In people with COVID‑19, the natural peptide humanin drops a lot, while another mitochondrial peptide called MOTS‑c goes up. Taking standard antiviral drugs didn’t change these levels, suggesting the changes are part of the disease itself rather than the treatment.

Coronavirus Disease 2019 (COVID-19) is a life-threatening and persistent pandemic with high rates of mortality and morbidity. Although a dysfunction in the mitochondria occurs in COVID-19 pathogenesis, the contribution of mitochondrial-derived peptides to its pathophysiology has not yet been completely elucidated. The goals of this research were to assess the circulating humanin and mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) levels in COVID-19 patients and explore the effects of antiviral drug therapy on these peptide levels. Thirty adult COVID-19 patients and 32 gender-matched healthy volunteers were enrolled in this study. Circulating humanin and MOTS-c levels were detected using the ELISA method during pretreatment (before drug therapy) and post-treatment (on the 7th day of drug therapy). We found that there was significant attenuation of the serum humanin levels in COVID-19 patients (P < 0.001). However, we detected a significant augmentation in serum MOTS-c levels when compared to controls (P < 0.01 for pre-treatment and P < 0.001 for post-treatment). Interestingly, antiviral drug therapy did not modify the serum MOTS-c and humanin levels. Our findings suggest that MOTS-c and humanin were involved in the COVID-19 pathogenesis. Our data may also imply that elevated MOTS-c could act as a compensatory mechanism to eliminate the effects of decreased humanin levels.