Immune determinants of covid-19 disease presentation and severity

Immune determinants of COVID-19 disease 

presentation and severity

Petter Brodin   

1,2

 ✉

COVID-19, caused by SARS-CoV-2 infection, is mild to moderate in the majority of previously healthy individuals, but can cause 

life-threatening disease or persistent debilitating symptoms in some cases. The most important determinant of disease severity is 

age, with individuals over 65 years having the greatest risk of requiring intensive care, and men are more susceptible than women. 

In contrast to other respiratory viral infections, young children seem to be less severely affected. It is now clear that mild to severe 

acute infection is not the only outcome of COVID-19, and long-lasting symptoms are also possible. In contrast to severe acute 

COVID-19, such ‘long COVID’ is seemingly more likely in women than in men. Also, postinfectious hyperinflammatory disease has 

been described as an additional outcome after SARS-CoV-2 infection. Here I discuss our current understanding of the immuno-

logical determinants of COVID-19 disease presentation and severity and relate this to known immune-system differences between 

young and old people and between men and women, and other factors associated with different disease presentations and severity.

Nature MeDICINe

 | VOL 27 | JanUaRy 2021 | 28–33 | 

www.nature.com/naturemedicine

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NATuRe MeDICINe

are being describe

by collaborative networks of pediatricians. Most MIS-C patients are 

treated with strong immunomodulatory regimens such as high-dose 

steroids, intravenous immunoglobulins and anti-cytokine therapies 

coupled with anti-coagulation to counter the microangiopathy and 

activation of both complement and coagulation cascades during the 

hyperinflammatory disease phas

,

unknown, but a delay of 2–6 weeks from initial SARS-CoV-2 infec-

tion indicates a role for adaptive immune responses and specific 

autoantibodies have been propose

,