COVID-19 pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Sabawoon Mirwais, M.B.B.S, M.D.[2] Syed Hassan A. Kazmi BSc, MD [3] Tayyaba Ali, M.D.[4]

Overview

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus named for the similarity of its symptoms to those caused by the severe acute respiratory syndrome. Unlike SARS-CoV, the transmission of COVID-19 takes place during the prodromal period when those infected are mildly ill and are carrying on with their usual activities. This contributes to the spread of infection. The main pathogenesis of COVID-19 is severe pneumonia, RNAemia, combined with the incidence of ground-glass opacities, and acute cardiac injury. Person-to-person transmission occurs primarily via direct contact or through droplets spread by coughing or sneezing from an infected individual.

Pathophysiology

Pathogenesis

Tropism

Activation of Host Immune Reponses

  • SARS-CoV2 is known to cause a delayed-type I interferon response during the initial phases of infection.
  • Infection and viral replication lead to an activation of neutrophils, macrophages, and monocytes. Th1/Th17 induced specific antibodies are produced.
  • RNA viruses such as SARS-CoV and MERS are recognized pathogen associated molecular patterns by endosomal RNA receptors, TLR3 and TLR7 and the cytosolic RNA sensor, RIG-I/MDA5.[20]
  • This leads to downstream activation of NF-KB signaling cascade and nuclear translocation of transcription factors, which in turn leads to the production of type 1 interferon pro-inflammatory cytokines.
  • Coronavirus Nucleocapsid Inhibits Type I Interferon Production by Interfering with TRIM25-Mediated RIG-I Ubiquitination.

Transmission and Infectivity

  • The fact that large number of infected people were exposed to the wet animal market in Wuhan City where live animals are routinely sold, it is suggested that COVID-19 is likely of zoonotic origin.[28]
  • Initial reports identified two species of snakes that could be the culprit reservoir of COVID-19. However, there is no consistent evidence of coronavirus reservoirs except mammals and birds.[29]
  • Genomic sequence analysis of SARS-CoV-2 has shown 88% identity with two bat-derived SARS-like coronaviruses, indicating mammals as the most likely link between the virus and humans.[30]
  • Between the two types of the virus (L and S), the L type is more prevalent (~70%) than the S type (~30%).[31]
  • The L type, derived from the SARS-CoV-2 ancestral S type, is found to have a higher transmission rate than the S type and has accumulated a significantly higher number of derived mutations. This hints towards a more aggressive nature of the L type.
  • The rapid spread of the disease and the occurrence of cases among people who did not visit the wet animal market in Wuhan hint at the fact that person-to-person transmission is actively taking place.[32][33]
  • Person-to-person transmission occurs primarily via direct contact or through droplets spread by coughing or sneezing from an infected individual.
  • A recent pilot study has shown that some patients' stool specimens tested positive to SARS-CoV-2 and some patients who tested positive to rectal swabs had detectable virus in the gastrointestinal tract, saliva, or urine.[34]
  • The epidemic can double in the number of affected individuals every 7 days and every patient can infect 2.2 other individuals on average (R0).[35]
  • The mean R0 ranges from 2.2 to 3.58. With mitigation measures and transmission precautions, the R0 may be decreased.

Transmission through gastrointestinal route

  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been detected in non-respiratory specimens, together with stool, blood, ocular secretions, and semen. However, the role of those sites in the transmission is unsure.[36][37][38][39][40][41]
  • Several reports are evident for the detection of SARS-CoV-2 RNA from a stool sample, even after no viral RNA is detected from the upper respiratory sample.[42][43]
  • According to studies, the SARS-CoV-2 antigen is detected in gastrointestinal epithelial cells of a biopsy sample.[44]
  • Live SARS-CoV-2 is also cultured from stool samples in rare cases, providing the evidence that SARS-CoV-2 has the possibility of fecal-oral transmission.[37][45]
  • According to a recent investigation, Researchers adopt the method of control volume-based computational fluid dynamics (CFD) to inspect fluid flow characteristics during toilet flushing. Researchers illustrate through computer simulation that toilet flushing can produce plenty of turbulence and vortices above the toilet bowl. These vortices can create a cloud of live virus-containing aerosol droplets that can climb up to 106.5 cm from the ground. These virus-containing droplets can be inhaled and settle onto surfaces.[46] The toilet flushing effect has been studied before for the spread of other diseases. However, the World Health Organization and US Center for Disease Control and Prevention have not verified the transmission of SARS-CoV-2 through this route.[47] [48]
  • In spite of the fact that it is hard to affirm, fecal-oral transmission has not been clinically depicted, and as indicated by a joint WHO-China report, didn't have all the earmarks of being a noteworthy factor in the spread of infection. [49]

Incubation Period

  • Based on the observational data, the mean incubation period is found to be 5 days.[50][51]
  • The median incubation period is 3 days (range: 0 - 24 days).

Associated Conditions

Histopathology

Lung histopathology may show the following:[54][55]

Reference

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