SARS-CoV-2 detection via metagenomic next-generation sequencing of bronchoalveolar lavage fluid/sputum in lymphoma patients receiving B-cell-depleting therapy: a case report of two cases

TL;DR

Two lymphoma patients on B-cell-depleting therapy showed SARS-CoV-2 in their lungs but not in nasal swabs, highlighting the need for alternative diagnostic methods in immunocompromised individuals.

Contribution

Demonstrates the utility of mNGS in detecting SARS-CoV-2 in lung samples when nasopharyngeal tests are negative in immunocompromised patients.

Findings

mNGS detected SARS-CoV-2 in BALF/sputum despite negative nasopharyngeal swabs.

Patients did not develop IgG antibodies but had favorable outcomes with antiviral therapy.

Viral clearance in the lungs lagged behind the upper respiratory tract in immunocompromised hosts.

Abstract

We describe two cases of coronavirus disease 2019 (COVID-19) infection in patients with lymphoma receiving B-cell-depleting therapy. Metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF)/sputum showed ongoing viral replication, despite repeated nasopharyngeal swabs being negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. The patients failed to develop seroconversion of IgG antibodies for SARS-CoV-2. However, they showed favorable clinical outcomes after treatment with nirmatrelvir/ritonavir or molnupiravir, despite the antiviral therapies being initiated later in the clinical course. Our case highlights that in immunocompromised hosts, viral clearance of SARS-CoV-2 in lung tissue may lag behind that in the upper respiratory tract. Thus, alternative diagnostic criteria are necessary, and clinical decisions and interventions should be tailored to each individual case.

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