This document summarizes information about SARS-CoV-2 and COVID-19. It describes the virus, how it is transmitted, symptoms of the disease, current treatments and vaccines in development. SARS-CoV-2 is a novel coronavirus that likely originated in bats and is genetically similar to coronaviruses that cause SARS and MERS. It is transmitted through respiratory droplets and contact with contaminated surfaces. COVID-19 symptoms range from mild to severe and can include fever, cough and breathing difficulties. Treatments include antiviral drugs and immune therapies, while several vaccine candidates are in development using different approaches.

1. COVID-19 /
SARS-CoV-2
All you wanted to know about
SARS-CoV-2 and COVID-19
Ed Rybicki
Professor in Microbiology, UCT
never
^

2. “The COVID-19 pandemic
has pushed the world into
a recession. For 2020 it will
be worse than the global
financial crisis. The
economic damage is
mounting across all
countries, tracking the
sharp rise in new
infections and
containment measures put
in place by governments.”
https://blogs.imf.org/2020/04/06/an-early-view-of-
the-economic-impact-of-the-pandemic-in-5-charts/

4. Background: Human infections with zoonotic coronaviruses (CoVs), including severe acute
respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have
raised great public health concern globally. Here, we report a novel bat- origin CoV causing
severe and fatal pneumonia in humans.
Methods: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five
patients with severe pneumonia from Jin Yin-tan Hospital of Wuhan, Hubei province,
China. Nucleic acids of the BAL were extracted and subjected to next-generation
sequencing.
Conclusion: A novel bat-borne CoV was identified that is associated with severe and fatal
respiratory disease in humans.
https://journals.lww.com/cmj/Abstract/publishahead/Identification_of_a_novel_coronavir
us_causing.99423.aspx 25/01/2020

5. “According to the International Committee on
Taxonomy of Viruses criteria, a new CoV
species could be defined if the nt identity is less
than 90% for the conserved RdRp sequence.
Thus, we considered that the novel CoVs
should be classified as a new species under
the subgenus Sarbecovirus of the genus
Betacoronavirus”
Genomics
approach to ID
cause: they
sequenced
EVERYTHING
out of samples
for 5 patients

6. ViralZone page on SARS-CoV-2
https://viralzone.expasy.org/764?outline=all_by_species

8. SARS2 Life Cycle
http://pdb101.rcsb.org/sci-art/goodsell-gallery/coronavirus-life-cycle

9. Virus Replication

10. The Virus
• SARS-CoV-2 is in the species SARS-like coronaviruses. At
125 nm, it is slightly larger than influenza, SARS and
MERS viruses.
• Most closely related to a Rhinolophus bat virus (> 96%
homologous). It is only 79% homologous with the
original SARS CoV
• 99% homology in receptor binding site to virus from
Malaysian pangolin, but only ~90% homology overall to
SARS-CoV-2
• Divergence dates between SARS-CoV-2 and the bat
sarbecovirus reservoir indicating that the lineage giving
rise to SARS-CoV-2 has been circulating unnoticed in
bats for decades
https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-020-01533-w
https://www.nature.com/articles/s41564-020-0771-4

11. Virus and Disease
• COVID-19 is the disease caused by the virus named
SARS-CoV-2. It first appeared in Wuhan, China, in
late 2019.
• The WHO declared COVID-19 a “Public Health
Emergency of International Concern” (PHEIC) on
30th January 2020
• …and declared it to be a pandemic - “an epidemic
occurring worldwide, or over a very wide area,
crossing international boundaries and usually
affecting a large number of people” - on 11th March
2020
• Rolling updates on COVID-19 from WHO are
available here.

12. Virus and Disease
• The symptoms of COVID-19 are fever, dry cough,
fatigue, nasal congestion, sore throat, loss of taste and
smell and (occasionally, not in SA) diarrhoea.
Breathlessness = more severe disease
• China CDC published (from 44,672 confirmed cases)
that COVID-19 was mild for 81% of patients and had an
overall case fatality rate of 2.3%.
• Only 2.2% were under 20 years old. Compared to
adults, children generally present with much milder
clinical symptoms (but have = viral loads).
• Those over 80 yrs had a CFR of 14.8%. The CFR also
increased in those with comorbidities such as
cardiovascular, diabetes, chronic respiratory disease,
hypertension, and cancer.
• The cause of death is respiratory failure, shock or
multiple organ failure.
https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-020-01533-w

13. https://ourworldindata.org/mortality-risk-covid
• People under 50 worldwide have a
case fatality rate (CFR) of less than 1%,
• people 50-59 have a CFR of 0.5 –
1.3%;
• 60-69 bracket a CFR of 1.8 – 3.6%;
• people of 70-79 a CFR of 4.5 – 12.8%,
• people over 80 a CFR of 13 – 20%
People over 80 are about ten times
more likely to die if they get COVID-
19, compared to people under 50

14. https://ourworldindata.org/mortality-risk-
covid

15. ••SARS-CoV-2 infection induces low IFN-I and -III levels
with a moderate ISG response
••Strong chemokine expression is consistent
across in vitro, ex vivo, and in vivo models
••Low innate antiviral defenses and high pro-inflammatory
cues contribute to COVID-19

17. https://coronavirus.westerncape.gov.za/covid-19-dashboard

18. NB: 6 000 –
12 000
people in
South Africa
die annually
of seasonal
flu

19. Virus Transmission
• Droplets from infected person, via sneezing or
coughing:
• Short range, direct transmission only by close contact
• Or via contaminated hard surfaces
• Can survive drying for hours
• Aerosolisation especially in confined spaces:
• Distributed via speaking or singing
• Much smaller particle size, travel much further, but dry
quicker = shorter duration infectivity?
• POSSIBLY via faeces:
• High viral load even in some patients without diarrhoea
http://www.cidrap.umn.edu/news-perspective/2020/03/study-covid-19-may-
spread-several-different-ways

20. Highly sensitive laser light scattering observations have
revealed that loud speech can emit thousands of oral fluid
droplets per second. In a closed, stagnant air environment, they
disappear from the window of view with time constants in the
range of 8 to 14 min, which corresponds to droplet nuclei
of ca. 4 μm diameter, or 12- to 21-μm droplets prior to
dehydration. These observations confirm that there is a
substantial probability that normal speaking causes airborne
virus transmission in confined environments.

23. Use of Masks
https://www.who.int/publications-detail/advice-on-
the-use-of-masks-in-the-community-during-home-
care-and-in-healthcare-settings-in-the-context-of-the-
novel-coronavirus-(2019-ncov)-outbreak

24. Tossing Spanners In
X
X X
X
RdRp inhibitor (nucleoside analogues)
Protease inhibitors
Fusion inhibitors
Antibodies
Cellular responses

25. Therapies
ANTIVIRAL DRUGS
• Remdesivir (viral polymerase inhibitor)
• Umifenovir (Fusion inhibitor)
• Lopinavir (Retrovirus protease inhibitor)
• Ritonavir (Retrovirus protease inhibitor)
• Hydroxychloroquine (anti-malaria drug)
• Dexamethasone (anti-inflammatory
corticosteroid)
ANTIBODIES
• Recovered patient serum and mAbs
• Anti-IL6 mAb

26. https://www.frontiersin.org/articles/10.3389/f
micb.2020.00658/full

27. The results from 10 severe adult cases showed
that one dose (200 mL) of CP was well tolerated
and could significantly increase or maintain the
neutralizing antibodies at a high level, leading to
disappearance of viremia in 7 d. Meanwhile,
clinical symptoms and paraclinical criteria rapidly
improved within 3 d.

28. Preliminary data show that [anti-IL6] tocilizumab,
which improved the clinical outcome immediately in
severe and critical COVID-19 patients, is an effective
treatment to reduce mortality.

30. Cape Times 03 August 2020

31. SARS-CoV-2 Vaccines
•Can one become immune to SARS-CoV-
2 / is reinfection possible?
•What are the correlates of protection –
or, what needs to be in a vaccine?
•What is the best kind of vaccine?
•How close are we to getting a vaccine?
•WILL WE GET VACCINES IN SOUTH
AFRICA??

32. CELL Preprint DOI: https://doi.org/10.1016/j.cell.2020.05.015
…circulating SARS-CoV-2−specific CD8+ and CD4+ T
cells were identified in ~70% and 100% of COVID-19
convalescent patients, respectively. CD4+ T cell
responses to spike, the main target of most vaccine
efforts, were robust and correlated with the
magnitude of the anti-SARS-CoV-2 IgG and IgA titers

34. We demonstrate a range of pre-existing memory
CD4+ T cells that are cross-reactive with comparable
affinity to SARS-CoV-2 and the common cold
coronaviruses HCoV-OC43, HCoV-229E, HCoV-NL63,
or HCoV-HKU1.

35. We developed a rhesus macaque model of SARS-CoV-2 infection and observed
that macaques had high viral loads in the upper and lower respiratory tract,
humoral and cellular immune responses, and pathologic evidence of viral
pneumonia. Following initial viral clearance, animals were rechallenged with
SARS-CoV-2 and showed 5 log10 reductions in median viral loads in
bronchoalveolar lavage and nasal mucosa compared with primary infection.
Anamnestic immune responses following rechallenge suggested that
protection was mediated by immunologic control. PROTECTION WAS NOT VIA
STERILISING Ab MEDIATED IMMUNITY
https://science.sciencemag.org/content/early/
2020/05/19/science.abc4776

36. Vaccines

40. Medicago doesn’t work with a
live virus. Instead, it uses
plants. It inserts a genetic
sequence into agrobacterium,
a soil bacteria, which is taken
up through the plants’ roots
— in this case, a close cousin
to tobacco. The plant begins
to produce the protein that
can then be used as a
vaccine. If the virus begins to
mutate, as is expected
of Covid-19, they can just
update the production using
new plants.
“That’s the difference
between us and egg-based
methods,” CEO Bruce Clark
said in an article in
defenseone.com. “We go
directly to producing the

41. Though the precise dosage for the vaccine in humans is not yet
determined, Medicago estimates its facilities in Quebec and
North Carolina could produce ~20 million and 100 million
annual doses of pharmaceutical-grade COVID-19 vaccines.
Millions of doses could be available by the end of the year as
needed.

43. Resources
• Scoop.it Virology news: https://www.scoop.it/topic/virology-
news
• Worldometer COVID-19:
https://www.worldometers.info/coronavirus/
• Frontiers Coronavirus hub: https://coronavirus.frontiersin.org/
• CDC COVID-19 / SARS-CoV-2 resources:
• https://www.cdc.gov/coronavirus/2019-nCoV/index.html
• WHO COVID-19 Pandemic resources:
https://www.who.int/emergencies/diseases/novel-coronavirus-
2019
• South Africa’s NICD: http://www.nicd.ac.za/diseases-a-z-
index/covid-19/?fbclid=IwAR2NIq02rOQxrc2ogxnbGdwbl0N8g7-
IwJ8Htk5oeiH03YyBt5Vw-7qhyNY
• New York Times distancing calculator:
https://www.nytimes.com/interactive/2020/03/25/opinion/coron
avirus-trump-reopen-america.html
• NY Times description of the virus:
https://www.nytimes.com/interactive/2020/04/03/science/coron
avirus-genome-bad-news-wrapped-in-protein.html