COVID 19- Basics beyond Basics by Dr. Brij Teli

COVID-19: Basics Beyond Basics
COPINGTHE CORONA CRISIS
Dr. Brij Teli
M.D. Medicine
Aumkar Hospital
Rajkot (Gujarat)
June 21, 2020 (4:30-5:10 PM)
Contact: brijteli@rediffmail.com

Declaration
 We are Still in Evolving Phase of Pandemic
 We are yet to fully understand the disease.
 Last 4 months have been full of Guidelines
and Publications, apart fromWorkload.
 We all work tirelessly in COVID Units.
 What was TrueYesterday, may not be true
today & so On…
 Not an Expert Discourse, rather a session
on mutual sharing of Experience and
Knowledge.
21/6/2020 Dr. Brij Teli (MD Medicine)

Today’s Agenda
 What we Know over last 4 Months (in
Brief)
 Where we stand ?
 Clinical Implications (Evidence Based)
 Research: Papers,Trials & Controversies
 Way Ahead !

Declared Pandemic- March 11 2020

March19 2020- First Case Noted in
Gujarat

The Saga so Far
 Surge of an UnknownVirus, over a period of Months.
 Viral Posts and (Fake) News (WhatsApp University)
 Myths and Myth Busters.
 Public Private Partnerships like Never Before.
 Guidelines and Regulations(keeps Modifying)
 We saw Real Life Large Scale Applications of
Principles of Public Health (Contact Tracing, Cluster
Containment, Screening, Isolation/Quarantine, etc)
 Lockdowns & Unlocks
 An ERA of SOPs (for What NOT !)
 Transition of All Possible Activities to ONLINE Mode.

From
Face to Face Interactions
to
WEBINARS
TIME FLIES FAST

The Saga so Far (contd.)
 Trainings and (Epidemic of !) Webinars
 Newer Techniques and Practices (Hand
Washing, Sanitization & Disinfection, Masks &
FaceShields, Social Distancing, IPC Practices,
Donning/Doffing, Cough Etiquette, etc)
 Trials, Papers and Publications (along with its
controversies)
 Emerging Diagnostics & Therapeutics.
 Evolution of CoronaWarriors.
 Change in Way of Life (The New Normal)

What We Know about COVID-19 ?
(BASICS)
 EPIDEMIOLOGY
 ETIOPATHOLOGY
 Clinical Presentation & History
 Transmission
 Case Definitions
 Infection Prevention & Control (IPC)
 Testing Strategies & Procedures
 Basic Principles and Guidelines Used for COVID
Management (includingVentilatory Management)
 Management of CoMorbidity.
 So, we will focus on aspects other than as well as
beyond these…

MASKOLOGY

N vs R vs P 95/99/100
 Difference is in Resistance to Oily mists.
 This is indicated by a letter (N, R or P).
 N-class filters are not resistant to oil.
 R-class filters are oil-resistant, but they may
only be used against oily mists for up to
eight hours.
 P-class filters are oil-proof; usually lasts for
40 hours of use or 30 days, whichever
occurs first.
 R/P- Might be preferred for (?)Orthopedic
Surgeons, Dentists, ENT Surgeon (Bone Drill
involved)

Powered
Hood/Helmet

Half Facepiece Reusable Respirator with Filter
Filter to be changed
every 6 Months
Shelf Life- 5Years

Strategy for COVID19 testing in India
(ICMRVersion 5, dated 18/05/2020)
1. All symptomatic (ILI symptoms) individuals with history of international
travel in the last 14 days.
2. All symptomatic (ILI symptoms) contacts of laboratory confirmed cases.
3. All symptomatic (ILI symptoms) health care workers / frontline workers
involved in containment and mitigation of COVID19.
4. All patients of Severe Acute Respiratory Infection (SARI).
5. Asymptomatic direct and high-risk contacts of a confirmed case to be tested
once between day 5 and day 10 of coming into contact.
6. All symptomatic ILI within hotspots/containment zones.
7. All hospitalised patients who develop ILI symptoms.
8. All symptomatic ILI among returnees and migrants within 7 days
of illness.
9. No emergency procedure (including deliveries) should be delayed
for lack of test. However, sample can be sent for testing if indicated
as above (1-8), simultaneously.

 ILI case is defined as one with acute respiratory
infection with fever ≥ 38◦C AND cough.
 SARI case is defined as one with acute
respiratory infection with fever ≥ 38◦C AND
cough AND requiring hospitalization.
 All testing in the above categories is
recommended by real time RT-PCR test only.

Rapid Antigen DetectionTest for COVID-19
(14/06/2020)
 Standard Q COVID-19 Ag detection kit
 Qualitative Rapid Chromatographic
Immunoassay
 Developed by SD Biosensor, South Korea
 Manufactured in Manesar, Gurugram, India.

Standard Q COVID-19 Ag detection
 1 Nasopharyngeal swab collected, no other sample to be
used.
 Viral extraction buffer, provided with the kit is used, usual
VTM does not work
 Test to be conducted at the site of sample collection
within 1 hour
 Test interpreted positive or negative with naked eyes
after 15 minutes
 Evaluated and validated by ICMR & AIIMS Delhi
 Specificity: 99.3 to 100% (High)
 Sensitivity: 50.6% to 84% (Low)
P.S.: Rapid Antibody tests are not recommended for diagnosis of
COVID-19 infection

 Due to high specificity while relatively low
sensitivity, ICMR recommends the use of Standard Q
COVID-19 Ag detection assay as a point of care
diagnostic assay for testing in the following settings in
combination with the gold standard RT-PCR test:
 A. Containment zones or hotspots (to be performed
onsite under strict medical supervision and maintaining kit
temperature between 2° to 30° C.):
I. All symptomatic Influenza Like Illness (ILI).
II. Asymptomatic direct and high-risk contacts with
co-morbidities (lung disease, heart disease, liver disease,
kidney disease, diabetes, neurological disorders, blood
disorders) of a confirmed case to be tested once between day
5 and day 10 of coming into contact.

 B. Healthcare settings (to be performed onsite under
strict medical supervision and maintaining kit temperature
between 2° to 30° C):
I. All symptomatic ILI patients presenting in a
healthcare setting and are suspected of having
COVID19 infection.
II. Asymptomatic patients who are hospitalized or seeking
hospitalization, in the following high-risk groups:
❑ Patients undergoing chemotherapy
❑ Immunosuppressed patients including those who are HIV+;
❑ Patients diagnosed with malignant disease;
❑ Transplant patients;
❑ Elderly patients (>65 yrs of age) with co-morbidities (lung
disease, heart disease, liver disease, kidney disease, diabetes,
neurological disorders, blood disorders)
III. Asymptomatic patients undergoing aerosol
generating surgical / non-surgical interventions:
❑ Elective/emergency surgical procedures like neurosurgery,
ENT surgery, dental procedures;
❑ Non-surgical interventions like bronchoscopy, upper GI
endoscopy and dialysis;

 Use of the rapid antigen test is recommended in
A & B categories above subject to the following
conditions:
◦ i) Suspected individuals who test negative for COVID-19
by rapid antigen test should be definitely tested
sequentially by RT-PCR to rule out infection, whereas a
positive test should be considered as a true positive
and does not need reconfirmation by RT-PCR test.
◦ ii) Samples (only nasopharyngeal swabs) to be
collected by a trained healthcare worker following full
infection control practices including use of proper
PPE.
◦ iii)The test should be conducted onsite under strict
medical supervision and within one hour of sample
collection in extraction buffer.

COVID-19 Radiology
 Plain radiograph[CXR(PA)] is the
first-line imaging modality used for
patients with suspected COVID-
19.
 Less sensitive than chest CT.
 May be normal in early or mild
disease.
 Findings are most extensive about
10-12 days after symptom onset.
 The most frequent findings are:
◦ Airspace opacities, whether
described as consolidation or, less
commonly, GGO.
◦ The distribution is most often
bilateral, peripheral, and lower zone
predominant.
◦ In contrast to parenchymal
abnormalities, pleural effusion is
rare (3%) .

ROLE of CT THORAX
 CT does not add diagnostic value; positive results can only be believed if
the pre-test probability of disease is high.
 Using CT diagnostically is not known to provide clinical benefit and could
lead to false security if results are negative.
 If COVID-19 is suspected, patients should be isolated pending confirmation
with (multiple) RT-PCR tests, or until quarantine has lapsed.The results of a
CT scan do not change this.
 Plain CT is recommended.
 The severity of the lung involvement on the CT correlates with the
severity of the disease.
 Sensitivity: 60% to 98% and Specificity: 25% to 53%,
 The PPV: 92% and NPV: 42 in a population with high pretest probability for
the disease (e.g., 85% prevalence by RT-PCR)
 The relatively low NPV suggests that CT may not be valuable as a
screening test for COVID-19 at least in earlier stages of the disease.
 The CT-findings of COVID-19 show overlap with other diseases like: H1N1
influenza, Other viral pneumonia; adenovirus, CMV, Organizing pneumonia,
Acute interstitial pneumonitis. 21/6/2020 Dr. Brij Teli (MD Medicine)

CORADS 5

CORADS 6

CYTOKINE STORM

 Studies reported that several pro-inflammatory
cytokines and chemokines, were higher in the plasma of
COVID-19 patients especially in those requiring ICU
admission as compared to healthy controls & those in
which the infection was less severe and did not require an
ICU admission.
 Overproduction of early response ProInflammatory
Cytokines (IFNα, IFNγ, IL-1β, IL-6, IL-12, IL-18, IL-33,TNFα,
TGFβ) and Chemokines (CXCL10, CXCL8, CXCL9, CCL2,
CCL3, CCL5) results in Cytokine Storm.
 To complicate this, there is also an increased secretion
Th2-immune-oriented cytokines such as IL-4 and IL-10,
whose main effect is to suppress inflammation.
 Taken together, this cytokine storm is followed by the
immune system “attacking” the body, which in turn will
cause:
◦ ARDS
◦ Vascular Hyperpermeability
◦ MultiOrgan failure
◦ Death when the high cytokine concentrations are unabated over
time 21/6/2020 Dr. Brij Teli (MD Medicine)

 IL-6 plays a key role in the pathogenesis of the
cytokine storm owing to its pleiotropic
properties:
◦ It is produced by almost all stromal cells and B
lymphocytes,T lymphocytes, macrophages, monocytes,
dendritic cells, mast cells and other non-lymphocytic
cells, such as fibroblasts, endothelial cells, keratinocytes,
glomerular Mesangial cells and tumor cells.
◦ IL-6 production is increased by IL-1β and TNF- α.
◦ Virus-driven dose-dependent production of IL-6 from
bronchial epithelium activatesT helper 17 (TH17) cells
in the dendritic cell. (TH17 Helper T-Cells are pro-
inflammatory triggers of Cell Mediated Immunity)
 High serum IL-6 levels are suggested as predictors
for COVID-19 disease severity.
 Tocilizumab is a humanized anti-IL-6 receptor
IgG1 monoclonal antibody.

 Tocilizumab may be considered in patients with moderate disease (Off
label use) with progressively increasing oxygen requirements (status
over 24-48 hours and requiring >4-6 L/min O2) and in mechanically
ventilated patients (for ≤48 hours) not improving despite use of steroids.
 High clinical suspicion for cytokine release syndrome supported by
◦ Serum IL-6 ≥3 x upper normal limit
◦ Ferritin >300 ug/L (or surrogate) with doubling within 24 hours
◦ Ferritin > 600 ug/L at presentation with LDH >250
◦ CRP > 100 mg/L with doubling within 24 hours.
◦ Elevated D-dimer (>1 mg/L).
 Patients should be carefully monitored postTocilizumab for secondary
infections and neutropenia.
 Active infections andTuberculosis should be ruled out before use.
 Dose: 8mg/kg (maximum 800 mg at one time) given IV slowly in 100 ml
NS over 1 hour; dose can be repeated once after 12 to 24 hours if
needed.

Steroids
 There has been controversy regarding whether
corticosteroid use may delay viral clearance in patients
with viral pneumonia for a long time.
 Initial studies for MERS and Influenza A (H7N9) viral pneumonia
has demonstrated that high doses of corticosteroids (>150 mg/d
MPS) are associated with increased risks of mortality and delayed
viral clearance, while there was no difference between patients in
the low-dose group (25–150 mg/d MPS) and controls.
 Initial COVID-19 Observational studies demonstrated
beneficial outcomes if given early in patients with moderate
disease.
 Hence, initial recommendations include Inj. MPS :-
 In Moderate disease- 0.5-1 mg/kg IV for 3 days in two
divided doses (preferably within 48 hours of
admission or if oxygen requirement is increasing and if
inflammatory markers are increased)
 In Severe disease- 1to 2mg/kg for 5 to 7 days in two
divided doses, if not already given

What’s it with Dexamethasone ?

 IV as well as Oral Dexamethasone reduced the
28-day mortality rate by 17% amongst
hospitalized patients who required ventilatory
support or oxygenation.
 Benefit was NOT seen for patients who did not
require oxygen.
 In the UK, Dexamethasone has been approved
for all hospitalized patients with COVID-19
requiring Oxygen (includingVentilated ones)

RECOVERYTRIAL
 UK based large, randomised controlled trial of
possible treatments for patients admitted to NHS
hospitals with COVID-19.
 Still Ongoing & only preliminary unpublished reports
are out. (Keep a watch on Updates)
 It studies the following:-
◦ Lopinavir-Ritonavir
◦ Low-dose Dexamethasone
◦ Hydroxychloroquine (which has now been stopped due
to lack of efficacy)
◦ Azithromycin
◦ Tocilizumab
◦ Convalescent plasma (collected from donors who have
recovered from COVID-19 and contains antibodies
against the SARS-CoV-2 virus).

COVID-19-Associated Coagulopathy
(CAC)
 A picture distinct from but with Overlapping
Pathophysiology to DIC.
 Hypercoagulable State (like Compensated DIC)
 Major Clinical finding in CAC is Thrombosis, while
in Acute Decompensated DIC is Bleeding.
 Lab Findings may include:-
◦ PT/aPTT: Normal or Slightly
◦ Platelets: Normal or (sometimes decrease)
◦ Fibrinogen (low in DIC)
◦ D-Dimer (like DIC & correlates with Disease
severity)
◦ High FactorVIII activity and VWF.

 Activation of coagulation pathways occur during
CYTOKINE STORM.
 Thrombin generation appears to be the key
determinant of the thromboinflammatory response
extent.
 Thrombin apart from being ProThrombotic, also
exerts multiple cellular effects and can further
augment inflammation.
 Endothelial damage as well as activation of hemostatic
components cause this prothrombotic picture.
 Microvascular thrombi impair the blood flow all over
the body, with a vascular shunt due to capillary
obstruction.
 This determines hypoxia and tissue dysfunction at
several organs, being the lung the more affected one.

 Prophylactic doses of (LMWH) are recommended in most medical
patients admitted to the hospital.
 Recent studies suggest the benefit of the anticoagulation in
severely ill COVID-19 patients, with an important reduction in
mortality.
 LMWH also has anti-inflammatory properties that might be
beneficial in COVID-19.
 A new paradigm for increasing the dose of LMWH could be
proposed with following considerations:
◦ All COVID-19 patients admitted to the hospital must be assessed on
their thrombotic and hemorrhagic risk.
◦ Unless contraindicated, LMWH at prophylactic dose must be
administered.
◦ When the pro-coagulant profile is confirmed, an extended or
intermediate dose of LMWH should be considered, mainly in patients
admitted to an ICU.
◦ In the case of severe disease progression, with maintained high pro-
coagulant parameters or highVTE suspicion, mainly if a certain
diagnosis is not possible, the increase of the LMWH dose up to
therapeutic one should be considered.
◦ Therapeutic anticoagulation with LMWH should be the standard
treatment when the diagnosis of any thrombotic event is confirmed.

Total SOFA in Sepsis Induced
Coagulopathy

SIC SCORE

MOHFW- 13/06/2020

The Controversial H Drug-
HydroxyChloroQuine
 HCQ has demonstrated in vitro activity
against SARS-CoV2 and was shown to be
clinically beneficial in several small single
center studies though with significant
limitations.
 Large observational studies with severe
methodologic limitations have shown no
effect on mortality or other clinically
meaningful outcomes.
 Many Ongoing Studies:
◦ For Antiviral Role (with or without Azithromycin)
◦ For Chemoprophylaxis (Pre and Post Exposure)
 HCQ has already seen its share of
controversies.

 We have concluded that there is no beneficial
effect of hydroxychloroquine in patients
hospitalised with COVID-19.We have therefore
decided to stop enrolling participants to the
hydroxychloroquine arm of the RECOVERY
Trial with immediate effect.

“While additional clinical trials continue to evaluate the
potential benefit of these drugs in treating or preventing
COVID-19, we determined the emergency use authorization
was no longer appropriate.This action was taken following a
rigorous assessment by scientists in our Center for Drug
Evaluation and Research”

 This randomized trial did not demonstrate a
significant benefit of hydroxychloroquine as
postexposure prophylaxis for Covid-19.Whether
pre- exposure prophylaxis would be effective in
highrisk populations is a separate question, with
trials ongoing.

 Currently in India(recommended with monitoring):-
◦ For Rx of Mild & Moderate COVID-19 infections (13-06-20)
◦ For Prophylaxis in (22-05-20):-
 Asymptomatic Healthcare Workers (COVID + NON-COVID)
 Asymptomatic Frontline Workers (COVID Related)
 Asymptomatic household contacts of laboratory confirmed cases.

 Remdesivir was superior to placebo in shortening the time to recovery in
adults hospitalized with Covid-19 and evidence of lower respiratory tract
infection.(11 days vs 15 days)
 Remdesivir may be considered in patients with moderate disease (those
on oxygen) with none of the following contraindications:
◦ AST/ALT >5 times Upper limit of normal (ULN)
◦ Severe renal impairment (i.e., eGFR <30ml/min/m2 or need for hemodialysis)
◦ Pregnancy or lactating females
◦ Children (< 12 years of age)
(Under Emergency Use Authorization only)
 Dose: 200 mg IV on day 1 followed by 100 mg IV daily for 5 days

JUNE 3, 2020
 Among patients with severe or life-threatening COVID-19, convalescent
plasma therapy added to standard treatment, compared with standard
treatment alone, did not significantly improve the time to clinical
improvement within 28 days.
 IN INDIA, Convalescent plasma (Off Label) may be considered in
patients with moderate disease who are not improving (oxygen
requirement is progressively increasing) despite use of steroids.
 Special prerequisites while considering convalescent plasma include:
◦ ABO compatibility and cross matching of the donor plasma
◦ Neutralizing titer of donor plasma should be above the specific threshold (if the
latter is not available, plasma IgG titer (against S-protein RBD) above 1:640
should be used)
◦ Recipient should be closely monitored for several hours post transfusion for any
transfusion related adverse events
◦ Use should be avoided in patients with IgA deficiency or immunoglobulin allergy
 Dose: Variable ranging from 4 to 13 ml/kg (usually 200 ml single dose given
slowly over not less than 2 hours)

Early Self‐Proning in Awake,
Non‐intubated Patients
 Any COVID-19 patient with respiratory
embarrassment severe enough to be admitted to the
hospital may be considered for rotation and early
self-proning.
 Care must be taken to not disrupt the flow of
oxygen during patient rotation
 Typical protocols(NIH) include 30–120 minutes in
prone position, followed by 30–120 minutes in left
lateral decubitus, right lateral decubitus, and
upright sitting position
(Caputo ND, Strayer RJ, Levitan R.Academic Emergency Medicine 2020;27:375–378)

THE WAY AHEAD…
 It would still take years to develop full
understanding about COVID-19.
 Our current Concepts might evolve over
time.
 The Way ahead is Keeping an Eye on the
Progress in terms of Vaccines,
InvestigationalTherapies, as well as other
Management Aspects and Apply it in the
Best interests of the Patients…

VACCINES

Therapies Under Trial
 Lopinavir/Ritonavir (HIV Protease Inhibitors)
 Favipiravir (inhibits RNA-dependent RNA polymerase),
also in combination with Umifenovir
 Peginterferon Alfa-2a, IFN Beta-1a, IFN Beta-1b
 Baricitinib (Janus Kinase Inhibitor)
 Anakinra (IL-1 inhibitors)
 Sarilumab & Siltuximab (IL-6 inhibitors)
 Non-SARSCoV-2 Specific IVIG
 Monoclonal Antibody 47D11 (against SARSCoV2)
 Gimsilumab (IV antibody to GM-CSF)
 MultiStem (Stem cell based)
 Others: Azithromycin, Ivermectin, Nitazoxanide,
Doxycycline, CHQ,Vit-C,Vit-D, Zinc, BCGVaccine,
Oseltamivir, Montelukast, etc. 21/6/2020 Dr. Brij Teli (MD Medicine)

 Oral AntiViral (Fabiflu)
 Approval for Mild to
Moderate COVID-19
patients.
 For restricted Emergency
use in India.
 Every patient(age 18-75)
must have signed
informed consent before
treatment initiation.

Reliable Sources
(Today’s References)
Dr. Brij Teli (MD Medicine)21/6/2020
 Indian Guidelines and Updates:
◦ https://www.mohfw.gov.in/
◦ https://www.icmr.nic.in/
◦ https://ncdc.gov.in/index.php
◦ https://idsp.nic.in/
 International Guidelines and Updates:
◦ https://www.who.int/
◦ https://www.nih.gov/coronavirus
◦ https://www.coronavirus.gov/
◦ https://www.cdc.gov/
◦ https://coronavirus.jhu.edu/#covid-19-basics
 Clinical Trials and Publications:
◦ https://www.ncbi.nlm.nih.gov/research/coronavirus/
◦ https://covid-trials.org/
◦ https://clinicaltrials.gov/
◦ https://www.clinicaltrialsregister.eu/

ULTIMATELY

THANKYOU
WE DEFEATED SWINE FLU
WE SHALL DEFEAT CORONA TOO
JAI HIND
Join «COVID 19 Research Outreach India» on
Telegram: https://t.me/covindia

COVID 19- Basics beyond Basics by Dr. Brij Teli

Recommended

Recommended

More Related Content

Similar to COVID 19- Basics beyond Basics by Dr. Brij Teli

Similar to COVID 19- Basics beyond Basics by Dr. Brij Teli (20)

Recently uploaded

Recently uploaded (20)

COVID 19- Basics beyond Basics by Dr. Brij Teli