COVID-2019 - A comprehensive pathology insight

Abstract

Corona virus disease-2019 (COVID-19) caused by severe acute respiratory syndrome corona virus-2 (SARS CoV-2), a highly contagious single stranded RNA virus genetically related to SARS CoV. The lungs are the main organs affected leading to pneumonia and respiratory failure in severe cases that may need mechanical ventilation. Occasionally patient may present with gastro-intestinal, cardiac and neurologic symptoms with or without lung involvement. Pathologically, the lungs show either mild congestion and alveolar exudation or acute respiratory distress syndrome (ARDS) with hyaline membrane or histopathology of acute fibrinous organizing pneumonia (AFOP) that parallels disease severity. Other organs like liver and kidneys may be involved secondarily. Currently the treatment is principally symptomatic and prevention by proper use of personal protective equipment and other measures is crucial to limit the spread. In the midst of pandemic there is paucity of literature on pathological features including pathogenesis, hence in this review we provide the current pathology centered understanding of COVID-19. Furthermore, the pathogenetic pathway is pivotal in the development of therapeutic targets.

Keywords: AFOP; ARDS; COVID-19; Pathology; SARS CoV-2; Therapeutic targets.

Fig. 1

Structure of SARS CoV-2 Virion. Spike (S) protein - helps in attachment to host cell. Membrane (M) protein - nutrient transport. Envelope (E) - virion outermost layer. " helps in viral assembly and budding " for the E protein function in the legend. Hemagglutinin esterase (HE) - inhibits host defenses. Nucleo-capsid (N) - encloses and protects viral genome. Viral genome- positive sense single stranded RNA.

Fig. 2

Pathogenesis of COVID-19. SARS CoV-2 infection in humans is possibly acquired from Rhinolopus bats or Pangolins or Civets and through an currently unknown intermediate host. The viral entry into host cell is mediated initially by S1 fraction of Spike protein binding to ACE2-R on target cells and subsequently by S2 fraction cleavage by TMPRSS2 (host cell origin) enabling viral internalization. Inside host cells viral genome undergoes replication with the help of RNA dependent RNA polymerase to form new virions, which infects other cells. In response to this there is excessive synthesis and release of pro-inflammatory factors mediated by angiotensin-II which is responsible for clinical presentation.

Fig. 3

Preventive and Therapeutic Targets for COVID-19. There are various structural and functional preventive and therapeutic targets (1) Spike protein by sub-unit vaccine. (2) ACE2-R saturation by exogenous soluble ACE which makes the receptor unavailable for viral binding.(3)ACE R binding by monoclonal antibodies and drugs blocking viral attachment. (4) TMPRSS2 inhibitors prevent viral entry into host cells by blocking cleavage of S2 fraction of S protein important for membrane fusion. (5) RNA dependent RNA polymerase inhibitors block viral transcription. (6) Viral protein synthesis inhibitors block viral translation.