coronavirus COVID-19 SARS-CoV2 Management treatment investigations ivermectin remdesivir radiology Lopinavir convalescent plasma hydroxychloroquine antiinflammatory anticoagulant NSAIDs colchicine tocilizumab laboratory diagnosis antiviral herbal

2. “Primum non nocere”, then Do
Good

3.  COVID-19 pandemic has changed the way of doing medicine: we are presently
moving away from EBM towards a more observational approach
 “frenzy to publish” in relation to COVID-19 should be abandoned and
downright avoided

4. SARS-CoV 2 is a single stranded
positive sense RNA large virus

5. After 200 days of 1st report of SARS-
CoV-2 infection, no approved antiviral
or vaccine is available

6. Transmission:
•Droplet
•Air-borne
•Fecal-Oral (Theoretical)
•Body fluids (vomits)
•Direct contact with surfaces
•No vertical
•Case reports of Breast milk
•Average R0 is 2.2
•Cummulative attack rate is 0-50 fold of flu

8. Infectivity and shedding:
• Live virus is present up to 7-8 days of onset of symptoms, longer with severe
disease
• Longer time of viral shedding (not alive) may occur in severe disease, for weeks in
respiratory secretions and longer in faeces
• Elderly seems to shed more virus and have higher viral load
• Highest time for viral shedding is at time of start of symptoms
• Asymtomatic patients shed and infect
• Virus is present in respiratory secretions, salive, tears, urine, faeces, blood, and
lastly in breast milk

9.  Experimentally, animals infected with other coronaviruses, showed resistance
for re-infection and SARS-CoV 2 seems the same
 Re-infection or relapse is very low with good prognosis
 Low titre of antibodies may be not protective
 Seroconversion is less in asymptomatic and immunocomprom (up to 30%)
 Although of lack of seroconversion, almost all patients developed antibodies

10.  Time-table for PCR, Serology and biomarkers in COVID-19 patients

11. Symptoms and signs:

14. • The duration from onset of symptoms to ARDS is about 8-
12 days
• Symptoms in pregnant are similar to non-pregnant with
tendency to severity

15. Children:
•In 1391 asymptomatic or symptomatic children in close contact to confirmed
COVID-19 patients in Wuhan, 3 were admitted to ICU and only one died (with
underlying chronic lung disease)
•Most children have mild disease

16. Neurotropism in COVID-19 patients:
•Anosmia (Cacosmia)
•Dysguesia
•Periphearl sensory and motor neuropathy
•Happy (silent) hypoxia
•Respiratory failure
•stroke
•Cavernous sinus thrombosis

17. ABO blood Grouping:
• Group (A) more infection
• Group (O) least

18. Blood donation:
• No blood donation within 21 days of contact with a positive case
• No blood donation except after 4 weeks after recovery for patients with COVID-19
with completion of treatment

19. • Coinfection with other viruses occured in 5.8% og 8000 confirmed COVID-19
patients in Wuhan
• The cost of short term containment is less than the cost of long term viral spraed
• 80% of cases are asymtomatic or mild

20. Death rate:
•0.1-5%
•Mean 2.5%
•My opinion 0.3-0.8%

21. Radiological evaluation:

23. HRCT Chest:
•Negative mostly in 1st 24-48 hours of symptoms
•50% positive in non respiratory symptoms
•97% positive in patients with respiratory symptoms and positive RT-PCR
•Severe disease if more than 50% lung infiltrates

27.  Halo Sign

30. Laboratory:
•Leucocytosis in 24-30%
•Leukopenia in 9-34%
•Lymphopenia in 63-83%
•High ALT AST in 37%
•Thrombocytopenia in 34%

31. Markers of cytokine storm and bad
prognosis:
1.Ferritin more than 2000-2500
2.Elevated ALT AST
3.Increased fibrinogen more than 2.5 gm/dl
4.High triglyceride
5.Cytopenia in CBC (worse with increasedv lineage)
6.Temperature more than 38,5 C

33. • Blood and serum markers

34. Serological tests for SARS-CoV 2 virus:
 Cross reactivity with other coronaviruses: Theoretical while not documented in
reality
 By week three, nearly all patients have seroconversion, and start by day 3-6
 IgG remains for at least 2 months
 Antibody response of other coronaviruses decay in few years, SARS-CoV 2, may
be the same

35. RT-PCR for SARS-CoV 2:
•The most accepted and sensitive primer is RDRP
•To be Positive, it needs 100-1000 copies in the examined sample
•RT-PCR is highly specific, false positive is weak possibilty esp. in asymptomatic
patient
•Sensitivity is 60-80%
•Test may be positive in 50% of persons without symptoms
•Single test does not exclude infection

36. Sample for RT-PCR:
•1st case was diagnosed by BAL through FOB
•Preferred sample nasopharyngeal and Oropharynges
•More positivity in sputum and LRT samples
•If MV, use tracheal aspirate rather than BAL
•Sample is kept at 2-8 C

39. Management:

40. Isolation:
•Is fundamental
•Home isolation in mild cases is ideal with good nutrition and hydration
•Isolation of a case at home decrease infectivity by 75%

43. CDC
Symptomatic patients with COVID-19 should remain in Transmission-Based
Precautions until either:
Symptom-based strategy
At least 3 days (72 hours) have passed since recovery
At least 10 days have passed since symptoms first appeared (10 plus 3)
Test-based strategy
Resolution of fever without the use of fever-reducing medications and
Improvement in respiratory symptoms (e.g., cough, shortness of breath), and
Negative results of 2 consecutive swabs for RT-PCR, at least 1 day apart

44. Vitamins and supplements:

46. Zinc :
•50-200 mg daily
•HCQ is an ionophore for Zn and enhance its uptake by lysosomes
•In healthy, RDA is 15-30 mg
•Long term high dose Zn may cause decreased HDL, anemia, copper deficiency and
possible genitourinary complications

47. Vitamin C (Ascorbic acid)
•Neutralize free radicals, antioxidant
•Has antiviral activity especially in Influenza
•1.5 mg/kg per day
•High doses (2-10 gm per day) improved oxygenation

48. Lactoferrin

49. AtiCoagulants:

50. • There is a thrombotic component in the development of respiratory distress for
these patients.
• The positive effect of heparin are consistent and its use, when indicated, could be
considered in clinical settings.
• Randomized controlled trials are necessary to complement observational studies
and clinical outcomes.
• Heparin is easy to administer, its use in ambulatory patients, to prevent
admissions, or reduce their duration

51. AtiCoagulants:
•Are the best approved drugs in COVID-19 patients
•LMWH are preferred
•NOAC can be used
•UFH in case of renal impairement
•Patients on long term warfarin are kept on without adding new anticogulants
•rTPA may be tried in end stage persistent hypoxemia, hypotension patients with
optimistic anecdotal reports

56. Antiviral Drugs:

57. To date, persuasive evidence of important
benefit does not exist for any antiviral
treatment, although important benefit has
not been excluded for each agent

58. Remdesivir:
•A prodrug of adenosine analogue
•RDRP inhbitor
•1st used for Ebola virus, with failure
•It has broad antiviral activity in vitro and in vivo againt HBV, HIV, MERS-CoV,
SARS-CoV
•WHO consider it 1st priority reasearch drug in COVID-19 patients
•In a study of 199 patients, it showed no Survival benefit
•safe in pregnancy

59. Lopinavir/Ritonavir:
•Pretease inhibitor
•Used in HIV treatment
•10/2.5 mg per kg twice daily for 14 days up to 400/100 twice daily
•in first 7 days of disease
•Be cautious when used with HCQ as it may increase its level
•In 41 patients, this combination with B0interferon and Ribavarin improved mortality
•WHO considerd it 2nd priority research agent in COVID-19 patients
•Limited efficacy in other studies
•Monitor ALT AST
•Safe in pregnancy
•Crushing tablets decrease their efficacy as per manufactrurer

60.  We suggest that clinicians using lopinavir-ritonavir as an off-label treatment
for Covid-19 should consider starting it earlier rather than later in the course
of the illness (within 7 days)

61. Favipiravir (Avigan):
•Guanine analogue
•RDRP inhibitor
•Approved for drug resistant influenza in Japan
•In vitro activity against SARS-CoV and SARS-CoV 2
•400 mg twice daily for 5-14 days

62. Unifenovir (Arbidol):
•For treatment and prophylaxis of influenza in Russia and China
•200 mg/ 8 hours oral
•It has in vitro antiviral activity against many viruses

63. Ribavarin:
•No conclusive resultsd
•Teratogenic
•Hemolytic anemia
•Hepatotoxicity

64. Oseltamivir (Tamiflu-Taminil):
•Neuraminidase inhibitor
•Used in Influenza treatment
•Best action within the first 2-3 days of symptoms
•It has no role in COVID-19 patients
•It was given emperically due to fears regarding co-infection of COVD-19 patients
with seasonal flu

65. Anti-Parasitic:

66. HCQ:
•FDA advised against use except in clinical trials
•Weak base
•May attenuate progression
•May inhibit cytokine storm
•Inhibit viral entery to cell
•Inhibity endosome
•Inhibit ACE2R glycosylation
•7-8 mg/kg twice 1st day, then same once daily

67. HCQ:
•HCQ is more potent tahn chloroquine
•side effects: diarrhea, ECG changes , arrhythmias, headache, abdomenal pain and
extrapyramidal manifestations
•The earlier the better, although of nonconclusive data
•Can be used in all trimesters with higher dose as it has a large VD

68. Neuropsychiatric rare side effects of
HCQ:
•Psychosis
•Delerium
•Agitation
•Suicidality
•Depression
•Sleep disturbances

69. RECOVERY study, funded by the U.K. government
We have concluded that there is no beneficial effect of hydroxychloroquine in
patients hospitalized with COVID-19. We have therefore decided to stop enrolling
participants to the hydroxychloroquine arm of the RECOVERY Trial with immediate
effect.
 ‘A total of 1542 patients were randomised to hydroxychloroquine and compared
with 3132 patients randomised to usual care alone. (of 11.000)
There was no significant difference in the primary endpoint of 28-day mortality
(25.7% hydroxychloroquine vs. 23.5% usual care; hazard ratio 1.11 [95% confidence
interval 0.98-1.26]; p=0.10). There was also no evidence of beneficial effects on
hospital stay duration or other outcomes.

70. Ivermectin :
•In comparison to HCQ, Ivermectin has a wide safety margin
•Ivermectin is present in lung at concentartion that is 2.8-3 folds of the plasma after
one week of a single dose
•FDA approved dose is 150-200mcg/kg
•400 mcg per kg was used for dengue fever safely
•10 higher of approved dose in a single dose was studied safely in phase 1 trial
•120 mg once and 60 mg every 3 days for total 3 doses was well tolerated. This dose
gave a 1/5th IC50 of that of Caley et al 2020

71. Ivermectin :
•Very limited accumulation after high single or 3 doses per week
•The most common side effects were headach, nausea, dzziness and rash. The
reporetd side effects were noticed in 24% of Iveremctin group and 35% of placebo
group
•One preclinical study proved safety of inhaled Ivermectin up to 28 days. Not
performed yet in humans

72. Ivermectin :
•In a study vy Caley et el it vanished the SARS-CoV 2 genomic material in 48-72 hours
in culture.
•It mostly acts through inhibition of imortin-alpha1 Beta1 mediated nuclear import of
viral proteins
•it may act also as an ionophere
•Ivermectin and HCQ may have a synergitic effect

73. Very rare side effects of Ivermectin:
•Muscle waekness
•Tachycardia
•Hypotension
•Mydriasis
•Agitation
•Ataxia
•Rhabdomyolysis
• in high doses, Ivermectin can pass BBB acting on GABA causing neurotoxicity

74. Ivermectin :

79.  Niclosamide is used in treatment of H.Nana, Diphyllobothrium latum , Tenia
solium and Saginata
 Because niclosamide has been used for the treatment of parasite diseases in
humans, this drug may be considered for immediate use in the treatment of
SARS patients, alone or in combination with other drugs.

80. Nafamostal and Nitazoxanide:
•Nafamostal is a serine protease inhibitor
•Nitazoxanide is antiprotozoal
•They have possible in vitro antiviral activity
•In Mexico, a study shown that Nitazoxanide was not better than placebo

81. Antiotics

82. Antibiotics:
•Azithromycin may have antiinflammatory action
•No evidence that antibiotics prevent superinfection
•In critically ill COVID-19 patients, antibiotic may be useful due to superimposed
infection and its choice is according to hospital profile and protocol
•Procalcitonin has no role in diagnosis of COVID-19 patients

83. Teicoplanin (Targocid):
•Inhibit host cell Cathepsin L and B responsible for cleavage of viral glycoprotein
•It showed in vitro activity against Ebola virus, Influenza virus, Flavivirus, HCV,
HIV SARS-CoV and MERS-CoV
•RCT in SARS-CoV 2 is underway

84. AntiInflammatory and Immunomodulation
Interventions

85. Aspirin:
•No document, no guidelines, no previous in vitro or in vivo study has advised or
used ASA for treatment of SARS-CoV2 infection
•There is one ongoing prospective study for ASA 100 mg in patients with SARS-CoV2
infection

86. NSAID:
•the existing literature does not currently provide conclusive evidence for or against
the use of NSAIDs in the treatment of COVID-19 patient
•Ibuprofen is under study in COVID-19 patients, while naproxen and indomethacin
are candidates

87. Glucocorticoids:
•Controversial ,as usual , as regard indication and sose
•Best in:
higher infiltrates
Septic shock
Persistent fever
In SARS and MERS-CoV, They were associated with higher mortality

88. Tocilizumab (Actemra):
•IL-1 soluble and membrane receptor antagonist
•It is used in RA and large vessel vasculitis
•May precipitate severe bacterial infection, activate dormant TB
•One dose of 4-6 mg per kg can be repeated once only in 12-24 hours
•Higher ferritin, CRP and fibrinogen may guide its use

89. Colchicine
•Inhibit Il-1 production and inflammasome
•Phase 3 RCT study is underway
•Some reports are found against its use

91. Convalescent plasma:
•Severeal studies showed shorten of LOS and lower mortality in SARS
•In COVID-19, on 10 patients, it helped symtom resolution , decreased radiological
shadows, better inflammatory markers
•In a study of 5 patients on MV, 3 discharges and 2 weaned in stable condition after
37 days. But Plasma here was given with many other treatment and the results can
not be exclusive for convalescent plasma and it was given too late (10-22 days of
admission)

92. Convalescent plasma:
•1st RCT showed no mortality benefit
•Many RCT are underway
•Plasma can be stored for years. But, its NAb may be ineffective after years due to the
cummulative viral mutations
•In 1-3 doses, ever 12-24 hours each 200-250 ml

93. The possibility to use it as a prophylactic in HCW and
high risk group is good, but u ethical in the Pandemic
time. It will be used for rich and Political leads.

94. IVIG:
•0.3-0.5 gm/kgm
•Pooled polyclonal IgG from at least 1000 healthy donors
•A systematic review in SARS patients was inconclusive , although some studies
showed benefit in SARS and MERS
•In 58 COVID patients, it reduced MV, LOS with earlier recovery, but not the
moratlity rate at 28 days (23 died)
•More than 100 studies are underway for IVIG and convalescent plasma

95. IV MSCs:
•It was studied as case reports in COVID-19 and showed promising results

96. Blood Purification therpaies:
•CRRT has proven efficacy in small studies of patients with cytokine storm
•CRRT showed no benefit in sepsis patients
•In one study, its introduction in stage 2 AKI showed signficant lower mortality at 90
days
•RCT showed no benefit

97. Miscellaneous

98. Amiodarone

99. Thiazolidinediones:
•Used in treatment of type II diabetes
•Protective against lung injury induced by RSVand H1N1 infection
•They have the potential to upgrade ACE2R
•Their potential role in COVID-19 was not explored

100. Janus Kinase Inhibitors (Ruxolitinib)
•Used in treatment of myelofibrosis
•Trade name: Jakavi, cost 36 K Egyptians pounds for 56 tablets
•It is in phase 3 study in COVID-19 patients
•US NIH panel advised against its use in COVID-19 because of its broad
immunosuppression
•Baricitinib has conflicting results
•Bruton Kinase inhibitors shows a promise in severe cases (akalbrutinib)

101. Oxygenation and Ventilation

102. Oxygenation:
•O2 if SpO2 less than 93% or respiratory disteess with concious prone
•Keep O2 no more than 96%
•CPAP/BiPAP early if no improvement
•If failed early MV with OLV with prone position
•ECMO last resort

103. ECMO:
•Mortality rate in COVID-19 patients on ECMO is 82%
•ECMO in old patients with multiple comorbidities should be rare
•Patients with more than 7 days on conventional MV are poor candidates
•No lung or cardiac recovery with ECMO after 21 days means futile treatment
•Renal failure is not a contraindication

104. Indications for ECMO:
(1) PaO2/FiO2 < 50 mm Hg > 3 hours;
(2) PaO2/FiO2 < 80 mm Hg > 6 hours;
(3) FiO2 = 1.0, PaO2/FiO2 < 100 mm Hg;
(4) pH < 7.25, and PaCO2 > 60 mm Hg > 6 hours, and R > 35 /min;
(5) R > 35/min, pH < 7.2, and Pplat> 30 cmH2O;
(6) Severe pulmonary air leak syndromes;
(7) Cardiac arrest or cardiogenic shock.

109. Vaccine:
•British pharma giant AstraZeneca has started to mass-produce its experimental
AZD1222 vaccine, being developed by Oxford University, and plans to roll out up to
two billion doses of a coronavirus vaccine in September
•Oxford University began initial trials of its Covid-19 vaccine with hundreds of
volunteers in April, and is now expanding them to 10,000 participants.
•The Cambridge-based firm has signed deals to produce 400 million doses for the US
and 100 million for the UK if it is successful in human trials.
•As of early June, governments and philanthropic organizations have given over $4.4
billion to pharmaceutical corporations for the research and development for Covid-
19 vaccines

110. Some Herbal Therapy:

113. Astragalus membranaceus

114. Glycyrrhiza uralensis

115.  rhizoma atractylodis macrocephalae