Combination of two rare mutations in the SARS-CoV-2 M gene in patients with severe and prolonged COVID-19.

Background: The SARS-CoV-2 virus significantly changed our knowledge about coronaviruses. The interplay between SARS-CoV-2 and the human host, the infection ranges from asymptomatic to lethal, and differences in the degree of disease severity are important examples.

Methods: In this retrospective study, 24 nasopharyngeal swabs from 21 out of 457 patients with SARS-CoV-2 infection were analysed by whole-genome sequencing. The principal selection criteria were the duration of infection and disease severity.

Results: Two co-occurring rare mutations in the SARS-CoV-2 M gene were detected in six samples. Three of these samples were collected from an immunocompromised patient with fatal outcome, two from an immunocompetent patient, and one from a patient with severe disease and fatal outcome, all with a prolonged course of infection.

Conclusions: Although this interesting finding was demonstrated in a small number of patients, the results increase the knowledge regarding the significance of mutations in the M gene of SARS-CoV-2 in the context of persistent infection and viral escape mechanisms.