coronavirus and its variants ,replication cycle and its clinical signs and symptoms

1. Coronaviridae
Human Corono Virus (HCoV)

3. Introduction
• Coronaviruses are large, enveloped, spherical, non-segmented,
positive-sense RNA viruses
• They are the largest known RNA viruses, with genomes ranging from
25 to 32 kb and a virion of 118–136 nm in diameter.
• Known to infect humans and a wide variety of animals.
• Cause mainly respiratory diseases in humans, although other organ
systems are also affected with varying severity.

4. Viral Proteins
• The major virion proteins of the member viruses of the
subfamilies Coronavirinae and Torovirinae include:
• a nucleocapsid protein (N) and
• several envelope proteins:
• (1) the spike glycoprotein trimer (S);
• (2) a triple-spanning transmembrane protein (M);
• (3) a minor transmembrane protein (E), which together with the M protein is
essential for coronavirus virion assembly and budding.
• Toroviruses lack a homolog of the coronavirus E protein, which may explain the
structural differences between the coronaviruses and toroviruses

6. REPLICATION
• CYTOPLASMIC
• Attachment of the viral S protein to host receptors mediates endocytosis of the virus into the host cell.
• Fusion of virus membrane with the endosomal membrane (probably mediated by S2), ssRNA(+) genome is
released into the cytoplasm.
• Synthesis and proteolytic cleavage of the replicase polyprotein.
• Replication occurs in viral factories. A dsRNA genome is synthesized from the genomic ssRNA(+).
• The dsRNA genome is transcribed/replicated thereby providing viral mRNAs/new ssRNA(+) genomes.
• Synthesis of structural proteins encoded by subgenomic mRNAs.
• Assembly and budding at membranes of the endoplasmic reticulum (ER), the intermediate compartments,
and/or the Golgi complex.
• Release of new virions by exocytosis.

7. Taxonomy
• Order Nidovirale
• Family Coronaviridae
• Subfamily Coronavirinae
• Genus Alphacoronavirus
• Genus Betacoronavirus
• Genus Deltacoronavirus
• Genus Gammacoronavirus
• Subfamily Torovirinae
• Genus Torovirus
• Toroviruses have been isolated from mammals with
gastroenteritis, but rarely from humans. Virions are
enveloped, about 120–140 nm in diameter. They have
surface spikes and a doughnut-shaped nucleocapsid

8. Human Coronavirus Types

9. Diseases Caused by Coronaviruses
• Until 2002, human coronaviruses (HCoVs) were associated only with mild
respiratory tract disease, with estimates that they caused 15%–25% of all
“common colds.”
• That changed in 2002, when a human coronavirus was identified as the
cause of an apparently new disease called SARS.
• The SARS outbreak was controlled, but in 2014 another novel CoV was
isolated from patients hospitalized with severe respiratory disease in Saudi
Arabia.
• As most infected patients lived in or had traveled to Middle East countries,
the new disease was named MERS and the coronavirus responsible is
called HCoV-MERS.

10. Severe Acute Respiratory Syndrome
SARS facts:
• SARS-CoV emerged in the human population in China in 2002.
• Epidemiologic studies and genetic analysis indicated the virus most likely jumped from
bats into farm-raised Himalayan palm civets (Paguma larvata) and then into humans.
• Human to human transmission was by respiratory and fecal routes.
• Approximately 8000 cases were reported worldwide.
• Twenty-six countries were affected.
• Seven hundred and seventy-four deaths occurred (~10% case mortality rate).
• In July 2003, WHO reported that the last known human chain of transmission was broken.
• Bats and birds are natural reservoirs of SARS-like viruses.
• Laboratory-associated infections occurred in China in 2004.

11. SARS Disease
• SARS-infection causes a triphasic pattern of disease.
• The first phase is nonspecific with fever, cough, sore throat, and myalgia. Breathing
difficulties (dyspnea) show up 7–14 days after appearance of the first symptoms.
• The second phase of the disease includes shortness of breath, fever, onset of hypoxia,
and often diarrhea.
• In the most serious cases, patients progress to a third phase with development of acute
respiratory distress requiring hospitalization and mechanical respiration.
• Three viral proteins have been implicated in HCoV-SARS pathogenesis.
• An accessory protein (encoded from orf3a) interferes with cell signaling pathways,
another accessory protein (encoded from orf6) interferes with interferon signaling and
the E glycoprotein is a strong inducer of proinflammatory cytokines.
• All of these proteins are dispensable for virus replication in cell cultures, but in mouse
models of disease their deletion reduces disease.

13. Middle East Respiratory Syndrome
MERS facts:
• MERS begins with coughing, fever, and breathing problems but may progress to pneumonia and kidney
failure.
• Over 1600 human cases and the outbreak is ongoing.
• Case fatality rate >30%.
• Cases are sporadic and cannot be linked to a single source (based on genome sequencing).
• Countries most affected include those in the Arabian Peninsula (Bahrain, Iran, Jordan, Kuwait, Lebanon,
Oman, Qatar, Saudi Arabia, United Arab Emirates, and Yemen).
• Casual transmission from person to person very rare.
• Most person to person transmission occurs in a hospital setting.
• Many healthy camels in the Arabian Peninsula have antibodies specific to CoV-MERS (indicating past
infection) but infections often occur among people with no known contact with camels.
• A virus very similar to CoV-MERS has been found in some bats (sequence analysis suggests that the virus
moved from bats to camels).
• Many questions about the epidemiology of CoV-MERS remain unanswered.
• Sporadic cases of MERS continue to be reported. Strict infection control procedures in hospitalized patients
limit person to person spread in that setting and transmission among casual or household contacts is rare.

14. SARS-CoV vs MERS-CoV
• While MERS-CoV and SARS-CoV are both betacoronaviruses, they derive
from different sources and have unique characteristics.
• SARS-CoV has a tropism for ciliated respiratory epithelial cells and its
receptor is ACE2.
• In contrast MERS-CoV has a tropism for nonciliated respiratory epithelial
cells and its receptor is DPP4.
• Continued comparison of these two viruses will provide new insights into
CoV transmission and pathogenesis.
• The propensity for CoV recombination, and their ubiquitous presence in
bats, makes a case for close surveillance and study of these potential human
pathogens.

15. SARS-CoV2
Pandemic

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• Droplet - respiratory secretions from
coughing or sneezing landing on
mucosal surfaces (nose, mouth, and
eyes)
• Aerosol - a solid particle or liquid
droplet suspended in air
• Contact -Touching something with
SARS-2 virus on it and then touching
mouth, nose or eyes
• Other possible routes: Through fecal
matter
COVID-19 is spread from
person to person mainly
through coughing,
sneezing, and talking and
breathing.
Transmission

17. Incubation period
• The incubation period is the time between exposure to a virus and
the onset of symptoms.
• With COVID-19, symptoms may show 2-14 days after exposure.
• CDC indicates that people are most contagious when they are the
most symptomatic.
• Several studies show people may be contagious before developing
symptoms.
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18. COVID-19 can cause mild to severe
symptoms
Most common symptoms include:
• Fever
• Cough
• Shortness of breath
Other symptoms may include:
• Sore throat
• Runny or stuffy nose
• Body aches
• Headache
• Chills
• Fatigue
• Gastrointestinal: diarrhea, nausea
• Loss of smell and taste
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19. 19
• Most people will have mild symptoms and should
recover at home and NOT go to the hospital or
emergency room.
• Get medical attention immediately if you have:
• Difficulty breathing or shortness of breath.
• Persistent pain or pressure in the chest.
• New confusion or inability to arouse.
• Bluish lips or face.
Severe symptoms – emergency warning
signs for COVID-19

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COVID-19 poses a greater risk for severe illness for people with underlying
health conditions:
• Heart disease
• Lung disease such as asthma
• Diabetes
• Suppressed immune systems
The elderly have higher rates of severe illness from COVID-19. Children and younger adults have had less
severe illness and death. Because COVID-19 is new, there are a lot of scientific unknowns such as the
impact on pregnant women and their fetuses.
Increased risk of severe illness

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• A person who has both consistent signs or symptoms and risk factors as follows:
Suspect Case
A potential exposure within
14 days before the onset of
symptoms.
Symptoms, including cough,
fever, and shortness of
breath.
What is a person under investigation?

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A confirmed case is a suspect case with laboratory-
confirmed diagnostic evidence of SARS-CoV-2 virus
infection.
U.S. Centers for Disease Control and Prevention via AP
Confirmed case

23. Testing for coronavirus, SARS-CoV-2
• Viral RNA can be detected by polymerase
chain reaction (PCR, or quantitative PCR,
qPCR, sometimes referred to as “real-time
PCR” or RT-PCR, causing confusion with
another term, “reverse transcriptase PCR”)
(Figure 5). In this test, the virus’s single-
stranded RNA is converted to its
complementary DNA by reverse
transcriptase; specific regions of the DNA,
marked by so-called primers, are then
amplified. This is done by synthesizing new
DNA strands from deoxynucleoside
triphosphates using DNA polymerase.
Occasional false negatives have been
reported.

24. Treatment and vaccines
• In December 2020, the FDA gave
emergency use authorization to two
COVID-19 vaccines, with many more
in the pipeline.
• There is no specific FDA -Cleared
medication or treatment for COVID-
19.
• Treatment is supportive.
• People who are mildly ill with COVID-
19 should isolate at home during
their illness.
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25. The Role of the Vaccine
• Cases of COVID-19 will decrease with the administration of the
vaccine.
• With uptake of the vaccine and continued workplace controls in
place, occupational exposures will decrease.
• People who are vaccinated can still be exposed and potentially expose
someone else even if they don’t become sick.
• A continued focus on maintaining workplace preventive measures is
important to protect workers in all industries.
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26. After Vaccination
▪ Continue COVID-19 prevention measures:
Cover your
nose and mouth
with a mask.
Stay at least 6
feet from people
who don’t live
with you.
Avoid crowds
and poorly
ventilated
spaces.
Wash your
hands.
Clean and
disinfect
frequently touched
surfaces.
▪ If you have questions about your health and vaccination, call your doctor, nurse,
or clinic.

27. How long does SARS-CoV-2 survive
outside of the body?
• It is not clear yet how long the coronavirus can live on surfaces, but it seems to
behave like other coronaviruses.
• Virus may persist on surfaces for a few hours or up to several days, depending on conditions and
the type of surface.
• It is likely that it can be killed with a simple disinfectant on the EPA registered list
below.
https://www.epa.gov/pesticide-registration/list-n-disinfectants-use-against-sars-cov-2
There are ongoing investigations to learn more.
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28. Seasonal flu vs. COVID-19
• COVID-19 has the potential to cause
more deaths and hospitalizations
• SARS-CoV-2 is much more infectious
and spreads faster than the seasonal
flu
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29. Seasonal flu vs. COVID-19
• So far, the case fatality rate (CFR) of COVID-19 is estimated to be at
around 2%. The CFR of seasonal influenza is estimated to be around
0.1%, making SARS-CoV-2 about 20 times more deadly than the
seasonal flu.
• An estimated 15-20% of infected individuals may suffer from severe
symptoms that require medical attention, including pneumonia with
shortness of breath and lowered blood oxygen saturation.
• No Treatment
• Immunity: unknown how long it will last post illness or vaccination.
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30. 30
• Be informed and prepared.
• Wear a mask.
• Maintain social distancing (6 feet).
• Wash your hands frequently.
• Use alcohol-based hand sanitizer.
• Avoid touching your eyes, nose, and mouth.
• Stay home when you are sick.
• Cough or sneeze into a tissue or your elbow.
• Clean and disinfect frequently touched objects and
surfaces such as cell phones.
What can individuals do?

31. Five steps to proper handwashing
• Wet your hands with clean, running water (warm or
cold), turn off the tap, and apply soap.
• Lather your hands by rubbing them together with
the soap. Lather the backs of your hands, between
your fingers, and under your nails.
• Scrub your hands for at least 20 seconds. Need a
timer? Hum the “Happy Birthday” song from
beginning to end twice.
• Rinse your hands well under clean, running water.
• Dry your hands using a clean towel or air dry them.
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32. Healthcare facility identification and isolation
The most important steps to prevent spread of COVID-19
• Procedures for rapid identification and isolation of suspect COVID-19
cases.
• Community and hospital procedures to ensure symptomatic people are
not in public places, waiting rooms, reception areas, emergency
departments, or other common areas
• Collect a travel history for patients presenting with fever, cough, or shortness of
breath.
• Immediately isolate – using standard, contact, and droplet precautions for
suspect or confirmed cases.
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33. Community/workplace connection
Examples of work settings
• schools
• sports and arts events
• social services
• high density of coworkers
• high contact with the general
public including retail and
grocery stores
Examples of job activities
• classroom instruction
• aiding clients
• serving customers
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When a community outbreak occurs, any workplace or event location
where people gather has a high potential for exposure.