Persistent Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Immunocompromised Host Displaying Treatment Induced Viral Evolution

Monrad, Ida; Sahlertz, Signe Risgaard; Nielsen, Stine Sofie Frank; Pedersen, Louise Ørnskov; Petersen, Mikkel Steen; Kobel, Carl M.; Tarpgaard, Irene Harder; Storgaard, Merete; Mortensen, Klaus Leth; Schleimann, Mariane H.; Tolstrup, Martin; Vibholm, Line K.

doi:10.1093/ofid/ofab295

Cited by 22 publications

(15 citation statements)

References 18 publications

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“…Rituximab therapy has been associated with severe forms of COVID‐19 in patients with rheumatic diseases or hematologic malignancies. 8 , 9 , 10 , 11 Cases of prolonged SARS‐COV‐2 shedding or a COVID‐19 relapse in patients treated with rituximab have also been reported 12 , 13 in patients with hematologic malignancies. The patient failed to produce antibodies against SARS‐CoV‐2 supporting the conclusion drawn from previous studies that patients on rituximab are unable to produce neutralizing antibodies, resulting in more severe and more prolonged diseases.…”

Section: Discussionmentioning

confidence: 99%

Severe relapse of SARS-CoV-2 infection in a kidney transplant recipient with negative nasopharyngeal SARS-CoV-2 RT-PCR after rituximab

Morel

Imbeaud

Scemla

et al. 2022

American Journal of Transplantation

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Immunocompromised patients may experience prolonged viral shedding after their initial SARS‐CoV‐2 infection, however, symptomatic relapses after remission currently remain rare. We herein describe a severe COVID‐19 relapse case of a kidney transplant recipient (KTR) following rituximab therapy, 3 months after a moderate COVID‐19 infection, despite viral clearance after recovery of the first episode. During the clinical relapse, the diagnosis was established on a broncho‐alveolar lavage specimen (BAL) by RT‐PCR. The infectivity of the BAL sample was confirmed on a cell culture assay. Whole genome sequencing confirmed the presence of an identical stain (Clade 20A). However, it had an acquired G142D mutation and a larger deletion of 3‐amino‐acids at position 143–145. These mutations located within the N‐terminal domain are suggested to play a role in viral entry. The diagnosis of a COVID‐19 relapse should be considered in the setting of unexplained persistent fever and/or respiratory symptoms in KTRs (especially for those after rituximab therapy), even in patients with previous negative naso‐pharyngeal SARS‐CoV‐2 PCR.

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Section: Discussionmentioning

confidence: 99%

Severe relapse of SARS-CoV-2 infection in a kidney transplant recipient with negative nasopharyngeal SARS-CoV-2 RT-PCR after rituximab

Morel

Imbeaud

Scemla

et al. 2022

American Journal of Transplantation

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“…The host immune response typically clears SARS-CoV-2 infections by 15 to 25 days 1–4 , and this short duration of active virus replication limits within-host evolution. In contrast, infections in immunocompromised individuals can be prolonged, with the most prolonged previously documented infection lasting 333 days 5 . Prolonged infections may facilitate SARS-CoV-2 evolution by providing time for within-host selection to act, potentially driving the emergence of immunologic escape variants (reviewed in 6 ).…”

Section: Introductionmentioning

confidence: 99%

Evolution of a globally unique SARS-CoV-2 Spike E484T monoclonal antibody escape mutation in a persistently infected, immunocompromised individual

Halfmann

Minor

Haddock

et al. 2022

Preprint

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Prolonged infections in immunocompromised individuals may be a source for novel SARS-CoV-2 variants, particularly when both the immune system and antiviral therapy fail to clear the infection, thereby promoting adaptation. Here we describe an approximately 16-month case of SARS-CoV-2 infection in an immunocompromised individual. Following monotherapy with the monoclonal antibody Bamlanivimab, the individual's virus was resistant to this antibody via a globally unique Spike amino acid variant (E484T) that evolved from E484A earlier in infection. With the emergence and spread of the Omicron Variant of Concern, which also contains Spike E484A, E484T may arise again as an antibody-resistant derivative of E484A.

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“…Moreover, a strong selection on SARS-CoV-2 has been reported after convalescent plasma therapy in immunosuppressed individuals, leading to the emergence of viral variants with reduced susceptibility to neutralizing antibodies [12,21,22,32]. Interestingly, the presence of mutations was more frequently observed in samples of days 143 and 207 compared to the earliest available one, and it led to the identification of multiple intra-host microevolution pathways considering the 7-month period of infection.…”

Section: Discussionmentioning

confidence: 99%

“…To the best of our knowledge, it is one of the longest SARS-CoV-2 persistent asymptomatic infections reported to date. Although few reports of year-long SARS-CoV-2 detection in immunocompromised hosts have been described, it is unusual to observe a fully asymptomatic patient carrying the virus for more than 6 months [ 21 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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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.

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Persistent Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Immunocompromised Host Displaying Treatment Induced Viral Evolution

Cited by 22 publications

References 18 publications

Severe relapse of SARS-CoV-2 infection in a kidney transplant recipient with negative nasopharyngeal SARS-CoV-2 RT-PCR after rituximab

Severe relapse of SARS-CoV-2 infection in a kidney transplant recipient with negative nasopharyngeal SARS-CoV-2 RT-PCR after rituximab

Evolution of a globally unique SARS-CoV-2 Spike E484T monoclonal antibody escape mutation in a persistently infected, immunocompromised individual

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

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