# COVID‐19 Infection Confirmed by Bronchoalveolar Lavage Fluid Metagenomics ‐Next‐Generation Sequencing Instead of Pharyngeal Swabs in Follicular Lymphoma: Three‐Case Report and Literature Review

## TL;DR

This paper reports three cases where bronchoalveolar lavage fluid metagenomics confirmed late-stage COVID-19 in patients with weakened immune systems, despite negative throat swabs.

## Contribution

The study highlights the importance of using BALF mNGS for diagnosing persistent or recurrent COVID-19 in immunocompromised patients with B lymphocyte deficiency.

## Key findings

- Three follicular lymphoma patients with B lymphocyte deficiency had confirmed SARS-CoV-2 in BALF despite negative throat swabs.
- These patients showed low IL-6 levels in blood despite severe symptoms, indicating atypical immune responses.
- mNGS in BALF provided a more accurate diagnosis of lower respiratory tract SARS-CoV-2 infection in immunocompromised individuals.

## Abstract

Hematologic malignancy patients with B lymphocytopenia after anti‐CD20 monoclonal antibody or anti‐CD19 chimeric antigen receptor (CAR) T cell therapy often face prolonged SARS‐CoV‐2 positivity on pharyngeal swabs and persistent or recurrent COVID‐19 infection, resulting in high mortality.

Here, we describe three follicular lymphoma (FL) patients with persistent fever, cough, and hypoxemia, but they were ruled out for bacterial, viral, fungal, and other pathogen infections, and the throat swabs were consistently SARS‐CoV‐2 negative. These FL patients with B lymphocyte deficiency who were diagnosed with COVID‐19 infection confirmed by bronchoalveolar lavage fluid (BALF) metagenomics next‐generation sequencing (mNGS). Their COVID‐19 infection was characterized by differences in viral load in the upper and lower respiratory tracts. When this particular COVID‐19 infection occurred, although their percentages and absolute values of CD8+ T cells and CD4+ T cells were normal, they all had B lymphocyte deficiency and hypogammaglobulinemia. They all had low expression of interleukin (IL)‐6 in peripheral blood inconsistent with clinical infection symptoms.

The patients received a combination therapy of molnupiravir and methylprednisolone; then their symptoms were relieved over the next 2 weeks–2 months.

Therefore, for immunocompromised patients, especially those with B lymphocyte deficiency, hypogammaglobulinemia, and low expression of IL‐6 in peripheral blood inconsistent with clinical infection symptoms, mNGS for BALF should be performed as soon as possible in this particular condition to confirm the diagnosis of COVID‐19 infection.