Covid-19 Pathophysiology

Covid-19 Pathophysiology

Introduction:

In December 2019,WHO was informed of cases of pneumonia of unknown cause in Wuhan city,China.It was identified that the cause for the unusual pneumoniawas novel corona virus by Chinese authorities and was temporarily named “2019-nCoV”.

A novel corona virus is a new strain that has not been previously identified in human.The  new virus was subsequently named as “COVID-19 Virus”.On March 11 2020, WHO director announced that the outbreak could be characterized as pandemic due to the rapid increase in number of cases outside china.

Countries are racing to slow down the spread of virus.The pandemic is moving like a wave.

Pathophysiology:

The term Pathophysiology derived from Greek word “pathos”-suffering,”physis”-nature and “logos”-the study of.It refers to the study of deranged function in an individual or organ that are the causes,consequences of disease processes.

Pathophysiological research aims at identifying factors and mechanisms that are appropriate for answering questions like “how” and “why” certain disorders and diseases develop.This is about answering to the questions on etiology and pathogenesis.

COVID-19

COVID-19 is caused by SARS-CoV-2(Severe Acute Respiratory Syndrome-CoronoVirus-2),a beta corona virus.It is comprised of a single stranded RNA structure that belongs to the Coronovirinaesubfamily,a part of Coronaviridae family.

Its genome is almost similar to the previously identified coronavirus strain that caused the SARS outbreak in 2003.Coronavirus are divided into four genera;α,β,γ,δ based on their genomic structure.α and β coronavirus infect only mammals.SARS-COV-2 is classified to β coronavirus.

 

SARS-CoV-2 invasion to host cell

The life cycle of virus with host cell consists of the following 5 stages.

1. ·      Attachment
2. ·      Penetration
3. ·      Biosynthesis
4. ·      Maturation
5. ·      Release

Attachment-Once virus enters into host body,It binds with human receptors.

Penetration-They enter host cell through membrane fusion or endocytosis

Biosynthesis-Viral contents are introduced into host cell and Viral RNA enters host nucleus for replication.Viral mRNA is used to produce viral proteins.

Maturation-New viral particles with nucleus are produced.

Release-These new viral particles are released.

Coronovirus consist of four structural proteins

• ·      Spike
• ·      Membrane
• ·      Envelope
• ·      Nucleocapsid

Spike comprises of two functional subunits;

S1-responsible for binding to the host receptor cells

S2-responsible for the fusion of virus and cellular membranes

ACE2-Angiotensin Converting Enzyme 2 was identified as a functional receptor of SARS-CoV. Structural and functional analysis shows that SARS-CoV 2 also bound to ACE-2.

Host response to SARS CoV-2

The pathophysiology of SARS-CoV-2 infection closely resembles that of SARS-CoV infection, with aggressive inflammatory responses strongly resulting in the damage to the airways

SARS-CoV-2 primarily affects the respiratory system.This ranges from mild symptoms to severe respiratory failure with multiple organ failure.Atfirst,lower respiratory tract infection related symptoms including fever,dry cough and syspnea were reported as the symptoms.later,in addition to previously mentioned symptoms,few symptoms were also observed such as headache,dizziness,vomitingetc..It is now widely recognized that respiratory symptoms of COVID-19 are extremely heterogeneous.

Immunological studies were reported in Severe COVID-19 patients.Some Patients with severe symptoms showed lymphopenia(reduction in the number of leukocytes).Some other patients showed increased plasma concentrations of proinflammatory cytokines,including Interleukin-6,Interleukin-10,Granulocyte colony stimulating factor,Monocytechemoattractant protein 1,macrophage inflammatory protein,Tumor necrosis factor.Infiltration of a large number of inflammatory cells were observed in some patient’s lungs.Thrombosis and pulmonary embolism have also been observed in some cases.

Some studies have found that Coronovirus may enter CNS through several routes like intranasal inoculation,peripheral nerves etc…Coronavirueses predominantly infect neurones in the brain stem associated with cardio-respiratory control.It causes injury to these areas and it may exacerbate or even lead to respiratory failure.One of the underappreciated symptoms of COVID-19 is olfactory dysfunction(deceased sense of smell).

Using numerous data some studies have suggested  that COVID-19 is common in patients with diabetes, hypertension, and cardiovascular disease.ACE2, the host cell surface receptor for SARS-CoV-2, has been shown to be expressed throughout the aerodigestive tract, including the mucosa of the nasal cavity as well as the mucosa of the oral cavity, and in the epithelium of the lungs and enterocytes of the gastrointestinal tract. Single-cell RNA sequencing has shown that ACE2 may be expressed in tissues throughout the body (such as in the heart and kidneys), suggesting direct viral pathogenesis as a potential mechanism for extraaerodigestive symptoms of COVID-19.

COVID-19 data shows a difference in mortality rate between males(2.8%) and females(1.7%)This may be due to the ACE-2 receptor which is located on the X chromosome.Alternatively ,sex hormones like oestrogen and testosterone have different immunoregulatory functions which may also cause the difference in mortality rates.

In some studies it has been found that the pathophysiology of COVID-19 severe respiratory failure may be caused due to pulmonary vascular endothelial dysfunction and thrombosis that responds to thrombolysis and anticoagulation.

Sinonasal pathophysiology plays an important role in the transmission of COVID-19.The sinonasal cavity may be an important route for infection and virus shed from the sinonasal cavity may be an important source of transmission.