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Case Reports
. 2023 Jan 28;15(2):377.
doi: 10.3390/v15020377.

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

Rodrigo Villaseñor-Echavarri  1   2 , Laura Gomez-Romero  3 , Alexandra Martin-Onraet  2 , Luis A Herrera  3   4 , Marco A Escobar-Arrazola  3   4 , Oscar A Ramirez-Vega  3   4 , Corazón Barrientos-Flores  1 , Alfredo Mendoza-Vargas  3 , Alfredo Hidalgo-Miranda  3 , Diana Vilar-Compte  1 , Alberto Cedro-Tanda  3
Affiliations
Case Reports

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

Rodrigo Villaseñor-Echavarri et al. Viruses. .

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.

Keywords: COVID-19; SARS-CoV-2; mutational landscape; non-Hodgkin’s lymphoma.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Clinical course and viral load. Timeline of clinical course and SARS-CoV-2 viral load across the five different collection days. The copy number in LOG10 of the three viral genes detected in RT-qPCR is shown. N: Nucleocapsid, S: spike and ORF1a. Solid lines correspond to calendar days and dashed orange lines correspond to elapsed days. The number of mutations per collection date including only those mutations that change their presence/absence status over time is shown per each collection date. Panel (A). Chest CT of the first flare. Panel (B). Chest CT at COVID-19 diagnosis. Panel (C). Chest CT of the second flare.
Figure 2
Figure 2
SARS-CoV-2 hierarchical clustering gene expression map. Euclidean distance was used as the distance metric in the hierarchical clustering algorithm. The colored maps show amino acid substitutions with at least one change within days of nasopharyngeal swab collection. Not available means that the region could not be covered during sequencing, so it does not have mutation data. Panel (A). Hierarchical clustering was applied over mutations to cluster mutations with similar temporal patterns, and isolates were sorted by collection date. Panel (B,C). Hierarchical clustering was applied over collection days to cluster isolates with similar mutation profiles, and mutations were sorted by genomic position. In panel (C), day 102 was removed from the clustering since 4 out of 12 mutations corresponded to missing data, which diminishes the clustering confidence.
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