One of SARS-CoV-2’s deepest mysteries is why it hits some people extremely hard and spares others completely. Researchers are gathering evidence on a theory that immune deficiencies based on genetics may underlie some of Covid-19’s un­pre­dict­able impact.

Jean-Laurent Casanova, M.D., Ph.D. is head of a laboratory at Rockefeller Uni­ver­sity. He has spent over 25 years investigating the hypothesis that life-threaten­ing disease can result from inborn errors of immunity, even in young, healthy people and even from otherwise typically mild or benign infections.

Dr. Casanova and colleagues are recruiting volunteers worldwide who have had severe cases of Covid-19 and been admitted to an ICU, and who are under the age of 50 and free of co-morbidities. The COVID Human Genetic Effort will scrutinize the DNA of these volunteers for shared genetic anomalies that may degrade the ability of their immune systems to fight SARS-CoV-2.

Such genetic deficiencies — called inborn errors of immunity or IEIs — have been found to affect the body’s response to an extensive list of viral, bacterial, fungal, and parasitic challenges. These include HIV, norovirus, plasmodium vivax, influenza, rhinovirus (one of the causes of the common cold), herpes simplex, varicella zoster, Epstein-Barr virus, and many others, over 400 in all. These discoveries have led to new clinical solu­tions for sometimes severe conditions that had defied treatment.

Here is a video of Dr. Casanova describing the COVID Human Genetic Effort.

The researchers write:

If this proves true, it may open the door to novel approaches to treatment and prevention of Covid-19.

Quanta Magazine has an excellent summary of this research initiative, and of the history of investigations into IEIs’ role in human immune reactions to a wide variety of diseases.