COVID-19 Science

SARS-CoV-2: Chronic Infection and Variants of Concern

Updated Dec 10, 2021

3 DEC 2020: Persistence and Evolution of SARS-CoV-2 in an Immunocompromised Host (NEJM)
“Phylogenetic analysis was consistent with persistent infection and accelerated viral evolution. Amino acid changes were predominantly in the spike gene and the receptor-binding domain, which make up 13% and 2%” 

5 FEB 2021: SARS-CoV-2 evolution during treatment of chronic infection (Nature)
“These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy, which is associated with the emergence of viral variants that show evidence of reduced susceptibility to neutralizing antibodies in immunosuppressed individuals.”

5 MAY 2021: Researchers Tie Severe Immunosuppression to Chronic COVID-19 and Virus Variants (JAMA)

27 JUN 2021: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Sequence Characteristics of Coronavirus Disease 2019 (COVID-19) Persistence and Reinfection (Clinical Infectious Diseases)
”Patients with persistent coronavirus disease 2019 (COVID-19) demonstrated more rapid accumulation of sequence changes than seen with community-driven evolution with continued evolution during convalescent plasma or monoclonal antibody treatment.”

26 AUG 2021: The continuous evolution of SARS-CoV-2 in South Africa: a new lineage with rapid accumulation of mutations of concern and global detection (medRxiv preprint)
“Like several other VOCs, C.1.2 has accumulated a number of substitutions beyond what would be expected from the background SARS-CoV-2 evolutionary rate. This suggests the likelihood that these mutations arose during a period of accelerated evolution in a single individual with prolonged viral infection through virus-host co-evolution.” 

19 OCT 2021: A cancer survivor had the longest documented COVID-19 infection. Here’s what scientists learned (Science)
PREPRINT: Year-long COVID-19 infection reveals within-host evolution of SARS-CoV-2 in a patient with B cell depletion (medRxiv)
“The unique viral mutations found in this study highlight the importance of analyzing viral evolution in protracted SARS-CoV-2 infection, especially in immunosuppressed hosts, and the implication of these mutations in the emergence of viral variants.” 

7 DEC 2021: Emergence of SARS-CoV-2 resistance mutations in a patient who received anti-SARS-COV2 spike protein monoclonal antibodies: a case report (BMC Infectious Diseases)
“We here report the case of an immunosuppressed patient infected with a B.1.1.7 variant, who received a combination of monoclonal antibodies, and subsequently selected mutations K417N, E484K and Q493R on Spike protein of SARS-CoV-2.”

7 DEC 2021: De novo emergence of a remdesivir resistance mutation during treatment of persistent SARS-CoV-2 infection in an immunocompromised patient: A case report (medRxiv preprint)
”In summary, we identified the de novo emergence of a RDV-resistance mutation, E802D, following initiation of RDV in an immunocompromised patient with persistent SARS-CoV-2 infection. While the finding is limited to a single case and requires confirmation of its generalizability in larger patient populations, it suggests that RDV may impart a selective pressure in vivo to drive evolution of the virus.”

7 DEC 2021: SARS-CoV-2 evolved during advanced HIV disease immunosuppression has Beta-like escape of vaccine and Delta infection elicited immunity (medRxiv preprint)
“What surprised us in the participant with prolonged infection was that, over the 6-month period where SARS-CoV-2 titer was high, infection was for the most part asymptomatic. One explanation is that the virus evolved attenuated pathogenicity or had low pathogenicity to begin with. Another may that high pathogen levels over time are tolerated because immunosuppression reduces the inflammatory response.”