COVID-19 ups risk of pulmonary fibrosis

Infection with COVID-19 may increase the risk of pulmonary fibrosis, and patients with a severe disease are at greater risk of developing this complication, suggests a recent study.

“COVID-19 appears to be associated with an increased risk of pulmonary fibrosis and the magnitude of the association increases with COVID-19 severity,” the investigators said.

A total of 2,894,801 adults without a diagnosis of pulmonary fibrosis were analysed in this nested case-control study. The underlying cohort included members of the largest healthcare provider in Israel aged at least 18 years as of 1 May 2020. Participants were followed up from study entry until 30 June 2022 for the occurrence of pulmonary fibrosis.

Subsequently, the investigators matched 10 randomly selected controls to each case of pulmonary fibrosis based on age, sex, and calendar time. They also used a lag time of 60 days to account for surveillance bias and to ascertain prior COVID-19 and COVID-19 severity.

A total of 1,284 patients had a diagnosis of pulmonary fibrosis during follow-up and been matched with 12,840 control participants. [Am J Med 2023;136:1087-1093.E2]

In multivariable conditional logistic regression models, the chance of developing pulmonary fibrosis was higher in patients with COVID-19 compared with those without COVID-19 (odds ratio [OR], 1.80, 95 percent confidence interval [CI], 1.47‒2.19).

Of note, the likelihood for the occurrence of pulmonary fibrosis increased with COVID-19 severity: mild (OR, 1.33, 95 percent CI, 1.06‒1.68), moderate (OR, 2.98, 95 percent CI, 1.16‒7.65), and severe COVID-19 (OR, 9.30, 95 percent CI, 5.77‒14.98).

The extent of the association between COVID-19 and pulmonary fibrosis decreased but remained statistically significant for severe disease when the lag time was extended to 180 days: mild (OR, 1.08, 95 percent CI, 0.78‒1.49), moderate (OR, 2.37, 95 percent CI, 0.75‒7.46), and severe (OR, 5.34, 95 percent CI, 2.75‒10.36).

Additionally, several factors related to COVID-19 severity showed an association with pulmonary fibrosis development. These factors included male sex, intensive care unit admission, invasive and noninvasive mechanical ventilation, longer hospital stay, and steroid, antibiotic, and immunoglobulin treatment. [Ann Med Surg (Lond) 2022;77103590; Medicine (Baltimore) 2022;101:e28639]

“These findings further highlight the need for COVID-19 prevention and the importance of early treatment initiation in high-risk patients with mild to moderate disease,” the investigators said.

Viral infection

Different viruses could cause pulmonary fibrosis by inducing persistent lung damage, abnormal wound healing, or both, or by triggering immune-mediated injury.

“Macrophages, neutrophils, eosinophils, and Th2 cells aggregate at the site of injury and release a large number of proinflammatory and profibrotic cytokines and factors, such as transforming growth factor-β, tumour necrosis factor-α, matrix metalloproteinases, tissue inhibitor of metalloproteinases, interleukin (IL)-1, IL-4, IL-5, IL-6, IL-13 and IL-17,” the investigators said.

Viruses that had been previously observed to induce pulmonary fibrosis were cytomegalovirus, influenza, avian flu, SARS-CoV, and MERS-CoV. [J Transl Med 2021;19:496]