What happens when
patients with ILD get COVID-19

Interstitial lung diseases (ILDs) affect 1 in 1000 people in Europe, so with this high prevalence, it is likely that many patients with ILD will develop COVID-19, despite public health messages, such as the need to shield and undergo vaccination.

The commonest ILD is sarcoidosis, but one of the most severe ILDs is idiopathic pulmonary fibrosis (IPF). IPF tends to affect older people, over 70 years of age, and men are affected more than women. IPF is associated with diabetes mellitus type 2, hypertension and ischemic heart disease. Patients with other ILDs that are not IPF, tend to be younger, more likely to be female, and often receive immunosuppressive therapy. All patients with ILDs, but particularly those with IPF, may suffer an acute exacerbation, with a high mortality rate. The cause of an acute exacerbation is not known, but viral infection may play a role.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may lead to coronavirus disease (COVID-19), characterized by a severe viral pneumonia and adult respiratory distress syndrome (ARDS) in approximately 20% of patients admitted to the hospital. Patients most at risk of severe COVID-19 include elderly males with comorbidities including obesity, diabetes mellitus type 2, hypertension and ischemic heart disease, with similarities to risk factors for severe IPF.

Research at UCL and UCLH

We took part in an international multicentre analysis of 161 patients with ILD who were admitted to various hospitals, between 1 March 2020 and 1 May 2020, with COVID-19, and this study is now published (https://doi.org/10.1164/rccm.202007-2794OC).

Of the 161 patients admitted, 68 had IPF and 93 had other ILDs. During the same period, 164 patients with ILD were admitted for reasons other than COVID-19 diagnosis, of whom 69 (42.1%) had IPF. Overall, the in-hospital mortality for patients with ILD and COVID-19 was 49% (79/161) compared with 17% (28/164) for patients with ILD admitted for other reasons.

In another part of the study, 161 patients with ILD were compared with 322 patients admitted to the hospital between March 1 and May 1, 2020, but without ILD or other chronic lung disease. There was significantly higher mortality in patients with ILD than in those without ILD (49% vs. 35%). Of patients with non-IPF ILD, those with chronic hypersensitivity pneumonitis and rheumatoid ILD had the highest mortality (50% and 40%, respectively), whereas those with sarcoidosis and connective tissue disease (excluding rheumatoid)–related ILD had the lowest observed mortality (33% and 23%, respectively).

The study showed that patients with existing ILD were at very high risk of death when hospitalized with COVID-19, especially if they were elderly males, with reduced prior lung function (less than 80% predicted) or obesity. Most died without being offered mechanical ventilation; in those who were ventilated, mortality was very high.

It was interesting that obese patients with ILD had a substantially increased risk of mortality which may reflect reduced exercise in this group because of worsening lung disease, or may suggest that ILD is independently associated with obesity.

Unfortunately, the study was not able to evaluate specific treatment effects, such as the use of antifibrotics, or steroids. The study was done before the RECOVERY trial and so steroids were not widely used. However, reassuringly, there was no suggestion of harm from any of the background therapies for ILD in patients with COVID-19, although further studies are needed.

There is some evidence that ILD may need a ‘second-hit’ and this might be provided by a viral infection. So that COVID-19 may ‘unmask’ ILD that was previously undiagnosed. This may explain why a tiny proportion of patients, around 1-2%, appear to do very badly with progressive fibrosis after COVID-19, having not previously been diagnosed with an ILD.

There is also interest in whether COVID-19 can cause a progressive ILD in patients who are not suffering from an undiagnosed ILD. We are involved in a large UKRI funded study to investigate the incidence of post-COVID-19 ILD in patients who had normal lungs beforehand. We hope to report the results of this study in late 2022.

Conclusions

These findings show that patients with ILD, and in particular, fibrosis ILD are at higher risk of dying from COVID-19 than patients without ILD. The risk is worse in older males, with obesity and poor lung function.

We would recommend that all patients with ILD and impaired lung function follow national guidelines for vulnerable individuals regarding self-isolation and vaccination.

 

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