Coronavirus (COVID-19) Pandemic outbreak

Coronavirus (COVID-19)
Pandemic Outbreak
Dr. Anwar Yusr
Critical Care Consultant
USTH
19/3/2020

The Early Days
Chen et al. 2020. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a
descriptive study. The Lancet. 395:507-513
https://www.sciencemag.org/news/2020/01/novel-human-virus-pneumonia-cases-linked-seafood-market-china-stir-concern
https://www.theguardian.com/environment/2020/jan/30/make-coronavirus-ban-on-chinese-wildlife-markets-permanent-says-environment-expert-aoe
Dec 30th 2019: First hints of trouble: Local media reports that the
Wuhan Municipal Health Commission asked local hospitals to report
unusual cases of pneumonia.

The Early Days
https://www.theguardian.com/environment/2020/jan/30/make-coronavirus-ban-on-chinese-wildlife-markets-permanent-says-environment-
Dec 30th 2019: First hints of trouble: Local media reports that the Wuhan
Municipal Health Commission asked local hospitals to report unusual cases of
pneumonia.
Dec 31st 2019: Authorities announce 27 cases of pneumonia linked to
Huanan Seafood Market. Seven of the 27 were in serious condition.

The Early Days
Municipal Health Commission asked local hospitals to report unusual
cases of pneumonia.
Jan 1st 2020: Huanan Market is closed.

The Early Days
cases of pneumonia.
Jan 3rd 2020: Determined that disease is most likely caused by
an unknown virus.

The Early Days
cases of pneumonia.
Jan 3rd 2020: Determined that disease is most likely caused by an
unknown virus.
Jan 7th 2020: Causative agent determined to be a novel coronavirus.

The Early Days
cases of pneumonia.
unknown virus.
Jan 7th 2020: Causative agent determined to be a novel coronavirus.
Jan 11th 2020: First death reported.

The Early Days
expert-aoe
cases of pneumonia.
Jan 1st 2020: Huanan Market is closed
unknown virus
Jan 7th 2020: Causative agent determined to be a novel coronavirus
Jan 11th 2020: First death reported
Jan 23rd 2020: Wuhan enters general quarantine. All
transport modes in and out of Wuhan are suspended.

WHO : COVID-19 Global
 China:
 80,894 confirmed.
 3,273 deaths.
 69601 Discharged.
 8056 still.
 2622 critical.
 Outside of China:
 109969 confirmed.
 162 countries.
 4601 deaths.
 Expanded local transmission in South Korea,
Japan, Iran and Italy.
Data as of March 19, 2020. Source: WHO
NOVEL WHO CORONAVIRUS MAP
 208,760 confirmed cases
 8,743 reported deaths
 67,003 recovered*
Last updated 12:37am Mar 19, 2020

What are coronaviruses?
Coronaviruses are nothing new.
They are widespread in humans and other animals.
Electron micrograph:
Scott Camazine/Almay
Named for the crown or ―corona‖
of club-shaped spikes
Four strains of coronavirus that
commonly affect humans. They
cause ~20% of common colds.
Since 2003, 3 “spillovers” of
an animal coronavirus to
humans have occurred.
1. Severe Acute Respiratory Syndrome
(SARS-CoV).
2. Middle East Respiratory Syndrome
(MERS-Cov).
2019 novel coronavirus.
Virus name: SARS-CoV-2.
Name of disease: COVID-19.

2012
MERS-CoV
(SaudiArabia)
2494 cases
Mortality - 37%
Death - 858
2019
2019 nCoV (China)
80,894 cases
3,273 death
2002
SARS-CoV (China)
8098 cases
Mortality 15%
774 deaths

― The outbreak is believed to have originated at a meat and seafood
market in Wuhan where live animals were slaughtered and wild
animals were also sold… The new coronavirus, like SARS and MERS, is
a zoonotic viral disease, meaning the first patients who were infected
acquired these viruses directly from animals.
Vice- Scientists Now Think They Know What Started China's Deadly Coronavirus: Bats

Animal Origins
Bats and Pangolins are the prime
suspects, but bats are the more
likely source.
96%
sequence
similarity
Photos: shutterstock
However, SARS and the sequence
from its animal source (bats via palm
civets) were 99.8% similar. More
work needs to be done to ID the
source of COVID-19.
Zhang et al. 2020. Pangolin homology associated with 2019-
nCoV. Biorxiv. https://www.biorxiv.org/content/
10.1101/2020.02.19.950253v1.full.pdf
https://www.nature.com/articles/d41586-020-00548-w
“By screening respiratory and fecal samples
collected from a wide range of animals, we
identified the first coronavirus in bats .”

What is a coronavirus?
1. Large, enveloped,
positive- stranded RNA
viruses
2. Largest genome among
all RNA viruses, packed
inside a helical capsid
3. Spike proteins mediate
entry into host cells,
determine host range and
tissue tropism and induce
immune response
4. Spikes > crown-like (‗corona‘
in Latin)
Image credit: Scientific Animations (CC BY-SA 4.0), Creative
Commons
Fun facts
ssRNA (+sense) 32 kb
Largest known RNA virus genome
Mutate and change at a high rate

Coronaviruses
1. Usually affect mammals and birds – but occasionally mutate
and affect humans too (and person -to- person
transmission).
2. No previous exposure -> No natural immunity, no vaccines
and no specific treatment.
3. This may lead to outbreaks and eventually, pandemics (SARS
in 2003, MERS in 2012, 2019-nCoV).
2019-nCoV
Year when first
detected.
Novel CoronaVirus

How is it spread?
Through
the air by
coughing
or
sneezing
Touching a
surface with
the virus on
it, then
touching
your mouth,
nose, or
eyes
Close
personal
contact, such
as touching or
shaking
hands

 COVID-19 spreads through
droplets which are released
when people sneeze or cough.
 Typically, with most respiratory viruses, people are thought to
be most contagious when they are most symptomatic.
 With 2019-nCoV, however, there have been reports of
spread from an asymptomatic infected patient to a close
contact.

How is it spread?
Can linger in the air for ~30 min

How is it spread?
https://www.nytimes.com/2020/03/02/health/coronavirus-how-it-
spreads.html
You walk into a crowded classroom. Another student is
infected by SARS-CoV-2. What puts you at the most risk of
being infected by that person?
Four factors likely to play a role
(1) How close you get.
(2) How long you are near the person.
(3) Whether that person projects viral droplets on you.
(4) How much you touch your face.

24
Travellers have brought the virus into
other countries
 Many countries have now
detected the virus in travellers.
 Some people who were in
contact with these travellers
were infected by them.
 It is possible that other locations
will have cases of 2019-nCoV.
 Although there is a lot we don’t
know yet about this new virus,
we can still prevent the disease
and stop an outbreak.

How Coronavirus Hijacks Your Cells
It attaches to cells in the upper respiratory system via a protein
called ACE2.
By Jonathan Corum and Carl Zimmer: https://www.nytimes.com/interactive/2020/03/11/science/how-
coronavirus-hijacks-your-cells.html

How Coronavirus Hijacks Your Cells
Each infected cell can release millions of copies of the virus before the
cell finally breaks down and dies.
By Jonathan Corum and Carl Zimmer: https://www.nytimes.com/interactive/2020/03/11/science/how-
coronavirus-hijacks-your-cells.html

How easily is it spread?
R0 (pronounced “R naught”) is the basic reproduction number,
an estimate of the number of people who catch the virus from a
single infected person.
The current estimate for SARS-CoV-2 is between 2 and 3
Animation website: https://www.nytimes.com/interactive/2020/world/asia/china-coronavirus-contain.html
del Rio et al. 2020. COVID-19—New insights on a rapidly changing epidemic. JAMA. doi:10.1001/jama.
2020.3072

Compare with the seasonal flu
Animation website: https://www.nytimes.com/interactive/2020/world/asia/china-coronavirus-contain.html
SARS-CoV-2: R0= 2.6 Flu: R0= 1.3

33
Symptoms start like many other
illnesses
Fever Cough
Shortness of
breath
Muscle
aches
DiarrhoeaSore
throat
 Symptoms start about 2 to 10 days after exposure,
but can be as long as 14 days.
 Incubation period until symptom onset: 2 to 14 days.
 Some people have no symptoms, most have a mild illness. It
can be severe and sometimes fatal.
Main symptoms:
Fever (>80% of the patients)
Cough (>80%)
Shortness of breath (31%)
Muscle ache (11%)

 Mild (no or mild pneumonia) was reported in 81 %.
 Severe disease (eg, with dyspnea, hypoxia or >50% lung
involvement on imaging within 24 to 48 hours) that requires
hospitalization and oxygen support was reported in 14%.
 Critical disease(eg, ARDS, sepsis and septic shock, MODS)
need admission to an ICU was reported in 5%.
 Recent multivariable analysis confirmed older age, higher Sequential Organ
Failure Assessment (SOFA) score, severe lymphopenia and D-dimer
>1μg/L on admission were ass with higher mortality approximately 49%.
 In children with COVID-19 the symptoms are usually less severe than
adults and present mainly with cough and fever, and co-infection has
been observed.
 There is currently no known difference between the clinical manifestations
of pregnant and non-pregnant women or adults of reproductive age.
The overall case fatality rate was 2.3%.
No deaths were reported among noncritical cases.

WHO Case Definition
1: suspect
A. A patient with acute respiratory illness (fever and at least one sign/symptom of
respiratory disease (e.g., cough, shortness of breath), AND with no other etiology
that fully explains the clinical presentation AND a history of travel to or residence
in a country/area or territory reporting local transmission of COVID-19 disease
during the 14 days prior to symptom onset. OR
B. A patient with any acute respiratory illness AND having been in contact with a
confirmed or probable COVID-19 case in the last 14 days prior to onset of Sx.
OR
C. A patient with severe acute respiratory infection (fever and at least one
sign/symptom of respiratory disease (e.g. cough, shortness breath) AND requiring
hospitalization AND with no other etiology that fully explains the clinical
presentation.
2: Probable case
A suspect case for whom testing for COVID-19 is inconclusive.
3: Confirmed
A case with positive PCR irrespective of symptoms and signs.

The most common Laboratory abnormalities
In patient hospitalized with Pneumonia:
 Lymphopenia (83%)
 Mild thrombocytopenia (36%)
 Leukopenia (34%)
 Normal Procalcitonin (95%)
 Elevated CRP (61% with CRP > 10 mg/L).
 Respiratory viral panel will NOT be positive for
coronavirus.
 Elevated troponin.

Investigations to confirm 2019-nCoV
 Combined nasopharyngeal/ throat swab is recommended.
 If positive repeat every 4 days from the of sample collection
date till negative.
 If negative repeat after 24 hours.
Lower respiratory specimen is preferred when applicable.
 Airborne / contact isolation is recommended.
 Confirmed cases can be cohorted in case of shortage of single
isolation rooms.
 For further information contact your infection control
practitioner.
If 2 consecutive negative isolation can be
discontinued.

 China shared the genetic sequence of the novel
coronavirus on 12 January.
 Specific diagnostic kits used in patients
withlaboratory-confirmed 2019-n CoV
infection:
1.
2. Next-generation sequencing.
ByReal-time RT-PCR
Request CBC, CMP, CRP, Chest X-ray, Respiratory panel including
COVID-19 PCR as baseline investigations.
Request electrocardiogram (ECG) for all patients above 40 years of age
and for all patients with comorbidities regardless of their age.
Consider repeating other blood tests ,CT Chest if clinically indicated

 Perform real-time Reverse-Transcription Polymerase Chain
Reaction (RT-PCR) assays for SARS-CoV-2 in all patients with
suspected infection.
 Collect lower respiratory tract specimens (sputum, endotracheal
aspirate, bronchoalveolar lavage) where possible and depending
upon the patient‘s condition.
 Upper respiratory tract specimens (nasopharyngeal aspirate or
combined nasopharyngeal and oropharyngeal swabs) may be used
if lower respiratory tract specimens cannot be collected.
 If initial testing is negative in a patient who is strongly suspected
to have COVID-19, recollect specimens from multiple respiratory
tract sites (nose, sputum, endotracheal aspirate) and retest.
Sent for-------- RT-PCR

 CXR in patients suspect to have pneumonia
 75% bilateral disease, while 25% have Unilateral
disease.
 CT chest:
 Bilateral multiple lobular and subsegmntal consolidation.
 Ground Glass Opacification.
Radiology
Largest cohort- reported sensitivity of CT was 97 %( probable over
estimation of sensitivity) and specificity of 25%.
Should not be used to diagnose COVID.
CT should ONLY be done if it will lead to changes in clinical
management, and other diagnostic methods are unreliable.

Radiology conclusions:
 Up to approximately 50% of patients with COVID-19 infection may
have normal CT scans 0-2 days after onset of flu-like symptoms
from COVID-19.
 COVID-19 RT- PCR sensitivity may be as low as 60-70%;
therefore patients with pneumonia due to COVID-19 may have lung
abnormalities on chest CT but an initially negative RT-PCR.
 Lung abnormalities during the early course of COVID-19 infection
usually are peripheral focal or multifocal ground glass opacities
affecting both lungs in approximately 50-75% of patients.
 As the disease progresses, crazy paving and consolidation
become the dominant CT findings, peaking around 9-13 days
followed by slow clearing at approximately 1 month and beyond.
 A study published by a team at the Tongji Hospital
in Wuhan on 26 February 2020 showed that a
chest CT scan for COVID-19 has more sensitivity
(98%) than the polymerase chain reaction (71%).

Prevention and Control of COVID-19 infection
General principles—
 There is no specific treatment for COVID-19.
 There is no vaccine available at this time to prevent COVID-19.
Researchers are working to develop one.
 Many people can recover at home, but those with more severe illness
may need to receive care in the hospital.
 Illness can range from mild to severe. Some people have died from their
illness.
 People with advancing age(60-80Ys) or chronic conditions such as
lung disease, heart disease, diabetes or immune problems are at a higher
risk for severe illness. This is similar to the high risk groups for influenza.
 The key to prevention is to control the spread from person-to-person.
According to WHO, CDC and FDA there are currently no medications or
vaccines proven to be effective for the treatment or prevention of the
2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Management of mild COVID-19: symptomatic treatment
and monitoring
 Patients with mild disease do not require hospital interventions,
but isolation is necessary to contain virus transmission and will
depend on national strategy and resources.
 Provide patients with mild COVID-19 with symptomatic treatment
such as antipyretics for fever.
 Counsel patients with mild COVID-19 about signs and symptoms of
complicated disease. If they develop any of these symptoms, they
should seek urgent care through national referral systems.

Management of severe COVID-19: oxygen therapy and
monitoring
 Give oxygen therapy immediately to patients with SARI and Resp
distress, hypoxaemia or shock and target SpO2 > 94%.
 Closely monitor patients with COVID-19 for signs of clinical
deterioration, such as rapidly progressive respiratory failure and
sepsis and respond immediately with supportive care interventions.
 Vital signs, Early Warning Signs of deterioration
 LAB and Chemistry for Renal, Liver, Cardiac….
 Understand the patient‘s co-morbid condition(s) to tailor the
management of critical illness.
 Use conservative fluid management in patients with SARI when
there is no evidence of shock.

Management of severe COVID-19: treatment of co-
infections
 Give empiric antimicrobials to treat all likely pathogens causing
SARI and sepsis as soon as possible, within 1 hour of initial
assessment for patients with sepsis.
 Management of critical COVID-19: ARDS.
 Management of critical COVID-19: Septic Shock.
 Patients with severe disease often need oxygenation support:
 High-flow oxygen.
 Noninvasive positive pressure ventilation.
 Intubation with mechanical ventilation.
 ECMO may be indicated in patients with refractory hypoxia.

Treatment
1. Treatment is symptomatic and based on patient‘s clinical condition.
2. Supportive treatment includes oxygen therapy, hydration and fever/pain
management and antibiotics if bacterial co-infection is present.
3. Medicines to stock as per your country‘s or institution‘s formularies or clinical
recommendations: antimicrobial agents, antipyretic and analgesic treatment,
corticosteroids, intestinal microecological preparations, other gastrointestinal
treatment, antitussive treatment, sputum removal treatment, anti-asthmatic
treatment.
4. Antiviral medicines: Remdesivir (nucleotide analogue prodrug in
development) has been used in USA and France and is being used in China
too; recombinant human interferon; lopinavir/ritonavir; ribavirin, CPA list).
antiviral medications are not recommended for use in young, healthy patients
with mild symptoms and no underlying comorbid conditions.

Psychological
Dr.Anas Ameer Khan 49
 Infected individuals may experience distress from
quarantine, travel restrictions, side effects of
treatment, or fear of the infection itself.
 To address these concerns, the National Health
Commission of China published a national guideline for
psychological crisis intervention on 27 January 2020.

Treatment Protocol for ASymptomatic patient with
+ COVID-19 PCR

Treatment Protocol for Symptomatic patient with
+ COVID-19 PCR
A. Positive COVID-19 PCR with uncomplicated upper respiratory tract inf.
Patients with upper respiratory tract viral infection, may have symptoms
like fever, cough, sore throat, nasal congestion, malaise, headache,
muscle pain or malaise providing that they do not have any signs of
dehydration, sepsis or shortness of breath and without lung infiltrate.

Treatment Protocol for Symptomatic patient with
+ COVID-19 PCR
B. Positive COVID-19 PCR Pneumonia (documented pneumonia inCXR/CT).
 Mild: Patient with documented pneumonia in CXR.
 Severe :t with documented pneumonia in CXR + one of the following:
Respiratory Rate >30 breaths/min, SpO2 <90% on room air.
CURB65 and/or PSI can be used to assess pneumonia severity.

C. Treatment Protocol for patient with + COVID-19 PCR
Requiring ICU (Septic Shock/ARDS).
Admit the patient
Strict infection control measures should be maintained all the time.

CORTICOSTEROIDS
 The WHO and CDC recommend glucocorticoids not be used
in patients with COVID-19 pneumonia unless there are
other indications.
when considering patients with sepsis and septic shock for
glucocorticoid therapy:
 For adult patients with sepsis and septic shock, we suggest
not routinely using intravenous glucocorticoid therapy as part
of initial therapy.
 We use glucocorticoid therapy on a case-by-case basis in
select patients with refractory shock (defined as a systolic
blood pressure <90 mmHg for more than one hour following
both adequate fluid resuscitation and vasopressor
administration).
Follow intensive care recommendations.

NOVELTREATMENT
Randomised controlled trial has
been initiated quickly to assess
the efficacy and safety of
combined use of Lopinavir
and Ritonavir in patients
hospitalized with 2019-nCoV
infection.

The coronavirus pandemic can be dramatically
slowed, or stopped, with the immediate widespread
use of high doses of vitamin C. Physicians have
demonstrated the powerful antiviral action of
vitamin C for decades. There has been a lack of
media coverage of this effective and successful
approach against viruses in general, and coronavirus
in particular.

When Se-deﬁcient virus-infected hosts were supplemented
with dietary Se, viral mutation rates diminished and
immunocompetence improved. Herein is described the role of
micronutrient Se deﬁciency on the evolution of some contemporary
RNA viruses and their subsequent VIDs.
Distinguishing cellular and biomolecular evidence for several VIDs
suggests that environmental conditions conducive to chronic
dietary Se deprivation could be monitored for bioindicators of
incipient viral virulence and subsequent pathogenesis.

Really wash your hands and stop touching your
face
Image credit: @BrodHiggins

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