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CORONA VIRUS

Corona ? 


COVID-19, also known as coronavirus disease 2019, is a respiratory infection caused by severe acute respiratory syndrome coronavirus (SARS COV-2)?

Transmission mainly occurs via direct contact or respiratory droplets. The infection may present asymptomatically, as a mild “flu-like” illness, or severely, with shortness of breath and life-threatening complications. Individuals who are over 65 years of age, immunosuppressed, or have preexisting conditions have a higher risk of developing severe symptoms and complications. Management is based on supportive care.


Etiology


Coronaviruses (CoVs) are a family of enveloped, positive-sense, single-stranded RNA viruses. They tend to cause mild upper respiratory diseases in humans

  • Severe acute respiratory disease coronavirus (SARS-CoV): emerged in 2003 in southern China from civet cats
  • Middle East respiratory syndrome coronavirus (MERS-CoV): emerged in 2012 in Saudi Arabia from dromedary camels
    • SARS-CoV-2: emerged in November 2019 in China from bats (still under investigation)
    • The genome is 96.2% identical to bat coronavirus RaTG13
    • It has not yet been determined whether the virus is transmitted directly from bats or through an unknown intermediate host

Diseases caused by Coronaviruses


Common Cold

GI tract infection

Incubation

3 days

3 days

Incidence

Most common

Rare

Prognosis

Complete resolution

Complete resolution(up to 25% fatal for NEC)

Clinical manifestation

Sneezing, rhinorrhea, headache, sore throat, malaise, fever, chills

Diarrhea, gastroenteritis, neonatal necrotizing enterocolitis


Severe acute respiratory syndrome (SARS)

2019 nCoV (Wuhan City, China)

Incubation

4–6 days

2–14 days

Incidence

Rare

Current pandemic

Prognosis

30% resolution

70% severe infection

10% fatal

80% resolution

15% severe infection

5% critical infection

4.9% fatal (as of July 1, 2020, based on identified cases and may change)

Clinical manifestation

Fever > 37,8°C (100,0°F), muscle pain, lethargy, cough, sore throat, malaise

Shortness of breath/ pneumonia (direct viral or sencondary bacterial)

Asymptomatic

Mild infection: fever, dry cough, muscle pain, lethargy, dehydration

Severe infection: high fever, shortness of breath, chest pain, hemoptysis

Complications: pneumonia, ARDS, sepsis, multi-organ failure

Structure

The SARS-CoV-2 virion is approximately 125 nm in diameter and its genome ranges from 26–32 kb, the largest of all RNA viruses. It has 4 structural proteins: spike (S), envelope (E), membrane (M), and nucleocapsid (N).

  • S, E, and M proteins create the viral envelope. 
  • N protein forms a complex with RNA (nucleocapsid) and aids in the regulation of viral RNA synthesis.
  • M protein projects on the external surface of the envelope, spans the envelope 3 times, and is important in viral assembly. 
  • E protein has an unclear function, although it may aid in viral release.
    • S protein is a club-shaped surface projection, giving the virus its characteristic crown-like appearance on electron microscopy. It is responsible for receptor binding and fusion with the host cell membrnae 


In January 2020, population genetic analysis concluded that SARS-CoV-2 had evolved into 2 separate genotypes:

  • L type: more aggressive and more prevalent (approximately 70% of cases in the early stages of outbreak; prevalence has since decreased) 
  • S type: evolutionary older, less common, and less aggressive (approximately 30% of cases) 

Pathogenesis


SARS-CoV-2 attaches to the host cell by binding its S protein to the receptor protein, angiotensin-converting enzyme 2 (ACE2). ACE2 is expressed by epithelial cells of the intestine, kidney, blood vessels, and, most abundantly, in type II alveolar cells of the lungs. 

The human enzyme transmembrane protease, serine 2 (TMPRSS2), is also used by the virus for S protein priming and to aid in membrane fusion. The virus then enters the host cell via endocytosis.


SARS-CoV-2 affects the expression and presentation of ACE2, contributing to its pathogenesis in the following ways:

  • Viral entry causes internalization of the receptor, leading to its reduced availability on the cell surface. Because ACE2 is a negative regulator of the RAAS system, its downregulation directly affects cardiovascular function.
  • ACE2 inhibition induces ADAM17 gene expression, leading to the release of tumor necrosis factor α (TNFα) and cytokines such as interleukin 4 (IL-4) and interferon γ (IFNγ).
  • Increased cytokine concentrations activate further proinflammatory pathways, leading to a cytokine storm.
  • ADAM-17 also promotes the cleavage of ACE2 receptors.
  • SARS-CoV-2’s affinity for ACE2 also results in direct and acute injury to the lung, heart, endothelial cells, and, potentially, other organs.

explanation-mark-green.svg

High levels of ACE2 expression are associated with certain chronic conditions, especially cardiovascular disease, ??and are linked to a higher risk of severe cases of COVID-19.?


The expression of ACE2 is significantly increased through the use of ACE inhibitors or angiotensin II receptor blockers (ARBs).

So aCE inhibitors are contraindicated in corona virus infection.(not sure research in progress) 


Transmission 


  • Coronaviruses are zoonotic; that is, they are transmitted to humans through animals. It is hypothesized that horseshoe bats are the natural reservoir of SARS-CoV-2, since the virus’s genome is 96.2% identical to that of a bat coronavirus. At this time, the intermediate host is still unknown.

Once in humans, the virus is transmitted when respiratory droplets from coughing, sneezing, or talking of infected individuals come into direct contact with the mucous membranes of another individual, including the eyes, nose, or mouth. In the air, larger droplets tend to drop toward the ground, within 1 m (3 ft) of the infected person, while smaller droplets can travel over 2 m (6 ft) and remain viable in the air for up to 3 hours under certain conditions. Other forms of transmission include the following:

  • Direct transmission through hand-to-face contact from infected surfaces
  • Fecal–oral transmission is also believed to occur (SARS-CoV-2 RNA has been detected in stool specimens, but fecal–oral transmission has not been clinically described).
  • Vertical transmission (mother-to-child) has not been reported.


COVID-19 is not considered to be airborne, as coughing, sneezing, and talking do not generate droplets small enough to behave as aerosols. However, certain medical procedures can generate virus-laden aerosol clouds, which put healthcare personnel at a higher risk of becoming infected.


  • Many factors can extend the range of respiratory droplet dispersion past 2 m (6 ft). Certain actions, such as forced expiration during yelling, singing, and exercise, can increase the volume and distance that respiratory droplets can travel.

The reproductive number (R0), or the number of secondary infections generated from 1 infected individual, is 2–2.5, higher than for influenza (0.9–2.1). COVID-19 is highly contagious for the following reasons: 

  • Production of high viral loads
  • Efficient and prolonged shedding of virions from the upper respiratory tract
    • Median duration of viral RNA shedding from the upper respiratory tract is 20 days.
    • Viral shedding can outlast the resolution of symptoms.
  • Asymptomatic individuals are also infectious, posing a significant challenge for contagion prevention. 
    • Viral loads peak before symptom onset, leading to asymptomatic or presymptomatic spreading of the virus and making symptom-based detection and isolation ineffective. 
    • Asymptomatic patients can produce high viral loads in secretions of the upper respiratory tract and can shed the virus for the same amount of time as symptomatic patients.
  • SARS-CoV-2 can remain infectious on surfaces outside of a host from a few hours to a few days.
    • Viral lifespan depends on the type of surface, temperature, and humidity levels.
    • There is currently no evidence to suggest that COVID-19 can be acquired from mail and packaged goods.



  • The period of highest infectivity for symptomatic cases ranges from 2 days before the onset of symptoms up to 3 days after their resolution (exact limits are still under investigation).

Epidemiology


The first case of COVID-19 was traced back to the city of Wuhan, China, in late November 2019, with an outbreak developing in December. 


  • The COVID-19 outbreak was declared a Public Health Emergency of International Concern on January 30, 2020, and a pandemic on March 11, 2020, by the World Health Organization (WHO).


Clinical Presentation

The incubation period for COVID-19 ranges from 2–14 days, with an average of 5 days. 

  • 80% of infections are mild or asymptomatic
  • 15% of infections are severe (requiring oxygen therapy)
  • 5% of infections are critical (requiring intensive care unit [ICU] admission and ventilation)

The proportion of severe and critical-to-mild cases is higher than in influenza infections.

Asymptomatic cases:

  • These individuals can transmit the virus.
  • They represent > 50% of all infections (still under investigation).
  • They do not develop any noticeable symptoms.
  • Anosmia, hyposmia, and dysgeusia have been reported in many laboratory-confirmed cases of patients who were otherwise asymptomatic.
  • It has not been clearly determined how long asymptomatic individuals remain contagious after initial infection.
  • These individuals can present radiological and laboratory findings characteristically found in symptomatic COVID-19 patients


Mild cases:

  • May present with dry cough and moderate fever
  • Include common flu-like symptoms such as fatigue, malaise, myalgia, runny nose, nasal congestion, and sore throat
  • Less frequently experience diarrhea, nausea, vomiting, diffuse abdominal pain, productive cough, headache, and muscle or joint pain
  • Dermatologic symptoms have been reported, including maculopapular, urticarial, and vesicular eruptions, transient livedo reticularis, perniosis-like red or purple tender nodules on the distal digits (“COVID toes”)
  • Have a recovery time of approximately 2 weeks

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Rishita Dhaka

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