Dear Editor,
In their recent retrospective analysis (n=525), Saho et
al 1. have demonstrated that pre-existing interstitial
lung disease (ILD), characterized by inflammation and fibrotic scarring
of pulmonary interstitial tissue, can elevate the risk of pneumonia
after SARS-CoV-2 infection, especially in males, elderly adults, and
those undergoing corticosteroid treatment1. This study
is commendable for its case definition and subgroup stratification
within interstitial lung diseases (ILDs), where idiopathic pulmonary
fibrosis (IPF), interstitial pneumonia with autoimmune features (IPAF),
and connective tissue disease (CTD)-associated ILD cases were prevalent
in the pneumonia group. However, I have few points, requiring further
discussion on the subject matter.
Frist, it is imperative to highlight, that the association between ILD
and SARS-CoV-2 infection led pneumonia is a vice-versaphenomenon. A contemporary retrospective analysis (n =391) by Günayet al2 shows that patients with post SARS-CoV-2
pneumonia are at increased risk of persistent clinical symptoms, and
development of ILD (pulmonary parenchyma
involvement)2. This risk is particularly heightened
among smokers, males, elderly adults, and those who required high nasal
flow cannula2. Contrast to SARS-CoV-2 infection,
vaccine induced ILD is rare phenomenon3, can’t be
attributed to specific vaccine, but rather an individual case specific
adverse event. Pre-versus post ILD events have different adversities and
should be monitored case by case.
Second, corticosteroid use has contrasting effects1,2.
In pre-existing ILD with SARS-CoV-2 pneumonia, it poses a risk for
pneumonia1. However, in patients with
SARS-CoV-2-induced pneumonia who later develop ILD, corticosteroids
reduce the risk of ILD2, possibly by reducing
inflammation. What is Saho et al 1.’s
perspective on corticosteroids as a risk factor for COVID-19 pneumonia?
Third, in this retrospective analysis, ~50% of ILD
patients (275 of 525) never received any approved COVID19 vaccine. This
decision was often due to safety concerns expressed by both patients and
physicians. However, such risky decision can increase COVID19
adversities among individuals IPAF4 who are receiving
immunosuppressive therapies. IPAF patients are frequent recipients of
immunosuppressive medications such as cyclophosphamide (CTX) and
mycophenolate mofetil (MMF) 1. China has 8 approved
COVID-19 vaccines5, including mRNA vaccines, but their
safety durability of immune protection, and dosing strategies are not
well defined for ILD patients. In some cases, vaccination can lead to
the exacerbations (dyspnoea, cough, and sputum production) of
pneumonia6,7, furthering emphasizing the need for
case-by-case vaccination at physicians’ discretion.
Forth, ILD is a common clinical manifestation of many autoimmune
diseases such as Sjögren’s syndrome, systemic sclerosis, systemic lupus
erythematosus, rheumatoid arthritis (RA), polymyositis/dermatomyositis,
anti-synthetase syndrome, ANCA-associated
vasculitides8, and there are sparse studies evaluating
adversity, safety and immunogenicity of different vaccines. It seems
imperative to understand whether reported ILD conditions is not arising
as a clinical manifestation of autoimmune disease. A recent
retrospective analysis in the Lancet eClinicalMedicine, reports the risk
of post COVID emergence of various autoimmune disease including
suchspondyloarthritis, RA, psoriasis, pemphigoid, Graves’ disease,
anti-phospholipid antibody immune mediated thrombocytopenia, multiple
sclerosis, and vasculitis9. There is an intricate
relationship between, autoimmunity. It can be understood that avoiding
SARS-CoV-2 vaccination, along with administration of immunosuppressants
could have adverse effects on ILD. In the worst case scenarios, ILD both
before and SARS-CoV-2 infection could pose a double
risk10.
In summary, Saho et al 1. meticulously
demonstrated how pre-existing ILD can increase the risk of COVID-19
pneumonia. However, the emergence of ILD as a post-acute COVID-19
sequelae or its onset after COVID-19 vaccination poses a severe risk to
patients with comorbid conditions such as elderly age, male sex,
immunosuppression, or systemic conditions with pulmonary manifestations,
requiring further clarification. I applaud Saho et
al 1 for their excellent work and looking forward for
their repones.