Understanding Life-threatening COVID-19 Pneumonia

COVID-19Understanding Life-threatening COVID-19 Pneumonia

What causes severe COVID-19 symptoms? Evidences suggest inborn errors of type I Interferon immunity and autoantibodies against type I Interferon are causal for critical COVID-19. These errors can be identified using whole genome sequencing, thereby leading to proper quarantine and treatment.

A recent paper throws light on causal mechanism underlying severe COVID-19 pneumonia.

More than 98% of the infected persons do not get any symptoms of the disease or develop mild disease. Less than 2% of the infected persons develop severe pneumonia 1-2 weeks after infection and need to be hospitalised for acute respiratory distress and/or organ failure. Less than 0.01% of the infected persons develop severe systemic inflammation resembling Kawasaki disease (KD).

Advanced age was found to be major risk for life-threatening COVID-19 pneumonia. Most of the persons requiring hospitalisation are more than 67 years of age – critical disease was found to be 3.5 times higher in persons more than 75 years of age than persons less than 45 years. Men are at higher risk of developing severe symptoms.

People with comorbidities like hypertension, diabetes, chronic cardiac disease, chronic pulmonary disease, and obesity are at higher risk of developing severe symptoms.

Some genotypes were causal for the severe COVID-19 phenotype. Inborn errors of interferon immunity play key role in development of severe symptoms. Patients with deleterious variants at 13 loci (that code for immunologically connected proteins) have defective interferons. These errors disrupt type I Interferon immunity thus causing excessive inflammation and critical COVID-19 symptoms. Further, neutralising autoantibodies against type I interferons are present in at least 10% of patients with severe life-threatening illness.

This paper concludes that inborn errors of type I Interferon immunity and autoantibodies against type I Interferon are causal for critical COVID-19.  

Perhaps identifying people with such genotypes will go a long way in preventing and treating severe outcome of the disease. Whole genome sequencing of people can be used to identify the vulnerable patients leading to their proper quarantine and treatment.



Zhang Q., Bastard P., Bolze A., et al., 2020. Life-Threatening COVID-19: Defective Interferons Unleash Excessive Inflammation. Med. Volume 1, Issue 1, 18 December 2020, Pages 14-20. DOI:  


Umesh Prasad
Umesh Prasad
Chief Editor, Scientific European

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