No abstract

Novel coronavirus (COVID-19) led to infected pneumonia and acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI). The entry-point receptor for COVID-19 is angiotensin-converting enzyme 2 (ACE2) at lung, and dipeptidyl peptidase-4 (DPP-4) is a receptor for Middle East respiratory syndrome coronavirus (MERS-CoV). There is 80% similarity between MERS-CoV and COVID-19. This study was planned to review the potential link between the incidence and severity of COVID-19 regarding the modulation of DPP-4 and ACE2 by DPP-4 and renin angiotensin system (RAS). In COVID-19, SARS-CoV2 binds ACE2 which is highly expressed by the epithelial cells of the blood vessel, intestine, and lung. However, pulmonary ACE2 seems to be a protective defense pathway during ARDS. DPP-4 is not concerned with the entry of COVID-19 but mediates the inflammatory reactions and cytokine storm that induced ARDS and AKI by COVID-19. The interaction between DPP4i and RAS inhibitors seem to augment the expression of AT2 receptor and ACE2 which are under extensive researches to find the pathophysiological pathway of COVID-19 infection. This beneficial interaction between DPP4i and RAS shed light for possible attenuation of COVID-19-induced ARDS and AKI mainly in critically ill patients with systemic hypertension.

Primary infection of SARS-CoV-2 (novel coronavirus or 2019-nCoV), which leads to Covid-19, targets specific cells, such as nasal, bronchial epithelial and pneumocytes, through the viral structural spike (S) protein that binds to the angiotensin-converting enzyme 2 (ACE2) receptor. Also, type 2 transmembrane serine protease (TMPRSS2) present in the host cell promotes viral uptake by cleaving ACE2 and triggering the SARS-CoV-2 S protein, which facilitates SARS-CoV-2 entry into host cells. One of the TMPRSS2 inhibitors with a greater distribution capacity into the lung tissue is bromhexine hydrochloride which attenuates the entry and proliferation of SARS-CoV-2. Bromhexine is an effective drug in the management and treatment of Covid-19 pneumonia via targeting ACE2/ TMPRSS2 pathway. However, prospective and controlled clinical trials are recommended to confirm this observation.

The novel coronavirus which is also called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for COVID-19 (coronavirus disease 2019). SARS-CoV-2 is known to cause substantial pulmonary disease, including pneumonia and acute respiratory distress syndrome (ARDS), clinicians have observed many extra-pulmonary manifestations of COVID-19. SARS-CoV-2 infection is associated with a variety of pro-inflammatory mediators that may play important roles in the pathophysiology of cardiac and arrhythmic complications. Systemic inflammatory response syndrome (cytokine storm) is another putative mechanism of myocardial injury. In addition to lung damage, there may be significant cardiac involvement in patients with COVID-19, which is responsible for worsening the clinical condition of the host. The main cardiac manifestations can be oedema, pericarditis, cardiac fibrosis, myocarditis, impairment of contractile function and cardiac electrophysiology. The cardiac status of patients with ongoing SARS-CoV-2 infection of surviving patients in convalescence period should be carefully monitored.