Immune response to SARS-CoV-2 in severe disease and long COVID-19

COVID-19 is mild to moderate in otherwise healthy individuals but may nonetheless cause life-threatening disease and/or a wide range of persistent symptoms. The general determinant of disease severity is age mainly because the immune response declines in aging patients. Here, we developed a mathematical model of the immune response to SARS-CoV-2 and revealed that typical age-related risk factors such as only a several 10% decrease in innate immune cell activity and inhibition of type-I interferon signaling by autoantibodies drastically increased the viral load. It was reported that the numbers of certain dendritic cell subsets remained less than half those in healthy donors even seven months after infection. Hence, the inflammatory response was ongoing. Our model predicted the persistent DC reduction and showed that certain patients with severe and even mild symptoms could not effectively eliminate the virus and could potentially develop long COVID.