Clinical phenotype and outcome of persistent SARS-CoV-2 replication in immunocompromised hosts: a retrospective observational study in the Omicron era

Infection. 2024 Jun;52(3):923-933. doi: 10.1007/s15010-023-02138-0. Epub 2023 Dec 14.

Abstract

Purpose: This study aims to describe clinical, virological and radiological characteristics as well as treatment strategies and outcomes of immunocompromised patients with persistent SARS-CoV-2 replication.

Methods: We performed a retrospective cohort study of immunocompromised patients at the University Medical Center Freiburg between 01/2022 and 05/2023. Patients with substantial immunosuppression and persistent SARS-CoV-2 detection (Ct-value < 30 after 14 days) were included.

Results: 36 patients in our cohort reported mainly fever, dyspnoea or continuous cough. Viral load was significantly higher in concurrent samples taken from the lower respiratory tract (Ct-value = 26) than from the upper respiratory tract (Ct-value = 34). Time of detectable viral RNA after start of antiviral treatment was shorter in patients receiving two antivirals (median 15 days vs. 31 days with one antiviral agent). Short-course antiviral therapy (≤ 5 days) was less efficient in reduction of symptoms and viral load than prolonged therapy > 10 days. In 30% (8/27) of patients with repeated CT scans, we found the emergence of chronic pulmonary changes, which were more frequently in patients with B cell depletion (37%, 7/19) compared to patients with organ transplantation (12%, 2/17).

Conclusion: Ongoing SARS-CoV-2 replication in the lower respiratory tract is a relevant differential diagnosis in patients with severe immunosuppression and continuous cough, fever or dyspnoea even if nasopharyngeal swabs test negative for SARS-CoV-2. Especially in B cell-depleted patients, this may lead to inflammatory or fibrotic-like pulmonary changes, which are partially reversible after inhibition of viral replication. Antiviral therapy seems to be most effective in combination and over a prolonged period of time of > 10 days.

Trial registration number: DRKS 00027299.

Keywords: Antiviral therapy; Fibrotic-like lung changes; Immunosuppression; Lower respiratory tract; Omicron; SARS-CoV-2.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents* / therapeutic use
  • COVID-19 Drug Treatment
  • COVID-19* / diagnosis
  • COVID-19* / immunology
  • COVID-19* / physiopathology
  • COVID-19* / virology
  • Female
  • Humans
  • Immunocompromised Host*
  • Male
  • Middle Aged
  • Phenotype
  • Retrospective Studies
  • SARS-CoV-2*
  • Treatment Outcome
  • Viral Load* / drug effects
  • Virus Replication*

Substances

  • Antiviral Agents