The CoviD19 Saga: Symptomatology and Virology

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Background

COVID 19 is an infectious disease caused by SARS CoV 2. First identified in 2019 in Wuhan, China, it now has spread globally resulting in the coronavirus 2019-20 Pandemic.

The most common symptom is fever and patients may also develop cough and shortness of breath. Majority of cases are mild, but some may progress to pneumonia and multi organ failure.

The infection is spread from one person to another via respiratory droplets, through coughing and sneezing.

Time from exposure to the onset of symptoms is 2 to 14 days with an average of 5 to 6 days.

The standard diagnostic measure is by reverse transcription polymerase chain reaction (rRT-PCR) from a nasopharyngeal or throat swab.

Without this, a combination of symptoms, risk factors and chest CT scan findings showing features of Pneumonia provides a likely candidate for COVID19 infection. Recommended measures for Prevention include hand washing, social distancing and avoiding touching one’s face. The use of mask is not recommended except for those suspected of carrying the disease and their caregivers with Emphasis on healthcare workers who see patients regularly.  There is currently no vaccine or definitive treatment for COVID19, and management involves treatment of symptoms, supportive care, isolation and experimental measures.

SIGNS and SYMPTOMS: divided into Common, Uncommon and Severe.

One of the most important things to note from studies suggest that patients may be able to spread COVID19 before they experience signs and symptoms. An infected person may be asymptomatic thus may carry the disease unsuspectingly and infect others.

Common symptoms are fever (with the highest percentage at 87.9% seen in positive cases), dry cough (67.7%) and fatigue (38.1%)

Uncommon symptoms include Sputum production (33.4%), shortness of breath (18.6%), muscle or joint pain (14.8%), sore throat (13.9%), headache (13.6%), chills (11.4%), nausea or vomiting (5.0%), nasal congestion (4.8%) and diarrhea (3.7%)

Severe cases develop high Fever, haemoptysis or Coughing up Blood, leukopenia or decreased WBCs and evidences of kidney failure.

The most common presentation based on a US report is that early symptoms in the 1st week is composed of myalgia, malaise, cough, low grade fever.  Onset of the 2nd week of illness comes the difficulty of breathing (average of eight days). An average of nine days to pneumonia or pneumonitis. Cough persisted for a median of 19 days with 45% of patients still had cough upon discharge.

The Disease is also categorized as Mild, Severe or Critical

Milder forms are more common, patients usually recover and experience non pneumonia to pneumonia symptoms. Children are likely to have milder symptoms and have a much lower chance of severe disease than adults.

Diagnosing Severe Disease includes a criteria of the following:

  • Dyspnea
  • Respiratory rate of 30 or more
  • Blood oxygen Saturation of less than or equal to 93%
  • PAO2 / FiO2 ration < 300
  • Lung infiltrates > 50% of the lung field within  24 – 48 hours.

Critical cases are patients undergoing respiratory failure, septic shock and / or multi organ dysfunction or failure. Also, abnormal clotting and bleeding were noted in 90% of people with pneumonia. Liver injury as shown by blood markers of liver damage is frequently seen in severe cases, although liver failure has not been described as of March 2020.

The median time from onset to clinical recovery for mild cases is approximately 2 weeks.

While median time from onset to clinical recovery for people with severe or critical disease is three to six weeks. Among people who have died, the time from symptom onset to outcome ranges from 2-8 weeks.

THE AGENT: Severe acute respiratory syndrome coronavirus 2 (SARS CoV 2)

Digitally colourised electron micrographs of SARS-CoV-2 (yellow) emerging from human cells cultured in a laboratory
Digitally colourised electron micrographs of SARS-CoV-2 (yellow) emerging from human cells cultured in a laboratory

Thought to be of animal origin that was transmitted to humans through spillover infection –  a process in which a reservoir population (animal carriers with high pathogen prevalence) comes into contact with a novel host population (humans) – Bioinformatic analyses indicated it had features typically belonging to the Betacoronavirus 2B lineage. A full-length genome sequence and alignment of the virus showed the closest relationship was with the SARS-like bat coronavirus strain BatCov RaTG13.  Data was insufficient to separate it from SARS as a new species and thus was identified as a new strain.

Infection

The Primary Method of Transmission is via respiratory droplets from coughs and sneezes within a range of about 6 feet (1.8 m). Contact of contaminated surfaces and objects are possible causes of infection. Recently viral RNA has been found in stool samples from infected patients so there is a possibility of a fecal-oral route.

A March 16 2020 study on the outbreak in China before quarantine found that the best-fitting epidemiological model has a reporting delay of nine days from initial infectiousness to confirmation suggesting pre-symptomatic shedding may be typical among documented infections.

The study estimates that 86% of all infections were undocumented suggesting that most of the documented cases were infected by prior undocumented cases, and the reason they missed documentation is because at that time they were probably dismissed as benign cases.

Recently released data have suggested that asymptomatic patients are still able to transmit infection. A study by Zou et al found increases in viral loads at the time they became symptomatic. One patient never developed symptoms but was shedding the virus beginning at day 7 after presumed infection.

Based on this data, the pandemic’s threatening potential lies not just from the people with known cases but also those with mild symptoms, are asymptomatic and are undocumented – which in theory could mean everybody in the population including those who are healthy. This is why EVERYBODY should follow strict regulations and precautions which includes staying at home, washing of hands, maintaining social distancing – lest you unknowingly become a herald of death and disease.

Reservoir and Origins

The first known infections from the SARS-CoV-2 strain were discovered in Wuhan, China. The original source of viral transmission to humans remains unclear. Experts have agreed that the natural reservoir of the virus is bats. Pangolins were suggested to be the intermediate hosts but its still debated. READ more on: the COVID Saga Origins

Structural Biology

It is a positive-sense single-stranded RNA virus, and is a member of the coronavirus family. Coronaviruses range from being relatively harmless (causing common colds) to causing worldwide pandemics (SARS, MERS)

SARS COV 2 measures approximately 50-200 nanometers in diameter and is composed of four structural proteins, the spike (S), envelope (E), membrane (M), and Neuclocapsid (N). The N protein holds the RNA genome and the rest form the viral envelope. Of importance is the S protein which allows the virus to attach to a membrane of a host cell.

Affinity to ACE2 receptors

Studies have shown that the Spike protein has sufficient affinity to the angiotensin converting enzyme 2 (ACE2) receptors of human cells, using them as a mechanism of cell entry, as evidenced in a Jan 22 study using reverse genetic methods, scientists in China and US independently and experimentally demonstrated that ACE2 could act as the receptor for SARS CoV 2.  ACE2 is most abundant in type 2 alveolar cells of the lungs thus it’s the most affected organ.

Some suggest decreasing ACE2 levels might help fight the infection but some studies show that ACE2 has a protective effect, since interaction with the virus’ spike protein drops the levels of ACE2, which could possibly induce lung injury.

Alternative studies have suggested a close co-morbidity link between hypertension and heart disease and COVID-19 which may be related to these patients normally being prescribed ACE inhibitors.

ACE inhibitors (Captopril) upregulate ACE2 which is expressed in the lungs, intestines, kidney and blood vessels. Increased expression facilitates infection with SARS COV or SARS COV 2. Hence patients with diabetes or hypertension treated with ACE inhibitors may be at increased risk of COVID 19 infection

Essential for SARS-CoV 2 entry and thus being studied for treatment purposes are transmembrane protease, serine 2 (TMPRSS2) which primes the spike as it attaches to the host cell then cuts it open in which the virion releases its RNA – which then forces the host cell to replicate it. There are three coronavirus virulence factors Nsp1, Nsp3c and ORF7a related to interfering host’s innate immunity and assisting coronavirus escape immune response that are currently being studied for targeted antiviral therapies.

Take Home Reminder

That the Chinese state suppressed data regarding human to human transmission, thus early infection data could possibly be skewed. In effect, documentation quality was not the best as people failed to act accordingly since they were unsure of the virus’ capabilities. A mild flu, which is one of the commonest symptoms of CoviD-19, could have been easily brushed aside as simply that, a mild flu, thus escaping proper documentation.

As we go through this pandemic a lesson from these discoveries is of utmost importance. The uniqueness of how the virus spreads prompts careful and meticulous monitoring of personal health; conditions of those immediately surrounding you; and conditions of those you’ve encountered recently.

This in turn teaches us that the fight against the pandemic will be won not through one’s defeat of the virus, but when everyone else triumphs against it. Funny how such calamities enforces us to go hand in hand, symbolically, cause that is physically not allowed.

For now.

REFERENCES:
Symptoms
“Coronavirus Disease 2019 (COVID-19) Symptoms”. Centers for Disease Control and Prevention. United States

Clinical Course and Complications
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. (2020). “Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study”.

The Lancet.
Studies on Liver Injury
Xu, Ling; Liu, Jia; Lu, Mengji; Yang, Dongliang; Zheng, Xin (14 March 2020). “Liver injury during highly pathogenic human coronavirus infections”. Liver International: Official Journal of the International Association for the Study of the Liver.

SARS CoV 2 Lineage, WHO
PHOTOS of SARS CoV 2 from
NIAID Rocky Mountain Laboratories (RML), U.S. NIH – And NIAID

Infection
On undocumented Infection Rates
Li, Ruiyun (16 March 2020). “Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV2)”

Asymptomatic Carriers
Coronavirus Disease 2019, Medscape.
Structural Biology and Affinity to ACE2 receptors
Structure and Importance of the Spike Protein
Wu C, Liu Y, Yang Y, et al. (February 2020). “Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods”. Acta Pharmaceutica Sinica B.

ACE2 Receptor Affinity
Letko M, Marzi A, Munster V (February 2020). “Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses”. Nature Microbiology.

Hypertensives and Diabetic Risks
Fang L, Karakiulakis G, Roth M (March 2020). “Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?”. The Lancet. Respiratory Medicine.

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