COVID19 Virus To Infection – What Lies in the Genes

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In a research paper published in Nature, Scientists chronicle the journey of the covid virus from genome to infectome, that’s how its genes became an infecting virulent gene. 

Today we are going to look into that analysis to better understand the virus.

How COVID19 Became an Infecting Virus?

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) belongs to the group of Betacoronaviruses. The SARS-CoV-2 is closely related to SARS-CoV-1 and probably originated either from bats or pangolins. 

SARS-CoV-2 is an etiological agent of COVID-19, causing mild to severe respiratory disease which escalates to acute respiratory distress syndrome (ARDS) or multi-organ failure. 

  • The virus was first reported from the animal market in Hunan, Hubei province of China in the month of December, 2019, and was rapidly transmitted from animal to human and human-to-human. 
  • The human-to-human transmission can occur directly or via droplets generated during coughing and sneezing. 
  • Globally, around 53.9 million cases of COVID-19 have been registered with 1.31 million confirmed deaths.
  •  The people > 60 years, persons suffering from comorbid conditions and immunocompromised individuals are more susceptible to COVID-19 infection. 
  • The virus primarily targets the upper and the lower respiratory tract and quickly disseminates to other organs. 
  • SARS-CoV-2 dysregulates immune signaling pathways which generate cytokine storm and leads to the acute respiratory distress syndrome and other multisystemic disorders.

How The COVID Genome Infects

The Betacoronavirus have been reported to undergo recombination within bats. The SARS-CoV-2 belongs to Sarbecovirus and shares similarity with two bat derived Coronavirus strains bat-SL-CoVZC45 and bat-SL-CoVZXC21. 

  • The SARS-CoV-2 genome shows 96% similarity to horse-shoe bat virus RaTG13 Rhinolophus affinis 
  • The ecological separation of bats from human population makes an obvious note on the presence of an intermediate host, where SARS-CoV-2 develops adaptive changes, before transmitting to humans. 
  • This is supported by the difference in the key genomic features of SARS-CoV-2 from RaTG13 and SARS-CoV-1 
  • Although RaTG13 is 96% similar to SARS-CoV-2, but the receptor binding domain (RBD) of SARS-CoV2 spike protein shares only 85% similarity with the RaTG13 and only one out of six critical amino acid residues of RBD is similar in RaTG13 and SARS-CoV-2 
  • The five of the six amino acid residues differ between the SARS-CoV-1 and SARS-CoV-2 
  • The SARS-CoV-2 spike proteins contain a polybasic furin cleavage site insertion (residues PRRA) at the junction of S1 and S2, which is probably enhancing the infectivity of the SARS-CoV-2 and is not present in any other Coronavirus 
  • The coronaviruses reported in Pangolin exhibit a strong similarity to SARS-CoV-2. The Malayan pangolins Manis javanica illegally imported into southern China (Guangdong and Guangxi provinces) were reported to be infected with SARS-CoV-2 related virus 
  • Several SARS-CoV-2 related viruses have been reported in Malayan Pangolins.
  •  The sequencing data from these strains show them to be very closely related to SARS-CoV-2 and share 92.4–99.8% sequence identity. The Receptor Binding Motif (RBM) of Spike protein of these strains is also identical to SARS-CoV-2 and differs only in one out of five critical amino acid residues 
  • Therefore, SARS-CoV-2 might be a recombinant form of bat and pangolin coronaviruses, and the homologous recombination events might have occurred in spike glycoprotein genes between bat and pangolin CoVs 

It has been reported that the cats and ferrets can also get infected with SARS-COV-2 and are susceptible to air-borne transmission.

However, the virus replicates poorly in dogs, pigs and chicken Though, to ascertain the exact pattern and genomic ancestors of the recombination events, a wider sampling of the viral diversity is required to resolve the evolutionary events.

How It Targets Cells?

The COVID-19 has been regarded as Public Health Emergency of International Concern (PHEIC) on January 30, 2020 by WHO.

  • SARS-CoV-2 shares 96% genome similarity with a bat Coronavirus
  • The primary targets are the type-II alveolar epithelial cells and airway-epithelial cells, which highly express the Angiotensin converting enzyme-2 (ACE2) receptor on their surface. 
  • The ACE2 receptor is used for internalization, similar to SARS-CoV-1 and Human Coronavirus-229E (HCoV-229E)
  •  The SARS-CoV-2 quickly replicates inside the cells and kick-start the plethora of signaling cascade, from activating the pro-inflammatory response to antiviral response leading to cytokine storm. 
  • The virus rapidly disseminates through peripheral blood to other organs like, heart, kidney, liver, spleen, etc. 
  •  However, the pathogenicity of SARS-CoV-2 is notably less than SARS-CoV-1 and MERS-CoV, but its high transmissibility led to the pandemic, which resulted in the global lock-down and affected the global health scenario adversely.

The rapid development of the diagnostic tools and therapeutics in the form of antivirals and vaccines are the need of an hour to overcome the present situation.

How it affects different people?

As per the global scenario, about 53.9 million people have been reported to be positive for COVID-19 with 1.31 million confirmed deaths and 34.7 million recovered till November 14, 2020. 

  • The top five worst COVID-19 affected countries include, United States, India, Brazil, France and Russia with > 1.5 million cases till November 14, 2020.
  • The early reports from USA, China and Italy indicated the SARS-CoV-2 infection among people > 60 years of age . However, the recent reports (June–August, 2020) indicated the increased rate of infection (4.5% to 15%) among age groups of 15–29 years.
  • This dramatic shift in the infection cases in terms of age groups may be due to the reversion of younger population to their work place, Universities, colleges and schools etc.
  • Therefore, the COVID-19-related mortality has a varying age distribution starting from 10 to 80 years of age with a greater number of cases reported among patients suffering from other co-morbid conditions.
  •  The case fatality rate (CFR) is defined as total number of deaths to the total number of cases reported. In case of COVID-19 the CFR differs from country to country due to the differences in the medical and health infrastructure, co-morbidities and population age.
  • The major co-morbid conditions leading to the severity of COVID-19 include 10.5% for cardiovascular disease (CVD), 37.3% for diabetes, 8.3% for chronic obstructive pulmonary diseases (COPD), and 55.4% for hypertension, and 8.1% for cancer patients.
  • The sex-disaggregated COVID-19 data, collected from 26 countries indicate that males and females are almost equally susceptible to SARS-CoV-2 infection, however the mortality rate is 2.4 times higher in males compared to females.
  • The high mortality rates among males may be correlated to the co-morbidities like, diabetes, hypertension, cardiovascular diseases, and chronic kidney diseases etc.
  • The higher levels of circulating ACE2 have been reported in the plasma of males suffering from COVID-than females. This condition indicates the higher levels of ACE2 receptor expression on tissues, which help in virus internalization.

Overall, the COVID19 related mortalities have been reported to be higher in males than females due to the differences in immunological, genetic, endocrinological, social and behavioral factors.

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Source: Nature

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