Immunogenomic phases of COVID-19 and appropriate clinical management.

In their Article in The Lancet Microbe, Bernadette Schurink and colleagues found that multiorgan involvement of COVID-19 is not directly virus induced but mainly due to the pathobiological immune alterations. Their outstanding study further outlined the urgent need of crucial biomarkers indicating clinicobiological phase of COVID-19 relevant to key decision making at the bedside of a patient with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

We have described three immunogenomic phases (“initial”, “propagating”, “complicating”) of coronavirus (CoV) infections and their corresponding transcripts (ACE2, ANPEP, EGFR, IGF2R, IFN) as potential biomarkers.2, 3 At the “initial” and “propagating” phases of CoV infection, crucial renin-angiotensin system family genes were up-regulated (ACE2, ANPEP) while some others (EGFR, IGF2R) were down-regulated. Antivirals and immunomodulation with immune plasma or intravenous immunoglobulin seem to be appropriate treatments during the first two phases of CoV infections. During the “complicating” phase, there is an increase in the expression of some key immune system genes, particularly IFN-family genes. Glucocorticoids, monoclonal antibodies, and other immunosuppressive regimens might be most useful during the third “complicating” phase of CoV infections, the phase associated with macrophage activation and exaggerated or disproportionate immune attack.

Schurink and colleagues disclosed multisystemic COVID-19-associated inflammatory changes in the lungs, heart, kidneys, and brain. All of those organs have a local autocrine tissue renin-angiotensin system that could be affected by the SARS-CoV-2 ACE2 interactions and their immunoinflammatory pathological outcomes. Therefore, directed renin-angiotensin system modulator medicines, such as soluble ACE2, APN01, angiotensin (1–7), TXA127, and MAS receptor agonists,3, 4, 5 might be considered to be so-called drugs of hope for the pharmacobiological management of the all three stages of CoV infection on the basis of future controlled clinical trials.