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COVID-19: A Comprehensive Overview
Hira Amir, MD and Ally PH Prebtani, BScPhm, MD, FRCPC
About the Authors
Hira Amir is a medical graduate currently working as a research volunteer at McMaster University.
Ally PH Prebtani is with the Division of Endocrinology & Metabolism, Department of Medicine, McMaster University
Submitted: April 20, 2020. Accepted June 20, 2020. Published: July 2, 2020. Ahead of issue. DOI: 10.22374/cjgim.v15i3.462
Methods
We carefully conducted a literature review for the pathogenesis,
microbiology, clinical presentation, diagnosis and available
effective management and prevention options for COVID 19.
The articles for review were primarily retrieved from UpToDate,
WHO, PubMed, Elsevier, Medscape and peer-reviewed journal
articles including The New England Journal of Medicine (NEJM),
Journal of American Medical Association (JAMA), The Lancet, and
Canadian Medical Association Journal (CMAJ) using ‘COVID
19’, ‘SARS-CoV2’, and ‘Human Coronavirus’ as keywords for
our search. Most articles were dated between January to April
2020. We screened the references provided in most publication to
avoid errors of missing publications. We restricted our search to
publications in English and excluded abstracts from conferences
and observations.
Virology and Pathogenesis
The coronavirus belongs to a family within Nidovirale order
that uses nested set of mRNAs to replicate. Human coronavirus
is from two of the four genera of virus family: alpha and beta
coronaviruses.
1
The pathogen, which is a beta coronavirus, is
similar to SARS (Severe Acute Respiratory Syndrome) and MERS
(Middle Eastern Respiratory Syndrome).
1
The Angiotensin
Converting Enzyme 2 (ACE2) receptor appears important
for viral entry into the pneumocytes.
2
It is known to mutate
and combine rapidly, serving as an ongoing challenge to our
understanding of disease spectrum and patient management
(Figure 1).
Viral Transmission
The respiratory pathogen was initially thought to have a zoonotic
transmission, however, currently its main mode of transmission
remains person-to-person via respiratory droplets (more than
5–10 micrometers in diameter which travel less than 2 meters
or 6 feet), resembling the spread of influenza.
4,5
In certain
circumstances, transmission via aerosol droplets less than 5
micrometers in diameter which may travel more than 2 metres
or 6 feet is possible in aerosol-generating medical procedures,
Abstract
Coronaviruses are important pathogens reported in humans and animals. A novel coronavirus,
formally known as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), was
identified as a cause of pneumonia cases in Wuhan, China, in late 2019. Since its outbreak in
China, it has disproportionately affected many countries. Coronavirus disease 2019 (COVID-19)
was officially declared a pandemic on March 11, 2020 and remains a global concern. A spectrum
of disease severity has been reported with a variable course of illness from mild upper respiratory
symptoms, pneumonia to acute respiratory distress syndrome (ARDS), shock, multiorgan
dysfunction and death. The worldwide dissemination of the virus justifies the global efforts in
identifying potential treatment strategies and a vaccine for improved clinical and long-term
outcomes. This article will reflect on human viral replication and transmission, variable clinical
presentation, assessment, treatment and discussion of complications. Isolation precautions
according to infection prevention and control including protective apparel will be discussed
with emphasis on criteria for discontinuation of transmission precaution.
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which in turn necessitates the use of enhanced personal protective
equipment (PPE) and dual transmission precautions (contact
and airborne) to reduce contagion rate.
4
Fecal-oral transmission
remains insignificant in the spread of the infection.
5
The viral incubation period, which is the time of viral
exposure to symptom development, is found to be 2 weeks after
exposure with varying time of symptom onset but usually between
2–5 days. This phase, also referred to as ‘pre-symptomatic’ or
asymptomatic” phase, and is known to be contagious for some
individuals due to increased viral shedding in the upper respiratory
tract even before development of significant symptoms.
6
This
necessitates mass testing of high-risk population such as residents
or caregivers of residents in LTC facilities, group homes, retirement
homes and other places where there are mass numbers living
under one dwelling.
7
The proposed testing approach will allow
proper isolation of infected individuals (symptomatic and pre or
asymptomatic) and quarantine those that are exposed, ultimately
severing the chain of infection spread especially in those that
are at elevated risk for the infection.
Factors for Viral Transmission
Longer incubation period and pre-symptomatic viral shedding
contribute to rapid viral dissemination with COVID-19.
Another feature that helps quantify the transmission rate is the
basic viral reproductive number (R). It is the median number
of new infections that result from a single infected person in a
susceptible group. An R below 1 indicates that an outbreak is
declining rather than growing, explained by the fact that each
infected individual will transmit/infect less than one person in
that community. Alternatively, higher Ro means more people get
infected before the end of this pandemic. It is difficult to have a
precise Ro, as it fluctuates with various factors such as contact
with people, physical distancing and measures like lockdowns
to mitigate the viral spread.
8
Figure 1. Interaction between SARS-CoV-2 and the Renin–Angiotensin–Aldosterone System.
Adapted from: The New England Journal of Medicine (NEJM)
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Another parameter is the effective reproductive number
(Re), which is comparable to R but not fully dependant on the
vulnerable population. R is not altered by immunity against a
viral infection either by vaccination or natural infection but
immunity in the given population can impact Re. Having said
that population immunity can successfully shrink the outbreak
if the Re is below 1.
9
Depending on these factors and possible measures to control
viral dissemination, COVID 19 cases may appear in waves with
perhaps distinct intervals shown in the Figure 2 (see Figure 1
in the link).
Disease Spectrum
Patients with COVID-19 may present with a range of clinical
manifestations, initially mild respiratory tract symptoms, which
may progress to pneumonia and severe disease. The latter may
result in complications like sepsis with multiorgan dysfunction
and respiratory failure, requiring advanced oxygenation and
ventilation with hemodynamic support.
Prevention and Treatment
Given the present situation, isolation precautions such as droplet
precautions are recommended in most situations depending
upon degree of interaction with a COVID-19 patient. Airborne
precautions are recommended in special circumstances where
aerosolization is more than in usual situations such as aerosol-
generating medical procedures (AGMPs).
10,11
To date there has been no approved, effective, and safe
pharmacologic and/or preventive treatment, including vaccines,
for COVID 19 with the exception of Remdesivir for emergency
use in severe illness in United States. Several drugs are undergoing
clinical and human trials and may be considered as potential
therapies for treatment of COVID 19 in the future with ongoing
efforts for vaccine development.
Clinical Picture
The COVID-19 illness has a variable presentation ranging from
an asymptomatic form, mild pneumonia to a severe or critical
form of the disease. Approximately 15 % of the individuals with
clinically evident infection develop severe form of the disease,
with an overall case fatality rate from 1-14% which varies with
time, region, comorbidities, age and accurate reporting of data.
12
Common symptoms include fever, dry cough, myalgias,
anorexia and fatigue, not explained by a pre-existing medical
condition.
13
In addition, pneumonia remains a serious manifestation
of COVID 19 illness. Upper respiratory tract infection symptoms
like headache, sore throat, nasal congestion and rhinorrhea also
occur in COVID 19 patients. A fair number of cases have been
reported with gastrointestinal symptoms of nausea, vomiting,
diarrhea and anosmia with taste disturbances.
5,13
Moderate to
severe disease can result in hemoptysis, dyspnea and multiorgan
dysfunction.
14
Patients may have a history of exposure and/or travel to an
individual and/or area of an outbreak of COVID 19, respectively.
However, at present, this component of clinical assessment may
not impact/limit the screening, diagnosis, medical management
and therapeutic interventions for COVID 19 patients, as many
may present without a travel and/or exposure history as more
community transmission is occurring (Figure 3).
The clinical presentation may vary in extremes of ages
and states of immunosuppression i.e. children and elderly can
present with atypical presentations such as hypothermia instead
of high-grade fever, delirium, falls, acute decline in functional
status, worsening of pre-existing medical conditions, unexplained
fatigue and multisystem inflammatory syndrome in children and
adolescents with clinical features coinciding with toxic shock
syndrome and Kawasaki disease.
13
There are no reported classic physical findings in COVID 19
illness. However, it is recommended that the clinicians should be
aware of the respiratory and hemodynamic indicators of disease
severity. These include shock and respiratory distress with ARDS.
Risk Factors for Disease Severity
Risk factors for severe disease include advanced age with
comorbidities such as cardiovascular disease including
hypertension, diabetes mellitus, chronic lung disease, stroke,
smoking, malignancy, advanced chronic kidney disease, liver
disease, obesity and immunosuppression.
5,15
Immune Responses
The natural development of immunity after COVID-19
infection is a graduated process typically requiring up to 2
weeks.
16
This broadly involves innate and adaptive responses.
The immediate response against most infections is with innate
immunity utilizing macrophages, neutrophils and dendritic cells
to slow the infection and thus preventing the symptom onset.
Subsequently, developing adaptive responses including antibody
production and generation of T-lymphocytes, i.e., the humoral
and cellular immune response, respectively. The combined effect
of both humoral and cellular immunity helps to reduce the viral
progression and its elimination from the body (Figure 4).
16
Two immunoglobulins against SARS-CoV-2 infection can
be detected by laboratory tests namely, neutralizing antibodies
(Nabs) and spike-binding antibodies.
18
These tend to appear 10–15
days post-infection. However, 30% of infected patients recovered
without the development of NAbs even after 2 weeks of infection
suggesting that T-cells and cytokine production, other than
antibody production plays a vital role in fighting against COVID
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