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Dr.Rajni Sharma
Mahamana Pandit Madan Mohan
Malviya Cancer Centre, Varanasi
Department of Atomic Energy, (Government of India)
What is COVID-19
 The virus responsible for COVID-19, SARS-CoV-2, is in the species SARS-
like corona viruses.
 At 125 nm, it is slightly larger than influenza, SARS and MERS viruses.
 It is almost certainly a descendant from a bat corona virus of which
there are many.
 The closest is a virus that originated from the Rhinolophus bat which is
> 96% homologous with the current SARS-CoV-2 virus. It is only 79%
homologous with the original SARS CoV .
EPIDEMIOLOGY
In December, 2019, Wuhan city, the capital of Hubei
province in China, became the centre of an outbreak
of pneumonia of unknown cause. By Jan 7, 2020,
Chinese scientists had isolated a novel coronavirus,
severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2; previously known as 2019-nCoV), from
these patients with virus-infected pneumonia,1 which
was later designated coronavirus disease 2019 (COVID-
19) in February, 2020, by WHO.
The novel Coronavirus outbreak called COVID-19 has
been declared a pandemic by World’s Health
Organization in 2020.
Global distribution of confirmed COVID-19 cases. (Map was reproduced from WHO Coronavirus
Disease (COVID-2019)
Global Trend
Global trend of confirmed COVID-19 cases and associated
deaths from January 23 through March 9, 2020. (Data were
obtained from WHO Coronavirus Disease (COVID-2019)
Situation Reports
Outbreak
The outbreak is likely to have started from
a zoonotic transmission event associated
with a large seafood market that also
traded in live wild animals.
It soon became clear that efficient
person-to-person transmission was also
occurring.
The Structure
Coronaviruses (CoVs) are
relatively large viruses
containing a single-stranded
positive-sense RNA genome
encapsulated within a
membrane envelope.
The viral membrane is studded
with glycoprotein spikes that
give coronaviruses their
crown-like appearance
Cryo-EM structure analysis has
revealed that the binding affinity of
SARS-CoV-2 S protein to ACE2 is about
10–20 times higher than that of SARS-
CoV S protein.
It is speculated that this may
contribute to the reported higher
transmissibility and contagiousness of
SARS-CoV-2 as compared to SARS-
CoV
Pathophysiology
 The betacoronavirus genome encodes several structural
proteins, including the glycosylated spike (S) protein that
functions as a major inducer of host immune responses.
 This S protein mediates host cell invasion binding to a
receptor protein called angiotensin-converting enzyme
2 (ACE2) located on the surface membrane of host cells.
 Priming is facilitated by the host cell-produced serine
protease TMPRSS211
The viral genome also encodes several nonstructural proteins including RNA-dependent RNA
polymerase
Upon entrance to the host cells, the viral genome is released as a single-stranded positive
RNA.
Translated into viral polyproteins using host cell protein translation machinery, which are then
cleaved into effector proteins by viral proteinases 3CLpro and Plpro.
Results in Immune suppression
Synthesis of a full-length negative-strand RNA template to be used by RdRp to make more
viral genomic RNA.
The interaction between viral S protein and ACE2 initiate the infection process.
Classification
There are four classes of coronaviruses designated
alpha, beta, gamma, and delta.
The betacoronavirus class includes severe acute
respiratory syndrome (SARS) virus (SARS-CoV), Middle
East respiratory syndrome (MERS) virus (MERS-CoV), and
the COVID-19 causative agent SARS-CoV-2.
Host
While coronaviruses
infect both humans and
animals, certain types of
animals such as bats that
host the largest variety of
coronaviruses appear to
be immune to
coronavirus-induced
illness.
•Recent travel from or residence in an
area with ongoing community spread
of COVID-19 as determined
by CDC or WHO
•Close contact with someone who
has COVID-19 — such as when a family
member or health care worker takes care
of an infected person
RISK FACTORS
Causes
It's unclear exactly how contagious the new
coronavirus is.
It appears to spread from person to person
among those in close contact.
 It may be spread by respiratory droplets
released when someone with the virus coughs or
sneezes.
It may also be spread if a person touches a
surface with the virus on it and then touches his
or her mouth, nose or eyes.
RISK FACTORS
The severity of the disease appears to be
associated with age, with the elderly most
at risk; those over 80 years of age had a
Case Fatality Rate (CFR) of 14.8%.
The CFR was also increased in those with
comorbidities including cardiovascular,
diabetes, chronic respiratory disease,
hypertension, and cancer.
 The cause of death is respiratory failure,
shock or multiple organ failure.
Incubation period
 Incubation period — The incubation period for COVID-19 is thought to be
within 14 days following exposure, with most cases occurring approximately
four to five days after exposure.
 Spectrum of illness severity — The spectrum of symptomatic infection ranges
from mild to critical; most infections are not severe
Clinical Manifestations/
Clinical Presentation Asymptomatic infection
 Mild upper respiratory tract illness, and severe viral
pneumonia
 Respiratory failure
 Death
 Fever(Fever was defined as axillary temperature of at
least 37·3°C)
 Dry cough
 Dyspnoea
 Fatigue
 Nasal congestion
 Sore throat
 Diarrhoea
Clinical Investigations
 Throat-swab specimens
 PCR
ROUTINE BLOOD INVESTIGATIONS LIKE
 Complete blood count
 Coagulation profile(Coagulopathy was defined as a 3-second extension of
prothrombin time or a 5-second extension of activated partial thromboplastin
time)
 Serum biochemical tests (including renal and liver function, creatine kinase,
lactate dehydrogenase, and electrolytes)
 myocardial enzymes
 interleukin-6 (IL-6), serum ferritin
 Procalcitonin
 Hypoproteinaemia was defined as blood albumin of less than 25 g/L.
Chest CT in patients with COVID-19 most
commonly demonstrates ground-glass
opacification with or without consolidative
abnormalities, consistent with viral pneumonia.
Complications
Complications can include:
Pneumonia in both lungs
Organ failure in several organs
Death
Prevention
WHO and CDC recommend following these precautions for
avoiding COVID-19:
•Avoid large events and mass gatherings.
•Avoid close contact (about 6 feet) with anyone who is sick or has symptoms.
•Keep distance between yourself and others if COVID-19 is spreading in your
community, especially if you have a higher risk of serious illness.
•Wash your hands often with soap and water for at least 20 seconds, or use an
alcohol-based hand sanitizer that contains at least 60% alcohol.
•Cover your mouth and nose with your elbow or a tissue when you cough or
sneeze. Throw away the used tissue.
•Avoid touching your eyes, nose and mouth if your hands aren't clean.
•Avoid sharing dishes, glasses, bedding and other household items if you're
sick.
•Clean and disinfect surfaces you often touch on a daily basis.
•Stay home from work, school and public areas if you're sick, unless you're
going to get medical care. Avoid taking public transportation if you're sick.
WHO also recommends that you:
•Avoid eating raw or undercooked meat or animal organs.
•Avoid contact with live animals and surfaces they may
have touched if you're visiting live market areas that have
recently had new coronavirus cases.
CDC doesn't recommend that healthy
people wear a face mask to protect themselves from
respiratory illnesses, including COVID-19. Only wear a
mask if a health care provider tells you to do so.
Medical Management
There is no proven treatment at this
early stage but we will doubtless
have more information about this
soon.
It can be assumed that non-
pharmacologic approaches are
effective such as fluid support,
oxygen and ventilatory support.
Extra Corporeal Membrane
Oxygenation (ECMO) is potentially of
benefit.
Vaccine and other therapeutics
 Phase 1 trials for safety and immunogenicity in human populations
are likely within 3 months.
 In terms of therapeutics there is no known effective pharmaceutical
agent.
 Putative agents include antivirals; Griffithsin, a spike protein inhibitor,
nucleoside analogues eg. remdesivir, ribavirin and protease inhibitors
such as lopinavir/ritonavir.
 Immunomodulatory and other host targeted agents include
interferon, chloroquine and immunoglobulins.
 Corticosteroids will potentially have benefit for immune mediated
lung damage late in the course of disease
Favipiravir, a purine nucleoside leading to inaccurate viral
RNA synthesis, was originally developed by Toyama
Chemical of Japan, and has recently been approved for a
clinical trial as a drug to treat COVID-19.
Chloroquine, an antimalarial drug, has proven effective in
treating coronavirus in China.
RNA Therapies:
RNA interference (RNAi) is a biological process wherein small
complementary RNA duplexes target and neutralize specific
mRNA molecules, resulting in inhibition of gene expression or
genetic translation
RNA Aptamers
Antisense Oligonucleotides:Antisense
oligonucleotides have also been
developed to reduce the severity of SARS
virus infections and to prevent or treat
SARS virus-associated disease.
Attenuated Virus Vaccines
DNA-Based Vaccines
References
 1Gorbalenya, A. E. The species severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and
naming it SARS-CoV-2. Nature Microbiology 2020,DOI: 10.1038/s41564-020-0695-z [Crossref], Google Scholar
 2Kupferschmidt, K.; Cohen, J. Will novel virus go pandemic or be contained?. Science 2020, 367 (6478),610–
611, DOI: 10.1126/science.367.6478.610 [Crossref], [ PubMed], [ CAS], Google Scholar
 3 Coronavirus Disease (COVID-2019) Situation Reports 1–45; World Health
Organization, 2020.https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports.Google
Scholar
 4 Coronavirus is now expected to curb global economic growth by 0.3% in
2020. https://www.forbes.com/sites/sergeiklebnikov/2020/02/11/coronavirus-is-now-expected-to-curb-global-
economic-growth-by-03-in-2020/#5de149ad16da.Google Scholar
 5Anthony, S. J.; Johnson, C. K.; Greig, D. J.; Kramer, S.;Che, X.; Wells, H.; Hicks, A. L.; Joly, D. O.; Wolfe, N. D.;Daszak,
P.; Karesh, W.; Lipkin, W. I.; Morse, S. S.; Mazet, J. A. K.; Goldstein, T. Global patterns in coronavirus diversity.Virus
Evol 2017, 3 (1), vex012, DOI: 10.1093/ve/vex012 [Crossref], [ PubMed], Google Scholar
 6Su, S.; Wong, G.; Shi, W.; Liu, J.; Lai, A. C.K.; Zhou, J.;Liu, W.; Bi, Y.; Gao, G. F. Epidemiology, genetic recombination,
and pathogenesis of coronaviruses.Trends Microbiol. 2016, 24 (6), 490– 502, DOI: 10.1016/j.tim.2016.03.003 [ Crossref],
[ PubMed], [CAS], Google Scholar
 7Zhu, N.; Zhang, D.; Wang, W.; Li, X.; Yang, B.; Song, J.;Zhao, X.; Huang, B.; Shi, W.; Lu, R.; Niu, P.; Zhan, F.; Ma,
X.;Wang, D.; Xu, W.; Wu, G.; Gao, G. F.; Tan, W. A novel coronavirus from patients with pneumonia in China, 2019.N.
Engl. J. Med. 2020, 382 (8), 727– 733, DOI: 10.1056/NEJMoa2001017 [ Crossref], [ PubMed], [CAS], Google Scholar
 8Tang, B.; Bragazzi, N. L.; Li, Q.; Tang, S.; Xiao, Y.; Wu, J.An updated estimation of the risk of transmission of the novel
coronavirus (2019-nCov). Infect Dis Model 2020, 5,248– 255, DOI: 10.1016/j.idm.2020.02.001 [ Crossref], [PubMed],
[ CAS], Google Scholar
Covid 19 rajni sharma

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Covid 19 rajni sharma

  • 1. Dr.Rajni Sharma Mahamana Pandit Madan Mohan Malviya Cancer Centre, Varanasi Department of Atomic Energy, (Government of India)
  • 2. What is COVID-19  The virus responsible for COVID-19, SARS-CoV-2, is in the species SARS- like corona viruses.  At 125 nm, it is slightly larger than influenza, SARS and MERS viruses.  It is almost certainly a descendant from a bat corona virus of which there are many.  The closest is a virus that originated from the Rhinolophus bat which is > 96% homologous with the current SARS-CoV-2 virus. It is only 79% homologous with the original SARS CoV .
  • 3. EPIDEMIOLOGY In December, 2019, Wuhan city, the capital of Hubei province in China, became the centre of an outbreak of pneumonia of unknown cause. By Jan 7, 2020, Chinese scientists had isolated a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; previously known as 2019-nCoV), from these patients with virus-infected pneumonia,1 which was later designated coronavirus disease 2019 (COVID- 19) in February, 2020, by WHO.
  • 4. The novel Coronavirus outbreak called COVID-19 has been declared a pandemic by World’s Health Organization in 2020. Global distribution of confirmed COVID-19 cases. (Map was reproduced from WHO Coronavirus Disease (COVID-2019)
  • 5. Global Trend Global trend of confirmed COVID-19 cases and associated deaths from January 23 through March 9, 2020. (Data were obtained from WHO Coronavirus Disease (COVID-2019) Situation Reports
  • 6. Outbreak The outbreak is likely to have started from a zoonotic transmission event associated with a large seafood market that also traded in live wild animals. It soon became clear that efficient person-to-person transmission was also occurring.
  • 7. The Structure Coronaviruses (CoVs) are relatively large viruses containing a single-stranded positive-sense RNA genome encapsulated within a membrane envelope. The viral membrane is studded with glycoprotein spikes that give coronaviruses their crown-like appearance
  • 8. Cryo-EM structure analysis has revealed that the binding affinity of SARS-CoV-2 S protein to ACE2 is about 10–20 times higher than that of SARS- CoV S protein. It is speculated that this may contribute to the reported higher transmissibility and contagiousness of SARS-CoV-2 as compared to SARS- CoV
  • 9. Pathophysiology  The betacoronavirus genome encodes several structural proteins, including the glycosylated spike (S) protein that functions as a major inducer of host immune responses.  This S protein mediates host cell invasion binding to a receptor protein called angiotensin-converting enzyme 2 (ACE2) located on the surface membrane of host cells.  Priming is facilitated by the host cell-produced serine protease TMPRSS211
  • 10. The viral genome also encodes several nonstructural proteins including RNA-dependent RNA polymerase Upon entrance to the host cells, the viral genome is released as a single-stranded positive RNA. Translated into viral polyproteins using host cell protein translation machinery, which are then cleaved into effector proteins by viral proteinases 3CLpro and Plpro. Results in Immune suppression Synthesis of a full-length negative-strand RNA template to be used by RdRp to make more viral genomic RNA. The interaction between viral S protein and ACE2 initiate the infection process.
  • 11.
  • 12.
  • 13. Classification There are four classes of coronaviruses designated alpha, beta, gamma, and delta. The betacoronavirus class includes severe acute respiratory syndrome (SARS) virus (SARS-CoV), Middle East respiratory syndrome (MERS) virus (MERS-CoV), and the COVID-19 causative agent SARS-CoV-2.
  • 14. Host While coronaviruses infect both humans and animals, certain types of animals such as bats that host the largest variety of coronaviruses appear to be immune to coronavirus-induced illness.
  • 15. •Recent travel from or residence in an area with ongoing community spread of COVID-19 as determined by CDC or WHO •Close contact with someone who has COVID-19 — such as when a family member or health care worker takes care of an infected person RISK FACTORS
  • 16. Causes It's unclear exactly how contagious the new coronavirus is. It appears to spread from person to person among those in close contact.  It may be spread by respiratory droplets released when someone with the virus coughs or sneezes. It may also be spread if a person touches a surface with the virus on it and then touches his or her mouth, nose or eyes.
  • 17. RISK FACTORS The severity of the disease appears to be associated with age, with the elderly most at risk; those over 80 years of age had a Case Fatality Rate (CFR) of 14.8%. The CFR was also increased in those with comorbidities including cardiovascular, diabetes, chronic respiratory disease, hypertension, and cancer.  The cause of death is respiratory failure, shock or multiple organ failure.
  • 18. Incubation period  Incubation period — The incubation period for COVID-19 is thought to be within 14 days following exposure, with most cases occurring approximately four to five days after exposure.  Spectrum of illness severity — The spectrum of symptomatic infection ranges from mild to critical; most infections are not severe
  • 19. Clinical Manifestations/ Clinical Presentation Asymptomatic infection  Mild upper respiratory tract illness, and severe viral pneumonia  Respiratory failure  Death  Fever(Fever was defined as axillary temperature of at least 37·3°C)  Dry cough  Dyspnoea  Fatigue  Nasal congestion  Sore throat  Diarrhoea
  • 20.
  • 21. Clinical Investigations  Throat-swab specimens  PCR ROUTINE BLOOD INVESTIGATIONS LIKE  Complete blood count  Coagulation profile(Coagulopathy was defined as a 3-second extension of prothrombin time or a 5-second extension of activated partial thromboplastin time)  Serum biochemical tests (including renal and liver function, creatine kinase, lactate dehydrogenase, and electrolytes)  myocardial enzymes  interleukin-6 (IL-6), serum ferritin  Procalcitonin  Hypoproteinaemia was defined as blood albumin of less than 25 g/L.
  • 22. Chest CT in patients with COVID-19 most commonly demonstrates ground-glass opacification with or without consolidative abnormalities, consistent with viral pneumonia.
  • 23. Complications Complications can include: Pneumonia in both lungs Organ failure in several organs Death
  • 25. WHO and CDC recommend following these precautions for avoiding COVID-19: •Avoid large events and mass gatherings. •Avoid close contact (about 6 feet) with anyone who is sick or has symptoms. •Keep distance between yourself and others if COVID-19 is spreading in your community, especially if you have a higher risk of serious illness. •Wash your hands often with soap and water for at least 20 seconds, or use an alcohol-based hand sanitizer that contains at least 60% alcohol. •Cover your mouth and nose with your elbow or a tissue when you cough or sneeze. Throw away the used tissue. •Avoid touching your eyes, nose and mouth if your hands aren't clean. •Avoid sharing dishes, glasses, bedding and other household items if you're sick. •Clean and disinfect surfaces you often touch on a daily basis. •Stay home from work, school and public areas if you're sick, unless you're going to get medical care. Avoid taking public transportation if you're sick.
  • 26. WHO also recommends that you: •Avoid eating raw or undercooked meat or animal organs. •Avoid contact with live animals and surfaces they may have touched if you're visiting live market areas that have recently had new coronavirus cases. CDC doesn't recommend that healthy people wear a face mask to protect themselves from respiratory illnesses, including COVID-19. Only wear a mask if a health care provider tells you to do so.
  • 27. Medical Management There is no proven treatment at this early stage but we will doubtless have more information about this soon. It can be assumed that non- pharmacologic approaches are effective such as fluid support, oxygen and ventilatory support. Extra Corporeal Membrane Oxygenation (ECMO) is potentially of benefit.
  • 28. Vaccine and other therapeutics  Phase 1 trials for safety and immunogenicity in human populations are likely within 3 months.  In terms of therapeutics there is no known effective pharmaceutical agent.  Putative agents include antivirals; Griffithsin, a spike protein inhibitor, nucleoside analogues eg. remdesivir, ribavirin and protease inhibitors such as lopinavir/ritonavir.  Immunomodulatory and other host targeted agents include interferon, chloroquine and immunoglobulins.  Corticosteroids will potentially have benefit for immune mediated lung damage late in the course of disease
  • 29. Favipiravir, a purine nucleoside leading to inaccurate viral RNA synthesis, was originally developed by Toyama Chemical of Japan, and has recently been approved for a clinical trial as a drug to treat COVID-19. Chloroquine, an antimalarial drug, has proven effective in treating coronavirus in China. RNA Therapies: RNA interference (RNAi) is a biological process wherein small complementary RNA duplexes target and neutralize specific mRNA molecules, resulting in inhibition of gene expression or genetic translation
  • 30. RNA Aptamers Antisense Oligonucleotides:Antisense oligonucleotides have also been developed to reduce the severity of SARS virus infections and to prevent or treat SARS virus-associated disease. Attenuated Virus Vaccines DNA-Based Vaccines
  • 31. References  1Gorbalenya, A. E. The species severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nature Microbiology 2020,DOI: 10.1038/s41564-020-0695-z [Crossref], Google Scholar  2Kupferschmidt, K.; Cohen, J. Will novel virus go pandemic or be contained?. Science 2020, 367 (6478),610– 611, DOI: 10.1126/science.367.6478.610 [Crossref], [ PubMed], [ CAS], Google Scholar  3 Coronavirus Disease (COVID-2019) Situation Reports 1–45; World Health Organization, 2020.https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports.Google Scholar  4 Coronavirus is now expected to curb global economic growth by 0.3% in 2020. https://www.forbes.com/sites/sergeiklebnikov/2020/02/11/coronavirus-is-now-expected-to-curb-global- economic-growth-by-03-in-2020/#5de149ad16da.Google Scholar  5Anthony, S. J.; Johnson, C. K.; Greig, D. J.; Kramer, S.;Che, X.; Wells, H.; Hicks, A. L.; Joly, D. O.; Wolfe, N. D.;Daszak, P.; Karesh, W.; Lipkin, W. I.; Morse, S. S.; Mazet, J. A. K.; Goldstein, T. Global patterns in coronavirus diversity.Virus Evol 2017, 3 (1), vex012, DOI: 10.1093/ve/vex012 [Crossref], [ PubMed], Google Scholar  6Su, S.; Wong, G.; Shi, W.; Liu, J.; Lai, A. C.K.; Zhou, J.;Liu, W.; Bi, Y.; Gao, G. F. Epidemiology, genetic recombination, and pathogenesis of coronaviruses.Trends Microbiol. 2016, 24 (6), 490– 502, DOI: 10.1016/j.tim.2016.03.003 [ Crossref], [ PubMed], [CAS], Google Scholar  7Zhu, N.; Zhang, D.; Wang, W.; Li, X.; Yang, B.; Song, J.;Zhao, X.; Huang, B.; Shi, W.; Lu, R.; Niu, P.; Zhan, F.; Ma, X.;Wang, D.; Xu, W.; Wu, G.; Gao, G. F.; Tan, W. A novel coronavirus from patients with pneumonia in China, 2019.N. Engl. J. Med. 2020, 382 (8), 727– 733, DOI: 10.1056/NEJMoa2001017 [ Crossref], [ PubMed], [CAS], Google Scholar  8Tang, B.; Bragazzi, N. L.; Li, Q.; Tang, S.; Xiao, Y.; Wu, J.An updated estimation of the risk of transmission of the novel coronavirus (2019-nCov). Infect Dis Model 2020, 5,248– 255, DOI: 10.1016/j.idm.2020.02.001 [ Crossref], [PubMed], [ CAS], Google Scholar