SARS-CoV-2 Genome Variations in Viral Shedding of an Immunocompromised Patient with Non-Hodgkin’s Lymphoma

Abstract

Background. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) is the most transmissible ß-coronavirus in history, affecting all population groups. Immunocompromised patients, particularly cancer patients, have been highlighted as a reservoir to promote accumulation of viral mutations throughout persistent infection. Case presentation. We aimed to describe the clinical course and SARS-CoV-2 mutation profile for 102 days in an immunocompromised patient with non-Hodgkin’s lymphoma and COVID-19. We used RT-qPCR to quantify SARS-CoV-2 viral load over time and whole-virus genome sequencing to identify viral lineage and mutation profile. The patient presented with a persistent infection through 102 days while being treated with cytotoxic chemotherapy for non-Hodgkin’s lymphoma and received targeted therapy for COVID-19 with remdesivir and hyperimmune plasma. All sequenced samples belonged to the BA.1.1 lineage. We detected nine amino acid substitutions in five viral genes (Nucleocapsid, ORF1a, ORF1b, ORF13a, and ORF9b), grouped in two clusters: the first cluster with amino acid substitutions only detected on days 39 and 87 of sample collection, and the second cluster with amino acid substitutions only detected on day 95 of sample collection. The Spike gene remained unchanged in all samples. Viral load was dynamic but consistent with the disease flares. Conclusions. This report shows that the multiple mutations that occur in an immunocompromised patient with persistent COVID-19 could provide information regarding viral evolution and emergence of new SARS-CoV-2 variants.

Intra-Host Evolution Analyses in an Immunosuppressed Patient Supports SARS-CoV-2 Viral Reservoir Hypothesis

“…Previous work has shown how SARS-CoV-2 can persist in different anatomical locations during infection, as well as months after the infection has been cleared from the respiratory system, accumulating mutations leading to new SARS-CoV-2 sequences. Recent evidence, including a study involving a patient with non-Hodgkin lymphoma [ 13 ], has highlighted the potential for novel substrains possibly from viral reservoirs, originating from initial infecting strains, to reinfect and replicate in the respiratory tract. Our intra-host phylogenetic analysis contributes to this growing body of evidence, emphasizing the role of viral reservoirs in the emergence of SARS-CoV-2 variants from prolonged infections in immunocompromised individuals.…”

“…Because there is more opportunity for viral evolution and the collection of samples in protracted infections of immunosuppressed individuals, these cases can be useful in understanding the dynamics of viral reservoirs. Recent studies have begun to fill this gap, providing longitudinal datasets of sequences collected from these individuals at different time points during their infections [ 11 , 12 , 13 ]. These datasets can give insights into evolutionary events that are not observed in acute infections, such as an instance of recombination between two viral strains [ 14 ] or the presence of distinct viral populations with immune escaping mutations in a single sample [ 15 ].…”

Radiologic Abnormalities in Prolonged SARS-CoV-2 Infection: A Systematic Review

“…Additional methodological details are provided in Figure 1 and in the Supplementary Methods and Supplementary Tables 1, 2 . This review included 19 studies that reported on a total of 24 patients (median age, 54.5 years [interquartile range (IQR) 44–64 years]; 15 male) [ 7 8 9 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 ].…”