Prolonged Severe Acute Respiratory Syndrome Coronavirus 2 Replication in an Immunocompromised Patient

Abstract

We describe a case of chronic coronavirus disease 2019 (COVID-19) in a patient with lymphoma and associated B-cell immunodeficiency. Viral cultures and sequence analysis demonstrate ongoing replication of infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for at least 119 days. The patient had 3 admissions related to COVID-19 over a 4-month period and was treated twice with remdesivir and convalescent plasma with resolution of symptoms. The patient's lack of seroconversion and prolonged course illustrate the importance of humoral immunity in resolving SARS-CoV-2 infection. This case highlights challenges in managing immunocompromised hosts, who may act as persistent shedders and sources of transmission.

Keywords: COVID-19; SARS-CoV-2; antibody; evolution; immunocompromise.

Figure 1.

A, Timeline of case. Color is by stage of infection, orange (initial presentation); yellow (largely outpatient); purple (recrudescence and readmission). Key events and treatments are shown above the timeline and key laboratory values are shown below it. B, Immunofluorescence microscopy of viral cultures. The patient’s samples (days 106 and 119) and a positive control (WA-1 strain) viral stock were cultured on Vero E6 cells until cytopathic effect was observed. Huh-7 cells were infected with cell-free supernatants from the Vero E6 cultures and stained 48 hours later with Hoechst (blue, nuclei) and an anti–severe acute respiratory syndrome coronavirus 2 nucleocapsid antibody (magenta). C, Maximum likelihood phylogenetic tree of whole genome consensus sequences for 9 samples from this case (red tips) and 100 other samples from inpatients at the same hospital (see Supplementary Table 1, color coded by lineage). Tree is rooted to Wuhan-Hu-1. Bootstrap support (1000 replicates) at nodes for the samples from the case and for all lineages is >90. D, Consensus mutations in the 9 samples sequenced. All nucleotide substitutions are shown. Amino acid substitutions are indicated for all nonsynonymous substitutions. Mutations in blue were in the original day 7 sample and persisted. Mutations in orange were detected in 1 of 2 day 29 samples and then at days 93 and 106. Mutations in purple were first detected in the day 93 sample and persisted at day 106. Mutations in red were fixed in the day 106 sample only. Abbreviations: Ct, cycle threshold; E, envelope; IgG, immunoglobulin G; ND, not detected; NP, nasopharyngeal; ORF, open reading frame; S, spike.