corona virus disease 2019

1. COVID19
PRESENTED BY – RADHE KRISHNA MANDAL, 4TH YEAR, MBBS,16TH BATCH, NMCTH, BIRGUNJ

2. STRUCTURE

3. SARS-COV-2

4. GLOBAL PANDEMIC

5. CORONAVIRUS OUTBREAKS
 SARS Regional Epidemic – 2002 AD
 MERS Regional Epidemic – 2012 AD
 2019-nCoV(COVID19) – 2019 – 2020 AD – GLOBAL PANDEMIC Declared by WHO

6. COVID19: AT A GLANCE
Coronavirus disease
(COVID-19) is an
infectious disease
caused by a newly
discovered
coronavirus.
Most people infected
with the COVID-19
virus will experience
mild to moderate
respiratory illness and
recover without
requiring special
treatment. Older
people, and those
with underlying
medical problems like
cardiovascular
disease, diabetes,
chronic respiratory
disease, and cancer
are more likely to
develop serious
illness.
The best way to
prevent and slow
down transmission is
be well informed
about the COVID-19
virus, the disease it
causes and how it
spreads. Protect
yourself and others
from infection by
washing your hands
or using an alcohol
based rub frequently
and not touching
your face.
The COVID-19 virus
spreads primarily
through droplets of
saliva or discharge
from the nose when
an infected person
coughs or sneezes, so
it’s important that
you also practice
respiratory etiquette
(for example, by
coughing into a
flexed elbow).
At this time, there are
no specific vaccines
or treatments for
COVID-19. However,
there are many
ongoing clinical trials
evaluating potential
treatments. .
More than 130
Vaccines are under
trial.
5 vaccines are in
clinical trials.

7. INTRODUCTION-COVID19
 Coronaviruses are pleomorphic, single-stranded RNA viruses that measure 100-160 nm in diameter. The
name derives from the crown-like appearance produced by the club shaped projections that stud the viral
envelope. Coronaviruses infect a wide variety of animal species and have been divided into four genera.
Coronaviruses that infect humans (HCoVs) fall into two genera: Alphacoronavirus and Betacoronavirus.
Severe acute respiratory syndrome coronavirus(SARS-CoV) and Middle East respiratory syndrome
coronavirus.
 In general, human corona viruses have been difficult to cultivate in vitro, and some strains grow only in
human tracheal organ cultures rather than in tissue culture. SARS-CoV and MERS-CoV are exceptions
whose ready growth in African green monkey kidney(Vero E6) cells greatly facilitates their study.

8. NOVEL CORONA VIRUS DISEASE
 Coronaviruses are a group of viruses that cause diseases in mammals and birds that include diarrhea in
cows and pigs, and upper respiratory disease in chickens. In humans, the virus causes respiratory
infections, which are often mild, but in rare cases are potentially lethal. There are no vaccines or antiviral
drugs that are approved for prevention or treatment.
 Coronaviruses are viruses in the subfamily Ortho coronaviridae in the family Corona viridae, in the order
Nido virales. Coronaviruses are enveloped viruses with a positive-sense single-stranded RNA genome
and with a y 26 to 32 kilo bases, the largest for an RNA virus.
 It is a communicable viral disease, caused by a new strain of a novel(new),coronavirus(termed “2019-
nCoV”).It was first detected in Wuhan City, Hubei Province, China.
 Coronavirus differs considerably in genetic structure from previously recognized coronavirus.
 The most common symptoms are; Fever, malaise, shortness of breath, chills, headache, myalgia,
dizziness, cough, sore throat and running nose.

9. VIRUS CLASSIFICATION
 UNRANKED VIRUS
 Kingdom(Realm): Ribovira
 Phylum: incertae sedis
 Order: Nidvirales
 Family: Coronaviridae
 Genus: Betacoronavirus
 Subgenus: Sarbecovirus
 Species: Severe acute respiratory syndrome- related coronavirus
 Strain: Severe acute respiratory syndrome coronavirus 2(SARS CoV2)

10.  SARS-CoV-2 has strong genetic similarity to bat Coronaviruses, from which it likely originated. An
intermediate reservoir such as pangolin is also thought to be involved. From a taxonomic perspective SARS-
CoV-2 is classified as a strain of the species severe acute respiratory syndrome- related coronavirus(SARS-
CoV).
 SARS-CoV-2 is the cause of the ongoing 2019-20 coronavirus outbreak, a Public Health Emergency of
International Concern that originated in Wuhan, PR China. Because of this connection, the virus is
sometimes reffered to informally as the “Wuhan coronavirus”, among other names, although the World
Health Organization(WHO) discourages the use of names based upon locations. To avoid confusion with
the disease SARS, the WHO sometimes refers to the virus as “the virus responsible for COVID-19” in public
health communications.

11. HUMAN CORONAVIRUSES
 Human coronaviruses
 There are seven known strains of human coronaviruses:
 Human coronavirus 229E (HCoV-229E)
 Human coronavirus OC43 (HCoV-OC43)
 SARS-CoV
 Human coronavirus NL63 (HCoV-NL63, New Haven coronavirus)
 Human coronavirus HKU1
 Middle East respiratory syndrome coronavirus (MERS-CoV), previously known as novel coronavirus
2012 and HCoV-EMC.
 Novel coronavirus (2019-nCoV),also known as Wuhan pneumonia or Wuhan coronavirus.('Novel' in this
case means newly discovered, or newly originated, and is a placeholder name).

12. CASE DEFINITION
 Case Definition for Novel Coronavirus (2019-nCoV)
 Person under Investigation for 2019-nCoV
 A person with fever and acute respiratory illness, or pneumonia
 AND any of the following:
 Travel to Wuhan, China in the 14 days before onset of illness
 OR
 Close contact with a confirmed or probable case of 2019-nCoV
 OR
 Close contact with a person with acute respiratory illness who has been to
 Wuhan, China within 14 days prior to their illness onset

13. PRESUMTIVE POSITIVE CASE
 Presumptive Positive Case for 2019-nCoV
 A person in whom the laboratory screening test for 2019-nCoV was positive from the
 Public Health Ontario Laboratory but not confirmed by the National Microbiological
 Laboratory.
 Confirmed Case for 2019-nCoV
 A person with laboratory confirmation of infection with 2019-nCoV which consists of
 positive real-time PCR on at least two specific genomic targets or a single positive
 target with sequencing AND confirmed by NML by nucleic acid testing.

14. INFECTION
 Human-to-human transmission of the virus has been confirmed during the 2019–20 coronavirus
outbreak. Transmission occurs primarily via respiratory droplets from coughs and sneezes within a range
of about 6 feet (1.8 m). Indirect contact via contaminated surfaces is another possible cause of infection.
Viral RNA has also been found in stool samples from infected patients.
 It is possible that the virus can be infectious even during the incubation period, but this has not been
proven, and the World Health Organization (WHO) stated on 1 February 2020 that "transmission from
asymptomatic cases is likely not a major driver of transmission" at this time. Thus, most infections in
humans are believed to be the result of transmission from subjects exhibiting symptoms of coronavirus
disease 2019.

15. RESERVOIR
 The first known infections from the virus were discovered in Wuhan, China. Researchers are unsure of the
original source of viral transmission to humans. However, research into the origin of the 2003 SARS outbreak
has resulted in the discovery of many SARS-like bat coronaviruses, most originating in
the Rhinolophus genus of horseshoe bats. Two viral nucleic acid sequences from Rhinolophus
sinicus published in 2015 and 2017 show a resemblance of 80% to SARS-CoV-2. A third viral nucleic acid
sequence from Rhinolophus affinis, "RaTG13" collected in Yunnan province, has a 96% resemblance to SARS-
CoV-2.
 Researchers from Guangzhou claimed to have discovered a "99% identical" viral nucleic acid sequence in a
pangolin sample on February 7. The paper releasing the sequence states that "the receptor-binding domain
of the S protein of the newly discovered Pangolin-CoV is virtually identical to that of 2019-nCoV, with one
amino acid difference." Pangolins are protected under Chinese law, but poaching and trading of pangolins
for traditional medicine remains common. A metagenomic study published in 2019 previously revealed that
SARS-CoV, the strain of the virus that causes SARS, was the most widely distributed coronavirus among a
sample of Malayan pangolins. Microbiologists and geneticists in Texas have independently found evidence of
recombination in coronaviruses suggesting pangolin origins of SARS-CoV-2; they acknowledged remaining
unknown factors while urging continued examination of other mammals.

16. PHYLOGENETICS AND TAXONOMY
NCBI genome ID - MN908947Genome, Size - 29,903 bases, year of completion - 2020

17.  SARS-CoV-2 belongs to the broad family of viruses known as coronaviruses. It is a positive-sense single-
stranded RNA (+ssRNA) virus. Other coronaviruses are capable of causing illnesses ranging from the
common cold to more severe diseases such as Middle East respiratory syndrome (MERS). It is the seventh
known coronavirus to infect people, after 229E, NL63, OC43, HKU1, MERS-CoV, and the original SARS-CoV.
 Like the SARS-related coronavirus strain implicated in the 2003 SARS outbreak, SARS-CoV-2 is a member of
the subgenus Sarbecovirus (beta-CoV lineage B). Its RNA sequence is approximately 30,000 bases in length.
 With a sufficient number of sequenced genomes, it is possible to reconstruct a phylogenetic tree of the
mutation history of a family of viruses. By 12 January 2020, five genomes of SARS-CoV-2 had been isolated
from Wuhan and reported by the Chinese Center for Disease Control and Prevention (CCDC) and other
institutions; the number of genomes increased to 81 by 11 February 2020. A phylogenetic analysis of those
samples showed they were "highly related with at most seven mutations relative to a common ancestor",
implying that the first human infection occurred in November or December 2019.
 On 11 February 2020, the International Committee on Taxonomy of Viruses (ICTV) announced that according
to existing rules that compute hierarchical relationships among coronaviruses on the basis of five conserved
sequences of nucleic acids, the differences between what was then called 2019-nCoV and the virus strain
from the 2003 SARS outbreak were insufficient to make it a separate viral species. Therefore, they identified
2019-nCoV as a strain of severe acute respiratory syndrome-related coronavirus.

18. STRUCTURAL BIOLOGY OF
COVID19

20.  Digitally colorized electron micrographs of SARS-CoV-2 (yellow) emerging from human cells Like other
coronaviruses, SARS-CoV-2 has four structural proteins, known as the S (spike), E (envelope), M
(membrane), and N (nucleocapsid) proteins; the N protein holds the RNA genome, and the S, E, and M
proteins together create the viral envelope. The spike protein is responsible for allowing the virus to
attach to the membrane of a host cell.
 Protein modeling experiments on the spike protein of the virus suggest that it has sufficient affinity to
the angiotensin converting enzyme 2 (ACE2) receptors of human cells to use them as a mechanism of
cell entry. By 22 January 2020, a group in China working with the full virus genome and a group in the
United States using reverse genetics methods independently and experimentally demonstrated that
ACE2 could act as the receptor for SARS-CoV-2. Studies have shown that SARS-CoV-2 has a higher
affinity to human ACE2 than the original SARS virus strain. An atomic-level image of the S protein has
been created using cryogenic electron microscopy.
 SARS-Cov-2 produces at least three virulence factors that promote dissemination of new virions from
host cells and inhibit immune response.

21. EPIDEMIOLOGY
1)PROBLEM STATEMENT - GLOBAL
 Based upon the low variability exhibited among known SARS-CoV-2 genomic sequences, the strain is
thought to have been detected by health authorities within weeks of its emergence among the human
population in late 2019. The virus subsequently spread to all provinces of China and to more than fifty other
countries in Asia, Europe, North America, South America, Africa, and Oceania. Human-to-human
transmission of the virus has been confirmed in all of these regions except Africa and South America. On 30
January 2020, SARS-CoV-2 was designated a Public Health Emergency of International Concern by the
WHO.
 As of 4 March 2020 (07:00 UTC), there were 93,160 confirmed cases of infection, of which 80,270 were
within mainland China. While the proportion of infections that result in confirmed infection or progress to
diagnosable disease remains unclear, one mathematical model estimated the number of people infected in
Wuhan alone at 75,815 as of 25 January 2020, at a time when confirmed infections were far lower. The total
number of deaths attributed to the virus was 3,198 as of 4 March 2020 (07:00 UTC). Over 90% of all deaths
have occurred in Hubei province, where Wuhan is located.
 The basic reproduction number ( R0, pronounced R-nought or R-zero) of the virus has been estimated to be
between 1.4 and 3.9. This means that, when otherwise unchecked, each infection from the virus would
typically be expected to result in 1.4 to 3.9 new infections.

22.  The COVID-19 epidemic has spread very quickly. It only took 30 days to expand from Hubei to the rest
of Mainland China. Since Dec 8, 2019, several cases of pneumonia of unknown aetiology have been
reported in Wuhan, Hubei province, China.
 Most patients worked at or lived around the local Huanan seafood wholesale market, where live animals
were also on sale. In the early stages of this pneumonia, severe acute respiratory infection symptoms
occurred, with some patients rapidly developing acute respiratory distress syndrome (ARDS), acute
respiratory failure, and other serious complications. On Jan 7, a novel coronavirus was identified by the
Chinese Center for Disease Control and Prevention (CDC) from the throat swab sample of a patient, and
was subsequently named 2019-nCoV by WHO.

24.  As of dated 31-05-2020 AD ,
 6,082,549 – global confirmed cases.
 369,544 – global deaths.
 212 - countries, areas or territories with cases.
Source – JOHNS HOPKINS UNIVERSITY AND MEDICINE

25. PROBLEM STATEMENT: NEPAL
 In January, 2020, the outbreak of the 2019 novel coronavirus (2019-nCoV) in China spread progressively to
other countries, with WHO declaring it a Public Health Emergency of International Concern.
 Among the affected countries beyond China (where 12 307 cases and 259 deaths were reported as of Feb
1, 2020) are others in Asia, including Nepal. On Jan 13, 2020, a 32-year-old man, a Nepalese student at
Wuhan University of Technology, Wuhan, China, with no history of comorbidities, returned to Nepal. He
presented at the outpatient department of Shukraraj Tropical and Infectious Disease Hospital, Kathmandu,
with a cough. He had become ill on Jan 3, 6 days before he flew to Nepal. He indicated no exposure to the
so-called wet market in Wuhan. Throat swabs obtained from the patient tested positive for 2019-nCoV on
real-time RT-PCR assays at the WHO laboratory in Hong Kong.
 As of May 16, 2020 AD, There are
Total of 1567 cases,
Total death- 8
Total recovered – 220
Total tested samples-PCR tested – 69582

26. Total RDT tested- 111,109
Total negative result of the samples- 68,015
people in quarantine-110,078
In Isolation – 1339
Source- Ministry of Health & Population, Government of Nepal.

27. EPIDEMIOLOGICAL DETERMINANTS;
AGENT;
 Agent - + sense ssRNA SARS CoV-2 Virus.
 Source of Infection – inhalation or ingestion of viral droplets as a result of coughing and sneezing and
touching infected surfaces are primary source of infection.
MOA
The virus most likely to attach to ACE-2 receptors of the type-2 Pneumocyte cell of the alveoli of the
lung,
On the cell membrane allowing the virus entry by spike protein present on the surface of the virus,
The virus is ingested by the process of endocytosis,
Inside the cytoplasm, the endosomes opens to reveal the virus genetic material ,a single stranded-
RNA.,
The virus hijacks the cell machinery to replicate the RNA and uses the ER to form its M – protein, outer
layer and all important S- protein,
After replication, the virus carried by the Golgi bodies ,out of the cell in a process known as exocytosis
so that it can infect other cells meanwhile the stress of viral production on the ER eventually leads to
Apoptosis or Cell death.

29. PATHOPHYSIOLOGY

30. HOST FACTORS;
 Age- mainly old age but can infect everyone regardless of age.
 Sex- it is completely a new virus but study shows that male are more prone due to smoking and
occupational hazard which ultimately affect the lung.
 Immunity- not studied yet.

31. ENVIRONMENTAL FACTORS AND TRANSMISSION OF VIRUS AND
INCUBATION PERIOD
>ENVIRONMENTAL FACTORS
not completely studied yet.
>TRANSMISSION OF VIRUS
Respiratory droplets- 3-6 feet , rest on surface approximately 24 hours.
Airborne within 3 hours period.
can also be transmitted through faeco -oral route.
>INCUBATION PERIOD
4-14 days(some- 24 days).

32. CLINICAL FEATURES OF COVID19
>PATIENT COMES IN WITH COVID19.
Temperature(98% chance overall) with (37.3’C to 38’C = 20% chance (38.1’C to 39’C =
44% chance)(39’C= 34% chance).(fever- >_ 100.4 F).
Dry cough (76% chance) and/or sore throat.
Body aches/Fatigue (44% chance).
Rapid breathing rate of >24 breaths per minute(29% chance).
Typically 8 days later (ranging from 5 to 13 days);
(55% chance) serious Respiratory illness/Pneumonia(viral induced).

33. CLINICAL FEATURES OF COVID19
 Patients comes in with COVID19.
-fever(most common)
-cough
-shortness of breath S.O.B.
-U.R.I. symptoms (rhinorrhea, congestion, sore throat ,headache)
-G.I. symptoms( nausea, vomiting)

34. CLINICAL FEATURES OF COVID19
 Specific Vital Sign
-increased HR
-increased RR
-decreased SPO2
-+/- or decreased BP

35. >In kidney; kidney damage
-increased BUN
-increased creatinine
>In Liver; liver not getting enough blood releasing specific inflammatory enzymes
-increased AST
-increased ALT
-increased Bilirubin
-Acute Phase Reactant Proteins:
-CRP increased
-fibrinogen increased
-IL6,IL1,TNF alpha increased

36. DIAGNOSTICS
 1)Rule out Influenza A/B – take naso -pharyngeal or oro -pharyngeal swab.
 2)RT-PCR - Sensitivity(30-40%),take lot of time. Sputum, aspirates and serology.
 OR, Nucleic Acid Amplification Test (NAAT). NOTE: RT-PCR & NAAT are essentially the same test. And the
test is expensive also.
 3)CBC (RBC, WBC, Platelets)
>Lymphopenia(80%)
>CMP(Comprehensive Metabolic Panel)
-LFTs: increased BUN, increased Creatinine

37.  Normal Procalcitonin, if primarily of covid19,but if there is super infection by Bacteria then : increased
PCT(COVID19 + Bacterial Superinfection).
 Non-specific markers but can elevated in COVID19 infection.
-increased CRP
-increased ESR
-increased IL-6
-increased LDH
-increased D-dimer(massive inflammation)
-increased Ferritin
>> If not enough perfusion to the Heart, high mortality associated with (increased Troponins I & T),(increased
CK-MB); leading to possible Myocardial Infarction(MI)-Heart Attack.

38. DIAGNOSTICS ; CXR
 4)Chest X-ray(CXR) – Ground glass opacities are seen.

39. DIAGNOSTICS ; CT -SCAN
 5)CT-SCAN
 Ground glass opacities in the peripheral Lung Fields,
 Consolidation,
 “Crazy paving pattern” – ground glass opacity with superimposed inter and intra lobular septal
thikckening.

40. CT-SCAN

41. DIAGNOSTICS; USG
 6)USG
-Pleural line thickening
-increasing B- lines within specific zones
-Consolidation with Air Bronchogram

42. USG

43. PREVENTION
 Prevention
 There is currently no vaccine to prevent 2019-nCoV infection. The best way to prevent infection is to avoid being
exposed to this virus. everyday preventive actions to help prevent the spread of respiratory viruses, including:
 Wash your hands often with soap and water for at least 20 seconds. Use an alcohol-based hand sanitizer that
contains at least 60% alcohol if soap and water are not available.
 Avoid touching your eyes, nose, and mouth with unwashed hands.
 Avoid close contact with people who are sick.
 Stay home when you are sick.
 Cover your cough or sneeze with a tissue, then throw the tissue in the trash.
 Clean and disinfect frequently touched objects and surfaces.
 These are everyday habits that can help prevent the spread of several viruses.

44.  Face masks.
 Eye protection.
 Surgical gloves.
 Bleach.
 Anti-viral hand gel sanitizer.

45. TREATMENT
1)I.V. Fluids
-LR(Ringers lactate solution)
-NS(Normal Saline)
-Fluids Sparingly
2)Drugs
i) Antipyretics(e.g. Tylenol to decrease fever)
ii) Remdesivir (antiviral- used in Ebola virus treatment)
iii) Chloroquine
iv) Ritanavir
v) Tocilizumab(blocks IL-6 which decrease the inflammation)

46. vi)Vaccine- in 2021 AD(130 vaccines are under trial).
vii)Mechanical Ventilation
-HFNC(High Flow Nasal Canula)
-NIPPV(Non-Invasive Positive Pressure Ventilation). (but can aerosolized the virus).
viii)Inhaled PGI2(prostacyclin).
ix)Paralytics(NM Blocker).
x)Prone Positioning.
xi)+- ECMO(Extra Corporeal Membrane Oxygenation or Extra Corporeal Life Support).
-Keep Alveoli OPEN

48.  NOTE: To date, effective and permanent treatment is lacking or unavailable; however clinical trials
investigating the efficacy of several agents , including REMDESIVIR and HYDROXYCHLOROQUINE are
underway in USA & PR CHINA.
 Currently , Effective Infection , Prevention Control (IPC) measures and Intervention as guided by the WHO is
the only way to prevent the spread of SARS-CoV-2.

49. PRECAUTIONS
 Self Quarantine/Isolation.
 Wash your hands.
 Use of Hand-Sanitizer.
 Don’t touch your T-Zone( Eyes, Noses & Oral mucosa).
 Decreasing Travel.
 Avoiding large crowds.
 Maintain 6 ft distance.

50. PRECAUTIONS
 In Health-care settings.
-N95 masks.
-Surgical masks.
-Eye protection.
-PPE(Personal Protective Equipment).
-proper gowns.
-Double gloving.

51. INTERIM GUIDELINES FOR THE MANAGEMENT OF SEVERE ACUTE
RESPIRATORY ILLNESS CAUSED BY NOVEL CORONA VIRUS 2020 - WHO
 Triage
 Immediate implementation of appropriate prevention and control(IPC) measures.
 Early supportive therapy and monitoring.
 Collection of specimens for laboratory diagnosis.
 Management of hypoxemic respiratory failure and ARDS.
 Management of septic shock.
 Prevention of complications.
 Specific anti-Novel-CoV treatments and clinical research.
 Special considerations for pregnant patients.

52. PREVENTION IS BETTER THAN CURE

55. REFERENCE
 Chinese online and print media.
 Johns Hopkins University, USA
 National health commission, PR China.
 Image credits – google & You tube.
 CDC, USA.
 WHO
 The Lancet Journal.
 EDCD
 Ministry of Health & Population, Nepal
 Gov of Nepal

56. THANK YOU
RAKESHKRISHNAMANDAL
@gmail.co
m