# 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.

## Key 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.