COVID-19 is a global infectious disease pandemic with high morbidity and mortality for at risk individuals. This slide is intended for the medical students, medical doctors and those in training for masters of medicine (MMED).

1. COVID-19
Denis Katatwire
MMED1-Internal Medicine

2. Outline
i. Introduction
ii. Epidemiology
iii. Pathogenesis
iv. Clinical presentation
v. Diagnosis.
vi. Pharmacology of the drugs used for treatment of COVID-19

3. Introduction
• Coronaviruses are important human and animal pathogens
(zoonoses).
• Together with other zoonoses, this disease form group of
emerging and reemerging zoonoses
• At the end of 2019, a novel coronavirus was identified as the
cause of a cluster of pneumonia cases in Wuhan, a city in the
Hubei Province of China.
• It rapidly spread, resulting in an epidemic throughout China,
with sporadic cases reported globally.
• In February 2020, the WHO designated the disease COVID-19,
which stands for coronavirus disease 2019.

4. Cont..
• The virus that causes COVID-19 is designated severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2); previously,
it was referred to as 2019-nCoV, this large viruses containing
a single-stranded positive-sense RNA genome enveloped by a
membrane.
• The disease spread throughout the world and on 11th March
2020, WHO declared it as the pandemic.
• To date, there are no SARS-CoV-2-specific antiviral agents,
most of the drugs used for treatment are used for treatment
of other infectious disease.

5. Epidemiology
• The worlwideCOVID-19 statistics as of 22nd May 2020
i. Total confirmed cases: 5.11million
ii. Death: 333,001 (6.5%)
iii. Recovered: 1.95 million(38.2%)
iv. Currently infected patients: 2.83 million (55.3%)
• The United Republic of Tanzania reported its 1st case of
COVID-19 on 16th March 2020

6. Cont…
• Epidemiologic investigation in Wuhan at the beginning of the
outbreak identified an initial association with a seafood
market that sold live animals, where most patients had
worked or visited and which was subsequently closed for
disinfection.
• However, as the outbreak progressed, person-to-person
spread became the main mode of transmission.
• ?? The origin of the virus still possess a lot of questions as
there have been reports that It may have originated from the
labs at the Wuhan Institute of Virology and then spread to the
community

7. Cont..
• Person-to-person spread of severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) is thought to occur mainly via
respiratory droplets, resembling the spread of influenza.
• With droplet transmission, virus released in the respiratory
secretions when a person with infection coughs, sneezes, or
talks can infect another person if it makes direct contact with
the mucous membranes; infection can also occur if a person
touches an infected surface and then touches his or her eyes,
nose, or mouth.

8. Cont..
• The incubation period of COVID-19 ranges between 2- 14
days, about 80% of the patients will show no/mild symptoms
but they are potential source of viral transmission to other
individuals
• According to the WHO, recovery time appears to be around
two weeks for mild infections and three to six weeks for
severe disease.
• People with advanced age, with Comorbidities such as HIV, D.
mellitus, cancer, Heart failure, Obesity and CKD have increased
morbidity and mortality

9. Pathogenesis
• Patients with COVID-19 show clinical manifestations including
fever, nonproductive cough, dyspnea, myalgia, fatigue, normal
or decreased leukocyte counts, and radiographic evidence of
pneumonia that includes ground glass opacification.
• Although the pathogenesis of COVID-19 is not wholly
understood, the knowledge of SARS-COV & MERS-COV
pathogenesis and available data on SARS-CoV-2 give an insight
to the current knowledge
• In ~ 80% of the infected patients, the disease will be mild and
mostly restricted to the upper and conducting airways.

10. Cont..
• Preliminary reports suggested that the reproductive number
(R₀), the number of people who acquire the infection from an
infected person, was estimated to be 2.2 to 3.3.
• However, the R₀ may actually be lower in light of social
distancing measures that have been instituted.
• The secondary attack rate for SARS-CoV-2 is estimated to be
0.45% for close contacts of US patients.

11. Virology
• This is an intracellular microorganism
• 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 crownlike appearance.
• There are four classes of coronaviruses designated as alpha,
beta, gamma, and delta.

12. Cont…
• the evidence from the phylogenetic analysis indicates that the
COVID-19 belongs to the genus betacoronavirus, which
includes SARSCoV, that infects humans, bats, and wild animals
• The betacoronavirus class includes:
i. Severe acute respiratory syndrome (SARS) virus (SARS-CoV)
ii. Middle East respiratory syndrome (MERS) virus (MERS-CoV)
iii. COVID-19 causative agent SARS-CoV-2 (with has 85%
genetic homology with SARS-CoV)

13. Cont…
• Similar to SARS-CoV and MERS-CoV, SARS-CoV-2 attacks the
lower respiratory system to cause viral pneumonia, but it may
also affect the gastrointestinal system, heart, kidney, liver, and
central nervous system leading to multiple organ failure.
• Evidences indicates that SARSCoV-2 is more contagious than
SARS-CoV

14. Cont…
• SARS-CoV2 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 by both SARS-CoV
and SARS-CoV-2 via binding to a receptor protein called
angiotensin-converting enzyme 2 (ACE2) located on the
surface membrane of host cells.
• The invasion process requires S protein priming which is
facilitated by the host cell produced serine protease
TMPRSS211.

16. Cont..
• In addition, the viral genome also encodes several
nonstructural proteins including RNA-dependent RNA
polymerase (RdRp), coronavirus main protease (3CLpro), and
papain-like protease (PLpro).
• Upon entrance to the host cells, the viral genome is released
as a single-stranded positive RNA. Subsequently, it is
translated into viral polyproteins using host cell protein
translation machinery, which are then cleaved into effector
proteins by viral proteinases 3CLpro and PLpro.

17. Cont…
• PLpro also behaves as a deubiquitinase that may
deubiquinate certain host cell proteins, including interferon
factor 3 and NF-κB, resulting in immune suppression.
• RdRp synthesizes a full-length negative-strand
RNA template to be used by RdRp to make more viral genomic
RNA.

18. Coronavirus entry and replication
• The inhaled virus SARS-CoV-2 likely binds to epithelial cells in
the nasal cavity and starts replicating, Coronavirus S protein is
regarded as a major determinant of virus entry into host cells.
• The envelope spike glycoprotein binds to its cellular receptor,
ACE2 for SARS-CoV and SARS-CoV-2 , CD209L(a C-type lectin,
also called L-SIGN) for SARS-CoV, DPP4 for MERS-CoV.
• The virus propagates and migrates down the respiratory tract
along the conducting airways, and a more robust innate
immune response is triggered.

19. Cont…
• The entry of SARS-CoV into cells was initially identified to be
accomplished by direct membrane fusion between the virus
and plasma membrane however it has been identified that
critical proteolytic cleavage event occurs at SARS-CoV S
protein at position (S20) mediating the membrane fusion and
viral infectivity.
• Besides membrane fusion, the clathrin-dependent and -
independent endocytosis mediate SARS-CoV entry too.
• Upon entry, the viral RNA genome is released into the
cytoplasm and is translated into two polyproteins and
structural proteins resulting into subsequent viral genome
replication.

20. Cont…
• The newly formed envelope glycoproteins are inserted into
the membrane of ER or Golgi, and the nucleocapsid is formed
by the combination of genomic RNA and nucleocapsid protein
(post-translational modification).
• Then, viral particles germinate into the endoplasmic
reticulum-Golgi intermediate compartment (ERGIC). At last,
the vesicles containing the virus particles then fuse with the
plasma membrane to release the virus

22. Antigen presentation in coronavirus
infection
• Presentation to the antigen presentation cells(APCs) is a
central part of the body’s anti-viral immunity.
• Antigenic peptides are presented to the MHC/HLA and then
recognized by virus-specific cytotoxic T lymphocytes (CTLs)
which is important in comprehension of COVID-19
pathogenesis.
• The antigen presentation of SARS-CoV depends mostly on
MHC I molecules however MHC II molecules plays a role.

23. Cont..
• HLA-B*4601, HLA-B*0703, HLA-DR B1*1202 and HLA-
Cw*0801 genetic polymorphism have been associated with
increased susceptibility to SARS infection, on the other hand
HLA-DR0301, HLA-Cw1502 and HLA-A*0201 alleles offers
protection from SARS infection.
• Genetic polymorphisms of MBL (mannose-binding lectin)
associated with antigen presentation are related to the risk of
SARS-CoV infection.

24. Humoral and cellular immunity
• Antigen presentation results in stimulation of both humoral
and cellular immunity as the consequence of activation of
virus-specific B and T cells.
• Similar to common acute viral infections, the antibody profile
against SARS-CoV virus has a typical pattern of IgM and IgG
production.

25. Cont…
• SARS-specific IgM antibodies disappear at the end of week 12,
while the IgG antibody last for a long time, which indicates
IgG antibody may play a protective role, and the SARS-specific
IgG antibodies primarily are S-specific and Nspecific
antibodies.
• The most important cellular immunity response is the
significant reduction in CD4+ and CD8+ T cells in the
peripheral blood of SARS-CoV-2-infected patients (similar to
SARS-CoV) due to their excessive activation.

26. Cont..
• The interaction between viral S protein and ACE2 on the
host cell surface is of significant interest since it initiates the
infection process, 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.

27. Cont…
• ACE2 involvement with coronavirus infection is of further
interest since ACE2 is a potent negative regulator restraining
overactivation of RAAS (renin angiotensin aldosterone system)
that may be involved in elicitation of inflammatory lung
disease in addition to its well-known role in regulation of
blood pressure and balance of body fluid and electrolytes.
• Organs considered to be more vulnerable to SARS-CoV-2
infection due to their ACE2 expression levels include
pneumocytes type II of the lungs, heart, oesophagus, kidneys,
bladder, and ileum

28. Cont
• ACE2 enzyme catalyzes degradation of angiotensin II to
angiotensin (1-7).
• The balance between angiotensin II and angiotensin (1-7) is
critical since angiotensin II binds to angiotensin receptor (AT1)
to cause vasoconstriction, whereas angiotensin (1-7) elicits
vasodilation mediated by AT2.
• The chronic activation of ACE2 as a result of SARS-CoV-2
infection culminate in its downregulation which impair its
physiological functions resulting in pulmonary vascular
constriction and worsening hypoxemia

29. Cytokine storm in COVID-19
• ARDS is the main cause of death COVID-19.
• ARDS is the common immunopathological event for SARS-
CoV-2, SARS-CoV and MERS-CoV infections, it’s major
mechanism being the cytokine storm; the deadly uncontrolled
systemic inflammatory response resulting from the release of
large amounts of pro-inflammatory cytokines (IFN-a, IFN-g, IL-
1b, IL-6, IL-12, IL-18, IL-33, TNF-a, TGFb, etc.) and chemokines
(CCL2, CCL3, CCL5, CXCL8, CXCL9, CXCL10, etc.) by immune
effector cells in SARS-CoV/ SARS-CoV-2 infection.

30. Cont..
• The cytokine storm trigger a aggressive attack by the immune
system to the body resulting into ARDS and multiple organ
failure, and finally lead to death in severe cases of SARS-CoV-2
infection, just like what occurs in SARS-CoV and MERSCoV
infection.
• The cytokine storm results in activation of endothelium and
subsequent endothelial dysfunction culminating in excess
thrombin generation and fibrinolysis shutdown which cause a
hypercoagulable state, overt DIC occur in patients in later
stages of COVID-19 infection, while still hospitalized, often
with septic physiology and multiorgan failure.

31. Cont..
• In addition, the hypoxia found in severe COVID-19 can
stimulate thrombosis through not only increasing blood
viscosity, but also a hypoxia-inducible transcription factor-
dependent signaling pathway.
• Polyphosphates, derived from microorganisms, activates
platelets, mast cells, and FXII in the contact pathway of
coagulation, and exhibit other downstream roles in amplifying
the procoagulant response of the intrinsic coagulation
pathway. Complement pathways also contribute to activation
of coagulation factors.

32. Cont..
• Occlusion and microthrombosis formation in pulmonary small
vessels of critical patient with COVID-19 has been reported
from a recent lung organ dissection therefore early application
of anticoagulant therapy in severe COVID-19 have been
suggested in bid to improve outcome.
• Coagulopathy of COVID-19 presents with prominent elevation
of D-dimer and fibrin/fibrinogen degradation products, while
abnormalities in prothrombin time, partial thromboplastin
time, and platelet counts are relatively less pronounced
making it different from DIC.

33. Viral load and shedding
• High viral loads have been detected in nasal and throat swabs
soon after symptom onset, asymptomatic patients may have
similar viral load compared with symptomatic patients.
• Pharyngeal viral shedding is high during the first week of
symptoms when symptoms are mild or prodromal, peaking on
day suggesting active virus replication in upper respiratory
tract tissues.
• Duration of viral shedding is between 8 and 20 days after
symptoms resolution, virus can be detected in the sputum and
faeces for up to 39 days after negative pharyngeal swabs, it is
not clear if this phenomenon results in transmission of virus.
• Factors associated with prolonged viral shedding include male
sex, older age, comorbid hypertension, delayed admission to
hospital after symptom onset or severe illness on admission,
and use of invasive mechanical ventilation or corticosteroids.

34. Coronavirus immune evasion
• Multiple strategies are used by these viruses to avoid immune
responses.
i. Normally the evolutionarily conserved microbial structures
called pathogen-associated molecular patterns (PAMPs) are
recognized by pattern recognition receptors (PRRs) however
these viruses can induce production of double-membrane
vesicles which do not contain PRRs and then replicate in
these vesicles, thereby avoiding the host detection of their
dsRNA.
ii. IFN-I has protective effects in infection with these viruses
however its production is inhibited rendering them capable
of evading the immune system
iii. Down regulation of gene expression related to antigen
presentation

35. ??Why now…??Why not always
Zoonotic Evolution and Adaptation
• Quick rate of replication and reproduction in the background
of lacking Proof reading mechanisms = accumulation of
mutations. E.g. HIV-1 virus is thought to be the world’s fastest
evolving microbe (Cuevas et al, 2015).
• ?2002 China’s Guangdong twenty-first century’s first global
pandemic: SARS due to SARS-CoV = acquired two key
mutations in the receptor-binding domain of its S protein that
allowed it to use the human orthologue of the receptor ACE2
with high efficiency. The mutations enabled SARS-CoV to jump
from its natural reservoir which is bats into civets then to
human resulting into the outbreak.
• Seems to be the similar case for COVID-19 due to SARS-CoV2

36. ??Bioterrorism
• Conspiracy theorists have suggests that COVID-19 was
planned and the causative virus was created/manipulated in
the laboratory
• However SARS-COV-2 have 85% genetic homology with SARS-
COV, 50% to the MERSCoV and since zoonotic disease are
difficult to predict this may explain the normal process of
zoonotic evolution.
• Evidence from phylogenetic analysis shows that the virus was
not manipulated/manufactured in the laboratory

37. Clinical presentation of COVID-19
• The most common symptoms at onset of COVID-19 illness are
fever, cough, fatigue and anosmia as the disease progress the
patient develop sputum production, headache, haemoptysis,
diarrhoea, dyspnoea, and lymphopenia.
• Clinical features revealed by a chest CT scan presents as
pneumonia, however, there were abnormal features such as
RNAaemia, acute respiratory distress syndrome, acute cardiac
injury (myocarditis), and incidence of grand-glass opacities
that led to death.

38. Clinical course/natural hx of COVID-19
• Out of population of individuals who develop COVID-19, 80%
develop mild or no symptoms but are very infectious,
therefore they can be isolated and treated at home.
• About 20% develops moderate to severe symptoms with
pulmonary infiltrates and some of these will develop very
severe disease.
• About 5-10% develop severe symptoms with ARDS, Sepsis,
multiorgan failure and coagulopathy necessitating admission
into an ICU.

39. WHO classification
i. Mild illness (Upper respiratory tract symptoms)
ii. Moderate illness (Pneumonia)
iii. Severe illness (severe pneumonia, sepsis, septic shock and
multiorgan failure)

41. Diagnosis
• Thorough hx taking P.Examination: The respiratory clinical
manifestations consistent with COVID-19 (eg, fever, cough,
dyspnea). Symptomatic patients should also be asked about
recent travel or potential COVID-19 exposure in the prior 14
days to determine the need for evaluation for COVID-19.
• RNA PCR (RT-PCR) & Viral genetic sequencing
• Viral specific IgM & IgG titres
• Radiography..CXR (hazy bilateral , peripheral opacities), CT
Chest (GGO, consolidation, rarely may be unilateral), USS:
numerous B-lines, pleural line thickening, consolidation with
air bronchograms

42. Labs
• CBC: leukopenia & lymphopenia (>80%)
• RFT: Increased BUN/Cr
• LFT: Increased ASAT/ALAT/Total bilirubin
• Increased D-dimer, CRP, LDH
• Increased IL-6, Ferritin
• Low levels of procalcitonin, high levels Procalcitonin suggests
concurrent bacterial superinfection

43. Treatment of COVID-19
• Some patients with suspected or documented COVID-19 have
severe disease that warrants hospital care.
• Since there is limited clinical and basic research information at
this time, treatment options for COVID-19 currently comprise
investigational drugs and management of symptoms.
• Ensuring appropriate infection control and supportive care.
• High-flow oxygen and noninvasive positive pressure
ventilation, Acute respiratory distress syndrome warrant
intubation with mechanical ventilation; extracorporeal
membrane oxygenation may be indicated in patients with
refractory hypoxia, the aim is SPO2 >_94%

44. Cont..
• The WHO and CDC recommend against the use of
glucocorticoids in patients with COVID-19 pneumonia unless
there are other indications (eg, exacerbation of chronic
obstructive pulmonary disease (COPD)).
• Glucocorticoids have been associated with an increased risk
for mortality in patients with influenza and delayed viral
clearance in patients with MERS-CoV and SARS-CoV.
• Most drugs for the treatment of COVID-19 are still under
clinical trials and since most of the same are safe and have
demonstrated efficacy, they are used for the purpose of
COVID-19

45. Cont..
• Anticoagulation therapy early after admission for eligible
patients.
• Antimicrobial therapy for treatment of suspected bacterial
infection should be instituted based on the local guidelines,
clinical presentation and susceptibility pattern until blood
culture can rule out the infection.
• Use of the convalescent plasma of the recovered patients
• Use of intravenous Vitamin C
• Physiotherapy that includes chest physiotherapy; avoid lying
on their back as this makes coughing ineffective and chest
physiotherapy

47. Chloroquine/Hydroxychloroquine +/-
Azithromycin
• The sulfate and phosphate salts of chloroquine have both
been commercialized as antimalarial drugs.
• Hydroxychloroquine has also been used as an antimalarial, but
in addition is now broadly used in autoimmune diseases such
as lupus and rheumatoid arthritis.
• Of note, chloroquine and hydroxychloroquine are considered
to be safe and side-effects are generally mild and transitory.
• However, the margin between the therapeutic and toxic dose
is narrow and chloroquine poisoning can be life threathening.

48. Cont..
• MOA: increasing endosomal pH required for virus/cell fusion,
as well as interfering with the glycosylation of cellular
receptors of SARS-CoV2 . The anti-viral and anti-inflammatory
activities of chloroquine may account for its potent efficacy in
treating patients with COVID-19 pneumonia.
• Chloroquine is a cheap and safe drug that has been used for
more than 70 years. In light of the urgent clinical demand,
chloroquine phosphate is recommended to treat COVID-19
associated pneumonia in larger populations in the future.
• Safety concerns with hydroxychloroquine and azithromycin
include the potential for QTc prolongation, which is greater
when both agents are used together and may accounted for
increased mortality reported in some clinical trials.

51. Remdesivir
• =Novel antiviral drug developed for the treatment of Ebola
virus disease and Marburg virus infections.
• It is a prodrug of a nucleotide analog that is intracellularly
metabolized to an analog of adenosine triphosphate that
inhibits viral RNA polymerases.
• Remdesivir has broadspectrum activity against members of
several virus families, including filoviruses (e.g., Ebola) and
coronaviruses e.g., SARSCoV and MERSCoV).
• In vitro testing has also shown that Remdesivir has activity
against SARS-CoV-2 with an EC50 value of 1.76 μM

52. Cont
• The discussed drugs (specifically Chloroquine
/Hydroxychloroquine and Remdesivir ) have shown
improvement of symptoms and severity of the COVID-19
disease, however the their ability to improve mortality in
these patients remain inconclusive and require further clinical
trials involving large number of participants to reach such
conclusion

53. Prevention
In the health care setting
• Screening and precautions for fever or respiratory symptoms
— Screening patients for clinical manifestations consistent
with COVID-19 (eg, fever, cough, dyspnea) prior to entry into a
health care facility can help identify those who may warrant
additional infection control precautions. Symptomatic patients
should also be asked about recent travel or potential COVID-
19 exposure in the prior 14 days to determine the need for
evaluation for COVID-19.
• Any individual with these manifestations should wear a
facemask.
• PPE for healthcare workers

54. Management in Pregnancy & Paediatrics
• Pregnant women should be managed by a multidisciplinary
team, including obstetric, perinatal, neonatal, and intensive
care specialists, as well as mental health and psychosocial
support. There is no evidence to suggest that pregnant
women are more likely to contract COVID-19, or present with
increased risk of severe illness or fetal compromise.
• Mothers in labour/not in labour with suspected/confirmed
COVID-19 should isolated from the general wards , being in
room containing patients each!
• IPC guidelines should be adhered

55. • All other treatment should be done as indicated, delivery
should be conducted with other indications as COVID-19
infection is not an indication for delivery..the fetus is unlikely
to be infected during pregnancy
• When the mother has confirmed COVID-19: after delivery of
healthier baby should cared separately by a relative/caregiver
and must be tested for COVID-19.
• When with signs and symptoms of COVID-19 a baby should
admited into the NICU unless the symptoms are mild and
managed separately under care of Neonatologist .
• Other group of paediatric patients should managed with the
same protocol as adults however the drug doses and fluid
management should be adjusted accordingly.
Cont…

56. Cont…
• WHO recommends standard, contact, and droplet precautions
(i.e., gown, gloves, and mask), with eye or face protection.
• The CDC recommends that patients with suspected or
confirmed COVID-19 be placed in a single-occupancy room
with a closed door and dedicated bathroom. The patient
should wear a facemask if being transported out of the room
(eg, for studies that cannot be performed in the room).
• Adhering to Infection Prevention and Control Protocol.

57. Cont..
Preventing exposure in the community
• Diligent hand washing, particularly after touching surfaces in
public. Use of hand sanitizer.
• Respiratory hygiene (eg, covering the cough or sneeze).
• Avoiding touching the face (in particular eyes, nose, and
mouth).
• Screening and Quarantine of the contacts and travelers from
high risk geographical location
• Social distancing
• Cleaning and disinfecting objects and surfaces that are
frequently touched.
• Shielding extremely vulnerable people

58. Vaccine
• It is crucial to develop safe and effective vaccines to control
the COVID-19 pandemic, eliminate its spread, and ultimately
prevent its future recurrence.
• Since the SARS-CoV-2 virus shares significant sequence
homology with two other lethal coronaviruses, SARS and
MERS, the vaccines identified in these patents related to SARS
and MERS viruses could potentially facilitate the design of
anti-SARS-CoV-2 vaccines.

59. Cont...
• There is currently no vaccine for SARS-CoV2 however many
vaccines are undergoing clinical trials though others are still in
the animal phase and this may take up to another 12 months
to have at least one vaccine.
• The viral S protein subunit vaccines have been shown to
produce higher neutralizing antibody titers and more
complete protection than live-attenuated SARS-CoV, full-
length S protein, and DNA-based S protein vaccines.

60. Prognosis
• The following are associated with increased likelihood of poor
clinical outcome:
i. Advanced age
ii. Comorbidities: DM, COPD, Asthma, CVD, Obesity
iii. High SOFA score at admission
iv. Admission to the ICU
v. Labs findings: high levels of D-dimer, ferritin, troponin,
cardiac myoglobin
vi. Watch for complications such as secondary bacterial
infection, stress CM

61. What is next for COVID-19?
• COVID-19 does not yet have specific therapy!
• Individuals should adapt to live with the virus as cure will not
attained unless proper therapy is identified, 70% of the
population is infected and thus attaining herd immunity ( this
is not yet scientifically proven) and the safe and efficient
vaccine is developed.
• ?? There is likelihood of this disease developing 2nd/3rd …..
wave that may be more severe than what we have
experienced so far.

62. Questions
1. Distinguish suspected case from confirmed case of COVID-
19, How does their management differs?
2. Explain the major routes of transmission of SARS-CoV-2
3. Keeping in mind the Role of ACE2 receptor in pathogenesis
of COVID-19 in mind, should the patients on ACEIs/ARBs be
withheld? Explain you answer!
4. Use of Glucocorticoids are limited in these patients, when
would the continuation of steroid therapy be mandatory?
Which form of steroid therapy should not be withheld?
5. What are major causes of death in COVID-19 patients?
6. What is drug repurposing? When is it important?
7. What is the role of convalescent plasma in Management of
COVID-19?

63. Cont..
8. Can Chloroquine/Hydroxychloroquine be used as
prophylaxis against SARS-CoV-2? What gives this drug this
property? How is it safe and efficacious?
9. Where can the samples for RT-PCR testing be taken?? What
are their sensitivity and specificity?
10. What are the roles of different types of face masks in
prevention of COVID-19??
11. Discuss the role and timing of lockdown in prevention of
COVID-19 and its implication on social-economic aspects of
different societies
12. What are complications of COVID-19? Explain how they can
be managed!

64. Case scenario
• A 73-year-old man with hypertension and chronic
obstructive pulmonary disease calls to report that he has had
a fever (maximal temperature, 38.3°C) and a dry cough
for the past 2 days. He notes that his shortness of breath has
worsened. His medications include losartan and inhaled
glucocorticoids. He lives alone. How should he be
evaluated? If he has coronavirus disease 2019 (Covid-19), the
disease caused by severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2), then how should he be
treated?

65. References
• Notification of 2019-nCoV infection. National Health
Commission of the People's Republic of China. http://
www.nhc.gov.cn/xcs/yqfkdt/202002/18546da875d74445b
b537ab014e7a1c6.shtml (accessed February 17, 2020). (in
Chinese)
• Hussin A. Rothan and Siddappa N. Byrareddy, Journal of
Autoimmunity, https://doi.org/10.1016/j.jaut.2020.102433
• https://www.covid19treatmentguidelines.nih.gov/
• Mason RJ. Pathogenesis of COVID-19 from a cell biology
perspective. Eur Respir J 2020; 55: 2000607
[https://doi.org/10.1183/13993003.00607-2020]

66. References
• X. Li et al, Molecular immune pathogenesis and diagnosis of
COVID-19, https://doi.org/10.1016/j.jpha.2020.03.001
• Jianjun Gao, Zhenxue Tian, Xu Yang; Breakthrough:
Chloroquine phosphate has shown apparent efficacy in
treatment of COVID-19 associated pneumonia in clinical
studies
• Caren G. Solomon, M.D., M.P.H., Mild or Moderate Covid-19,
DOI: 10.1056/NEJMcp2009249.
• Parag Goyal, M.D et al, Clinical Characteristics of Covid-19 in
New York City, DOI: 10.1056/NEJMc2010419
• CDC Guidelines on COVID-19
• WHO Guidelines on COVID-19