UPDATE ON CORONAVIRUS

LUCIA DE SANTIS, FY1 17/03/2020

A CENTURY OF NASTY VIRUSES

Spanish Flu: 40-50m deaths (up to 100m) Hong Kong Flu (1m deaths) SARS (774 deaths) – 10% mortality rate

1918 1957 1968 2009 2003

Asian Flu (1.1m deaths) - Singapore Swine flu (500k deaths)

2019: Coronavirus
7519 deaths and up
THE CULPRIT

 Officially SARS-COV-2
 RNA virus, Nidovirales family, genera alpha, beta, gamma, delta
 COV first identified in 1960s, shown to cause common cold in
volunteers
 Coronaviruses infect humans and other vertebrates
 Large range of COV found in bats
 Seven coronaviruses known to infect humans: symptoms range from GI
upset, common colds and severe lower respiratory tract infection.
 Close cousins are SARS-CoV in 2002-2003 and MERS-CoV in 2012
QUICK VIROLOGY REFRESHER

 Viral genome encased in nucleocapsid and surrounded by

glycoprotein spikes membrane
 Host RNA polymerase hijacked for production of proteins

 Genome encodes 4 or 5 stuctural proteins

 Spike protein: facilitates binding and fusion to host membrane and
main target of antibodies
 Membrane protein: viral assembly
 Nucleocapsid protein: regulation of viral RNA synthesis
 Hemagglutinin-esterase glycoprotein: aids absorption of virus into
host membrane
 Small envelope protein: required for viral assembly
WAS IT BATS?
• Recent consensus that bats might be the most likely reservoir
• Zoonoses carried by bats include Ebola ad Marbug filovurses, Hentra and Nipah henipaviruses, SARS and MERS etc
• Special physiology allows bats to be carriers but not affected:
• Body temperature rises above fever level when flying

• When infected, coronaviruses affect GI tract in bats

• Spread through faeces  into urban areas
UPDATED WHO CASE DEFINITION

 A patient with acute respiratory tract infection (sudden onset of at least one of the following: cough, fever, shortness of
breath) AND with no other aetiology that fully explains the clinical presentation AND with a history of travel or residence in a
country/area reporting local or community transmission* during the 14 days prior to symptom onset;
OR
 A patient with any acute respiratory illness AND having been in close contact with a confirmed or probable COVID-19 case
in the last 14 days prior to onset of symptoms;
OR
 A patient with severe acute respiratory infection (fever and at least one sign/symptom of respiratory disease (e.g., cough,
fever, shortness breath)) AND requiring hospitalisation (SARI) AND with no other aetiology that fully explains the clinical
presentation.
EPIDEMIOLOGY 101

Epidemic or outbreak disease occurrence among a population that is in excess of what is

expected in a given time and place

Cluster group of cases in a specific time and place that might be more
than expected.

Endemic disease or condition present among a population at all times

Pandemic a disease or condition that spreads across regions

Rate number of cases occurring during a specific period; always

dependent on the size of the population during that period.
A RAPID PANDEMIC

 A cluster of pneumonia cases identified in

Wuhan, China in December 2019
 All appeared related to a ‘wet market’ in
Wuhan selling both dead and live animals
 Still unknown source of infection, animal
host and reservoir
 Disease has now spread to more than 100
countries in the world
 Incubation period ranges likely 5-6 days
Peak viraemia at end of incubation period

WHAT WE KNOW SO
Droplet spread and touching
FAR contaminated objects:
At risk of spread if within 2 meters for 15
minutes

Clinical manifestation varies:
Up to 20% asymptomatic
Mild upper respiratory to severe pneumonia +
ARDS, septic shock and multiorgan failure
Some groups high risk: advanced age +
comorbidities eg. Immunosuppression

Mainstay of treatment is supportive care: O2, IVF, Mechanical

ventilation

Death rates are difficult to Note: in Korea where extensive screening

has taken place, death rates are much
calculate: vary from 6.4% to 0.6% much lower
PRESENTATION
Study of 138 patients in Wuhan:

 Fever in 99%
Insight from unpublished evidence in Italy:
 Note low grade fever in other studies
 Fatigue in 70% 1. Main observation is fever without rigors, which
may not be noticed by patients.
 Dry cough in 59%
1. Fatigue and “slow-down”
 Anorexia in 40%
2. Different from influenza
 Myalgias in 35%
2. 5-7th day worst in symptoms with multi-organ
 Dyspnoea in 31% involvement and respiratory failure
 Sputum production in 27%

Headache, sore throat and rhinorrea + GI symptoms

are much less common
WHO IS MOST AT RISK AND THE CASE OF ITALY

 Mortality rate in Italy as of 13/03 is 6.7%, much

higher than the 2.3% quoted elsewhere
 Likely due to older population than china

 Sudden surge in cases has overwhelmed

healthcare system – no more ITU spaces
 Potential of virus mutation?
INVESTIGATIONS

 Hypoxic and hypocapnic alkalosis

 Lymphopenia and monocytosis

 Later can develop in neutrophilia with
Pneumonia

CT best image modality to visualise interstitium

1. Ground glass opacification
2. More likely to be bilateral
3. Peripheral distribution
4. Involve the lower lobes

Ai et al, doi: 10.1148/radiol.2020200642.

 WHEN TO TEST
The trust recommends testing in anyone requiring overnight hospital admission, regardless of travel hx with:
 Clinical or radiological evidence of pneumonia
OR
 ARDS
OR
 Fever plus respiratory symptoms

No routine testing for public and healthcare staff who have a continuous new cough or fever above 37.8 who self-isolate at home.

If well enough to go home, must meet clinical and epidemiological criteria to qualify for testing:
 Epidemiological criteria
 In the 14 days before the onset of illness:
 travel to specified countries and areas, including transit for any length of time in these countries or areas
 contact with confirmed cases of COVID-19

 Clinical criteria
 Acute respiratory infection of any degree of severity, including at least one of shortness of breath (difficult breathing in children) or cough (with or without fever)
 Fever with no other symptoms

NB: label all specimens on outside of bag as “inpatient”

 Where possible, from both lower and upper respiratory tracts:

TYPES OF LRT:

SPECIMENS •Bronchoalveolaral lavage

•Endotracheal aspiate
•Expectorated sputum
As per the European Centre
for disease prevention and URT:
control
•Nasopharyngeal swab
•Oropharyngeal swab
•Nasopharyngel aspirate or nasal wash

Additional specimens for later testing:

•Serum, acute and convalescent specimen (2-4 weeks after acute pahse)
•Other to consider: blood, urine and faeces

Limited information re: best point in time. Best collected

every 2-3 days until two negative results 24h apart
MANAGEMENT

Home

•Appropriate for mild infection who can be adequately isolated

Hospital care

•Supportive care: oxygen, NIV, intubation in most serious cases

•Alert ITU early
•Do not use glucocorticoids unless other indications (eg IECOPD) – increased risk of mortality in
patients with influenza and MERS, although used in SARS, no good evidence for COVID-19.
•Antivirals still in testing.. ?remdesivir ?lopinavir-ritonavir
PUBLIC CONTROL MEASURES
 China has taken aggressive control measures (which seem to have worked!)
 Quarantine cities
 Close schools and workplaces
 Cancel public events
 Screening at airports and train stations
 In the UK: police have been given powers to force those at risk into quarantine

1. Diligent hand washing, particularly after touching surfaces

Advice for the public
2. Respiratory hygiene (covering to cough or sneeze)

3. Avoiding touching the face

4. Avoiding crowds (particularly in poorly ventilated spaces)

5. Cleaning and disinfecting objects and surfaces that are frequently touched
THE ECDC RISK ASSESSMENT – RECOMMENDED MEASURES
Containment is no longer possible – must now mitigate

 Social distancing measures must be implemented early to delay the peak

 Include immediate isolation, suspension of mass gatherings, social distancing in the workplace, closures of schools,

 Ensuring public is aware of seriousness

 Educate on personal hygiene, coughing etiquette, self-monitoring and social distancing

 Prevention and control in hospitals and long-term care facilities

 Slow the demand for ICU beds, safeguard vulnerable populations, protect healthcare workers, minimise export of cases to other facilities

 Train staff

 Countries should identify healthcare units that can be designated to care for COVID-19 cases

 If resources of capacity are limited, rational approaches should be implemented to prioritise high yield actions

 National surveillance systems should initially aim at detecting cases and assessing community transmission,
DOCTORS ARE NOT IMMUNE
For previous SARS and MERS outbreaks, infection of healthcare staff was
a significant concern

For suspected AND confirmed cases meeting the definition:

• Apron
• Fluid resistant surgical mask
• Eye protection if risk of splashing
• Gloves

For confirmed cases requiring an aerosol generating procedure* and in CCU “In the situation we describe, 85% of
• Full PPE: FFP3 / hood health care workers were exposed
during an aerosol-generating
• Disposable eye protection procedure exposed while wearing a
• Long sleeved disposable gown surgical mask, and the remainder
were wearing N95 masks. That none
• Gloves of the health care workers in this
situation acquired infection suggests
that surgical masks, hand hygiene,
and other standard procedures
* NIV, CPAP, optiflow, intubation and protected them from being infected”
extubation, bronchoscopy, chest physio
DONNING AND DOFFING EQUIPMENT

1. Connect battery to 2. Screw filter onto unit, 4. Attach belt to unit

blower unit feel it click at the end

7. Place second washer at 5. Insert plastic washer at

6. Push hose at rear of
end of hose and screw end of hose
head top
cap on

10. Press power button to

Sessions this week and next: 5114 turn on, wait for green light
8. Attach other end of 9. Strap unit to belt (hold down to turn off),
hose to unit around your back before wearing hood
ADVICE RE:
CHRONIC HEALTH, Contact manager
PREGNANCY OR >60
Y/O STAFF
https://www.rcog.org.uk/en/guid
elines-research-
Contact health @ work for advice if manager
services/guidelines/coronavirus- unsure what to do
pregnancy/covid-19-virus-
infection-and-pregnancy/

Essentially at manager’s discretion whether

alternative work arrangements are reasonable
and practicable to restrict vulnerable staff from
duties which involve COVID-19 contact

*OccHealth advises however that these groups are restricted

IF YOU CATCH IT..

Health@Work: 6514
8.30am – 4pm
OR

Day 1-7: may return to work if asymptomatic

After Day 8: may return to work if afebrile for 2 days and cough is the only persistent symptom
IF THEY CATCH IT..
Advice for patients who fit criteria but are well enough to go home:

 No need for swab – If you have been swabbed, you will be contacted about the result by dedicated team

 Self-isolate for 7 days – if temperature lasts longer, stay home until back to normal
 Your cough may take a few weeks to resolve, you do not need to stay home for >7 days if you still have a cough

 To protect others: do not go to GP, pharmacy or hospital

 Look after yourself: rest and drink plenty of fluid, take paracetamol or ibuprofen, cover mouth when coughing or
sneezing, bin used tissues, wash hands regularly for at least 20s.
 If you’re not better after 7 days, use NHS 111 online assessment before you leave home/let visitors in

 If anyone lives with someone symptomatic they must self isolate for 14 days

NHS 111
WHY WE WORRY

1. Uncertainty. It’s new, and we don’t know much about it yet

2. Speed of diffusion: 31 cases in China on Dec 31, February 83694 in 53 countries
3. Mortality potential: rates difficult to estimate, at worst 2.3% - cfr flu, 0.1% mortality rate
1. Although quoted up to 14.8% in >80 y/o in China
2. Could be lower as mild cases not picked up yet Annual no. of hospital beds in UK from 2000 to 2017
70k fewer beds over 16 years
4. Lack of ITU beds – in UK as of 2017 5,912 ITU beds, 4/5 are occupied
5. Socio-economical impact: schools and workplace closed, huge effect on market – recession? Implication
for healthcare funding?
6. Potential to endanger international cooperation
7. Developing a vaccine is going to take likely >1 year
8. Coronaviruses show relative seasonality – infections can continue into spring/any time of year 
potential for prolonged infection
 WHAT WE NEED TO DO

A further peak is likely once

measures are lifted, but much
less severe than if they were
not implemented

At what point should stricter social distancing measures be introduced?

NEW DEVELOPMENTS
Low dose short duration steroids helpful in
critical cases of ARDS, not mild or early
- Inhibit inflammatory storm in late ARDS
- In early/mild: delay virus clearance and
increase mortality risk

191 patients observed

Longest duration of viral shedding observed up to 37 days, median duration 20 days
32 patients required mechanical ventilation – 31 died.
Average length of ITU stay 6 days.

Median incubation period 5.1 days, with 97% developing symptoms in 11.5 days
14d quarantine is reasonable (1% will develop symptoms after) to detect cases
REFERENCES

 Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li
Y, Wang X, Peng Z JAMA. 2020;

 A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Chan JF, Yuan S, Kok KH, To KK, Chu H, Yang J, Xing F, Liu J, Yip
CC, Poon RW, Tsoi HW, Lo SK, Chan KH, Poon VK, Chan WM, Ip JD, Cai JP, Cheng VC, Chen H, Hui CK, Yuen KY Lancet. 2020;395(10223):514. Epub 2020 Jan 24.

 Persons Evaluated for 2019 Novel Coronavirus - United States, January 2020. ajema KL, Oster AM, McGovern OL, Lindstrom S, Stenger MR, Anderson TC, Isenhour C, Clarke KR, Evans ME, Chu VT, Biggs HM,
Kirking HL et al 2019-nCoV PersonsUnder Investigation Team, 2019-CoV Persons Under Investigation Team

 Zou L Ruan F Huang M et al. SARS-CoV-2 viral load in upper respiratory specimens of infected patients. N Engl J Med. 2020; (published online Feb 19.)

 How will country-based mitigation measures influence the course of the COVID-19 epidemic? Roy M Anderson, Hans Heesterbeek, Don Klinkenberg, T Déirdre Hollingsworth, The Lancet, March 2020

 Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Fei Zhou, MD † Ting Yu, MD † Ronghui Du, MD † Guohui Fan, MS † Ying Liu, MD † Zhibo
Liu, MD † et al., The Lancet, 2020

 Coronavirus Disease 2019 (COVID-19), Kenneth McIntosh, Up To Date, March 2020

 Coronaviruses: An Overview of Their Replication and Pathogenesis, Anthony R. Fehr and Stanley Perlman, Methods Mol Biol. 2015

 Rapid risk assessment: Novel coronavirus disease 2019 (COVID-19) pandemic: increased transmission in the EU/EEA and the UK – sixth update