Multi‐Organ Spread and Intra‐Host Diversity of SARS‐CoV‐2 Support Viral Persistence, Adaptation, and a Mechanism That Increases Evolvability

Abstract

Intra-host diversity is an intricate phenomenon related to immune evasion, antiviral resistance, and evolutionary leaps along transmission chains. SARS-CoV-2 intra-host variation has been well-evidenced from respiratory samples. However, data on systemic dissemination and diversification are relatively scarce and come from immunologically impaired patients. Here, the presence and variability of SARS-CoV-2 were assessed among 71 tissue samples obtained from multiple organs including lung, intestine, heart, kidney, and liver from 15 autopsies with positive swabs and no records of immunocompromise. The virus was detected in most organs in the majority of autopsies. All organs presented intra-host single nucleotide variants (iSNVs) with low, moderate, and high abundances. The iSNV abundances observed within different organs indicate that the virus can mutate at one host site and subsequently spread to other parts of the body. In agreement with previous data from respiratory samples, our lung samples presented no more than 10 iSNVs each. But interestingly, when analyzing different organs we were able to detect between 11 and 45 iSNVs per case. Our results indicate that SARS-CoV-2 can replicate, and evolve in a compartmentalized manner, in different body sites, which agrees with the "viral reservoir" theory. We elaborate on how compartmentalized evolution in multiple organs may contribute to SARS-CoV-2 evolving so rapidly despite the virus having a proofreading mechanism.