COVID-19 Etiology, Transmission, Pathophysiology, Management, and Prevention

According to the World Health Organization, viral diseases continue to surface and represent a serious public health issue. In the last twenty years, several viral epidemics such as the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) in 2002–2003, the H1N1 influenza in 2009, the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in 2012 have been recorded.

Most recently on December 2019, an epidemic of cases with mysterious low respiratory infections detected in Wuhan, the largest metropolitan area in China’s Hubei province, was first reported to the WHO Country Office in China. As experts were unable to identify its cause, these first cases were categorized as ‘pneumonia of unknown etiology’. The Chinese Center for Disease Control and Prevention (CDC) organized a rigorous outbreak investigation program. The etiology of this illness is now ascribed to a novel virus belonging to the coronavirus (CoV) family.

On February 11, 2020, Dr. Tedros Adhanom Ghebreyesus – the WHO Director-General – declared that the disease caused by this new CoV was a “COVID-19” (coronavirus disease 2019). In the last twenty years, two additional coronavirus epidemics have occurred. SARS-CoV triggered a large-scale epidemic that started in China and involved two dozen countries with about 800 cases and 800 deaths, and the MERS-CoV that started in Saudi Arabia and has about 2,500 cases and 800 fatalities still causes sporadic cases.

This new virus is seems to be very contagious and has quickly spread around the world. In a meeting on January 30, 2020, the outbreak was declared by the WHO as a Public Health Emergency of International Concern (PHEIC) as it has spread to 18 countries with 4 countries reporting person-to-person transmission.

At the outset, the new virus was known as 2019-nCoV. Subsequently, the International Committee on Taxonomy of Viruses (ICTV) termed it the SARS-CoV-2 virus as it is similar to the one that triggered the SARS outbreak (SARS-CoV).

The CoV family of viruses have become the major pathogens of emergent respiratory disease outbreaks. They are a large family of single stranded RNA viruses that can be isolated in diverse animal species. For some unknown reasons, these viruses can cross species barriers and can cause – in humans – illness ranging from the common cold to more severe diseases such as SARS, MERS, and now COVID-19. Remarkably, the SARS and MERS diseases have probably originated from bats and then moving into other mammalian hosts (the civet for SARS-CoV and the camel for MERS-CoV) before jumping to humans. Currently the dynamics of the SARS-Cov-2 virus are still unknown, but there is speculation that it has an animal origin as well.

Regarding COVID-19, the WHO raised the threat to the ‘very high’ level on February 28, 2020. On March 11, as the number of COVID-19 cases outside China and the number of countries reporting cases has vastly increased, the WHO declared the COVID-19 a pandemic.

Etiology

CoVs are positive-stranded RNA viruses that have a crown-like appearance when seen under an electron microscope. This crown-like appearance is due to the presence of the spike glycoproteins on the envelope. 

Members of the CoV family of viruses can cause enteric, hepatic, respiratory, and neurological diseases in diverse animal species, including bats, cats, cattle, and camels. To date, seven human CoVs (HCoVs) that are capable of infecting humans have been recognized. Some of these HCoVs were identified in the mid-1960s, while others were only identified in the new millennium.

Estimates suggest that about 2% of the population are healthy carriers of a CoV and that these viruses are accountable for approximately 5-10% of acute respiratory infections[1].

  • Some common human CoVs include HCoV-HKU1, HCoV-OC43, HCoV-NL63, and HCoV-229E. They can cause the common cold and self-limiting upper respiratory infections in immunocompetent individuals. In the elderly and in immunocompromised individuals, lower respiratory infections can occur as well.
  • Other human CoVs include SARS-CoV, MERS-CoV, and now the SARS-CoV-2. These HCoVs cause epidemics with variable clinical severity featuring respiratory manifestations. SARS-CoV and MERS-CoV have high mortality rates that are up to 10% and 35% respectively.

The SARS-CoV-2 virus belongs to the betaCoVs category. It has an elliptic or round and often pleomorphic form. Furthermore, it has a diameter of about 60–100 nm. Similar to other CoVs, it is sensitive to heat and ultraviolet rays. Moreover, these viruses can be successfully inactivated using lipid solvents such as chlorine-containing disinfectant, chloroform, peroxyacetic acid, ethanol, and ether (75%).

Transmission

Because the first cases of the COVID-19 disease were connected to direct exposure to the Huanan Seafood Wholesale Market of Wuhan, animal-to-human transmission was assumed to be the main transmission mechanism. However, subsequent cases were not linked with this exposure mechanism. Therefore, experts concluded that the virus could also be transmitted from one person to another, and symptomatic people are the most frequent source of the spread of COVID-19. The possibility of transmission before symptoms start to develop seems to be infrequent; however, it cannot be completely excluded. Furthermore, there are propositions that asymptomatic individuals could transmit the virus. This suggests that the use of isolation is one of the best ways to contain this pandemic.

As with other respiratory pathogens (i.e. rhinovirus and flu), transmission is thought to occur through respiratory droplets from sneezing and coughing. Aerosol transmission is also probable in case of extended exposure to elevated aerosol concentrations in closed spaces. Analysis of data related to the SARS-CoV-2 spread in China seems to indicate that close contact between infected individuals is necessary.

Pathophysiology

The CoV viruses are enveloped, positive-stranded RNAs with nucleocapsid. Virulence and pathophysiology mechanisms of CoVs, and therefore also of the SARS-CoV-2 virus have links to the function of structural proteins and non-structural proteins (nsps). For example, research emphasized that nsp is able to block the host innate immune response[2].

According to the latest research, a spike mutation which probable took place in late November 2019 activated jumping to humans. Particularly, experts compared the Sars-Cov-2 gene sequence with that of Sars-CoV. They examined the transmembrane helical segments in the ORF1ab encoded 2 (nsp2) and nsp3 and discovered that position 723 exhibits a serine instead of a glycine residue, while position 1010 is occupied by proline instead of isoleucine[3]. Further research is necessary to determine the structural features of SARS-COV-2 that cause its pathogenetic mechanisms.

History and Physical

COVID-19’s clinical spectrum ranges from asymptomatic forms to clinical conditions characterized by respiratory failure that requires mechanical ventilation and support in an intensive care unit, to systemic and multiorgan manifestations in terms of septic shock, sepsis, and multiple organ dysfunction syndrome.

The authors of the Chinese CDC report categorized the clinical manifestations of COVID-19 by their severity[4]:

  • Mild Disease: Non-pneumonia and mild pneumonia – this occurred in about 81% of cases.
  • Severe Disease: Dyspnea, blood oxygen saturation (SpO2) ≤ 93%, respiratory frequency ≥ 30/min, PaO2/FiO2 ratio or P/F, and the percentage of oxygen supplied < 300, and/or lung infiltrates > 50% within 24 to 48 hours – this occurred in about 14% of cases.
  • Critical Disease: Septic shock, respiratory failure, and/or multiple organ dysfunction or failure – this occurred in about 5% of cases.

Treatment/Management

Currently, there is no antiviral treatment recommended for COVID-19. No vaccine or treatment is currently available as well. The treatment is symptomatic and oxygen therapy is the major treatment intervention for patients with severe infection. Mechanical ventilation may be required in cases of respiratory failure, whereas hemodynamic support is crucial for managing septic shock.

Prevention

Preventive strategies are focused on the isolation of COVID-19 patients and careful infection control. This includes appropriate measures to be followed during the diagnosis and the provision of clinical care to an infected individual.

The WHO and other health organizations offer the following general prevention recommendations:

  • Avoid close contact with individuals suffering from acute respiratory infections.
  • Wash your hands frequently and properly, particularly after contact with infected individuals or their environment.
  • People with acute airway infection should cover coughs or sneezes with clothes or disposable tissues, wash their hands frequently, and keep their distance from others.
  • Immunocrompromised individuals and the elderly should avoid mass gatherings.

The best strategy is to observe proper and frequent hand washing. Also, use portable alcohol or sanitizer to clean your hands and avoid touching your face and mouth after interacting with a possibly contaminated environment.

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