A Covid-19 Clinical Case: Lessons & Current Management Strategies

1. A Covid-19 Clinical Case:
Lessons & Current Management
Strategies
Dr. Imad Salah Ahmed Hassan MD Immunology (UK),
MSc Infectious Diseases (UK), FACP, FRCPI
Head of Section, Medical Protocol Department,
King Abdulaziz Medical City, Riyadh,
Kingdom of Saudi Arabia

3.  Empower the audience with the critical domains
necessary for transforming the current practice of
caring for Covid-19 infected patients (including
prevention).
 Enlighten and galvanize the audience to employ
the current “best available literature evidence” for
reducing ICU admissions and death.
Aims of the Presentation

4. COVID-19
About the Patient01.
Diagnosis02.
Treatment & Hospital Course03.
Lessons Learnt04.
Currrent Thinking in Covid-19
Management05.

5. ABOUT THE
PATIENT
01
 This is a 65 years old male known case of
DM2 (latest A1C 11.8) and DLP.
Presented to ED with sore throat,
persistent dry cough, recurrent fever and
chills and poor oral intake of 4 days
duration.
 He denied contact with a sick patient.
 Over the previous 24 hours, fever became
continuous associated with SOB and 2
episodes of watery diarrhea.

6. ABOUT THE
PATIENT
01
 Non-smoker. No alcohol intake.
 Medications:
 Degludec (ultralong-acting basal insulin
analogue)-20 units
 Aspart Insulin 25 units TID
 Semaglutide (Oral GLP-1 receptor
agonist)
 Empagliflozin (sodium-glucose co-
transporter 2 (SGLT2) inhibitor) and
metformin (12.5/1000 mg ) BID
 Rosuvastatin 20 mg OD
 Neurobion (B1, B6, B12) OD
 No allergies

7. ABOUT THE
PATIENT
01
 O/E:
 Patient is alert oriented to TPP,GCS
15/15, not in pain or distress, saturating
well on RA.
 HR 86
 BP 111/60
 RR 20
 T 37.9
 O% 96 on RA
 BMI 26.5

8. ABOUT THE
PATIENT
01
 O/E:
 The only other abnormal physical sign
was fine lower zones crackles bilaterally.

9. ABOUT THE
PATIENT
01
 Investigations

10. ABOUT THE
PATIENT
01
 Investigations

11. ABOUT THE
PATIENT
01
 Investigations
NewOld

12. Neut % 56.00
Mono # 0.39
Mono % 9.00
Lymph % 31.00
Lymph # 1.36
Neut # 2.45
Atypical Lymph # 0.09
Band % 2.0
Atypical Lymph % 2.0
Band # 0.09

13. AGAP 25 (7-15 mmol/L)
Creatinine 1.31 mg/dl (0.72-1.24)
BUN 15.7 mg/dl (8.4-25.7)
HCO3- 13 (23-31 mmol/L)
eGFR 58
Glucose 7.4 (3.9-7.7 mmol/L)
Zinc Level 10.43 (10-16 umol/L)
UA Glucose >=1.000 mg/dL
UA Ketones 80
VIT D 25 OH 36.8 (50-125 nmol/L)
Adj Ca
2.07 (2.2-2.5 mmol/L)
PTH 11.830 (1.5-7.2 pmol/L)

14. ESR 89 mm/hr (0-20)
Ferritin
566.6 (21.8-274.6
ug/L)
LDH 351 (125-220 U/L)
PCT
0.15 (<0.08ng/ml)
CRP
98 (< 7 mg/L)
Lactic Acid
2.94 (0.5-2.2
mmol/L)
Fibrinogen 5.47 (1.5-4.1 gm/L)
D-Dimer 0.47 (0-0.5 mg/L)

15. 1. Bedside-Clinical Diagnosis Community Acquired Pneumonia
2. Eitiology Covid-19
3. Severity CURB-65= 1
4C Mortality Score: 8 (intermediate risk, 9.1-9.9% in-hospital mortality)
https://www.mdcalc.com/4c-mortality-score-covid-19
4. Problem List Vitamin D Deficiency, Increased Inflammatory Markers, Lactic
Acidosis, CKD, Poorly Controlled DM
5. Site of Care General Ward (Negative Pressure Room)
6. Symptomatic Anti-pyretic (Acetaminophen)
Antitussive (Dextromethorphan)
7. Supportive IV Fluids
Enoxaparin 40 mg Subcut OD
Aspirin 81 mg OD
Vitamin C, Vitamin D and Zinc
8. Specific Antibiotics: Ceftriaxone and Azithromycin
9. Specialty Referral Infection Control Team
Infectious Diseases Consult

16. Hospital Course
Day 1, 28/10 Day 5, 01/11 Day 6, 2/11 Day 7, 3/11 Day 14 10/11 Day 16, 12/11
Admission
(Day 5 of illness)
• Enoxaparin 40 mg
Subcut OD
• Aspirin 81 mg OD
• Vitamin C 1000 mg
OD, Vitamin D 50,000
units weekly and Zinc
Sulphate 100 mg OD
• Ceftriaxone 1 gm OD
and Azithromycin 500
mg OD
• Serial CRP, d-Dimer,
Procalcitonin, Ferritin
• CRP 98 on admission
• Procalcitonin 0.15

17. Hospital Course
Day 1, 28/10 Day 5, 01/11 Day 6, 2/11 Day 7, 3/11 Day 14 10/11 Day 16, 12/11
Admission
(Day 5 of illness)
Worsening CXR
Sats RA 93-95%
ABG Type 1
Respiratory Failure
• Enoxaparin 40 mg
Subcut OD
• Aspirin 81 mg OD
• Vitamin C 1000 mg
OD, Vitamin D 50,000
units weekly and Zinc
Sulphate 100 mg OD
• Ceftriaxone 1 gm OD
and Azithromycin 500
mg OD
• Serial CRP, d-Dimer,
Procalcitonin
• CRP 98 on admission
• Procalcitonin 0.15
Dexamethasone
Started
CRP143 on Day 5
Procalcitonin 241.7

18. pH 7.453
pCO2 31.6
pO2 57.4
HCO3 21.6
BE -1.4
P/F Ratio (PaO2/FIO2) 273.5
K+ 3.42
Ca2+ 1.200
SBP (mmHg) 139
DBP (mmHg) 70
Mean BP (mmHg) 83
HR (Freq./min) 93
RR (Freq./min) 21
T (℃) 38.3
SpO2 (%) 93-95
Flow rate (L/min) RA
Day 5 post-admission: fever and dry cough.
No shortness of breath.

19. Hospital Course
Day 1, 28/10 Day 5, 01/11 Day 6, 2/11 Day 7, 3/11 Day 14 10/11 Day 16, 12/11
Admission Worsening CXR
Sats RA 93-95%
ABG Type 1
Respiratory Failure
Increasing CRP,
Ferritin and D-
Dimer. Lower
Procalcitonin
Negative Multiplex,
Sputum culture
• Enoxaparin 40 mg
Subcut OD
• Aspirin 81 mg OD
• Vitamin C 1000 mg
OD, Vitamin D 50,000
units weekly and Zinc
Sulphate 100 mg OD
• Ceftriaxone 1 gm OD
and Azithromycin 500
mg OD
• Serial CRP, d-Dimer,
Procalcitonin
• CRP 98 on admission
Dexamethasone
Started
Shifted to Tazocin
(Piperacillin/
Tazobactam) 4.5
gm 6 hrly &
Doxycycline 100
mg 12 hrly
CRP143 on Day 5
Procalcitonin 241.7
CRP 152 on Day 6
Procalcitonin 99.1

21. Hospital Course
Day 1, 28/10 Day 5, 01/11 Day 6, 2/11 Day 7, 3/11 Day 14 10/11 Day 16, 12/11
Admission Worsening CXR
Sats RA 93-95%
ABG Type 1
Respiratory Failure
Increasing CRP,
Ferritin, D-Dimer
and Procalcitonin
Significant
improvement of
CRP, Procalcitonin
and d-Dimer
• Enoxaparin 40 mg
Subcut OD
• Aspirin 81 mg OD
• Vitamin C 1000 mg
OD, Vitamin D 50,000
units weekly and Zinc
Sulphate 100 mg OD
• Ceftriaxone 1 gm OD
and Azithromycin 500
mg OD
• Serial CRP, d-Dimer,
Procalcitonin
• CRP 98 on admission
Dexamethasone
Started
Shifted to Tazocin
4.5 gm 6 hrly &
Doxycycline 100
mg 12 hrly
CRP143 on Day 5
Procalcitonin 241.7
CRP 152 on Day 6
Procalcitonin 99.1
CRP 76 on Day 7
Procalcitonin 41.0

22. Day 4 Day 6 Day 8

23. A CT Cut from the CTPA: Classic
peripheral Ground Glass Opacification
GGO.

24. Hospital Course
Day 1, 28/10 Day 5, 01/11 Day 6, 2/11 Day 7, 3/11 Day 14 10/11 Day 16, 12/11
Admission Worsening CXR
Sats RA 93-95%
ABG Type 1
Respiratory Failure
Increasing CRP,
Ferritin, D-Dimer
and Procalcitonin
Significant
improvement of
CRP, Procalcitonin
and d-Dimer
Significant
improvement
/normalization of
CRP, Procalcitonin
but increasing d-
Dimer
PE on CTPA
• Enoxaparin 40 mg
Subcut OD
• Aspirin 81 mg OD
• Vitamin C 1000 mg
OD, Vitamin D 50,000
units weekly and Zinc
Sulphate 100 mg OD
• Ceftriaxone 1 gm OD
and Azithromycin 500
mg OD
• Serial CRP, d-Dimer,
Procalcitonin
• CRP 98 on admission
Dexamethasone
Started
Shifted to Tazocin
4.5 gm 6 hrly &
Doxycycline 100
mg 12 hrly
Shifted to
Therapeutic Dose
Enoxaparin
CRP143 on Day 5
Procalcitonin 241.7
CRP 152 on Day 6
Procalcitonin 99.1
CRP 76 on Day 7
Procalcitonin 41.0
CRP 6 on Day 14
Procalcitonin 0.35

25. Hospital Course
Day 1, 28/10 Day 5, 01/11 Day 6, 2/11 Day 7, 3/11 Day 14 10/11 Day 16, 12/11
Admission Worsening CXR
Sats RA 93-95%
ABG Type 1
Respiratory Failure
Increasing CRP,
Ferritin, D-Dimer
and Procalcitonin
Significant
improvement of
CRP, Procalcitonin
and d-Dimer
Significant
improvement
/normalization of
CRP, Procalcitonin
but increasing d-
Dimer
PE on CTPA
Improved d-Dimer
• Enoxaparin 40 mg
Subcut OD
• Aspirin 81 mg OD
• Vitamin C 1000 mg
OD, Vitamin D 50,000
units weekly and Zinc
Sulphate 100 mg OD
• Ceftriaxone 1 gm OD
and Azithromycin 500
mg OD
• Serial CRP, d-Dimer,
Procalcitonin
• CRP 98 on admission
Dexamethasone
Started
Shifted to Tazocin
4.5 gm 6 hrly &
Doxycycline 100
mg 12 hrly
Shifted to
Therapeutic Dose
Enoxaparin
Discharged
CRP143 on Day 5
Procalcitonin 241.7
CRP 152 on Day 6
Procalcitonin 99.1
CRP 76 on Day 7
Procalcitonin 41.0
CRP 6 on Day 14
Procalcitonin 0.35
CRP 5,
Procalcitonin 0.19
on Day of
discharge
(Shifted to
Apixaban in OPD)
Minimal clinical issues (No SOB, Chest pains or Fever). Major issues were troublesome dry
cough –managed with dextromethorphan -and later on steroid-induced hyperglycemia.

26. Day 2 Day 4 Day 6 Day 7 Day 8 Day 9 Day 10 Day 11 Day 12 Day 13 Day 14 Day 15 Day 16
D-Dimer (mcg/mL) *100 47 96 79 61 54 49 53 64 67 69 94 71 73
CRP (mg/L) 98 143 152 76 24 33 15 10 7 6 5 5
Procalcitonin (ng/mL) 0.18 241.75 99.06 42.03 12.71 4.69 2.06 1.09 0.64 0.52 0.35 0.26 0.19
47
96
79
61
54
49
53
64
67 69
94
71 73
98
143
152
76
24
33
0
15
10
7 6 5 5
0.18
241.75
99.06
42.03
12.71
4.69 2.06 1.09 0.64 0.52 0.35 0.26 0.19 0
20
40
60
80
100
120
140
160
0
50
100
150
200
250
300
Trends of Inflammatory Markers on the Different
Antibiotic Regimes in Covid Pneumonia
On Ceftriaxone
& Azithromycin
Day 1-5
On Tazocin
& Doxycycline
Day 6-12
Dexa started
Day 5
Bilateral Leg
Doppler
Day 13
-Ve
CTPA
Day 14
+Ve

27. Lesson 1
Use Covid-19 Scoring Tools
4C Mortality Score: 8 (intermediate
risk, 9.1-9.9% in-hospital mortality)
https://www.mdcalc.com/4c-
mortality-score-covid-19
ISARIC Coronavirus Clinical
Characterization Consortium (ISARIC-
4C).
Curb-65
Score does
not apply to
Covid-19
Pneumonia!

28. Lesson 2
Studies on Azithromycin with
Chloroquine are mostly negative.
 Increased Mortality from Chloroquine/Azithromycin:
Effect of hydroxychloroquine with or without azithromycin on the mortality of
coronavirus disease 2019 (COVID-19) patients: a systematic review and meta-
analysis. T Fiolet, A Guihur, ME Rebeaud… - Clinical …, 2020 – clinical
microbiology and infection …
 No benefit from Azithromycin
Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19.
AB Cavalcanti, FG Zampieri, RG Rosa… - … England Journal of …, 2020 - Mass
Medical Soc
Azithromycin
(with
Ceftriaxone)
likely not a
useful agent
for COVID-19!

29. Lesson 3
“Pulse oximetry should not replace
analysis of an arterial blood gas sample in
the clinical evaluation of oxygenation in
emergency patients”.Pulse
Oximetry
may be
misleading!
Above 92%:
more likely
to miss
hypoxemic
patients! A highly specific test means that there are few false
positive results i.e. correctly diagnose hypoxemia!

30. Lesson 3
“Silent Hypoxia”:
Severe hypoxia with no increased work of
breathing or symptoms specially in the
elderly!
Covid-19 is
different!

31. Lesson 4
Regular Dose
Prophylactic
anticoagulation
is not always
enough in
Covid-19
infection!

32. Lesson 4 We recommend that low-molecular
weight heparin be administered at twice
the normal prophylactic dose.
Thomboprophylaxis administration
should be guided by careful consideration of
the competing risks of thrombosis and
bleeding.
Regular Dose
Prophylactic
anticoagulation
is not always
enough in
Covid-19
infection!

33. Lesson 5 Have a high index of suspicion for the presence of
deep venous or pulmonary vascular
thromboembolism and investigate urgently where
clinical suspicion is raised, e.g. if a sudden
deterioration in gas exchange occurs, or if D-
dimers remain elevated or show a stepwise rise.
A rising d-Dimer with improving CRP is an
indication/ marker of active thrombosis!
Serial d-Dimer
(and CRP) tests
are essential in
patient
monitoring!

34. Lesson 6
CRP improved as well as Ferritin and
Procalcitonin.
D-Dimer kept rising!
Anticardiolipin Ab (Antiphospholipid Ab)
ACA IgM was POSITIVE in our patient!
The
pathophysiology
of hyper-
coagulability is
probably
different from
the
inflammatory
process!

35. Lesson 7 Although these phases represent
a continuum of disease, the varied behavior
observed in certain phases may lend
themselves to time-sensitive tailored
therapies.
Non-timely or delayed stage-specific
therapeutic interventions worsen the
outcome: e.g. early steroid therapy or
delayed antiviral therapy.
Covid-19
infection is a
“Phasic
Disease”: Close
Monitoring and
Stage-Specific
interventions
are mandatory!

37. Lesson 7
Pre-clinical Phase: Post-exposure, viral
replication phase
Average duration (Incubation): 5 days, 1-14 days.
Clinical Phase:Covid-19
infection is a
“Phasic
Disease”: Close
Monitoring and
Stage-Specific
interventions
are mandatory!
Stage 1
• Viral Infection +/-Interstitial Pneumonia-1st 5-7 days (Hospital admission
usually day 7 onward!).
Stage 2
• Hyper-inflammation: Following 5-10 Days i.e. second week.
(Immunopathology)/ARDS, Cytokine Storm etc.
Stage 3
• Hypercoagulability: third week on-wards.
Stage 4
• Post-Covid-19 Syndrome (Long COVID).

38. Guy's and St. Thomas' NHS Foundation Trust Severe
Respiratory Failure (SRF) Centre, UK

41. Hemophagocytic SyndromeThrombotic Microangiopathy
Antiphospholipid Syndrome
Sepsis-Induced Coagulopathy
Disseminated Intravascular
Coagulation

42. Incubation
Period
Pre-clinical
(Replication)
Viral Infection
Hyper-
inflammation
Coagulopathy
Post-Covid-19
Syndrome
Community
Community/
General Ward
General ward ICU
Hospital or
Community
Asymptomatic
RT-PCR +VE or
-VE
Flu symptoms
+/- Pneumonia
RT-PCR +VE
High CRP &
other
Inflammatory
Markers e.g.
IL-6
Progressive
Pneumonitis
Desaturation
High or
Increasing d-
Dimer
+ve Doppler,
CTPA
Multiorgan
Failure
Residual Organ
Dysfunction
Pre-clinical Phase Stage 1 Stage 2 Stage 3 Stage 4

43. Question 1 CRP Level mirrors the lung disease severity
and prognosis.
Low CRP levels in patients not requiring
oxygen (mean 11 mg/L, interquartile range 1-
20 mg/L) compared to patients who became
hypoxemic (mean 66 mg/L, interquartile
range 48-98 mg/L).
 Early changes in laboratory parameters are predictors of mortality and ICU admission in patients with
COVID-19: a systematic review and meta-analysis. Med Microbiol Immunol. 2020 Nov 21:1-15. Kiss S
et al.
 Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore. JAMA.
2020 Apr 21;323(15):1488-1494. Young BE et al.
Can we use the
CRP as a
surrogate
marker for
starting
steroids?

44. Question 1
 Two studies confirmed that CRP-Guided steroid
initiation was associated with improved outcome.
 Initiation when levels are low is associated with worse
outcome.
 In the Recovery Trial initiation in ward patients not
requiring O2 was non-beneficial. The benefit was
greatest in patients with symptoms for more than 7
days and patients who required mechanical
ventilation.
Effect of Systemic Glucocorticoids on Mortality or Mechanical Ventilation in Patients With COVID-19. MJ Keller, EA Kitsis, S Arora, JT
Chen… - Journal of hospital …, 2020 - europepmc.org
Comparison of efficacy of dexamethasone and methylprednisolone in moderate to severe covid 19 disease. SA Fatima, M Asif, KA
Khan, N Siddique… - Annals of Medicine and …, 2020 - Elsevier
Can we use the
CRP as a
surrogate
marker for
starting
steroids?

45. Question 2
1. Steroid
2. Vitamin D
3. Doxycycline
4. Tazocin
5. All
What brought
the CRP Down?
The MCQ!

46. Question 2
1. Steroid: Yes
2. Vitamin D= ?
3. Doxycycline= Yes
4. Tazocin=Yes
5. All=?
What brought
the CRP Down?
The MCQ!

47. Question 3  Doxycycline is well known to inhibit metalloproteinases
(MMPs), in particular MMP-9, which is likely required
for initial viral entry into the cell.
 Doxycycline inhibits interleukin (IL)-6, with both IL-6
and MMPs key regulators of the ‘cytokine storm’ often
associated with severe viral pneumonitis.
 Doxycycline is an established ionophore, helping
transport zinc intracellularly, with increased cellular
concentrations of zinc shown in vitro to inhibit
coronavirus replication.
Doxycycline &
Covid-19
Infection:
Potential
Benefit-Antiviral
& Anti-
inflammatory
Effects!

48. Question 3  Doxycycline inhibits nuclear factor (NF)-κB, which
may lower risk of viral entry due to direct inhibition
of DPP4 cell surface receptor and diminish a
hyperactive immune response following infection.
 In vitro antiviral activity of doxycycline against SARS-CoV-2. M
Gendrot, J Andreani, P Jardot, S Hutter, O Delandre… -
Molecules, 2020 - mdpi.com
 Dengue patients treated with doxycycline showed lower
mortality associated to a reduction in IL-6 and TNF levels. TM
Fredeking, JE Zavala-Castro… - Recent patents on …, 2015 -
ingentaconnect.com
Doxycycline &
Covid-19
Infection:
Potential
Benefit-Antiviral
& Anti-
inflammatory
Effects!

49. Question 3
 Doxycycline treatment of high-risk COVID-19-positive patients with
comorbid pulmonary disease. PA Yates, SA Newman, LJ Oshry… - Therapeutic
…, 2020 - journals.sagepub.com
 Clinical outcomes of early treatment with doxycycline for 89 high-risk COVID-
19 patients in long-term care facilities in New York. MM Alam, S Mahmud,
MM Rahman, JA Simpson… - Cureus, 2020 - ncbi.nlm.nih.gov
 A case series of 100 COVID-19 positive patients treated with combination of
ivermectin and doxycycline. MT Alam, R Murshed, E Bhiuyan, S Saber… -
Journal of Bangladesh …, 2020 - banglajol.info
 A novel approach to managing COVID-19 patients; results of lopinavir plus
doxycycline cohort. Y Cag, S Icten, B Isik-Goren, NB Baysal… - European
Journal of …, 2020 – Springer
Doxycycline &
Covid-19
Infection:
Publications
with Positive
outcomes.

50. Question 3 NICE National Institute for Health and Care Excellence
(NICE)
 NICE has already designated Doxycycline as the treatment of
choice for community acquired pneumonia (mild-moderate
and severe), during the COVID-19 pandemic.
https://www.nice.org.uk/guidance/ng165/chapter/4-Managing-suspected-or-confirmed-
pneumonia
 Doxycycline is preferred because it has a broader spectrum of cover
than amoxicillin, particularly against Mycoplasma pneumoniae and
Staphylococcus aureus, which are more likely to be secondary bacterial
causes of pneumonia during the COVID-19 pandemic. [amended 23
April 2020]
Doxycycline &
Covid-19
Infection:
NICE
Recommendation.

51. Question 4 Metanalysis confirmed the strong association
between Vitamin D Deficiency and Acute
Respiratory Infections and Community
Acquired Pneumonia.
 The association between vitamin D deficiency and community-acquired
pneumonia: A meta-analysis of observational studies. Zhou YF, Luo BA,
Qin LL. Medicine (Baltimore). 2019 Sep;98(38).
 Int J Environ Res Public Health . 2019 Aug 21;16(17):3020. Acute
Respiratory Tract Infection and 25-Hydroxyvitamin D Concentration: A
Systematic Review and Meta-Analysis. Hai Pham et al.
Vitamin D &
Covid-19
Infection:
Rationale for
use for
Prevention.

52. Question 4
Through its interactions with a multitude of cells,
vitamin D may have several ways to reduce the risk of
acute respiratory tract infections and COVID-19:
 activation by immune cells and enhancement of
immune function,
 reducing the survival and replication of viruses,
 reducing risk of inflammatory cytokine production,
 increasing angiotensin-converting enzyme 2
concentrations, and
 maintaining endothelial integrity.
Vitamin D &
Covid-19
Infection:
Rationale for
use for
Prevention.

53. Question 4 Fourteen observational studies
offer evidence that serum 25-
hydroxyvitamin D concentrations
are inversely correlated with the
incidence or severity of COVID-19.
 Nutrients. 2020 Nov; 12(11): 3361. Evidence Regarding
Vitamin D and Risk of COVID-19 and Its Severity. Joseph
Mercola et al.
Vitamin D &
Covid-19
Infection:
Rationale for
use for
Prevention.

54. The “intriguing” similarity between Corvid-19 Pathophysiology & Vitamin D Deficiency Pathogenic Effects!

55. Question 4
Vitamin D has been shown to reduce IL-6 Level (a
prognostic marker for severity and death in Covid-
19 infection) in both ward as well as in ICU
settings.
No effect on CRP in previous non-Covid-19
infection!
 Effects of High-Dose Vitamin D Replacement on the Serum Levels of Systemic Inflammatory
Biomarkers in Patients with Acute Exacerbation of Chronic Obstructive … F Dastan, J Salamzadeh, MH
Pourrashid… - COPD: Journal of …, 2019 - Taylor & Francis.
 The study of vitamin D administration effect on CRP and Interleukin-6 as prognostic biomarkers of
ventilator associated pneumonia. AE Miroliaee, J Salamzadeh, S Shokouhi… - Journal of critical care,
2018 – Elsevier.
Vitamin D &
Covid-19
Infection:
Rationale: The
Cytokine
connection.

56. Question 4
 Vitamin D level is markedly low in severe COVID-19
patients.
 Inflammatory response is high in vitamin D deficient
COVID-19 patients.
 This all translates into increased mortality in vitamin D
deficient COVID-19 patients.
 As per the flexible approach in the current COVID-19
pandemic authors recommend mass administration of
vitamin D supplements to population at risk for COVID-19.
 Sci Rep . 2020 Nov 19;10(1):20191. Analysis of vitamin D level among asymptomatic
and critically ill COVID-19 patients and its correlation with inflammatory markers.
Anshul Jain et al.
Vitamin D &
Covid-19
Infection:
Prevention.

57. Question 4
In a cohort of almost 200,000 patients, SARS-
CoV-2 positivity is strongly and inversely
associated with circulating 25(OH)D levels, a
relationship that persists across latitudes,
races/ethnicities, both sexes, and age ranges.
Our findings provide impetus to explore the
role of vitamin D supplementation in
reducing the risk for SARS-CoV-2 infection
and COVID-19 disease.
PLoS One . 2020 Sep 17;15(9). SARS-CoV-2 positivity rates associated with circulating 25-
hydroxyvitamin D levels. Harvey W Kaufman et al.
Vitamin D &
Covid-19
Infection:
Prevention.

58. Question 4  Interpretation
Vitamin D deficiency is a risk factor for COVID-19
seroconversion for NHS healthcare workers especially in
Blacks, Asian, Minority Ethnic BAME male staff.
 Conclusion
The available evidence demonstrate vitamin D
supplementation in individuals at risk of vitamin D
deficiency or shown to be deficient may help alleviate the
impact of COVID-19.
Eur Respir J . 2020 Dec 10;2004234. Vitamin D status and seroconversion for
COVID-19 in UK healthcare workers. Aduragbemi A Faniyi et al.
Vitamin D &
Covid-19
Infection:
Prevention.

59. Question 4
High-Dose Cholecalciferol Booster Therapy is Associated with a Reduced
Risk of Mortality in Patients with COVID-19: A Cross-Sectional Multi-
Centre Observational Study
Aim:
We aimed to determine whether COVID-19 mortality was affected by
……………cholecalciferol therapy, and to elucidate any other predictors of COVID-
19 mortality.
Population
A total of 986 participants with COVID-19 were studied, of whom 151 (16.0%)
received cholecalciferol booster therapy.
Outcome:
In this observational study, treatment with cholecalciferol booster therapy (pre-
admission), appears to be associated with a reduced risk of mortality in acute
in-patients admitted with COVID-19. This finding was replicated in a validation
cohort of 541 patients.
High-Dose Cholecalciferol Booster Therapy is Associated with a Reduced Risk of Mortality in Patients with COVID-19:
A Cross-Sectional Multi-Centre Observational Study. Ling SF et al. Nutrients. 2020 Dec 11;12(12):E3799.
Vitamin D &
Covid-19
Infection:
Evidence for
Preventative
Benefit:
Reducing
Mortality.

60. Question 4
High-Dose Cholecalciferol Booster Therapy is Associated with a Reduced
Risk of Mortality in Patients with COVID-19: A Cross-Sectional Multi-
Centre Observational Study-Majority were on 40,000 units per week.
High-Dose Cholecalciferol Booster Therapy is Associated with a Reduced Risk of Mortality in Patients with COVID-19:
A Cross-Sectional Multi-Centre Observational Study. Ling SF et al. Nutrients. 2020 Dec 11;12(12):E3799.
Vitamin D &
Covid-19
Infection:
Evidence for
Therapeutic
Benefit:
Reducing
Mortality.

61. Question 4 Vitamin D Supplementation Associated to Better Survival
in Hospitalized Frail Elderly COVID-19 Patients: The
GERIA-COVID Quasi-Experimental Study
Objective:
The objective of this quasi-experimental study was to determine whether
bolus vitamin D supplementation taken either regularly over the preceding
year or after the diagnosis of COVID-19 was effective in improving survival
among hospitalized frail elderly COVID-19 patients.
Conclusions.
Regular bolus vitamin D supplementation was associated with less
severe COVID-19 and better survival in frail elderly.
Vitamin D Supplementation Associated to Better Survival in Hospitalized Frail Elderly COVID-19 Patients:
The GERIA-COVID Quasi-Experimental Study. Annweiler G, et al. Nutrients. 2020 Nov 2;12(11):3377.
Vitamin D &
Covid-19
Infection:
Evidence for
Therapeutic
Benefit:
Reducing
Mortality.

62. Question 4
• Vitamin D &
Covid-19
Infection:
Treatment:
• Reducing
CRP, IL-6 and
less hypoxia.

63. Question 4  Aim/Design: Effect of high dose, oral cholecalciferol supplementation
on SARS-CoV-2 viral clearance. Randomized, placebo-controlled.
 Participants: Asymptomatic or mildly symptomatic SARS-CoV-2 RNA
positive vitamin D deficient (25(OH)D<20 ng/ml) individuals.
 Intervention: Participants were randomized to receive daily 60 000 IU
of cholecalciferol (oral nano-liquid droplets) for 7 days with therapeutic
target 25(OH)D>50 ng/ml (intervention group) or placebo (control
group).
 Conclusion: Greater proportion of vitamin D-deficient individuals with
SARS-CoV-2 infection turned SARS-CoV-2 RNA negative with a
significant decrease in fibrinogen on high-dose cholecalciferol
supplementation. No toxicity was noted.
Postgrad Med J . 2020 Nov 12;postgradmedj-2020-139065. Short term, high-dose vitamin D supplementation for COVID-19 disease:
a randomized, placebo-controlled, study (SHADE study). Ashu Rastogi et al.
Vitamin D &
Covid-19
Infection:
Prevention &
Treatment:
Reducing the
duration of Viral
Shedding! ?Less
infectivity
duration.

64. Question 4
 Results: Of 50 patients treated with calcifediol, one
required admission to the ICU (2%), while of 26 untreated
patients, 13 required admission (50 %) p value X2 Fischer
test p < 0.001.
 Conclusion: Our pilot study demonstrated that
administration of a high dose of Calcifediol or 25-
hydroxyvitamin D, a main metabolite of vitamin D
endocrine system, significantly reduced the need for ICU
treatment of patients requiring hospitalization due to
proven COVID-19.
J Steroid Biochem Mol Biol 2020 Oct;203:105751. "Effect of calcifediol treatment and best
available therapy versus best available therapy on intensive care unit admission and mortality
among patients hospitalized for COVID-19: A pilot randomized clinical study“. Marta Entrenas
Castillo et al.
Vitamin D &
Covid-19
Infection:
Treatment:
Reducing ICU
admissions.

65. Question 5
 Results:
Four hundred twelve patients were included in the study. Age 41-66
years. After adjusting for 8 confounding variables, aspirin use was
independently associated with decreased risk of mechanical
ventilation (adjusted HR 0.56, 95% CI 0.37-0.85, p=0.007), ICU
admission (adjusted HR 0.57, 95% CI 0.38-0.85, p=0.005), and in-
hospital mortality (adjusted HR 0.53, 95% CI 0.31-0.90, p=0.02). There
were no differences in major bleeding (p=0.69) or overt thrombosis
(p=0.82) between aspirin users and non-aspirin users.
 Conclusions:
Aspirin use may be associated with improved outcomes in
hospitalized COVID-19 patients.
Aspirin use is associated with decreased mechanical ventilation, ICU admission, and in-hospital mortality in hospitalized patients
with COVID-19. JH Chow, AK Khanna, S Kethireddy… - Anesthesia & …, 2020 - journals.lww.com
Aspirin & Covid-
19 Infection:
Evidence

66. Incubation
Period
Pre-clinical
(Replication)
Viral Infection
Hyper-
inflammation
Coagulopathy
Post-Covid-19
Syndrome
Immuno-
stimulants
e.g.
Vitamin D
Zinc
Vitamin C
Black Seed
Honey
Antivirals
e.g.
*Anti-covid-19
Monoclonals
e.g.
Bamlanivimab
(not for
hospitalized
patients).
*Vitamin D
*Doxycycline
*Remdesivir
*Favipiravir
*Interferons
(IFN-α2b,
intramuscular or
nebulized)
*Convalescent
Plasma
Anti-
inflammatory
e.g.
*Steroids
*Vitamin D
*Doxycycline
*Tocilizumab
*Anakinra
(IL-1 Inhibitor)
*Baricitinib
(JAK Inhibitor)
Anticoagulants
e.g.
*Aspirin,
*Heparins
(Double dose
heparins in the
Ward,
Therapeutic in
ICU)
Supportive
Pre-clinical Phase Stage 1 Stage 2 Stage 3 Stage 4

68. Lessons Learnt
Curb-65 is not a reliable prognostic scoring tool in Covid-
19 Pneumonia.01
Pulse oximetry should not be “fully” relied on for the
detection of hypoxemia/ initiation of Steroids in Covid-19
Pneumonia.
02
CRP is potentially a surrogate marker for initiating
steroids.03
Higher dose prophylactic anticoagulation is preferable to
classic dosing.04

69. Lessons Learnt
Vitamin D should be used as both a preventative strategy
specially for high-risk individuals e.g. healthcare workers,
those above 50 years or with comorbidities as well as
therapeutically (daily dosing) to improve prognosis.
05 Aspirin ought to be considered in patients above the age
of 40 years.
06
07
Serial CRP and d-Dimer are essential for patient
monitoring.

70. Lessons Learnt
Management should be Stage-specific (Precision
Medicine) BOTH preventatively and therapeutically guided
by the clinical picture and biomarkers.
08
09
Multifaceted combination therapy is needed to improve
prognosis in high-risk or hospitalized patients.
Doxycycline is a potential re-purposed therapy that may
be beneficial as an alternative to Azithromycin/
Respiratory quinolones in CAP antibiotic cover as both an
antibiotic (antiviral/antibacterial) and an anti-
inflammatory agent.
10

71. Future Directions
Doxycycline repurposing
studies: Retrospective &
Prospective

72. Pathogenesis-directed therapy
of 2019 novel coronavirus
disease.Stratton CW, Tang YW,
Lu H.J Med Virol. 2020 Oct 19.