COVID-19 - Toward a comprehensive understanding of the disease

Abstract

The evidence on the pathophysiology of the novel coronavirus SARS-CoV-2 infection is rapidly growing. Understanding why some patients suffering from COVID-19 are getting so sick, while others are not, has become an informal imperative for researchers and clinicians around the globe. The answer to this question would allow rationalizing the fear surrounding this pandemic. Understanding of the pathophysiology of COVID-19 relies on an understanding of interplaying mechanisms, including SARS-CoV-2 virulence, human immune response, and complex inflammatory reactions with coagulation playing a major role. An interplay with bacterial co-infections, as well as the vascular system and microcirculation affected throughout the body should also be examined. More importantly, a compre-hensive understanding of pathological mechanisms of COVID-19 will increase the efficacy of therapy and decrease mortality. Herewith, presented is the current state of knowledge on COVID-19: beginning from the virus, its transmission, and mechanisms of entry into the human body, through the pathological effects on the cellular level, up to immunological reaction, systemic and organ presentation. Last but not least, currently available and possible future therapeutic and diagnostic options are briefly commented on.

Keywords: COVID-19; SARS-CoV-2; acute respiratory distress syndrome; coagulation; epidemiology; immunology; therapy.

Figure 1

COVID-19 and the cardiovascular system. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enters host cells activating inflammation processes, and, subsequently, multiorgan failure. Severe micro- and macrovascular dysfunction, as well as proinflammatory processes, may lead to plaque instability and, consequently, the development of acute coronary syndrome. Infection of the respiratory tract activates a ‘cytokine storm’ and subsequently T cells/macrophages infiltrating myocardium and resulting in myocarditis and cardiac damage. Additionally, SARS-CoV-2 invades cardiac myocytes directly, causing myocardial dysfunction and further complications, i.e., acute heart failure and/or arrhythmias; CK — creatinine kinase; IL — interleukin; LDH — lactate dehydrogenase.

Figure 2

Phases and severity grading of COVID-19 — after Siddiqi and Mehra [47], modified. During early infection virus replication and shedding is rapidly accelerating within the first 4–10 days (Phase I). Together with the cytopathic effect of the virus replication clinical symptoms occur and the first immunological mechanisms are triggered (Phase II). With an occurrence of the first non-neutralizing antibodies, antibody-dependent augmentation of inflammation occurs, which together with local thrombosis and sepsis leads to multiple organ failure (MODS), acute respiratory distress syndrome (ARDS), acute kidney injury (AKI) and deep venous thrombosis (DVT) and pulmonary embolism (PE). COVID-19 may present with four stages of severity, either as a mild respiratory tract infection, viral pneumonia, severe pneumonia, or ARDS; ALT — alanine aminotransferase; AST — aspartate aminotransferase; CRP — C-reactive protein; hs-cTnI — high-sensitivity cardiac troponin I; Ig — immunoglobulin; IL — interleukin; LDH — lactate dehydrogenase; LMWH — low-molecular-weight heparin; NOAC — non-vitamin K antagonist oral anticoagulant; PCT — procalcitonin; SARS-CoV-2 — severe acute respiratory syndrome coronavirus-2; SIRS — systemic inflammatory response syndrome.