.
The mechanism behind these effects is linked to epigenetic changes in sperm. COVID-19 modified a set of small non-coding RNAs in male sperm, and these molecules have previously been identified as being able to "transmit" information about parental experience and influence the brain development of offspring. The researchers also obtained "grand-offspring" (second generation): they noticed a decrease in the number of litters and the weight of the mice, but no significant behavioral abnormalities were found in the "grandchildren".
It is important to emphasize that this study was conducted in mice and cannot be directly transferred to humans. However, previous data on the persistence of sperm changes after SARS-CoV-2 (up to approximately 110 days) and the results of this work together create the basis for additional studies in humans. Scientists call for a thorough study of the sperm and development of offspring of people who have had COVID-19 to find out whether similar mechanisms are at work in us.
So, the work by Hannan and colleagues rejects the simple idea that the effects of infection are limited to the affected individual: in a mouse model, a paternal infection can leave a “fingerprint” in sperm and affect the next generation. The next step is large and carefully designed clinical and epidemiological studies that will show whether this disturbing prospect has practical implications for humanity.
