covid 19 virology and evolution

1. COVID 19 primer
Dr M S ADITYA

5. Coronavirus
• large, enveloped, positive-sense, single-stranded RNA viruses
belonging to the order Nidovirales(viruses that replicate using a
nested set of mRNAs ), family Coronaviridae, subfamily Coronavirinae
• four genera(alpha, beta, gamma and delta) characterized by different
antigenic cross-reactivity and genetic makeup. Only the alpha- and
betacoronavirus genera include strains pathogenic to humans
• First reported infection was avian infectious bronchitis in 1937,
human report in 1965
• Probably living in humans from 500-600years probable originated
from bats

6. Coronaviruses
• Recognized as important veterinary
pathogen causing respiratory and
enteric illness in animals
• Alpha coronaviruses (HCoV-229E
and HCoV-NL63) and beta
coronaviruses (HCoV-HKU1, HCoV-
OC43, Middle East respiratory
syndrome coronavirus [MERS-CoV],
and the severe acute respiratory
syndrome coronavirus [SARS-CoV]

7. Structure
• Coronaviruses are so named
because of their characteristic
solar corona (crown-like)
appearance when observed
under an electron microscope
• peplomers of the spike [S]
glycoprotein radiating from the
virus lipid envelope
• five structural proteins, S, M, N,
HE, and E are recognized. HE is
not encoded in SARS group

8. • The host-derived membrane is studded with
glycoprotein spikes and surrounds the
genome, which is encased in a nucleocapsid
that is helical in its relaxed form but assumes
a roughly spherical shape in the virus particle
• Spike(S) protein binds to the receptor and has
antigens which provoke antibody response
• M protein has some role in virus assembly
• The nucleocapsid protein (N) associates with
the RNA genome to form the nucleocapsid
regulates virus RNA synthesis
• E protein role not known

9. REPLICATION
Replication of viral RNA occurs in the host
cytoplasm by a unique mechanism in which
RNA polymerase binds to a leader
sequence and then detaches and
reattaches at multiple locations, allowing for
the production of a nested set of mRNA
molecules with common 3' ends

10. Receptors
• Alphacoronavirus genus includes two human virus species, HCoV-
229E and HCoV-NL63. HCoV-229E, like several animal
alphacoronaviruses, utilizes aminopeptidase N (APN) as its major
receptor
• HCoV-NL63, like the SARS-CoV (a betacoronavirus), uses angiotensin-
converting enzyme-2 (ACE-2) receptor
• This binding with ACE-2 receptor has given rise to doubts whether
upregulation of the receptors can lead to increased infectivity

12. Coronaviruses –clinical presentation
• Respiratory tract illness –upper/lower/otitis
• Enteric illness-gastroenteritis
• Neurological- ADEM
• Kawasaki disease

13. What has been our experience with this
group of viruses
• In all 7 viruses have been found to have clinical implications
• 4 of them are known to cause only mild infection
• SARS were first noted in Guangdong Province, China, in November 2002.
Between November 16, 2002, and February 28, 2003, 792 cases were
reported in this province
• The 2002 to 2003 outbreak resulted in 8096 cases with 774 deaths and a
case-fatality rate of 9.6 percent
• Transmission to healthcare workers has been a common feature of most
SARS outbreaks. A possible contributing factor is that peak viral shedding in
respiratory secretions, as determined by polymerase chain reaction (PCR)
• Occurs 6 to 11 days following the onset of illness, at a time of severe
respiratory symptoms

14. LAB FAILS
• Two outbreaks that presumably originated in laboratories working
with the SARS coronavirus involved only a single case with no
secondary spread
• In a third laboratory-based outbreak that occurred in China in April
2004, there were nine cases in three generations of contacts and one
death
• Laboratory strains, represent strains that have been adapted to
spread among humans, can cause outbreaks
• Control of possible animal intermediaries is important in preventing
reemergence of SARS. Since 2004, China has banned all consumption
of palm civets

15. MERS(Middle East respiratory syndrome)
• September 2012, a case of novel coronavirus infection was reported
involving a man in Saudi Arabia who was admitted to a hospital with
pneumonia and acute kidney injury
• (MERS-CoV) is a lineage C betacoronavirus found in humans and
camels, closely related to several bat coronaviruses
• Dipeptidyl peptidase 4 (DPP4; also known as CD26), which is present
on the surfaces of human nonciliated bronchial epithelial cells, is a
functional receptor for MERS-CoV
• High mortality, requirement for ventilation. Multi organ involvement

16. COVID-19
• COVID-19 is a betacoronavirus in the same subgenus as the severe
acute respiratory syndrome (SARS) virus
• Two different types of SARS-CoV-2 were identified, designated type L
(accounting for 70 percent of the strains) and type S (accounting for
30 percent)
• Seasonality of corona virus outbreaks suggests more winter
transmission and some time spring/fall
• MERS while being similar to COVID-19 is genomically different
• MERS may have a camel/Bat transmission cycle
• SARS in 2002 probably had bat/civet cat cycle

17. COVID-19
• In December 2019, the city of Wuhan in Hubei Province has a
population of 11 million and is China's seventh largest city
• An immediate investigation of these clustered cases to identify a
novel coronavirus (nCoV) strain from the patient groups in Wuhan
The outbreak is believed to have started at a local seafood/wild
animal market
• Pangolins have been implicated as intermediate hosts
• Again bats implicated as source of the viruses, giving rise to suspicion
of direct spread in wet markets

18. How is it different/similar from SARS
• High transmission
rates/infectivity
• Lesser fatality
• Aerosol spread
• Global foot print
• Direct bat to human-human
transmission or pangolins
• Children spared largely
• Older age, co morbids same
• Winter spread
• Almost similar genome with
SARS

20. Diagnostic testing
• SARS-CoV-2 RNA is detected by reverse-transcription polymerase
chain reaction (RT-PCR)
• Negative test does not rule out infection, high specificity for broncho
alveolar fluid
• Antibody testing may be helpful in high suspicion negative test
• 210 symptomatic patients with suspected COVID-19; 30 tested
positive for another respiratory viral pathogen, and 11 tested positive
for SARS-CoV-2

21. IMMUNITY
• Initial experience suggests the development of antibody response
which is protective, but duration of response is doubtful
• Vaccination have had limited success, probably because of
inadequacy of response, changing strains
• Risk of severe response when natural infection follows
• Monoclonal antibodies, convalescent serum used for therapeutic
purposes

22. Disinfection
• very susceptible to 70% ethanol
• hexachlorophene [98], 2% glutaraldehyde [95] and 1% povidone-
iodine each produced satisfactory killing. It appears that susceptibility
of coronaviruses to
• 6% sodium hypochlorite (the active agent in bleach) solutions has
been variable, but satisfactory killing was achieved with
concentrations of 1:40 or higher
• Coronaviruses were not killed by benzalkonium chloride
or chlorhexidine

23. CONCLUSIONS
• Human wild animal contact increasing in recent times
• Vastly increasing travel and congestion in cities may contribute to
rapid spread
• Early typing and surveillance could help in spread of disease
• May not be entirely due to habits of Chinese
• Important to understand species and virology to understand
outbreaks better