Coronavirus for non virologists

Michal Caspi Tal, PhD

@ImmunoFever
Instructor
Stanford University School of Medicine
Big Questions
• How worried should I be about this?
• What is SARS-COV-2? How did it acquire the ability to spread from
human to human? What do we know about ACE2?
• Why is there a strong age distribution for COVID19 severity?
• What do we know about the immune response to SARS-COV-2 and is
it protective against re-infection?
• What can I do to reduce spread? Will there be a vaccine?
• Will this virus be seasonal?
• How can I help?
How worried should I be about this?

• Is this going to be like a zombie apocalypse? Should we be panicking?

NO and NO
• My employer is having me work from home. I’m a healthy adult under
50. Isn’t this excessive?
We have to slow the spread of disease so that our health systems can provide
care – working from home is a great way to slow disease spread.
 Interventions to slow disease spread are critical

https://twitter.com/CT_Bergstrom/status/1235865328074153986
We don’t have 2 million hospital beds like this
https://twitter.com/LizSpecht/status/1236095189074116608
 Social distancing
• Cancel in person seminars, meetings, conferences.
• Enable remote conferencing.
• Stop traveling & stay home.
• Protect the vulnerable (elderly, immunocompromised).
• Stop handshakes, high fives or hugs.

https://twitter.com/VirusesImmunity/status/1236651073881899008
Medical interventions

https://avatorl.org/covid-19/?page=ClinicalData1099
 Effect of Early Interventions on Epidemic Spread in 1918

Closed schools, churches, theatres,

large public gatherings before
reaching 30/100,000 CEPID

https://www-pnas-org.stanford.idm.oclc.org/content/104/18/7582
 Also for COVID19 - significant increase in mortality
% after 30 cases/100,000 or 3 cases/10,000

https://www.thelancet.com/action/showPdf?pii=S2214-109X%2820%2930068-1
PLEASE cancel ALL the parades, ALL the
cruises, ALL the large sporting events…
How Does SARS-COV-2 spread?
Transmissibility
The chance that an infected person will infect a susceptible person
An epidemic
A rapid spread of disease to a large number of
people in a short period of time

How infectious is this virus?

R0 (reproductive number): 2-3 for SARS-CoV-2
Attack rate (what proportion of the population
will get infected): Assumption 30-40%
https://twitter.com/AdamJKucharski/status/1236568643468746752
 Italy
Dr. Faris Durmo MD., Ma

• 10 % Lombardy doctors are infected

• AT least 1060 self-isolating at home
• AT least 2394 hospitalized
• AT least 462 intensive care
• Of 197 at least 49 are ages (62-95 yo)
• 4636 total cases 197deaths
• Death ratio of 4.25 % from 2.5%
• Approxim 9% admitted to ICU.
February 18: 3 cases
February 21: 20 cases
February 24: 231 cases
February 27: 655 cases
March 1: 1,694 cases
March 4: 3,089 cases
https://avatorl.org/covid-19/?page=ClinicalData1099 March 7: 5,883 cases
March 9 AM, 2020 https://coronavirus.1point3acres.com/en
 Cases and deaths per US state

March 9 morning, 2020 https://coronavirus.1point3acres.com/en

 Cases per California county

March 9 AM, 2020 https://coronavirus.1point3acres.com/en

 Timeline - Cases per day in China

First death

Wu et al., JAMA, 2020 (slide by Florian Krammer)

How did China slow down the outbreak?
• 57 million people
under lockdown in
Hubei province
• Widespread lockdowns
outside of Hubei
province

https://www.earthobser
vatory.nasa.gov/images/
146362/airborne-
nitrogen-dioxide-
plummets-over-china (slide by Florian Krammer)
What is SARS-COV-2?
How did it acquire the ability to spread from
human to human?
What do we know about ACE2?
 How it all started: On December 31st, several cases of pneumonia with
unknown etiology were reported in Wuhan, China to the WHO.

Huanan Seafood Wholesale Market

(slide by Florian Krammer) https://www.chinahighlights.com/wuhan/map.htm

…..it probably started earlier

Huang et al., NEJM, 2020

It is a coronavirus! (interim name 2019 nCoV)

(slide by Florian Krammer)

Hold on! What is a coronavirus???
• Family: Coronaviridae
• Corona  Crown
• Positive sense single stranded RNA viruses (+ssRNA,
large >30kb genome) Coronavirus. Source: CDC

• Enveloped
• 120nm in diameter
• Regular human coronaviruses (cause 30% of all colds):
• Alphacoronaviruses: NL63, 229E
• Betacoronaviruses: HKU1, OC43
• Zoonotic coronaviruses (all betacoronaviruses)
• SARS-CoV-1 (2002-2004)
• MERS-CoV

(slide by Florian Krammer)

How do we name it?
Disease: COVID-19 (WHO)
Coronavirus Disease 2019

Betacoronaviruses
Virus: SARS-CoV-2 (ICTV)
Severe Acute Respiratory
Syndrome Coronavirus 2
Alphacoronaviruses

(slide by Florian Krammer)

ICTV et al., Med Micro, 2020
https://twitter.com/virusninja/status/
1235773375076880387/photo/1
 Virus culture
What do we know about the virus?

Wuhan Institute of Virology

EM micrographs Antibody response Sampling sites, PCR methods

(slide by Florian Krammer)

How does the virus enter cells?
• Uses human ACE2 as
receptors
• Similar to SARS-CoV-1 and
NL63

(slide by Florian Krammer)

 Testing

https://www.wnyc.org/story/seattle-health-care-system-offers-drive-through-
coronavirus-testing-for-workers/
https://med.stanford.edu/news/all-news/2020/03/stanford-medicine-COVID-19-test-now-in-use.html
How does this virus mutate and what does
that tell us?
Your body is made of cells
Bacteria are cells too
Viruses are not
YOUR CELL

virus

bacteria
 YOUR CELL

virus

bacteria
Speed and error rate in replication
What is happening in Washington State?

https://bedford.io/blog/ncov-cryptic-transmission/
https://www.nature.com/articles/d41586-020-00676-3 Seattle Flu Study/Trevor Bedford
What is happening in Washington State?

https://twitter.com/trvrb/status/1236799358718185472
Seattle Flu Study/Trevor Bedford
Symptoms
80% mild cases
15% severe cases
5% critical cases

(slide by Florian Krammer)

https://en.wikipedia.org/wiki/2019%E2%80%9320_coronavirus_outbreak#/media/File:Symptoms_of_coronavirus_disease_2019_2.0.svg
Symptoms based on clinical data of 1099 patients

80% mild cases

15% severe cases
5% critical cases

https://avatorl.org/covid-19/?page=ClinicalData1099
Who gets (symptomatically) infected?
Based on >44,000 cases

(slide by Florian Krammer)

Coronavirus Pneumonia Emergency Response Epidemiology Team. The Epidemiological Characteristics of an
Outbreak of 2019 Novel Coronavirus Diseases (COVID-19) — China, 2020[J]. China CDC Weekly, 2020, 2(8): 113-122
 Children can catch SARS-COV-2, they just
aren’t as likely to show symptoms

https://www.medrxiv.org/content/10.1101/2020.03.03.20028423v1
More numbers:

Closed Case Fatality Rate: 6%  overestimate and hard to assess

(number of death/number of recovered*100)

Case Fatality Rate: 3.4%  overestimate, not all cases are captured (esp.
mild ones)
(number of deaths/number of cases*100)

Infection Fatality Rate: UNKNOWN, likely much lower

(number of deaths/number of infected*100)

(slide by Florian Krammer)

Case Fatality Rates depend on how many of
all infections are detected

https://www.wo
rldometers.info/
coronavirus/covi
d-19-testing/
(slide by Florian Krammer)
Case Fatality Rates vary by country due to
various factors: CFR

3.7%
0.7%
How many cases of all 3.2%
cases are detected? 3.3%
0.8%
How good is the health 2.0%
care system? 1.9%
0.0%

For how long has the 0.6%

0.0%
outbreak been ongoing?
8.3%

(slide by Florian Krammer)

 Case fatality rate by age based on
>44,000 confirmed cases in China
Overall CFR 2.3%

Males: 2.8
Females: 1.7

Hypertension, diabetes,
cardiovascular disease, chronic
respiratory disease, cancer: 5.6-10.5%

No deaths in kids 0-9 years of age

Cases are in the hospital for a long

time before they succumb to
infection (6-41 days)
(slide by Florian Krammer)
Coronavirus Pneumonia Emergency Response Epidemiology Team. The Epidemiological Characteristics of an
Outbreak of 2019 Novel Coronavirus Diseases (COVID-19) — China, 2020[J]. China CDC Weekly, 2020, 2(8): 113-122
What can I do to reduce spread?
Will there be a vaccine?
How does handwashing destroy coronaviruses?

https://twitter.com/PalliThordarson/status/1236549305189597189
Stay healthy
out there!
Host defense and collateral damage

pathogen Immune response

disease
Vaccines
Releasing a vaccine

• Tremendous regulation
• Phase I,II,III clinical trials
• Independent safety monitoring upon release
• To incorporate a vaccine into the childhood
vaccination schedule 60,000 pediatricians have to
consent that it is both safe and important
Can everyone be vaccinated?

•No
• Infants and immunocomprimised

•Community immunity
Figure 2 from Thompson, B. T., Chambers, R. C., & Liu, K. D. (2017). Acute Respiratory
Distress Syndrome. New England Journal of Medicine, 377(6), 562–
 Ly6E is an immune effector protein critical in
the response to SARS-COV-2

https://twitter.com/katrinabmar/status/1236647437651107843
https://twitter.com/jschoggins/status/1236633266108665856
 Therapeutics (clinical trials in progress)
Remdesivir (Gilead)
• Nucleoside analog (Gilead) Camostat Mesylate
• Works in non-human primates against MERS-CoV
• Effective against many CoVs
• Phase I safety data available Chloroquine

Lopinavir/ritonavir (produced by AbbVie as Kaletra/Aluvia)

• Licensed HIV protease inhibitors
• Used compassionately for SARS-CoV-1 in 2003
• Works against MERS-CoV in primates

Convalescent serum
• Anecdotal evidence that this is working (adapted from Florian Krammer)
What are we predicting about seasonality?
 SEASONAL FLU PEAKS
at low absolute humidity in northern/southern hemisphere
At high absolute humidity in the tropics
 ABSOLUTE
HUMIDITY

SUMMER WINTER
Mucosal Membranes
• The lining of your body cavities
• Every germ’s favorite route into your body
Older individuals and those with health conditions
will be at highest risk. How can we help?
• Minimize large gatherings
• Helping keep people at risk from going out
• Food delivery services (Meals on wheels etc)
• Research (indicators of severe responses, drug repurposing…)
Scientists I follow – much of this information has
been based on:
Florian Krammer
Ian Mackay
Trevor Bedford
Angela Rasmussen
Jeremy Konyndyk
Nathan Grubaugh
Kristian G. Andersen
Ellen Foxman
Katrina Mar
John Schoggins
Benhur Lee
Palli Thordarson
Akiko Iwasaki
Questions?
 Resources
https://www.cdc.gov/coronavirus/2019-ncov/index.html

https://medium.com/@edwardnirenberg/sars-cov-2-and-the-lessons-we-have-to-learn-from-it-
e2017fd5d3c
https://www.worldometers.info/coronavirus/
https://avatorl.org/covid-19/?page=ClinicalData1099
https://coronavirus.1point3acres.com/en