A study published in the Journal of Infection detailed potential indicators for pulmonary fibrosis in survivors of severe coronavirus disease 2019 (COVID-19).
Wenhui Huang, The First Affiliated Hospital, Guangdong, China, and colleagues performed an observational cohort study of 81 survivors who recovered from severe COVID-19 pneumonia to investigate the potential indicators for post-fibrosis. The median hospitalization was 26 days and all patients had at least three follow-up CT scans after discharge. Pulmonary fibrosis was diagnosed based on the extensive and persistent fibrotic changes, including parenchymal bands, irregular interfaces, reticular opacities, and traction bronchiectasis with or without honeycombing on the follow-up CT scans. Patients were divided into two groups: fibrosis (N = 42) and non-fibrosis (N = 39).
The study found that patients in the fibrosis group were older (63 vs 51 years) and disproportionately male (73.8% vs 48.7%). In addition, patients in the fibrosis group also had more underlying diseases – any disease (78% vs 41%), diabetes (31% vs 23%), hypertension (40% vs 23%), chronic pulmonary disease (21% vs 7%), chronic liver disease (19% vs 13%), cardiovascular and cerebrovascular diseases (29% vs 15%) – than those in the non-fibrosis group. Additionally, patients in the fibrosis group were more likely to have had a fever (90.5% vs 69.2%, P = 0.034), had longer prehospital duration of fever (median 7 vs 3 days, P = 0.001), and were more likely to experience shortness of breath (respiratory rate of 22 vs 20, P = 0.024) on admission.
Further, researchers observed that patients in the fibrosis group had higher leucocyte count (6.78 x 109/L vs 4.75 x 109/L, P = 0.001), neutrophil count (5.14 x 109/L vs 3.03 x 109/L, P < 0.001) as well as elevated levels of C-reactive protein (CRP) (35.62 vs 10.90 mg/L, P = 0.001) and D-dimer (1.41 vs 0.26 mg/L, P = 0.001). In addition, longitudinal analysis demonstrated that the levels of neutrophils, CRP, lactate dehydrogenase (LDH) and neutrophil to lymphocyte ratio (NLR) were markedly above the normal range within 4 weeks in the fibrosis group, while CRP “dramatically elevated” in the next 4 weeks, in contrast to other parameters which declined. Conversely, in the non-fibrosis group, CRP and LDH levels were elevated within 2 weeks, then “decreased sharply” to normal. Researchers also reported that lymphopenia and eosinopenia occurred in most patients on admission.
The study also found that more patients in the fibrosis group suffered from severe complications such as respiratory failure (59.5% vs 17.9%), secondary infections (23.8% vs 0%) and acute respiratory distress syndrome (23.8% vs 0%), resulting in higher rates of ICU admission (81.0% vs 28.2%), compared to those in the non-fibrosis group.
“The [study] reported a series of early indicators after tracing backwards to the features of disease progression between fibrosis and non-fibrosis groups. Other than common factors of advancing age, male and underlying diseases, that had been well described, it should be noted that the dynamic evolution of inflammatory markers within two weeks of hospitalization might point to fibrosis,” the researchers said.
“More importantly, the long prehospital duration of fever, the rapid and shallow breathing, and the absence of eosinophil on admission might be a combination of early indicators. All these can be readily obtained in clinical practice; thus, it holds great promise for large-scale use in a catastrophic pandemic,” they added.
“In our study, all survivors had varying degrees of fibrotic damage, ranging from subtle linear opacities to diffuse distribution of crazy-paving pattern; 52% (42/81) of patients showed extensive and unimproved fibrosis in a longitudinal analysis of CT findings. The radiographical abnormalities strongly correlated with long-term impairment of lung function. It remains unclear why certain individuals are able to recover from lung injury, whereas others develop into fibrotic damage,” the researchers wrote.
The researchers said that a large cohort of prospective and long-term analysis should be performed for more evidence and that patients with mild or moderate infection would be included in their further study as the current study only enrolled survivors of severe or critical COVID-19 with a high likelihood of lung injury.