# Delayed Viral Clearance Accompanied by Early Impaired Humoral and Virus-Specific T-Cell Response in Patients with Coronavirus Disease 2019 and Interstitial Lung Disease

## TL;DR

Patients with interstitial lung disease clear the virus more slowly and have weaker immune responses to SARS-CoV-2 compared to healthy individuals.

## Contribution

The study reveals impaired humoral and T-cell immunity in ILD patients during SARS-CoV-2 infection.

## Key findings

- ILD patients had higher viral loads compared to healthy controls.
- Neutralizing antibody levels against SARS-CoV-2 variants were significantly lower in ILD patients.
- Virus-specific T-cell responses were reduced in ILD patients 14 days after symptom onset.

## Abstract

Objectives: Patients with interstitial lung disease (ILD) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are at high risk of severe coronavirus disease 2019. It is unclear whether anti-viral cellular and humoral immunity is impacted in patients with ILD in the presence of immune disorders and immunosuppressive therapy. This results in poor control of viral infections following SARS-CoV-2 infection. We aimed to highlight the clinical management of patients with ILD with regard to the adjustment of anti-inflammatory therapy during SARS-CoV-2 infection. Methods: We compared viral clearance, antibody levels, and T-cell immune response between healthy controls and patients with connective tissue disease-related ILD (CTD-ILD) or interstitial pneumonia with autoimmune features (IPAF). Results: Patients with ILD exhibited a higher viral load than the control group (1.58 × 106 vs. 2.37 × 103 copies/mL, p = 0.018), as well as a significantly lower level of neutralizing antibodies against the wild-type (WT) virus (7.01 vs. 625.6, p < 0.0001) and Omicron BA.5 (7.19 vs. 128.4, p < 0.001). Similarly, a lower virus-specific T-cell (VST) immune response was observed 14 days post-symptom onset in the ILD group (CD4+ VSTs: 0.018 vs. 0.082, p = 0.005; CD8+ VSTs: 0.0008 vs. 0.047, p = 0.004). The ILD group had no other heightened inflammatory biomarkers compared with the control group. Conclusions: Our study provides novel evidence of the underlying interaction between virus clearance and host immune status and sheds light on the clinical management of patients with ILD with regard to the adjustment of anti-inflammatory therapy during SARS-CoV-2 infection.