How COVID-19 Has Impacted Patients With Interstitial Lung Disease

How COVID-19 Has Impacted Patients With Interstitial Lung Disease

By: Saniya Khan, MD, MBBS; Tejaswini Kulkarni, MD; Kathryn W. Hendrickson, MD; Sean Callahan, MD; Dan Reynolds, MD; Adrian Shifren, MBBCh, FCCP; and Corey D. Kershaw, MD, FCCP
Interstitial and Diffuse Lung Disease Network
Published: December 8, 2021

Worldwide, pulmonologists have dealt with the unique challenges of caring for patients with COVID-19 and preexisting interstitial lung diseases (ILD), along with the evolution of distinct entities related to identification of persistent COVID-related inflammatory changes.

Certain risk factors for the development of post-ARDS residual disease have been identified,¹ with factors such as hyperoxia, barotrauma, and superimposed bacterial infections likely being contributory factors. This, along with the interplay of toxic viral effects and virus-associated autoimmune reactions, has led to the entity described as "post-COVID interstitial lung disease," characterized by radiographic abnormalities persisting beyond the acute illness.^2,3,4 These findings range from patchy pneumonic infiltrates and diffuse ground glass disease, which have shown to have a predictable resolution, to varying patterns of interstitial thickening and fulminant fibrosis. The etiology of post-COVID-19 fibrotic changes remains unclear; hence, a predictable model for its resolution is also lacking.  

As uncertainties surround the future of the pandemic, this article aims to contribute toward the care of these complex lung entities through our shared experience along with currently available data. 

Impact of COVID in Patients With ILD

The abrupt changes in global health during this pandemic disrupted the routine care of patients with ILD. Several protocols have been adapted by health care systems to mitigate these effects, such as by providing care to patients via telemedicine visits and home visits by nurses.  

While these measures allowed us to interact with our patients, lack of objective measures of disease progression, including pulmonary function tests (PFT) and 6-minute walk (6MW) tests, resulted in suboptimal clinical assessment. Home spirometry to obtain an objective measure of disease progression gained traction during this pandemic; however, it has not been generalizable due to lack of standardization in comparison with in-clinic spirometry and cost effectiveness.  

Apart from these challenges, patients with ILD have a higher susceptibility to COVID-19 and greater risk for severe disease than those without ILD.⁵ One study reported an overall mortality of 49% in patients with ILD with COVID-19; poor lung function and obesity increased this risk of death.⁶  

In another study, severe disease and death was more common among patients with ILD and COVID-19 compared with age-, sex-, and race-matched controls without ILD.⁷ Among the ILD patients, nonsurvivors were older, had lower DLCO, and had an increased proportion of a usual interstitial pneumonia pattern on computed tomography (CT) scans; prior ILD-directed therapies did not affect the outcomes in this small cohort.⁷ It is not known yet if these risks are related to acute exacerbation phenotype, increased thrombotic events, or secondary infectious complications.  

Nonetheless, the impact of COVID-19 among patients with ILD is profound, and we should continue to seek improvement in available technologies, particularly home spirometry assessments, centralization of laboratory assessments, and remote pulmonary rehabilitation, to deliver safe care to this patient population. 

Post-COVID Fibrosis

As many as 53% of patients hospitalized with COVID-19 have evidence of ongoing lung disease on CT scan 6 months after discharge.⁸ For follow-up testing for the patient with persistent dyspnea or other chest symptoms following COVID-19, simple spirometry with DLCO and chest X-ray may be utilized. CT scans may show persistent ground glass, septal thickening, and bronchiectasis. These CT abnormalities correspond with lower forced vital capacity (FVC), DLCO, and 6MW distance, although spirometry is most often normal.⁹ Patients with severe disease are more likely to show persistently reduced function.¹⁰ PFT and 6MW changes are expected to improve and often normalize by 3 months.⁹ 

Data regarding treatment for post-COVID fibrotic lung disease are limited. Corticosteroids remain controversial; an observational study suggested some patients may improve with steroids. Thirty out of 35 patients with ongoing symptoms and imaging consistent with organizing pneumonia received 0.5 mg/kg oral prednisone with 3-week taper. Imaging, symptoms measured by Medical Research Council dyspnea score, FVC, and total lung capacity all improved in the study population receiving steroids, although there was no equal comparator group.¹¹ This study was not randomized or placebo-controlled, and established literature suggests harm when administering corticosteroids late in ARDS.¹² Similarly, there are no trial data supporting the use of antifibrotic drugs after COVID-19.¹³ This lack of robust data limits our ability to offer blanket suggestions for corticosteroids and antifibrotics, making time, patience, and support the backbone of post-COVID care. 

COVID-19 Vaccination for Patients on Immunosuppression and Timing of Boosters

Vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) offer robust protection, notably against severe infections requiring hospitalization.^14-16 However, lower circulating antibody levels in vaccinated immunosuppressed individuals contribute to more than 40% of breakthrough COVID-19 infections in all fully vaccinated hospitalized patients,^17,18 and vaccinated but immunosuppressed individuals have an 82-fold higher risk of breakthrough infection and 485-fold higher risk of infection with hospitalization and death.¹⁹ 

Data from immunosuppressed patients receiving SARS-CoV-2 mRNA vaccines suggest a less robust antibody response. Select reports in vaccinated solid organ transplant recipients have documented lower antibody levels, especially in patients receiving antimetabolites (eg, mycophenolate), glucocorticoids, and rituximab.^20,21 Similar findings were reported in a nontransplant immunosuppressed cohort, again in those receiving mycophenolate and rituximab.²² 

Additional doses of SARS-CoV-2 mRNA vaccines have been shown to increase antibody levels in solid organ transplant patients, with 40% of recipients mounting a significant antibody response after two doses but increasing to 68% after three doses.²³ The Centers for Disease Control and Prevention currently recommends that moderately to severely immunosuppressed patients receive a third dose of mRNA vaccine ≥28 days after the second dose, as well as an additional fourth dose ≥6 months after the third.²⁴ 

References

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24. Centers for Disease Control and Prevention. COVID 19 Vaccines for Moderately to Severely Immunocompromised People. Updated October 25, 2021. Accessed October 28, 2021. https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html#considerations-covid19-vax-immunocopromised

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