Key result
Persistent SARS-CoV-2 infection linked to ~11% greater intra-host viral diversity over time.
Why the study?
The reasons why some individuals develop persistent SARS-CoV-2 infection and how the virus survives long term are not fully understood.
Observational (n=33)
Yes
Absolute Event Rate: 16.4% vs 14.8%
p-value: p=0.005
During persistent SARS-CoV-2 infection, the virus undergoes significant intra-host evolution with increased diversity and mutations in key proteins, likely shaped by the host's innate immune response.
May warrant surveillance for evolving variants in persistent cases; leaves open effects on transmission, severity, or therapy.
Prolonged infection of SARS-CoV-2 represents a challenge to the development of effective public health policies to control the COVID-19 pandemic. The reason why some people have persistent infection and how the virus survives for so long are still not fully understood. For this reason, we aimed to investigate the intra-host evolution of SARS-CoV-2 during persistent infection. Thirty-three patients who remained RT-PCR positive in the nasopharynx for at least 16 days were included in this study. Complete SARS-CoV-2 sequences were obtained for each patient at two time points. Phylogenetic, populational, and computational analysis of viral sequences confirmed persistent infection with evidence for a transmission cluster in health care professionals that shared the same workplace. A high number of missense variants targeting crucial structural and non-structural proteins such as Spike and Helicase was found. Interestingly, longitudinal acquisition of substitutions in Spike protein mapped many SARS-CoV-2 predicted T cell epitopes. Furthermore, the mutational profiles observed were suggestive of RNA editing enzyme activities, indicating innate immune mechanisms of the host cell. Viral quasispecies analysis corroborates persistent infection mainly by increasing richness and nucleotide diversity over time. Altogether, our findings highlight a dynamic and complex landscape of host and pathogen interaction during persistent infection suggesting that the host’s innate immunity shapes the increase of intra-host diversity with possible implications for therapeutic strategies and public health decisions during the COVID-19 pandemic.
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Voloch et al. (2020) conducted an observational in Persistent SARS-CoV-2 infection (n=33). Prolonged infection duration (Time point 2) vs. Initial infection (Time point 1) was evaluated on Number of intra-host single-nucleotide variants (iSNVs) (p=0.005). Persistent SARS-CoV-2 infection was associated with a significant increase in intra-host viral diversity over time, with a mean of 16.4 variants at the second time point compared to 14.8 at the first (p=0.005).
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