COVID 19

 Home isolation and symptomatic treatment
 Hospitalization for patients with uncontrolled comorbidities#
(Age> 60
years, DM, HTN, immunocompromised, chronic liver and kidney
disease
 Monitor vitals: PR, RR, SpO2 (at rest and after walking for 6 minutes)
 Complete blood count and inflammatory markers to be checked, if
clinically indicated (on 5th
to 7th
day of clinical illness)
 May consider Favipiravir 1800 BD on day 1 followed by 800 mg BD
from day 2 (7-14 days)$
 Remdesivir may be used in special circumstances$
Mild disease
Fever and/or respiratory illness without dyspnea or hypoxemia*
COVID-19 treatment according to disease severity

 Oxygen support with nasal prongs or face mask. Target SpO2 92-96%
 Steroids: Dexamethasone 0.1-0.2 mg/kg or Methylprednisolone 0.5 to
1 mg/kg
 Anticoagulation: Inj Enoxaparin 1 mg/kg OD (if there is no
contraindication)
 Antivirals: Inj Remdesivir 200 mg single dose on day 1 and 100
mg once a day from day 2 to 5 (if there is no con- traindication)
 Investigational therapies^
 Monitor CBC, LFT, KFT, serum electrolytes and check inflammatory at
baseline and on 5th
day (early if clinically indicated)&
 Monitor blood sugars. Start insulin for high blood sugars
 High Resolution CT of thorax should be done in all patients.
Moderate disease
Pneumonia with RR≥24/min, SpO2≤94% and absence of signs of severe disease

 Oxygen support with HFNC/NIV
 Consider awake proning
 Consider intubation for those who are not tolerating HFNC/NIV and or worsening
breathlessness
 For intubated patients use lung protective ventilation strategy using ARDS net protocol
 Prone ventilation for refractory hypoxemia
 Steroids: Methylprednisolone 1-2mg/kg or Dexamethasone 0.2-0.4 mg/kg. Consider
methylprednisolone 250 to 500 mg for initial 1 to 3 days for very severe disease (SpO2/FiO2
<100 or PaO2/FiO2 <100)$
 Anticoagulation: : Inj Enoxaparin 1 mg/kg BD (if there is no contraindication)
 Antivirals: inj Remdesivir 200 mg single dose on day 1 and 100 mg once a day from day
2 to 5 (if there is no con- traindication)
 Investigational therapies^
 Monitor CBC, LFT, KFT, serum electrolytes and check inflammatory markers (every third day or
when indicated)&
 Monitor blood sugars. Start insulin for high blood sugars
Severe disease
RR≥30/min or SpO2<90% on room air

 Convalescent plasma therapy: 200 mg single dose, may be
repeated after 24 hours. May be considered in moderate to se- vere
disease not improving on steroids (with persistent or worsening
symptoms and raising inflammatory markers). Not to be used after
tenth day of illness. Antibody titres in the recpient should be negative
before using CPT.
 Tocilizumab: 8 mg/kg, maximum dose of 800 mg, as a single dose
may be considered in moderate to severe disease with progression of
disease despite of steroid treatment and raising inflammatory markers.
Dose may be repeated after 12 to 24 hours if there is no symptomatic
improvement with first dose. Exclude secondary infections clincally.
Investigational therapies

Myocarditis
 Myocarditis is one of the most dreaded complications of COVID19
 Myocarditis should be suspected in cases of new onset
arrhythmia, Tachycardia (>110 beath/minute) or severe
unexplained bradycardia (<50 beats per minute)
 Investigations: ECG, CKBM, TropI/T, echocardiography
 Monitoring: Inflammatory markers, ECG at regular intervals
 Management: Dexamethasone 0.1-0.2 mg/kg or
Methylprednisolone 0.5 to 1 mg/kg
 Anticoagulation: : Inj Enoxaparin 1 mg/kg BD (if there is no
contraindication) along with Aspirin

Footnote
 Hypoxemia is to be checked using a pulse oximeter, in right hand middle finger
for a duration of one minute (till the waveform stabilizes). Normal value of
saturation is 95% or above. Repeat assessment of hypoxemia has to be done
after walking for 6 minutes (in case of inability to walk, hand grip exercises for 6
minutes can be done). A fall of greater than 3% is considered clinically
significant.
well controlled co-morbidities like diabetes mellitus, heart failure, hypertension,
can be managed at home.
Low quality of evidence. Clinical efficacy in COVID19 is not known.
CBC must be done to document neutrophil to lymphocyte ratio (<3 is suggestive
of severe disease), Renal function test should be done to rule out COVID19
related kidney injury and eligibility for remdesivir. LFT should be done to rule out
hepatic injury due to COVID19 as well as eligibility for remdesivir. Inflammatory
markers must include CRP and ferritin.

Assessment of Dyspnea/respiratory Distress
 Complaint of breathlessness or cough is suggestive of pulmonary involvement in
COVID19
 Respirator rate should be measured in all subjects. Patients with RR >22/minute should be
admitted and monitored.
 Saturation should be measured in all patients by the method mentioned above
 Breath holding time is beneficial tool to pick cases of pulmonary involvement early
(BHT < 30 seconds in a afebrile patient should be an indication for HRCT thorax scan
for assessment of lung involvement).
 Similarly single breath count should also be measured in triage areas where saturation of
chest radiography are not easily available. SBC of <30 is suggestive of lung involvement.
 Inability to complete sentences is also suggestive of worsening severity of COVID19.

Home Isolation Practices
 Home isolation can be recommended for stable MILD cases with no other indication for
admission
 Facility of home isolation must be assessed prior to sending patient for home
isolation. Facility includes, separate room, attached washroom, presence of care
giver and 24 x 7 availability of emergency care.
 Use of experimental drugs like Ivermectin, alternative medicines should not be used
outside clinical trials.
 Hospitals should follow the cases who are sent on home isolation, daily and regularly.
 Utilization of remote monitoring applications like CARESHARE™should be encouraged
 Post recovery from COVID19 illness, all patient should be screened for signs of
depression or anxiety

MANAGEMENT OF COVID 19

Incubation
period
Exposure
Symptomatic
phase
Onset of symptoms
Early pulmonary
phase
ICU admission
Hyperinflammatory
phase
Cytokine storm/macrophage
activation syndrome/MODS
Death
Time line of COVID-19 disease

Timeline of autopsy studies
Virchows Archiv (2020) 477:359–372

Autopsy in COVID-19
• Presence of thrombosis and microangiopathy
in the small vessels and capillaries of the lungs,
with associated haemorrhage.
• Features of diffuse alveolar damage, including
hyaline membranes
• Cardiac findings included individual cell
necrosis without lymphocytic myocarditis.
• There was no evidence of secondary
pulmonary infection by microorganisms
Lancet Respir Med 2020; 8: 681–86

Electron microscopy in COVID 19
Numerous viral particles are enclosed in
single membrane vacuoles

CASE VIGNETTE
• A 42-year-old businessman presented with
• Fever-5 days
• Cough -5 days
• Diabetic (Metformin 500 mg BD
• Hypertensive (Telmisartan + Amlodipine - 40mg+5mg OD)
• Non smoker, non alcoholic

COVID-19 RT-PCR positive (Civil hospital on7/7/20)
referred to PGIMS for further management
• On examination:
• Conscious, oriented
• No pallor, icterus, cyanosis, clubbing,
lymphadenopathy, edema
• Temp- 101 F
• PR -102/ min
• B.P- 132/78 mm Hg
• RR-18 breaths/min
• SpO2 – 98 % on room air
• Chest- B/L vesicular breath sounds
• CVS – S1,S2+
• P/A – Soft, non-tender, no organomegaly
• CNS – No neck rigidity, plantar-flexor, no focal
neurological deficits
• Routine investigations:
• CH,LFT,KFT : WNL
• D-Dimer- 200 ng/ml (0- 500 ng/ml)
• CRP- 2 mg/L (0-5 mg/L)
• Chest radiograph-normal
• ECG-normal

What is Mild Covid-19?
Treatment guidelines, MOHFW, Govt of India,
3/7/20

Risk factors for Severe disease in patients with COVID-19
•Age ≥65 years
•Residence in a nursing home or long-term care facility
•Immunocompromised state, including solid organ transplant,
HIV infection, other immune deficiency, immunosuppressant
medication including systemic corticosteroids
•Chronic lung disease, including COPD, moderate to severe
asthma, cystic fibrosis, pulmonary fibrosis
•Cardiovascular disease
•Cancer
•Hypertension
•Overweight/ Obesity (BMI ≥30 kg/m2)
•Diabetes mellitus-uncontrolled
•Chronic kidney disease
•Chronic liver disease
•Cerebrovascular disease
•Neurologic disorders, including dementia
•Tobacco use disorder
•Hematologic disorders, including sickle cell disease and
thalassemia
•Pregnancy????

Management
• Isolated (Home/Hospital)
• Source control is most important strategy to prevent chain of
transmission
• Symptomatic treatment such as antipyretic (Paracetamol) for fever
and pain, antitussives for cough
• Adequate nutrition and appropriate hydration to ensured
*MOHFW, Govt of India, Treatment guidelines for Covid-19, version 5,last updated on
3/7/20

Home Isolation
• Increasingly practiced
• Readily accepted
• ‘Supervised’
• Emphasis on picking complications
early –
1. Breathlessness – pulse oximetry
2. Fever – indicator of cytokine
excess
3. Cough
When to seek medical attention?
• Difficulty in breathing
• Unremitting fever
• Dip in oxygen saturation (SpO2 < 95%),
• Persistent pain/pressure in the chest,
• Mental confusion or inability to arouse,
• Slurred speech/seizures,
• Weakness or numbness in any limb or
face,
• Developing bluish discolorations of
lips/face.
Separate room ✔️
Care giver. ✔️
Separate toilet ✔️

HCQ NOT RECOMMENDED

Role of Ivermectin....
• Broad-spectrum antiviral activity – in Vitro
• Inhibition of importin α/β-mediated nuclear transport of viral proteins.
• The clinical efficacy and utility of ivermectin in SARS-CoV-2 unpredictable at this
stage

Role of Favipiravir.. Evidence…
AVIFAVIR for Treatment of Patients with Moderate
COVID-19: Interim Results of a Phase II/III Multicenter
Randomized Clinical Trial
Clinc dis 2020 Aug 9;ciaa1176. doi: 10.1093/cid/ciaa1176
The rate of viral RNA clearance from upper respiratory
tract specimens at day 5 was higher with Favipiravir
compared with standard of care, which included
hydroxychloroquine (clearance rates of 62 versus 36
percent)
Experimental Treatment with Favipiravir for COVID-19:
An Open-Label Control Study
Cai Q, Yang M, Liu D, et al Engineering. 2020
FPV showed better therapeutic responses on COVID-19
in terms of disease progression and viral clearance.
These preliminary clinical results provide useful
information of treatments for SARS-CoV-2 infection.
Favipiravir versus Arbidol for COVID-19: A Randomized
Clinical Trial
medRxiv. 2020 doi: 10.1101/2020.03.17.20037432
In ordinary COVID-19 patients untreated with antiviral
previously, favipiravir has higher 7 day’s clinical
recovery rate and more effectively reduced incidence
of fever, cough except some antiviral-associated
adverse effects.
DATA EVOLVING

* Clinical signs of worsening
Unremitting fever/2nd peak
Cough
Breathlessness
Increase in Respiratory rate(>20)
Decreasing saturation (≤94%)
Altered sensorium
Decreased urinary output
COVID 19
Minimal symptomatic/Asymptomatic
Without Risk Factors
With Risk Factors
(Age > 60 years/Obesity/Diabetes/Hypertension/
Hypothyroidism)
Observation (Monitor symptoms BD)
Symptomatic treatment
Close monitoring for clinical worsening*
Tab HCQS 400mg BD (D1) followed by
200mg BD for 4 days (or)
Tab Favipiravir 1800mg BD(D1) followed by
800mg BD for 7-14 days
DAY 5-7
CBC, CRP, D-dimer, Ferritin, LDH
Warning signs
Clinical signs of worsening* and/or
Leucocytosis
N/L ratio >3.5
Eosinopenia
↑CRP, d – dimer, ferritin,
HRCT THORAX
?? Ivermectin12 mg OD x 3 days with or without Doxycycline (100 mg BD x 5 days- Data insufficient. Should be given only under clinical trials

CASE CONTINUED…
• Admitted in Isolation ward (8-7-20)
• Treatment given
• Inj. Ceftriaxone 1 gm/IV/BD
• Tab. Hydroxychloroquine 400 mg BD on day-1
followed by 200 mg BD from day-2 to day-5
• Other supportive treatment
• 2 Days later (10-7-20)
• Complained of breathlessness
• RR-24 breaths/min
• SpO2-92 % on room air and 97% with 4 lit of oxygen-
on nasal prongs
• Shifted to ICU
• Started on venturi mask (FiO2 requirement was 60%)
• Blood sugars-346 mg/dl- insulin was started (basal
bolus regimen- regular insulin and glargine)

MODERATE DISEASE
Treatment guidelines, MOHFW, Govt of India, 3/7/20
HDU/ICU

SpO2 On room air < 94%
Nasal cannula @1-6
L/min
NRBM@ 10-15
L/min
HFNC/NIV IMV
• Oxygenation not
improving
• Use of accessory
muscles of
breathing
• Oxygenation not
improving
• Use of accessory
muscles of
breathing
• Rising PaCO2 or
Obtundation
Oxygen Therapy
ECMO

Nasal
canula/NRBM
/venturi mask
•1 -6 L/min (NC)
•6-15 L/min (NRBM)
HFNC/CPAP/
NIV
•HFNC - Preferred modality (with triple ply mask)
•Flow rate 60-80 L/min
•FiO2 to target SpO2 > 84%
•Consider “Awake Proning”
•If HFNC not available – consider NIV (preferably Helmet mask/FFM)
•Use HME filter between mask and tube and tube and machine
•Look for signs of increased work of breathing (RR, accessory muscle usage)
IMV
• RSI by most experienced doctor
•Preoxygenation with HME filter attached between mask and reservoir bag
•CMV (VCV/PCV) with Low tidal volume strategy ( Vt 6-8 ml/PBW)*
•Initial PEEP 5-10 cm H20, titrate according PEEP – FiO2 table or to keep
driving pressure < 15 cm H20
•Adjust RR (< 35/min)
•Adequate sedation and analgesia (NMBs if necessary)
Proning
•Consider early Proning ( Within 36 hours of IMV)
•Mild to moderate ARDS (P/F < 150, FiO2 > 0.6)
•14- 16 hours/day until improvement in oxygenation
ECMO
•Refractory hypoxemia in spite of Proning and neuromuscular paralysis
•PaO2/FiO2 < 60 mmHg for > 6h
•PaO2/FiO2 < 50 mmHg for > 3h
•Ph < 7.2 + PaCO2 > 80 mmHg > 6h
*Dead Space Calculation
D
E
T
E
R
I
O
R
A
T
I
O
N
I
M
P
R
O
V
E
M
E
N
T
ACCEPT PERMISSIVE
HYPOXIA – SpO2 > 84%

Those who received remdesivir had a median recovery time of
10 days as compared with 15 days among those who received
placebo. The Kaplan–Meier estimates of mortality were 6.7%
with remdesivir and 11.9% with placebo by day 15
Better clinical status at day 11 in remdesivir group
compared to standard care
Patients hospitalized for severe Covid-19 who were treated
with compassionate-use Remdesivir, clinical improvement was
observed in 36 of 53 patients (68%)
Patients receiving Remdesivir had a faster time to
clinical recovery than placebo
REMDESIVIR

Remdesivir
NIH recommendations ( 01/9/20)
Patients With Mild or Moderate COVID-19
There are insufficient data to recommend either for or against the use of Remdesivir
Patients With COVID-19 Who Require Supplemental Oxygen
Remdesivir for 5 days or until hospital discharge, whichever comes first
Patients Who Require Oxygen Delivery Through HFNC,NIV,IMV, or ECMO
The Panel cannot make a recommendation either for or against starting remdesivir.
Duration of Therapy for Patients Who Have Not Shown Clinical Improvement After 5
Days of Therapy
There are insufficient data on the optimal duration of remdesivir therapy for patients who have not
shown clinical improvement after 5 days of therapy. In this group, some experts extend the total
remdesivir treatment duration to up to 10 days.

Convalescent plasma therapy
• Passive antibody therapy
• Mechanism of action
• Neutralising antibodies,
• Antibody-dependent cellular
cytotoxicity(ADCC) and
• Antibody-mediated
phagocytosis.
• ICMR trial finished allowed for
compassionate use in early
Pulmonary phase
PROVEN COVID < 10
days duration
Evidence of
respiratory failure
No clinical response
Treatment with steroids and
antivirals for 24-48 hours
Consider for
convalescent plasma
therapy
ELIGIBILITY CRITERIA FOR CPT:
Age > 18 years
Has any of the two
PaO2/ FiO2: 200-300
RR > 24/min and SaO2 < 93% on room
air
Availability of matched donor plasma
at the point of enrolment
Antibody negative

Corticosteroid...

Recovery trial
Inclusion:
Patients hospitalized with suspected or
laboratory confirmed COVID 19
Intervention: (1:2)
SOC + dexamethasone 10 mg up to 10 days or
hospital discharge Vs. SOC
Outcome
28 days mortality
Results :
• Dexamethasone decreased overall mortality.
• Most beneficial group was ventilated
patients.
• Increased mortality in patients not receiving
oxygen(not statistically significant)
• Decrease risk of progression to mechanical
ventilation (RR-0.76)
• More benefits after 7 days than before
DOI: 10.1056/NEJMoa2021436

Final word -Corticosteroids…
• Hypoxemic COVID-19 patients should receive dexamethasone(or equivalent) based
on current evidence, given the reduced risk of death and increased likelihood of
hospital discharge.
• Reduced length of oxygen therapy and risk of progression to invasive mechanical
ventilation among those on supplemental oxygen.
• No benefit among patients who do not require supplemental oxygen

Moderate illness
Persistent fever > 7days
Reappearance of fever
Unremitting high grade fever
Breathlessness
↑ Inflammatory parameters
Normal oxygen saturation
CT severity score >10/25
↑ Inflammatory parameters
SPO2< 94% (or)
RR > 24
Steroid* (Methylprednisolone 1-2 mg/kg body
weight/day) for 3-5 days
Inj. Enoxaprin (1mg/kg BW) S/C OD/BD
Remdesivir#
Steroid* (Methylprednisolone 1-2 mg/kg body
weight/day) x 5-10 days
Gradual tapering over 3 weeks
Remdesivir#
Inj. Enoxaprin (1mg/kg BW) S/C OD/BD
Awake proning
• Steroid 1-2 mg/kg of methyl prednisolone or equivalent dose
• Gradual tapering to prevent fibrosis
#Remdesivir (200mg on Day 1, 100mg from Day 2-5)
• Enoxaprin OD/BD as per d-Dimer values
** Convalescent plasma (200 ml in single dose, can be repeated after 24 hours from a different donor may
be considered in moderate to severe patients with persistent or increasing oxygen requirement). Both
donor and recipient must be screened for antibodies
*Strict control of blood sugars with insulin (Basal-bolus)
ACTIVE PRINCIPLE EQUIVALENT DOSE
Hydrocortisone 20 mg
Prednisolone 5 mg
Methyl
prednisolone
4 mg
Dexamethasone 0.75 mg

Case continued… 1 Day later (11-7-20)
• Complained increasing
breathlessness
• RR-28 breaths/min
• SpO2-84% on room air
and 88% with 10 lit of
oxygen- on NRBM
• Started on HFNC
On 60% FiO2
Arterial Blood Gas
pH 7.49
PCO2 32
PO2 53.7
SaO2 90.8
HCO3
- 24
BE 3.3
Na+ 134
K+ 3.6
COVID-19 ARDS

Severe COVID -19: classification
CDC
Severe Illness
1. RR >30 /minute
2. SpO2 <94% on room air at sea level
3. PaO2/FiO2 <300 mmHg
4. Lung infiltrates >50%.
Critical Illness
1. Respiratory failure
2. Septic shock, and/or
3. Multiple organ dysfunction.
MoHFW-GOI
Severe illness
clinical signs of Pneumonia plus one of the following :
1. Respiratory rate >30 breaths/min
2. Severe respiratory distress
3. SpO2 <90% on room air
ARDS : Berlin definition /Kiagli modification
Sepsis: Organ failure due to infection
(SOFA increased by ≥ 2)
Septic shock :
MAP <65 mm of hg or lactate ≥ 2 mmol/L after adequate
fluid resuscitation

Risk Factors &Laboratory markers of severity
✓ Severity of illness
✓ Mortality
▪ D-dimer >1000ng/ml
▪ CRP>100mg/L
▪ Ferritin >500 mcg/L
▪ LDH>245 U/L
▪ High sensitivity Troponin > 2 times of ULN
▪ CPK> 2times ULN
▪ Lymphocyte count <800/cu.mm
▪ NLR≥9
▪ NT Pro BNP
▪ Increasing SOFA
▪ SAA
▪ Urea, creatinine
▪ Older age
▪ Smoking
▪ Comorbidity: DM, HTN, CHD,
CLD, CKD, chronic pulmonary
diseases malignancy etc.
▪ Immunosuppressive conditions
▪ Obesity /Overweight

Tocilizumab
NIH (1/9/20)
• The Panel recommends against the use of anti-IL-6 receptor monoclonal antibodies (e.g.,sarilumab,
tocilizumab) or anti-IL-6 monoclonal antibody (siltuximab) for the treatment of COVID-19, except in a clinical
trial
MoHFW version 5. 3/7/20
• Tocilizumab (Off Label) may be considered in patients with moderate disease with progressively increasing
oxygen requirements and in mechanically ventilated patients not improving despite use of steroids.
• Special considerations before its use include:
• Presence of raised inflammatory markers (e.g., CRP, Ferritin, IL-6)
• Patients should be carefully monitored post Tocilizumab for secondary infections and neutropenia
• The drug is contraindicated in PLHIV, those with active infections(systemic bacterial/fungal), Tuberculosis, active
hepatitis, ANC < 2000/mm3 and Platelet count < 1,00,000/mm3

High dose/ Pulse corticosteroid
• Few case series and case reports
• High dose methylprednisolone 500-1000 mg for 3 days followed by rapid tapering
• Improvement in P/F ratio and early extubation
• Limitation : study design, small sample
• A case series from japan including 7 patients with COVID pneumonia and P/F <150 requiring
mechanical ventilation showed benefit of pulse steroid (1000 or 500 mg/day for three days
of methylprednisolone intravenously, followed by 1 mg/kg and tapered off, median
duration 13 days.) in terms extubation of the patients within seven days and hospital
discharge
[Respirology Case Reports, 8 (6), 2020, e00596]
• A RCT is under going comparing standard ICU care (± 6 mg dexa) Vs. standard ICU care +
24mg dexa ( NCT04395105)

COVID 19 and Coagulopathy
• 3000 individuals hospitalized with COVID-19
• Most patients received prophylactic-dose anticoagulation.
• Venous thromboembolism was seen in 16 percent (13.6 percent of individuals in the
intensive care unit and 3.6 percent on the medical ward).
• Arterial thrombosis (mostly myocardial infarction) was seen in 11.1 percent.
• Factors associated with increased thrombosis risk included older age, male sex, Hispanic
ethnicity, coronary artery disease, prior myocardial infarction, and high D-dimer on
presentation.
JAMA.

Echocardiography in fatal COVID19 Pulmonary Embolism

Dose & duration of anticoagulation
• Patients hospitalized for acute medical illness are at increased risk for VTE for up to
90 days after discharge.
• A symptomatic VTE incidence between 0-0.6% at 30-42 days post discharge has
been reported in patients with COVID-19.
• Routine post-discharge thromboprophylaxis – Not advised.
• Patients who warrant extended thromboprophylaxis following discharge from the
hospital:
• Patients with major prothrombotic risk factors such as a history of VTE or recent major surgery
or trauma BUT at the cost of increase in bleeding events
• Options for post-discharge prophylaxis include those used in clinical trials, such
as Rivaroxaban 10 mg daily for 31 to 39 days
https://www.hematology.org/covid-19/covid-19-and-vte-
anticoagulation

**INDICADTIONS FOR
TOCILIZUMAB/Pulse methyl
prednisolone:
• Rapid deterioration
• RR > 30 bpm,
• SaO2 < 93% on room air
• PaO2/FiO2 < 300 mm Hg in
room air, and
• Lung infiltrates > 50% within
24–48 h
CONTRAINDICATIONS:
• Coexistent infection other
than COVID-19;
• PaO2/FiO2 > 300 mm Hg;
chronic or current
glucocorticoid use
• H/O severe allergic
reactions to monoclonal
antibodies
• ANC < 500 per µL; platelets
< 50×10⁹
• Active diverticulitis, IBD , or
another symptomatic
gastrointestinal tract
condition that might
predispose patients to
bowel perforation;
• Severe haematological,
renal, or liver function
impairment.
# Evidence for pulse methyl prednisolone is evolving
Remdesivir (day 1-200 mg, day 2 to 5-100 mg once a day)*
Steroids - Methylprednisolone 1-2 mg/kg BW or equivalent
Inj. Enoxaparin 1 mg/kg SC q 12 hourly
Tab Aspirin 75 mg OD +
OXYGEN
Severe illness
Respiratory distress
RR > 30bpm or SpO2 < 90%
IMPROVED
Continue same treatment
Taper steroid gradually
NO IMPROVEMENT
Increasing( Double) the steroid dose
#Pulse methyl prednisolone 500 mg – 3 days
Anti IL-6 (Tocilizumab)**
NO IMPROVEMENT
Salvage therapies:
Low dose thrombolysis
Cytosorb
IVIG
Plasma exchange
Evolving immunomodulators
IMPROVEMENT
Taper steroids gradually
*REMDESIVIR NOT RECOMMENDED:
• AST/ALT > 5 times elevated
• Creatinine clearance < 30 ml/min
• Pregnant and breast feeding women
• Known hypersensitivity to study drug

Pathophysiology based management of COVID-19

Steroids
COVID positive patient with hypoxia
SpO2 <96%
RR > 24
Antivirals
Moderate to severe disease ?
Early use??
Tocilizumab/
Convalescent plasma
therapy
• No clinical response after 24-48hrs
of steroid and antiviral therapy
• Increasing CRP, ferritin, IL-6 levels
Anticoagulation
Moderate to severe disease with
D-dimer > 500 ng/ml
Learning points

Covid suspect but RT PCR -ve
Exclusion of other diagnosis:
• Negative influenza PCR test
• Negative respiratory viral panel
• Negative testing for clinically indicated respiratory
infections (urine antigen for legionella and streptococcus
pneumoniae, blood cultures, sputum cultures or BAL)
HRCT THORAX
REPEAT RT-PCR
ALTERNATIVE DIAGNOSIS CORADS 4/5
POSITIVE NEGATIVE
CLINICAL SUSPICION
HIGH
MANAGE AS COVID
LOW
LOOK FOR ALTERNATIVE
DIAGNOSIS

Courtesy: EVMS Critical Care COVID-19 Management Protocol
TIMING OF INITIATION OF ANTI INFLAMMATORY THERAPY
Remdesivir
days

COVID 19 is a steroid responsive disease, however timing is important
or Equivalent Dose of
Dexamethasone/Hydrocortisone
*Tab Apixaban 2.5mg BD
Adapted from EVMS Critical Care COVID-19 Management Protocol
5-17 days
*Use with caution with Tocilizumab – increased risk of bleeding

Blood Markers in Covid
1. C Reactive Protein
C-reactive protein (CRP) is a blood test marker for inflammation in the body. CRP is produced in
the liver.
•Normal Levels - 0-5 mg/L
•In general, the main causes of increased CRP and other markers of inflammation are a variety of
conditions, including burns, trauma, infections, such as pneumonia or tuberculosis, heart attack,
chronic inflammatory diseases such as lupus, vasculitis, or rheumatoid arthritis.
2. D-dimer
D-dimer (or D dimer) is a fibrin degradation product (or FDP), a small protein fragment present in
the blood after a blood clot is degraded by fibrinolysis.
•Normal Levels - mg/L or µg/mL < 0.5
3. S Ferritin
The ferritin test measures the level of ferritin, stored protein in the body.
•Normal Levels 12 to 300 ng/mL for males and 12 to 150 ng/mL for females.

BLOOD MARKERS IN COVID
4. Lactate dehydrogenase (LDH)
• LDH is expressed extensively in body tissues, such as blood cells and heart muscle.
Because it is released during tissue damage, it is a marker of common injuries and
disease such as heart failure.
• Normal Levels - 50 -150 U/L
5. Interlukin 6
• Interleukin 6 is an interleukin that acts as both a pro-inflammatory cytokine and
an anti-inflammatory myokine. In humans, it is encoded by the IL6 gene. In
addition, osteoblasts secrete IL-6 to stimulate osteoclast formation
• Normal Levels - 0– 16.4 pg/mL

6. Troponin I
• Troponin I is a cardiac and skeletal muscle protein family. It is a part of the troponin protein complex,
where it binds to actin in thin myofilaments to hold the actin-tropomyosin complex in place. Troponin I
prevents myosin from binding to actin in relaxed muscle. When calcium binds to the troponin C, it
causes conformational changes which lead to dislocation of troponin I. Afterwards, tropomyosin leaves
the binding site for myosin on actin leading to contraction of muscle. The letter I is given due to its
inhibitory character. It is a useful marker in the laboratory diagnosis of heart attack.[1] It occurs in
different plasma concentration but the same circumstances as troponin T - either test can be performed
for confirmation of cardiac muscle damage and laboratories usually offer one test or the other.[2]
• Normal Levels - 0 and 0.4 ng/mL
7. Pro Calcitonin
• Measurement of procalcitonin can be used as a marker of severe sepsis caused by bacteria and
generally grades well with the degree of sepsis,[50] although levels of procalcitonin in the blood are very
low. PCT has the greatest sensitivity (90%) and specificity (91%) for differentiating patients with systemic
inflammatory response syndrome (SIRS) from those with sepsis, when compared with IL-2, IL-6, IL-8,
CRP and TNF-alpha.[51] Evidence is emerging that procalcitonin levels can reduce unnecessary antibiotic
prescribing to people with lower respiratory tract infections.
• Normal Levels - 0.10 – 0.49 ng/mL

REMDESIVIR
• As an adenosine nucleoside triphosphate analog (GS-443902),[80] the active metabolite of
remdesivir interferes with the action of viral RNA-dependent RNA polymerase and evades
proofreading by viral exoribonuclease (ExoN), causing a decrease in viral RNA
production.[10][81] In some viruses such as the respiratory syncytial virus it causes the RNA-
dependent RNA polymerases to pause, but its predominant effect (as in Ebola) is to induce an
irreversible chain termination. Unlike with many other chain terminators, this is not mediated
by preventing addition of the immediately subsequent nucleotide, but is instead delayed,
occurring after five additional bases have been added to the growing RNA chain. For the RNA-
Dependent RNA Polymerase of MERS-CoV, SARS-CoV-1, and SARS-CoV-2 arrest of RNA
synthesis occurs after incorporation of three additional nucleotides. Hence, remdesivir is
classified as a direct-acting antiviral agent that works as a delayed chain terminator.
• Dosage - 200 mg IV on day 1 followed by 100 mg IV daily for 4 days (5 days in total).
• Note It is a heptatoxic and renal toxic drug so LFT and RFT should be monitored regularly.

PRECAUTIONS AND CHALLENGES
The medical operatories should gear themselves
Preparatory Phase(I), Implementation Phase(II) and Follow up (III)
Phase I: Preparatory phase for a medical clinic
• Doctor and health care prophylaxis against COVID 19.
• asymptomatic Health care workers not exposed to corona virus infection
are not required to undergo a test before resuming to work.
• asymptomatic healthcare workers involved in care of suspected or
confirmed cases of COVID-19 are advised to take HCQ prophylaxis after
medical consultation.

Ventilation air quality management in stand-alone clinics
I. Maintain air circulation with natural air through a frequent opening
of windows and exhaust.
II. Avoid the use of a ceiling fan while performing procedure.
III. Table fan behind the operator and let the airflow towards the
patient.
IV. window air condition system/ split AC should be frequently
serviced, and filters cleaned.
V. Use of indoor portable air cleaning system equipped with HEPA
filter and UV light may be used. Allow fresh air into rooms by opening
of windows or doors slightly.

Clinic entrance, reception and waiting :
• Display visual alerts at entrance (e.g., waiting areas or elevators) about
respiratory hygiene, cough etiquette, social distancing and disposal of
contaminated items in trash cans.
• Install glass or plastic barrier at the reception desk.
• Ensure availability of sufficient three-layer masks, sanitisers ,paper tissue at
the registration desk.
• Distant waiting chairs, preferably a meter apart.
• All areas to be free of all fomite such as magazines, toys, TV remotes or
similar articles. Contactless payment methods.
• A bin with lid should be available at triage.

Changing Room
Dedicated area for donning and doffing of PPE, sterilisation.
• A dedicated and trained person should be available to undertake
Transport, Cleaning, Drying, Packing, Sterilisation, Storage and Testing
the quality of sterilisation as per the standard guidelines and
manufacturer’s instructions.
space for storage of additional items of PPE, sterilisation, disinfection
instruments and chemicals must be ensured.
Washrooms: Sensor taps. No towels.

Instrumentation
I. Fumigation systems
II. High volume extra oral suction
III. The indoor air cleaning system
IV. Used hand pieces with anti-retraction valves only
V. Chemicals required for disinfection
VI. Appropriate PPE and ensure it is accessible to HCW.
VII. Maintain a supply of all consumables related to PPE, Sterilisation and
Disinfection

Training of Healthcare Workers (HCWs)
I. Train administrative personnel working in the reception of patients
on hand hygiene, social distancing, use of facemask, for them and
incoming patients.
II. Educate all HCW on proper selection and use of PPE. They may
require psychological support and morale-boosting to maintain
their level of confidence and strict adherence of guidelines.
III. Staff should rotate more frequently, preferably, should avoid long
working hours, should ensure proper nutrition and sleep.
IV. All staff and doctors must use surgical attire in the office, and all
personal clothing should be avoided.
Hand hygiene: As per the WHO guidelines Standard .

Donning and doffing:
Use of n95 masks:
Disinfection of Clinic :
• COVID-19 virus can potentially survive in the environment for several
hours/days.
• potentially contaminated areas to be cleaned before their re-use.
• Remove the majority of bioburden, and disinfect equipment and
environmental surfaces.

Environment and Surface Disinfection:
• Floors: 2 Step Cleaning Procedure (Detergent and freshly prepared
1% sodium hypochlorite with a contact time of 10 minutes. Mop
the floor starting at the far corner of the room and work towards
the door. Frequency: after any patient/ major splash or two hourly.
• Rest of the surfaces: Freshly prepared 1% sodium hypochlorite
(Contact Time: 10 minutes). Damp dusting should be done in
straight lines that overlap one another. Frequency: before starting
daily work, after every procedure and after finishing daily work
Delicate Electronic equipment: Should be wiped with alcohol-based
rub/spirit (60-90% alcohol) swab before each patient contact.

Phase II Implementation :
Tele-consult Tele-screening:
I. Encouraged as the first point of contact between the patient and the
dentist or reception office.
II. Current medical history and past history particularly pertaining to
symptoms of Severe Acute Respiratory Illness (fever AND cough and/or
shortness of breath) or All symptomatic ILI (fever, cough, sore throat,
runny nose) must be analysed.
III. Any positive responses to either of the questions should raise concern,
and care should be postponed for 3 weeks except in emergencies.
IV. Encourage all to download the Arogya Setu App.

Protocols of patient handling in the clinic area :
• For appointments (no aerosols) - only wear a triple layer surgical mask
with protective eyewear/face shield and gloves.
• Wear N95 face masks, protective eyewear/face shields and gloves along
with coverall for High Risk and very high-risk procedures.
• Increase shelf life of N95 masks( cover with surgical mask and discard
only the surgical mask).
• Moderate risks patient examination require all PPE as high risk except
coveralls can be substituted with surgical gowns.
• Practice non-aerosol generating procedures. Use of rubber dam is
encouraged. The 4-handed technique is beneficial for controlling the
infection.

Patient discharge protocol :
I. The patient drape will be removed by the assistant, the patient is
asked to perform hand wash and guided out of the clinic towards
reception and handed back his foot wears and belongings.
II. The procedures and prescription is recorded only after doffing the
PPE.
III. Patient to perform hand hygiene and to be provided with follow up
instructions.

Patient turn around and disinfection protocol
I. After patient leaves, Assistant will collect all hand instruments
immediately, rinse them in running water to remove organic matter
and as per standard sterilisation protocol.
II. All 3 in 1 syringe, water outlets, hand piece water pipelines, etc.
should be flushed with the disinfectant solution for 30-40 seconds.
III. Remove water containers and wash them thoroughly and disinfect
with 1% sodium hypochlorite using clean cotton/ gauge piece and then
fill with fresh 0.01% sodium hypochlorite solution

Protocol for clinic closure Fogging:
• It is used as 'No-touch surface disinfection' and not for disinfection of air after a
large area has been contaminated. The commercially available hydrogen
peroxide is 11% (w/v) solution which is stabilized by 0.01% of silver nitrate.
• A 20% working solution should be prepared. The volume of working solution
required for fogging is approximately 1000ml per 1000 cubic feet. After the
procedure has been completed in the operatory (in case of no negative
pressure), exit the room and close the operatory for half hour for the
aerosols/droplets to settle down.
• Perform the 2 Step surface cleaning followed by fogging. The fogging time is
usually 45min followed by contact time/dwell time of one hour.
• After that the room can be opened, fans can be switched on for aeration. Wet
surfaces can be dried/cleaned by using a sterile cloth or clean cloth (other
surfaces).

Protocol for health care workers on reaching home :
Follow all precautions and on return, follow the removal of shoes, change
of clothes, having a wash and disinfect your mobile wristwatch etc.

BMW GUIDLINES
1. COVID ISOLATION WARDS:
• separate colour coded bag and segregation as per BMWM rules. DOUBLE
layered bags for collection from covid 19 isolation wards(ensure
adequate strength and no leaks).
• Mandatory labelling- easy identification. “COVID-19 WASTE”. Separate
record from covid-19 isolation wards. Use dedicated trolleys and
collection bins.
• Both surfaces of container to be disinfected with 1%hypochlorite solution
daily.
• Report opening of covid-19 ward to SPCBs and respective CBWTF located
in area.
2. SAMPLE COLLECTION CENTRE AND LAB FOR COVID-19:
• Report to concerned SPCB.

3. RESPONSIBILTY OF PERSONS OPERATING QUARANTINE CAMPS/HOMES:
• General waste hand over to waste collector as per prevailing local method.
• Biomedical waste separately in yellow color bags by ULBs.
• Persons operating should call CBWTF operator. Any difficulty should be
reported to ULBs.
4. CBWTF-COMMON BIOMEDICAL WASTE TREATMENT FACILITY:
• Report receiving of waste. Ensure REGULAR sanitation of workers involved.
• Provide adequate PPEs. Dedicated vehicles sanitized by 1%sodium hypochlorite.

5. DUTIES OF SPCBs/PCCs:
• Maintain record in respective sates.
• ENSURE collection and disposal asper bmw rules.
• Allow CBWTFs to operate for extra hpurs as per requirement.
• Coordinate with CBWTFs and ULBs in adequate collection and disposal of covid
19 waste.
• In case large volume of yellowcolor waste HW incinerators at existingTSDFs by
ensuring separate arrangement.

Proposed Plan for Early Intervention in Home Isolation Cases in Haryana
There has been an increase in average daily new positive cases . It was due to the combined effect of
Festival seasons gathering, opening of all commercial establishments and non-compliance of Covid
Appropriate Behaviour by the public. This also resulted in increase in the death cases due to Covid during this
period (Aug -5, Sept- 49, Oct-71 and Nov 92).
As per Covid death audit 65% of total deaths were among age group >60 yrs and 20% in 50 - 60 yrs, 9%
in 40-50 yrs age group and 6% were less than 40 yrs of age. Similarly, 45% cases were suffering from
Diabetes Mellitus, 20% from Heart problems & Hypertension, 7% from Respiratory Diseases, 6% from Renal
Diseases, 2% carcinoma, 7% from other diseases and 14% had no co-morbid conditions. Out of total 227,
10% were either brought dead or at home and 90% were institutional death. In majority of cases, patient is
reporting late for investigation and admission when Health condition of patient has already become very
much compromised. This inappropriate behaviour (not testing timely) is due to the fear of getting positive and
thus their family will be under house arrest for 14 days with social stigma, not full faith in public hospitals &
high treatment cost in private hospitals. They are also worried about consequential loss of their earning. It has
also been found that many of these patients took self medication (as prescribed in social media) and lost the
precious time. When these patients report to health centre, their condition is already compromised and results
in increase in fatality rate.
Presently 87% of active cases are in Home Isolation and 13% are in institutional isolation. Hence, there is
need for early detection of complications and intervention in the Covid positive cases under Home isolation.

Following steps are proposed for the same:
1. Ward wise Screening: Urban Haryana is having 80% of total case load. It is divided in 20 MC Wards.
Ward wise House to House survey by Health Workers will be done and screening of all high-risk groups
will be done. Intensive efforts will be done in the areas where more cases are detected. Nigam Parshad
(Counsellor) of the area to be taken into confidence and with their help, people will be encouraged to
come forward to get tested early. All contacts to be encouraged to test well in time. Involvement of
personnel from Urban local bodies/Corporation and local Police authorities will also be solicited. It will
help in proper contact tracing, increase sampling rate and enforce administrative action if required.
2. First Contact: Once a patient is detected Covid positive, an early Telephonic/ Video consultation to be
given to the patients by a Doctor to allay their fears and detect cases with co-morbidities early. Services
of IMA Haryana doctors also to be taken for this purpose. Day of symptom onset to be recorded properly.
If assessment in elderly and patients with co- morbid conditions is made to keep them at home only,
various precautions and monitoring to be explained to the attendants. For this purpose, there will be a
need to setup a Unified Call Centre, which besides taking patients’ calls, will also connect them to their
treating doctor.

3. Follow up: Home isolation teams to follow up all cases diligently. Medicines and SpO2 monitors (Home Isolation Kit) to
be provided to cases in Home Isolation. Regular supply of required medicines to be ensured to home isolated
patients. Priority to be given to elderly and patients with co-morbidities. Patients and attendants to be taught SpO2
monitoring, both in resting and after a 6 minutes’ walk. Other symptoms to be asked for the purpose of assessing
complications, with special mention of:
a. Persistence/ recurrence of fever after three days
b. Cough and/or Breathlessness
c. Severe Fatigue/ weakness
d. Nausea
e. SpO2 <95%
Modified version of NEWS protocol to be used for assessment.
4. Physical Examination: If no other indication earlier, every patient to have a physical examination by a paramedical
staff or a doctor attached to home isolation team around 5th day of symptoms. Team should personally record SpO2,
both in resting and after a 6 minutes’ walk.

5. Lab Investigations: If not indicated earlier, following lab investigations of all cases to be carried out on 5th to 7th day of
symptoms:
a. CBC (Complete Blood Count) with NLR (Neutrophil-Lymphocytic Ratio)
b. RBS (Random Blood Sugar)
c. CRP (C-Reactive Protein) Quantitative
If reports are within normal limits, treatment to be continued as such, else treating doctor to make a call for need of
hospitalization of the patient.
 If CRP is raised up to four times the normal and other parameters are normal, it is to be repeated in two days, with
other investigations indicated.
 If CRP raised more than four times the normal, other investigations to be done immediately to detect complications
early. This may include other blood and Radiological investigations.
6. Managing Complications: In case of anticipated complications, on the basis of lab investigations or docors’
assessment, patient to be hospitalised as per entitlement in Private or Public setup.
7. Day Care: If treating doctor feels that patient doesn’t require Oxygen support but requires some other therapy (e.g.
Steroids, Heparin, Remdesivir etc) under supervision, same maybe allowed on Day-care basis. Ayushman charges
maybe allowed for the same.
8. Repeat Physical Examination: It will be carried out around 10th day of home isolation. Final assessment to be made in
consultation with the treating doctor about continuing care.
9. Discharge: If patient is not having any complications, patient to be discharged from Home Isolation as per guidance.

SOPs to be established
Blood Investigation Process:
MOU to be done with multiple local labs for home sample collection of above samples (CBC, RBS and
CRP Quantitative). A fixed rate to be arrived at by the Civil Surgeon, including Lab investigations and
Sample collection.
Cost of lab investigations to be borne by the affording patients and to be borne by the government in case
of poor patients. Advanced investigations (like D-Dimer, Ferritin, LDH, IL-6, Procalcitonin etc) to be done
as per MOU of GH Haryana.
Radiological Investigations:
As per indication and advice of the treating physician, HRCT Scan to be advised in cases having deranged
investigations or other high-risk factors. Same process of payment by the affording cases and subsidy by
the government for the poor patients may be worked out.

Role of IMA Doctors:
Many of IMA Doctors have volunteered for telephonic consultations. As patients are
comfortable talking to their own doctors, those on Home Isolation will be linked up with IMA
doctors, preferably one of their own choice. These doctors will be connected to the patients
through Haryana helpline control room. If attending doctor feels the need, patient will be shifted
to institutional care.
A detailed transcript for consultation to be made.
Request will be made to Covid Care Hospitals to keep a bed reserved for the patients
transferred from Home isolation.
Request will be made to these hospitals to make additional space available for the Day care
patients as per requirement.

Home Isolation Practice:
 Recommended to Asymptomatic and MILD symptomatic cases with NO OTHER
INDICATION (Uncontrolled Co-morbidities) for admission.
 Home must have facility for Separate Room with Separate Bathroom for the patient. A
Caretaker must be available.
 Patient and Caretaker must be given 24x7 contact number for any emergency.
 Patient and Caretaker must be trained in use of Pulse Oximeter and Six minutes’ walk test (6
minutes’ hand grip exercise, if patient is unable to walk).
 Kit containing medicines including Zinc tablets (50 mg OD), Vitamin C (500 mg BD) and
Vitamin D (1000 units OD) must be provided to the patient.
 Favipiravir to be provided to the patient on paid basis ONLY on demand. Dosage should be
1800 mg BD for first day and then 800 mg BD from day 2 for next 7-14 days.

Home Isolation Practice:
 Every patient to have a physical examination by a paramedical staff or a doctor attached to
home isolation team around 5th day of symptoms.
Team should personally record SpO2, both in resting and after a 6
minutes’ walk. Scoring on Modified NEWS protocol to be done.
 Lab Investigations also to be done on 5th day of symptoms. Radiological investigations to be
done only if indicated.
 If abnormalities on investigations or on examination, patient to be shifted to Institutional or
Day-care as advised by the treating physician.
 If patient remains asymptomatic throughout, then may be considered for discharge from
supervised care on 10th day of symptoms/ test being positive.

Modified Protocol For Home Monitoring
Parameter Finding Score Scoring
0 1 2 3
Age (in Years) <65 ≥65
Respiratory Rate (per minute) 12-20 9-11 21-24 ≥25
≤8
Sp02 (%) <95 94-95 92-93 ≤91
Systolic BP (mmHg) 111-219 101-110 91-100 ≥220
≤90
Pulse rate (per minute) 51-90 91-110
41-50
111-
130
≥131
≤40
Consciousness Alert Drowsy
Lethargy
Temperature (oC) 36.1-
38.0
38.1-39.0
OR
35.1-36.0
≥39.1 ≤35.0
Temperature (oF) 97-
100.4
100.6- 102.2
OR
95.2-96.8
≥102.4 ≤95
Total Score
Score Recommendation
0 Routine Monitoring to continue
1-4 Advise Lab Testing and Increased Monitoring
5-6 Immediately talk to Treating Physician and Transfer per advice
≥7 Immediately transfer to Casualty

RTPCR/ RAT Positive
Home Isolation
Telephonic Consultation
Institutional Care
Lab Investigations/ HRCT
Normal Deranged (CRP >4
times) HRCT Abormal
Borderline
(CRP Up to 4 times)
After 5 Days of Symptoms
Discharge
Process Flow For Home Isolation
Physical Examination
Re-Assess in 2 Days
After 10 Days of Symptoms
Daycare
SpO2 >95%
SpO2 <95%

AFTERMATH OF COVID19

A wave of chronically ill and slow-healing survivors is an
inevitability we can and must prepare ourselves for.

CASE VIGNETTE -1
• 43 yr old male doctor with no comorbidities presented with complaints
of fever and myalgias for 5 days
• Covid RT PCR was positive on 12/8/2020
• Spo2 – 95% on room air
• Started on antipyretics, antivirals (daclatasvir and sofosbuvir) and other
supportive management

INVESTIGATIONS- 12/8
HEMOGRAM
Hemoglobin 14.9 gm%
TLC 4,000 cells/cu mm
DLC P55%, L36%, M
7%,
Platelets 1.5Lakhs/mm3
ESR 38 mm/hr
CRP 11 mg/L
KIDNEY FUNCTION TESTS
Blood urea 23 mg%
Serum
creatinine
0.8 mg%
LIVER FUNCTION TESTS
AST 30 U/L
ALT 40 U/L
Alkaline phosphatase 94 U/L
Serum bilirubin 0.4 mg%
Direct/indirect bilirubin 0.1/0.3 mg%
Serum proteins 7gm%
Serum albumin 4.3 gm%
LDH 204U/L
Ferritin – 748mcg/l
D-dimer – 0.24 mcg/ml

CT THORAX-17/8

• Was on home quarantine
• Repeat PCR was negative on 19/8/2020
• On follow-up: Patient complaining persisting fever and myalgias

INVESTIGATIONS- 30/08
HEMOGRAM
Hemoglobin 13.9 gm%
TLC 11,000cells/cumm
DLC P80%, L16%, M
2%,
Platelets 2.0Lakhs/mm3
ESR 38 mm/hr
CRP 10 mg/L
KIDNEY FUNCTION TESTS
Blood urea 26 mg%
Serum
creatinine
1.0 mg%
LIVER FUNCTION TESTS
AST 77 U/L
ALT 148 U/L
Alkaline phosphatase 88 U/L
Serum bilirubin 0.6 mg%
Direct/indirect bilirubin 0.2/0.4 mg%
Serum proteins 6.4gm%
Serum albumin 3.9gm%
LDH 204U/L
Ferritin – 857mcg/l
D-dimer – 0.41 mcg/ml
Procalcitonin –ve
IL-6 – 39.2pg/ml

CT THORAX- 01/9

• Started on corticosteroids (methyl prednisolone 32mg) on 02/09/2020
• Fever subsided 2 days after steroid initiation, Inflammatory markers
normalised..
• Steroids gradually tapered (now on 8mg methyl prednisolone)
• Present issue : Persistent fatigue….

Defining post-acute covid-19
Symptom extension beyond 3 weeks from the onset of first
symptoms & Chronic covid-19 as extending beyond 12 weeks
BMJ 2020;370:m3026

COVID
ASYMPTOMATIC
40%
SYMPTOMATIC
60%
MODERATE TO SEVERE
REQUIRING HOSPITALISATION
20%
MILD DISEASE
DONOT REQUIRE
HOSPITALISATION
80%
ONLY 5% REQUIRE ICU
ADMISSION
10%
“LONG COVID”
The long haulers
Why are we discussing??

10%
“LONG
COVID”

• Post-acute covid-19 - “long covid” seems to be a “multisystem disease”
• Management of post covid-19 is currently based on limited evidence
• Approximately 10% of people experience prolonged illness after covid-19
• Many such patients recover spontaneously with holistic support, rest,
symptomatic treatment, and gradual increase in activity

• ANXIETY
• FATIGUE
• DYSFUNCTIONAL
BREATHING
• POST VIRAL COUGH
• VTE
• PTSD & COGNITIVE
IMPAIREMENT
• MANAGEMENT OF OXYGEN
REQUIREMENTS
POST COVID
HOLISTIC
MANAGEMENT
George PM, et al. Thorax 2020;0:1–8.
MULTISYSTEM DISEASE

JAMA. 2020;324(6):603-
605
Persistent symptoms in patients after acute
COVID-19

J Med Virol. 2020;1–10

Important distinction between….
Persistent
inflammation
Sequelae of
organ damage
Non specific
effects of
hospitalisation
& social
isolation

Myalgic encephalomyelitis / chronic fatigue syndrome
'My fatigue
was like
nothing I've
experienced
before'
'I don’t have a
life, I currently
have an
existence'

SPECTRUM OF CHRONIC FATIGUE SYNDROME

The Five Mutually Reinforcing Drivers Of CFS/ME
BMSystems 2020 CONFIDENTIAL www.bmsystems.org

Pathogenesis – Superposition of Humoral and cellular Responses???
BMSystems 2020 CONFIDENTIAL www.bmsystems.org

Management
BMSystems 2020 CONFIDENTIAL www.bmsystems.org

"Covid Recovery Plan"
“The Four Ps"
Post COVID-19 Patient information pack – NHS Foundation
Trust

• 55 Covid survivors included in the study
• Patients were followed up after 3 months
• The presenting symptoms during follow up included gastrointestinal (GI)
symptoms (30.91%), headache (18.18%), fatigue (16.36%), exertional
dyspnea (14.55%), as well as cough and sputum (1.81%).
Yu-miao Zhao et al, EClinicalMedicine,2020

CASE VIGNETTE -2
• A 42-year-old diabetic and hypertensive presented with
• Fever-5 days
• Cough -5 days
• Shortness of breath- 2 days
• On examination: RR-18 breaths/min, SPO2-96% on room air
• Covid-19 RT-PCR positive
• Initially received symptomatic treatment
• 2 days later- developed breathlessness and hypoxemia
• Dexamethasone 8 mg OD and Remdesivir started

• Symptoms persisted-Received HFNC
support and 2 doses of convalescent
plasma therapy
• Given tocilizumab in view of worsening
hypoxemia
• Patient improved clinically and weaned
off from HFNC support 21/7/20

• Hypoxemia persisted requiring 3 lit of oxygen
support with nasal prongs
• Blood investigations
• CRP-0.93 mg/L (0-5 mg/L)
• Ferritin-94.6 ng/ml (30-400 ng/ml)
• Pirfenidone (200 mg TDS) started in view of
persistent opacities (secondary to pulmonary
fibrosis) but was stopped due to drug intolerance
(diarrhoea)
• Advised home oxygen therapy at the time of
discharge
31/7/20

Serial Chest Radiographs
10/7/20 31/7/20
21/7/20

• He now presented to OPD with complaints of
• Persistent breathlessness
• Fatigue and
• Dry cough
• On examination:
• PR -82/ min
• B.P- 124/78 mm Hg
• RR-20 breaths/min
• SpO2 – 97 % on room air at rest and 94-95% on exertion

FOLLOW UP CT

Respiratory Issues Post Covid

• Fifty-seven patients completed the serial assessments.
• There were 40 non-severe cases and 17 severe cases.
• Compared with non-severe cases, severe patients showed higher incidence of
DLCO impairment (75.6% vs4 2.5%) and significantly lower %age of predicted TLC
and 6MWD.
ABNORMAL CT FINDINGS 54.3%
ABNORMAL PFTs 75.4%
DECREASE IN DLCO 52.6%
DECREASE IN TLC 12.3%
Huang et al. Respiratory Research (2020) 21:163
Pulmonary recovery in COVID-19 lags behind
virological clearance.

Respiratory symptoms
Cough
• Best managed with simple breathing
control exercises
• Medication where indicated (such as
proton pump inhibitors if reflux is
suspected)
• Adequate hydration
• Steam inhalation

Breathlessness
• One of the more serious
symptoms of COVID19—the
infection
• A degree of breathlessness is
common after acute covid-19.
• Etiology:
• Residual pulmonary fibrosis
• Residual pulmonary thrombi

Pulmonary fibrosis
Acute or chronic
inflammation
Alveolar epithelium
damage
Overexpression of
proinflammatory cytokines
Fibroblasts and myofibroblasts
activation
Excessive deposition
of collagen in ECM
J. Clin. Med. 2020, 9, 1917; doi:10.3390/jcm9061917

PULMONARY
FIBROSIS
TREATMENT
ANTIVIRALS
DRUGS FOR
IPF
(NINTEDANIB,
PIRFENIDONE)
PLASINOGEN
ACTIVATION
(tPA, STK,
Urokinase)
Hyperbaric
oxygen
Mesenchymal
Stem cells
Spironolactone
J. Clin. Med. 2020, 9, 1917; doi:10.3390/jcm9061917

Role of antifibrotics
• They do not address the immune dysregulation of SARS-CoV-2
infection, nor can they be expected to attenuate the prothrombotic
aspects of this complex pathogenic process.
• If antifibrotic therapy is to have a role, it is likely to take the form of
inclusion in combination regimens, once effective anti-inflammatory
treatments have been identified.

Pirfenidone: A novel hypothetical treatment for COVID-19
Inhibit
apoptosis
Downregulate
ACE receptors
expression
Decrease
inflammation
Ameliorate
oxidative
stress
Medical Hypotheses 144 (2020) 110005

Novel antifibrotics
Lancet Respir Med 2020; 8: 807–15

Lancet Respir Med 2020; 8: 807–15
Antiviral
effects???
Can be
preventive??

Uncertainties…
Choice of
drug
Duration of
treatment
Identification
of
biomarkers
(predictive &
prognostic)

RESPIRATORY FOLLOW-UP POST COVID

Patients at highest risk of COVID-19 pneumonia complications
• All patients managed on ICU/HDU
• All patients discharged with a new oxygen prescription.
• All patients with protracted dependency on high inspired fractions of
oxygen, continued positive pressure ventilation and bi-level non-
invasive ventilation.

George PM, et al. Thorax 2020;0:1–8

George PM, et al. Thorax 2020;0:1–8

Covid 19 and Heart

Circulation. 2020;142:342–353

Patients recently recovered from COVID-19 infection, CMR revealed cardiac
involvement in 78 patients (78%) and ongoing myocardial inflammation in 60
patients (60%), independent of pre-existing conditions, severity and overall course
of the acute illness, and time from the original diagnosis.
These findings indicate the need for ongoing investigation of the long-term
cardiovascular consequences of COVID-19.
JAMA Cardiol. doi:10.1001/jamacardio.2020.3557

MULTISYSTEM INFLAMMATORY
SYNDROME IN COVID-ADULTS

CRITERIA
1) Severe illness requiring hospitalization in a person aged ≥21 years
2) Positive test result for current or previous SARS-CoV-2 infection during admission
or in the previous 12 weeks
3) Severe dysfunction of one or more extrapulmonary organ systems
4) Laboratory evidence of severe inflammation
5) Absence of severe respiratory illness

Pathogenesis
Nat Rev Immunol. 2020 Aug;20(8):453-
454.
? Unknown

INTERVAL
• Interval between infection and development of MIS is unclear
• In patients who reported typical COVID-19 symptoms before MIS
onset, MIS was experienced approximately 2–5 weeks later

MANAGEMENT
• Aspirin
• Anticoagulation
• IvIg
• Corticosteriods
• Vasopressors
• Ventilatory management

Covid 19 & Psychiatric illness
The Hindu- August 2020

Covid 19 & Psychiatric illness
• Anxiety - 12 to 20%
• Depression - 15 to 25%
• Insomnia - 8%
• Traumatic distress - 35 to 49%
HCW
• Insomnia – 42 %
• Impaired attention or concentration – 38 %
• Anxiety – 36 %
• Memory impairment – 34 %
• Depressed mood – 33 %
• Confusion – 28%
Patients
JAMA Psychiatry.

PTSD
• Seen in upto 32%
• Epidemiological data indicate that
the median time for PTSD to remit is
✓ 36 months for individuals who sought help
✓ 64 months for individuals who never sought
help for a mental health problem.
Fear of infection,
social isolation,
stigmatisation
Witnessing of
patients who
suffer from,
struggle against
and die
Direct
experiencing and
suffering from
symptoms
Xiao et al. Global Health Research and Policy (2020) 5:29

COVID TRAUMA RESPONSE WORKING GROUP RAPID GUIDANCE

Rehabilitation for Severe COVID-19
• The illness may be complicated by respiratory failure and other forms
of multi organ failure, resulting in ICU admission with likely invasive
mechanical ventilation.
• Rehabilitation needs are typically related to the consequences of
ventilatory support, and prolonged immobilization

Rehabilitation for Severe COVID-19
• Impairments most likely to encounter:
• Physical deconditioning and muscle weakness, fatigue
• Impaired lung function
• Delirium and other cognitive impairments
• Impaired swallow and communication
• Mental health disorders and psychosocial support needs.
• Multi-disciplinary team approach is key
• Still many unknowns related to the pathophysiology of COVID-19
and the long-term complications, many organs can be affected

Acute
Objectives
- Optimize oxygenation
- Manage secretions
- Prevent complications
Post-acute
Objectives
- Identify and manage impairments for
affected functioning domains
- Facilitate safe discharge and onward
referral
Long-term
Objectives
- Optimize functioning/ minimize impact
of impairments on independence and
quality of life
Rehabilitation in COVID-19

Comprehensive Post Covid Care

Conclusion…
• The long-term effect of COVID-19 is still largely unknown.
• Potential areas of research and innovation need could include:
• Developing new treatments that prevent the deterioration of lungs in the acute
presentation of the virus.
• Understanding the mental impact of post COVID damage.
• Creating the tools to help people to self-manage their long-term recovery.
• Establishment of “Post Covid Care Clinics” with involvement of multidisciplinary
teams

BMJ 2020;370:m3565

THANKS