Host/genetic factors associated with COVID-19 call for precision medicine

Abstract

If the current rates of infection are to be better managed, and future waves of infection kept at bay, it is absolutely necessary that the conditions and mechanisms of exposure to Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) be better understood, as well as the downstream severe or lethal clinical complications. While the identification of notable comorbidities has now helped to define broad risk groups, the idiosyncratic responses of individual patients can nonetheless generate unexpected clinical deterioration which is difficult to predict from initial clinical features. Thus, physicians caring for COVID-19 patients face clinical dilemmas on a daily basis. The ability to decipher individual predispositions to SARS-CoV-2 infection or severe illness, in light of variations in host immunological and inflammatory responses, in particular due to genetic variations, would be of great benefit in infection management. To this end, this work associates the description of COVID-19 clinical complications, comorbidities, sequelae and environmental and genetic factors. We also give examples of underlying genomic susceptibility to COVID-19, especially with regard to the newly reported link between the disease and the unbalanced formation of neutrophil extracellular traps. As a consequence, we propose that the host/genetic factors associated with COVID-19 call for precision medicine in its treatment. This is to our knowledge the first article describing elements towards precision medicine for COVID-19 patients.

Neutrophil Extracellular Traps and By-Products Play a Key Role in COVID-19: Pathogenesis, Risk Factors, and Therapy

“…We hypothesize that this adverse, self-inflicted pathological effect, could almost certainly due to host factors in critically ill COVID-19 patients [ 87 ]. Those with the greatest risk of developing a serious form of COVID-19 are older adults or people with existing chronic medical conditions [ 1 , 88 , 89 ] ( Table 1 ).…”

“…These conditions correlate with the pathologies resulting from NET formation dysregulation, as described above. Given that context, it is obviously necessary to investigate the influence of comorbidities, individual immune response, previous or co-infections, previous diseases, ethnicity, and genetic or epigenetic alterations on COVID pathogenesis and NETopathies [ 87 ].…”

“…Recent findings have revealed that some ethnicities are more likely to develop serious COVID-19, in particular with respect to thrombotic risk [ 87 ]. For instance, Chinese patients experienced a three to four fold lower incidence of venous thromboembolism than Caucasians [ 90 ].…”

“…In view of the variations in host immunological and inflammatory responses, individual predispositions of various natures characterize COVID-19 physiopathology. We recently described possible COVID-19 host/genetic factors [ 87 ]. As we postulate that the exacerbation of NET formation plays a key role in COVID-19 pathogenesis, we also described a number of genetic factors affecting NET formation upon stimulation [ 87 ].…”

A Predictive Model and Risk Factors for Case Fatality of COVID-19

“…The relevance of genetic and biological factors for the susceptibility and evolution of COVID-19 have been described. There is increasing evidence that deficiency or overexpression of various immunological molecules and cellular populations as well as different genetic factors condition the clinical evolution and severity COVID-19 [ 51 , 52 , 53 ]. The inclusion of biological parameters of the immune-inflammatory and neuro-endocrine metabolic response of the patient to SARS-CoV-2 infection may improve the understanding of the pathogenesis of the disease and the clinical and therapeutic management of COVID-19 patients.…”