Some information on the 2019 coronavirus

1. COVID-19… EXPLAINED
Raj Mandavia
MBCHB YEAR 5
UZIMA UNIVERSITY OF HEALTH AND SOCIAL SCIENCES
KISUMU,KENYA

2. INTRODUCTION
• CO: Corona
• VI: Virus
• D: Disease
• 19: 2019
• Family: Coronaviridae
• SS RNA genome

3. Cont’d
• Ranges from: common cold to Middle East
Respiratory Syndrome (MERS), and Severe
Acute Respiratory syndrome (SARS).
• Zoonotic disease: Esp. from civet cats, camels,
bats.
• Incubation period: 2-12 days (avg. 5 days).

4. A CLOSER LOOK AT SARS-COV-2

5. Cont’d
• Like other coronaviruses, SARS-CoV-2 virus
particles are spherical and have mushroom-
shaped proteins called spikes protruding from
their surface, giving the particles a crown-like
appearance.
• The spike binds and fuses to human cells,
allowing the virus to gain entry.

6. Cont’d
• Mapping the 3D structure of the protein –
spike (S) glycoprotein will allow better
understanding of how the virus binds to
human cells.
• Knowing the structure of the spike protein
will, in turn, allow scientists to develop
vaccines and antivirals against the virus and
even better diagnostics.

7. INDIVIDUALS AFFECTED / MOST AT
RISK
• Immunocompromised individuals
• Individuals with chronic disease (bronchial asthma,
diabetes, cardiovascular disease, malignancies).
• Old-age individuals
• People aged 80 and above are at the highest risk of
dying due to COVID-19, according to case records
analyzed by the Disease Control and Prevention
Centers in China and South Korea.

8. PATHOGENESIS
Virus attaches to specific cellular receptors via the spike protein
↓
Transformational change, leading to fusion between the viral and cell membrane
↓
Release of nucleocapsid into the cell
↓
Alteration of DNA and production of proteins and certain specific enzymes
↓
Alteration of cell function and production
↓
Release of cytokines and chemokines (IL-1β, IL-6, IL-7, IL-9, IL-10, TNF-α)
↓
Increase in acute phase reactants (ESR↑, CRP↑, procalcitonin??)
#Hyperinflammation??
↓
Cause of death due to complications/effects caused by ‘cytokine storm syndrome’
-SARS (severe acute respiratory syndrome)
-Fulminant myocarditis (cardiac affinity)
-Sepsis
-Septic shock

9. PATHOPHYSIOLOGY
• ARDS
- Was thought to be the primary pathology,
characterized by diffuse alveolar damage (e.g.
including hyaline membranes).
- Pneumocytes with viral cytopathic effect are
seen, implying direct viral damage (rather
than a purely hyper-inflammatory injury).

10. Cont’d
• Cytokine Storm
- Emerging evidence suggests that some patients
may respond to COVID-19 with an exuberant
‘cytokine storm’ reaction (with some features of
bacterial sepsis or hemophagocytic
lymphohistiocytosis).
- Clinical markers of this may include elevations of
CRP and ferritin, which appear to track with
disease severity and mortality.

11. Important to Note…
• Note: From a recent ICU/NHS Nightingale teleconference, it was
revealed that the pathologic picture doesn’t seem to be classical
ARDS in early phases of the disease.
• ARDS type picture is seen as the disease progresses.
• COVID-19 does not appear to increase procalcitonin.
• Elevated procalcitonin may suggest an alternative diagnosis (e.g.
pure bacterial pneumonia).
• For patients who have been admitted with COVID-19, elevated
procalcitonin may suggest a superimposed bacterial infection.

12. Cont’d
• The disease is being treated in a similar way to
ARDS, as it has many similarities to ARDS.
• However, we are still unsure if it shows a
classical ARDS picture.

13. COAGULOPATHY IN COVID
• Inflammation correlates with coagulopathy.
• Inflammation and coagulopathy correlates
with survival.

15. STAGES OF ILLNESS
• There seem to be different stages of illness
that patients may move through:
1. Replicative stage
2. Adaptive immunity stage

16. 1. Replicative stage
• Viral replication occurs over a period of
several days.
• An innate immune response occurs, but it fails
to contain the virus.
• Relative mild symptoms may occur due to
direct viral cytopathic effect and innate
immune responses.

17. 2. Adaptive Immunity Stage
• An adaptive immune response eventually
kicks into gear. This leads to falling titres of
virus.
• However, it may also increase levels of
inflammatory cytokines and lead to tissue
damage – causing clinical deterioration.

18. Cont’d
• The progression from the replicative stage to
the adaptive immunity stage may explain the
clinical phenomenon wherein patients are
relatively OK for several days, but then
suddenly deteriorate when they enter the
adaptive immunity stage.

19. Cont’d
• This has potentially important clinical
implications:
- Initial clinical symptoms are not necessarily
predictive of future deterioration. Sophisticated
strategies may be required to guide risk-
stratification and disposition.
- Anti-viral therapies might need to be deployed
early to work optimally (during the replicative
stage).

20. SPREAD OF THE DISEASE
• Primarily through respiratory droplets of
infected people (coughing and sneezing).
• If a person touches a surface or object that
has been infected by the virus and then
touches his own mouth, nose, or eyes, he may
get infected (tables and desks).

21. CLINICAL PRESENTATION /
SYMPTOMS
• Symptoms appear within 2-14 days after exposure and include the
following:
• Fever
• Dry cough
• Fatigue
• Sputum production
• Shortness of breath / difficulty in breathing
• Myalgia or arthralgia
• Sore throat
• Headache
• Chills
• Nausea and vomiting
• Loss of sense of taste and smell
• Nasal congestion
• Diarrhea
• Hemoptysis
• Conjunctival congestion

22. Constitutional Symptoms
• Fever
• Myalgia
• Headache
Upper Respiratory Symptoms
• Rhinnorhea
• Sore throat

23. Lower Respiratory Symptoms
• Dyspnea
• Chest tightness
• Cough
• Sputum production
• Hemoptysis
Gastrointestinal Symptoms
• Nausea/vomiting
• Diarrhea

24. Mild and Moderate Illness (>80%)
• Fever
• Fatigue
• Myalgia
• Flu like symptoms/URTI symptoms (headache,
sore throat).
• Shortness of breath
• Cough: with/without sputum production
• Chest pain
• Breathing difficulties
• Pneumonia
• Nausea, vomiting, diarrhea

25. Severe Illness
• Severe pneumonia: breathing difficulties, pulmonary
edema
• Sepsis and septic shock
• Kidney failure
• Multiple organ failure
• Death

26. Important Notes…
• Gastrointestinal presentations:
- Up to 10% of patients can present initially with
gastrointestinal symptoms (e.g. diarrhea, nausea), which
precede the development of fever and dyspnea.
• Fever:
- Absence of a fever does not exclude COVID-19!
• ‘Silent hypoxemia’:
- Some patients may develop hypoxemia and respiratory
failure without dyspnea (especially elderly).
• Physical examination is generally nonspecific. About 2% of
patients may have pharyngitis or tonsil enlargement.

28. SCREENING /LABORATORY ANALYSIS
• WBC count may vary: leukopenia (<4000mm3) is more common than leukocytosis.
Tends to be normal mostly.
• ↓ sed. Lymphocyte count: lymphopenia (most common finding).
• ↑ sed. LDH levels (due to affinity of cytokines for cardiac tissue and hepatic
tissue).
• ↑ sed. Ferritin level (early finding).
• ↑ sed. AST, ALT (aminotransferases).
• ↑ ESR, ↑ D-Dimer, ↑ procalcitonin (may suggest alternative diagnosis, e.g. pure
bacterial pneumonia).
• Virus confirmed by RT PCR technique.

29. Cont’d
• A single negative RT-PCR doesn’t exclude
COVID-19 (especially if obtained from a
nasopharyngeal source or if taken relatively
early in the disease course).
• If the RT-PCR is negative but suspicion for
COVID-19 remains, then ongoing isolation and
re-sampling several days later should be
considered.

30. IMAGING STUDIES
• Chest X – Ray and CT Thorax
- Ground glass opacification with or without consolidation.
- Bilateral peripheral involvement, especially lower lobe. The
number of involved lung segments increases with more severe
disease.
- Infiltrates may be subtle on chest X – ray.
- Can be found even before onset of symptoms, but not specific
for COVID-19.

31. Cont’d
• Findings which are not commonly seen , and
might argue for an alternative or
superimposed diagnosis:
- Pleural effusion is uncommon (seen in only
approx. 5%).
- COVID-19 does not appear to cause masses,
cavitation, or lymphadenopathy.

35. MANAGEMENT
• Nothing has been postulated specifically.
• Hospitalization only for severe cases.
• Supportive measures:
- Maintain airway, breathing, circulation (A, B, Cs).
- Proning is essential and should be done early.
- Ventilatory support (if PO2 < 55%). Avoid spontaneous ventilation in
early ICU admission as it may be harmful.
- Isolation (to prevent spread).
- Correction of electrolyte imbalances.
- Correction of fever.
• Avoid corticosteroids: due to potential for prolonging viral
replication

36. Cont’d
• Drugs:
- Toclizumab (IL-6 blockade)
- Anakinra (IL-1 blockade) : agonist effects of cytokine storm.
- Remdesivir (in the spotlight these days for its effects shown).
- Lopinavir/ritonavir: protease inhibitors that block viral replication.
Lopinavir seems to be the drug that actually acts on the virus.
Ritonavir is a CYP3A inhibitor which functions primarily to reduce
metabolsim of lopinavir, thereby boosting lopinavir levels.
- Favilavir
- Hydroxychloroquine (less toxic derivative of chloroquine
phosphate): anti-malarial that has shown results.

37. Contraindications/cautions regarding
Lopinavir/Ritonavir
• Serious adverse effects may include:
- Hypersensitivity reaction, angioedema
- Stevens-Johnson syndrome / Toxic epidermal necrolysis
/ Erythema multiforme
- QT prolongation & Torsade de Pointes
- AV block & PR prolongation
- Hyperglycemia, hypertriglyceridemia
- Renal failure
- Anemia, leukopenia, neutropenia
- Pancreatitis
- Hepatotoxicity

38. Cont’d
• Common adverse reactions include:
- Nausea/vomiting, diarrhea
- Insomnia, anxiety
• Contraindicated in:
- Cardiac disease (ischemic heart disease,
cardiomyopathy, structural heart disease, QT
prolongation).
- Liver disease.

39. Cont’d
• There is no certain specific treatment protocol
published by WHO.

40. IPC MEASURES TO PREVENT COVID-19
• CONTACT PRECAUTIONS
- Wear gloves when dealing with patients always.
- Wear water proof gowns or plastic aprons.
- HCWs should protect their mucous membranes by using
medical/respirator masks and either face shields or goggles.
- Do not touch eyes, nose or mouth with contaminated gloves or
unclean hands.
- Doff PPEs appropriately and properly dispose at the end of every
interaction with patients and immediately perform hand hygiene.

41. Cont’d
• DROPLET PRECAUTIONS
- All patients must be placed at least 1m apart.
- Encourage suspected patients of COVID-19 to wear medical masks during
admission, and in hospital waiting areas.
- HCWs must wear masks; medical or respirators when attending to COVID-
19 patients.
- Patients must be placed in adequately ventilated rooms-60L/s, or in
negative pressure rooms.
- Discourage patients to spit in the open or on the ground/floor.
- Educate patients on coughing and sneezing etiquettes.

42. PREVENTIVE MEASURES
• Protect yourselves
- Regular hand washing with plenty of soap and water.
- Keep an alcohol-based hand sanitizer ready for times when soap
and water are not available.
- Don’t touch your eyes, nose, or mouth with unclean hands.
- Keep your distance of at least 1 meter from anyone coughing or
sneezing.
- Follow no-touch greeting for no germs contracted. Prefer ‘namaste’
or hand waving over handshake.

43. Cont’d
• Protect your loved ones
- Don’t sneeze or cough into your hands. Use a
tissue and throw it away immediately, or sneeze
in the inner side of your elbow.
- Don’t travel or visit crowded places if you are
sick.
- Do wear a mask if you are sick and also if you are
taking care of someone with the symptoms.

44. Cont’d
• Protect your community
- If you feel unwell, seek medical attention.
- If you have a fever, cough, or difficulty in
breathing, stay indoors. Call healthcare
professionals and follow their advice.
- Do not share ‘just any forwarded message’. Only
share authentic information coming through
medical experts.

47. TYPES OF MASKS TO WEAR
• 3-layer disposable surgical masks are good
enough to contain the virus.
• N-95 or N-99 masks are not mandated.

48. THANK YOU!