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COVID-19: What You Need To Know
The Update — Special Report  | Issue no. 13, April 2020

Table of Contents

 
A. Introduction | B. Important factors | C. Mode of Transmission | D. Pathophysiology | E. Clinical Features  | F. Possible Therapies

A. Introduction


Before December 2019, SARS-CoV-2 — the virus that causes the Covid-19 illness — was unknown to science. “A pneumonia of unknown cause” was first reported to the World Health Organization on December 31, after a slew of cases appeared in Wuhan, China. Since then, the virus has been detected in more than a million people worldwide, and killed tens of thousands.

This version of The Update will provide an in-depth summary of the most relevant science available to us at the time of writing. 
Total cases confirmed as of the time of writing: 1,225,360

Source: Coronavirus COVID-19 Global Cases by the Center for Systems Science and Engineering (CSSE) at John's Hopkins Last updated: 4/5/2020, 5:48:00 PM

 

What is "Coronavirus"?


SARS-CoV-2 is a coronavirus that causes "coronavirus disease 2019" (COVID-19). Coronaviruses, in general, are a family of viruses that target and affect mammals’ respiratory systems.

Only two coronaviruses have previously caused global outbreaks: SARS coronavirus in 2002, and MERS coronavirus in 2012.
 

Where and how did it originate?


SARS-CoV-2 is related to coronaviruses in bats, but its intermediate animal host and route to humans are not yet clear. There has been plenty of speculation that the intermediate host could be pangolins. Recently, a study by researchers in China suggested that pangolins may have been the initial propagators of SARS-CoV-2, as its genomic sequence appeared to be 99% like that of a coronavirus specific to these animals.

Researchers suspect the intermediate host animal was present in a live animal market in Wuhan, China—the capital city of China’s central Hubei Province and the epicenter of the outbreak. The market sold a wide range of seafood and live animals, some wild. Many of the initial SARS-CoV-2 infections were linked to the market; in fact, many early cases were in people who worked there.
 

The SARS-CoV-2 spike protein was so effective at binding the human cells, in fact, that the scientists concluded it was the result of natural selection and not the product of genetic engineering. The SARS-CoV-2 backbone differed substantially from those of already known coronaviruses and mostly resembled related viruses found in bats and pangolins.

B. Important Factors


In this section we discuss the factors that are contributing to the pandemic's rapid spread, high hospitalization and mortality rates. These are the parameters that have to be mitigated and managed to slow down the pandemic. 

 

Exponential Growth

 

In short, this is why the number of cases seems to "jump up" and double all of a sudden. 

"Exponential" growth is very different from how the human mind normally perceives of growth: in linear (or arithmetic) fashion. Think about these two sequences of numbers, one of which shows linear growth and one of which shows exponential growth.

  • 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, etc.
  • 2, 4, 8, 16, 32, 64, 128, 256, 512, 1024, etc.

Exponential growth is so powerful not because it's necessarily fast, but because it's relentless. Without introducing a factor to suppress it, exponential growth is an infectious disease doctor's nightmare, particularly as more time goes on.

In any biological system, if you put a living organism into an environment where it can thrive, with unlimited resources and no predators or competitors, it will always grow in the same fashion: exponentially. If these factors are modified, its spread can be hampered. 

In the case of the coronavirus COVID-19, exponential growth is caused and being tackled by focusing on the following:

  • There is at least one infected person in the population pool, many of whom are asymptomatic — being tackled using contact tracing and broad testing
  • Regular contact between infected and uninfected members of the population occurs — being tackled using case isolation
  • There are large numbers of uninfected potential hosts among the population. — being tackled via physical distancing, this prevents asymptomatic infected persons from infecting others, and healthy people from being infected
 

Case fatality rate (CFR)


An estimate of the risk of mortality from a contagious disease.

CFR = deaths / (deaths + recovered)

The CFR is time and location-dependent, and many different factors can influence the CFR, such as speed of diagnosis of cases, health system capacity, age and other demographic characteristics, among others.



The number of confirmed cases is lower than the number of total cases.
The main reason for this is limited testing. It is therefore very early to make any conclusive statements about what the overall mortality rate will be for the novel coronavirus, according to the World Health Organization.

But if we’re careful to acknowledge its limitations, CFR can help us to better understand the severity of the disease and what we should do about it.

Healthcare capacity

To respond to the pandemic, the capacity of the healthcare system is of great importance. This is illustrated by

  1. Medical doctors per 1,000 people
  2. Hospital beds per 1,000 people
  3. ICU beds per 1,000 people
  4. Availability of tests 

 
When you combine the exponential growth of confirmed cases with limited healthcare capacity, it leads to a situation where the healthcare system can easily be overwhelmed, this leads to more deaths as resources to those infected run out. 

This is the rationale behind the #FlattenTheCurve practice. Which members of the population can contribute to by staying at home and physical distancing. 
 
 

C. Mode of Transmission 


While understanding of the transmission risk is incomplete, we will outline our current understanding of it.
 

Person-to-person spread of SARS-CoV-2 is thought to occur mainly via respiratory droplets, resembling the spread of influenza. With droplet transmission, virus released in the respiratory secretions when a person with infection coughs, sneezes, or talks can infect another person if it makes direct contact with the mucous membranes; infection can also occur if a person touches an infected surface and then touches his or her eyes, nose, or mouth. A new study published in JAMA has indicated that the virus droplets can linger in the air and travel up to 3 to 27 feet (7-8 m) in the air.

On April 4th the UAE's Ministry of Health and Prevention recommended that residents should cover their faces whenever they leave home.

Learn More About Face Masks

D. Pathophysiology

 

The SARS-CoV-2 virus, like the closely-related MERS and SARS coronaviruses, affects its cellular entry via attachment of its virion spike protein (a.k.a. S protein) to the angiotensin-converting enzyme 2 (ACE 2) receptor.

This receptor is commonly found on alveolar cells of the lung epithelium, underlying the development of respiratory symptoms as the commonest presentation of COVID-19.

                        
 

E. Clinical Features


While our understanding of the transmission risk is limited, we outline the current understanding as follows:

Incubation period — The incubation period for COVID-19 is thought to be within 14 days following exposure, with most cases occurring approximately four to five days after exposure.

Spectrum of illness severity — The spectrum of symptomatic infection ranges from mild to critical; most infections are not severe.

  • Mild (no or mild pneumonia) was reported in 81 percent.
  • Severe disease (eg, with dyspnea, hypoxia, or >50 percent lung involvement on imaging within 24 to 48 hours) was reported in 14 percent.
  • Critical disease (eg, with respiratory failure, shock, or multiorgan dysfunction) was reported in 5 percent.

Risk factors for severe illness — Severe illness can occur in otherwise healthy individuals of any age, but it predominantly occurs in adults with advanced age or underlying medical comorbidities. The impact of age is discussed elsewhere. 

Comorbidities that have been associated with severe illness and mortality include:
  • Cardiovascular disease
  • Diabetes mellitus
  • Hypertension
  • Chronic lung disease
  • Cancer
  • Chronic kidney disease

Impact of age — Individuals of any age can acquire severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, although adults of middle age and older are most commonly affected, and older adults are more likely to have severe disease.

Clinical Manifestations

Initial presentation — Pneumonia appears to be the most frequent serious manifestation of infection, characterized primarily by fever, cough, dyspnea, and bilateral infiltrates on chest imaging. There are no specific clinical features that can yet reliably distinguish COVID-19 from other viral respiratory infections.

In a study describing 138 patients with COVID-19 pneumonia in Wuhan, the most common clinical features at the onset of illness were:

  • Fever in 99 percent
  • Fatigue in 70 percent
  • Dry cough in 59 percent
  • Anorexia in 40 percent
  • Myalgias in 35 percent
  • Dyspnea in 31 percent
  • Sputum production in 27 percent
Based on the current epidemiological investigations, the symptoms of COVID-19 may appear in as few as 1 day or as long as 14 days after exposure, mostly it is 3-7 days.

It is mainly manifested by fever, fatigue, and dry cough. A few patients have symptoms such as nasal congestion, runny nose, sore throat, myalgia and diarrhea. In many severe patients, breathing difficulty and/or hypoxemia occurs after one week, and those critical cases can quickly progress to acute respiratory distress syndrome, septic shock, metabolic acidosis and coagulation dysfunction that are difficult to be corrected, and multiple organ dysfunction syndrome (MODS), etc. Notably, severe and critical patients may have moderate to low-grade fever or even no obvious fever during the course of the disease.

Increasing evidence suggests that a lost sense of smell, known medically as anosmia, may be a symptom of COVID-19. This is not surprising, because viral infections are a leading cause of loss of sense of smell, and COVID-19 is a caused by a virus. On March 22nd, the American Academy of Otolaryngology–Head and Neck Surgery recommended that anosmia be added to the list of COVID-19 symptoms used to screen people for possible testing or self-isolation.

Some children and neonatal cases may have atypical symptoms, manifested as gastrointestinal symptoms such as vomiting and diarrhea, or only manifested as looking inactive and having shortness of breath.
Mild cases only show low-grade fever, mild fatigue, and no signs of pneumonia.
 

Laboratory findings — In patients with COVID-19, the white blood cell count can vary. Leukopenia, leukocytosis, and lymphopenia have been reported, although lymphopenia appears most common. 

Elevated LDH and ferritin levels are common, and elevated aminotransferase levels have also been described. On admission, many patients with pneumonia have normal serum procalcitonin levels; however, in those requiring ICU care, they are more likely to be elevated.

High D-dimer levels and more severe lymphopenia have been associated with mortality.


Imaging findings — Chest CT in patients with COVID-19 most commonly demonstrates ground-glass opacification with or without consolidative abnormalities, consistent with viral pneumonia. 

Case series have suggested that chest CT abnormalities are more likely to be bilateral, have a peripheral distribution, and involve the lower lobes. Less common findings include pleural thickening, pleural effusion, and lymphadenopathy.

Figure 2. Chest X-ray showed progression of prominent bilateral perihilar infiltration and ill-defined patchy opacities at bilateral lungs, which slowly resolved on the follow-up image. (a: January 20; b: Jan. 23; c: Jan. 27; d: February 04).

F. Possible Therapies


Certain investigational agents have been described in observational series or are being used anecdotally based on in vitro or extrapolated evidence. It is important to acknowledge that there are no controlled data supporting the use of any of these agents, and their efficacy for COVID-19 is unknown.

Remdesivir – Several randomized trials are underway to evaluate the efficacy of remdesivir for moderate or severe COVID-19 

Chloroquine/hydroxychloroquine – Both chloroquine and hydroxychloroquine have been reported to inhibit SARS-CoV-2 in vitro, although hydroxychloroquine appears to have more potent antiviral activity

Favilavir – The National Medical Products Administration of China has approved the use of Favilavir, an anti-viral drug, as a treatment for coronavirus. The drug has reportedly shown efficacy in treating the disease with minimal side effects in a clinical trial involving 70 patients. The clinical trial is being conducted in Shenzhen, Guangdong province.

IL-6 pathway inhibitors – Clinical features consistent with a cytokine release syndrome with elevated interleukin (IL)-6 levels have been described in patients with severe COVID-19.

Convalescent plasma – In the United States, the Food and Drug Administration is accepting emergency investigational new drug applications for use of convalescent plasma for patients with severe or life-threatening COVID-19 

Lopinavir-ritonavir – Lopinavir-ritonavir appears to have little to no role in the treatment of SARS-CoV-2 infection. This combined protease inhibitor, which has primarily been used for HIV infection, has in vitro activity against the SARS-CoV and appears to have some activity against MERS-CoV in animal studies.

References
- Coronavirus COVID-19 Global Cases by the Center for Systems Science and Engineering (CSSE) at John's Hopkins
- Coronavirus (COVID-19) Outbreak Glossary. Kaiser Family Foundation.
- Novel coronavirus: Your questions, answered. MedicalNewsToday.Com
- The Vox guide to navigating the coronavirus crisis. Vox.com
- Why 'Exponential Growth' Is So Scary For The COVID-19 Coronavirus. Forbes.com
- Coronavirus. OurWorldInData.Org
- Coronavirus: Public told to wear masks at all times as UAE confirms 241 new cases. TheNational.ae
- Coronavirus disease (COVID-19) advice for the public: When and how to use masks. WHO.int
- Coronavirus disease 2019 (COVID-19), UpToDate
Copyright © 2020 RAK Medical & Health Sciences University, All rights reserved.

For comments and corrections, please contact the authors:
Zaki Emad
- Subcommittee member, Committee on Science & Technology
ID: 15901071

Dean Allah Layth - MBBS Year 5. 
ID: 15901028


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PO Box. 11172, RAK, UAE
 






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