Long-term SARS-CoV-2 Asymptomatic Carriage in an Immunocompromised Host: Clinical, Immunological, and Virological Implications

Abstract

Purpose: SARS-CoV-2 infection in immunocompromised hosts is challenging, and prolonged viral shedding can be a common complication in these patients. We describe the clinical, immunological, and virological course of a patient with eosinophilic granulomatosis with polyangiitis, who developed the status of long-term asymptomatic SARS-CoV-2 carrier for more than 7 months.

Methods: Over the study period, the patient underwent 20 RT-PCR tests for SARS-CoV-2 detection on nasopharyngeal swabs. In addition, viral cultures and genetic investigation of SARS-CoV-2 were performed. As for immunological assessment, serological and specific T-cell testing was provided at different time points.

Results: Despite the patient showing a deep drug-induced B and T adaptive immunity impairment, he did not experience COVID-19 progression to severe complications, and the infection remained asymptomatic during the follow-up period, but he was not able to achieve viral clearance for more than 7 months. The infection was finally cleared by SARS-CoV-2-specific monoclonal antibody treatment, after that remdesivir and convalescent plasma failed in this scope. The genetic investigations evidenced that the infection was sustained by multiple viral subpopulations that had apparently evolved intra-host during the infection.

Conclusion: Our case suggests that people with highly impaired B- and T-cell adaptive immunity can prevent COVID-19 progression to severe complications, but they may not be able to clear SARS-CoV-2 infection. Immunocompromised hosts with a long-term infection may play a role in the emergence of viral variants.

Keywords: COVID-19; Latent; Monoclonal; Mutation; Persistent; Viral microevolution.

Fig. 1

Timeline of diagnostic tests and treatment for SARS-CoV-2. Dots on the graphic represent the cycle threshold (Ct) values of the 19 PCR testing on nasopharyngeal swab performed by the patient between days 0 and 238. Ct values were not available for the first five swabs (days 0–28 in brackets); the last one (day 238) was negative for SARS-CoV-2 (Ct values > 40)

Fig. 2

Linear map of SARS-CoV-2 genome with non-synonymous mutations, detected over three different times from an immunocompromised patient with prolonged infection. Mutations constantly detected in all samples are represented by a continuous blue line on the gene, while the dotted line indicates the presence of a mutation occurred with a relative frequency ≤ 90% in that sample

Fig. 3

Evaluation of CD4 + T cell response to SARS-CoV-2 antigens or polyclonal stimuli. Flow cytometry plots showing CD154 expression and interferon (IFN)-γ production by CD4 + T cells following SARS-CoV-2 spike (S), membrane (M), and nucleoprotein (N) or SEB stimulation in one healthy non-infected individual, one COVID-19 recovered subject, and in the patient at 3 different time points