Th1/Th2/Th17/TREG and TLRs Activation/KIR for COVID 19 Prediction of Outcome

COVID-19 is a disease with an initial viral phase followed, usually at the 7th day, of an
inflammatory state (cytokine storm) leading to respiratory distress, ICU admission and risk
of death. Thus, several biological agents, antagonists of the different cytokines (IL-6,
IL-1) have been used for patients with severe disease. However, there are no data about the
cytokine changes, at admission and after therapy, and its predictive value, a fundamental
knowledge to establish the best therapeutic strategy.

The first line of immune defense is the interaction of the virus with innate immunity cell
members. The toll like receptors (TLRs) family is a group of pattern recognition receptors
that include many different molecules (21-23). These bindings can activate dendritic cells,
monocytes, macrophages. There is an important RNA and DNA connection, activation of TLRs, the
production of type I interferons, and the development of some autoimmune diseases. TLR7 and
TLR8 specifically recognize simple-chain RNA of viruses and are expressed in endosomal
membranes. TLR8 is expressed in regulatory cells (Treg) and its activation results in
inhibition of its regulatory functions. Natural killer cells (NK) respond to alterations of
class I HLA molecules present in infected cells (24-26). An increase in class I HLA
expression could lead to an increase in NK activation by increasing its ability to produce
IFN-gamma. Therefore, the reasons for KIR binding are often variable between individuals and
between populations.