Covid

Covid-19 management
BY:
Dr Shaheen sultan
Fellow Nephrology
Admission criteria:
• Age > 65
• Comorbids
• Pregnancy
• Homeless person
• No home isolation
• Hypotension
• Hypoxemia
• Altered mental status
• Abnormal chest findings
• Signs of heart failure
• Q-sofa score 2 or greater.
Q SOFA Score
Operational definitions:
• Asymptomatic cases: +ve NP RT-PCR
• Mild cases: uncomplicated upper respiratory tract symtoms.
• Moderate cases: Fever, respiratory symptoms, CXR signs of pneumonia.
• Severe cases: Fever or RTI plus:
– Respiratory rate > 30 breaths/min
– Severe respiratory distress
– Central cyanosis
– Confusion, agitation, restlessness
– CURB 3 or 4 score
– Q-SOFA score 2 or more
– SpO2 ≤ 93% on room air
– Bilateral or widespread infiltrates on CXR
– PaO2/FiO2 ratio less than 300 OR PaO2 less than 65 OR Rising PaCo2
– Evidence of heart failure: Raised JVP, Gallop rhythm
Classification of severity
Mild disease
-Symptoms consistent wih COVID
-No chest infiltrates
- O2 sat > 94% on room air
-No hemodynamic compromise
Moderate
- Chest infiltrates < 50% of chest
-Mild Hypoxia : O2 sat <94% but >90%)
Severe
-Chest infiltrates>50of chest
-Significant hypoxia : O2 sat <90% on room air
-R.R >30
-severe respiratory distress
Note : Any of these parameters is sufficient to label as severe
Critical:
Severe COVID with any of :
-ARDS
-Septic shock ( viral sepsis)
-Multi organ
Assessment for Cytokine release syndrome (CRS)
• Any of the following in the presence of moderate , severe or critical disease :

• A- Ferritin >1000 mcg/L and rising in last 24 hrs
• B- Ferritin >2000 in patients with high oxygen demand
• C- Lymphopenia <800 cells/ml OR L% < 20% OR Neutrophil lymphocyte ratio
(NLR) > 5 and 2 of the following :
• ✓ CRP > 70mg/L and rising trend
• ✓ LDH > 300Iu an rising trend
• ✓ D-Dimer >1000 ng/ml (1 mcg/ml)and rising trend
• ✓ Ferritin > 700mcg/ml and rising trend
prophylaxis
• There is no role of prophylactic chloroquine or

hydroxychloroquine at this time.
• prophylactic use of these drugs is strongly discouraged.
Anticogulation
• adjustment will be required in case of renal impairment or morbid obesity (BMI ≥ 40kg/m2)
• If the patient was already on oral anticoagulation for another indication (such as atrial fibrillation):
• If the patient was not on anticoagulation at the time of admission

• • In moderate disease: Start standard DVT prophylaxis (enoxaparin 40 mg once daily once daily)
• • If Severe disease: Start aggressive prophylaxis (Enoxaparin 40mg every 12 hourly)
• Indications for therapeutic anticoagulation (any of the following):

• • Documented presence of thromboembolic disease (such as ultrasound doppler or CT for PE)
• • Strong suspicion for thromboembolic disease when investigation cannot be done
• • D-Dimer over 3 times normal upper limits
• Dose: Enoxaparin 1mg/kg every 12 hourly

• Dose adjustment
• Acute Renal Failure
• Prophylaxis:
• Cr Cl >30 ml/min 40mg OD or BD enoxaparin
• Cr Cl < 30 and >15 ml/min 30mg OD or BD enoxaparin
• Cr Cl < 15 ml/min Unfractionated Heparin preferred
• Dialysis Unfractionated Heparin preferred
• Therapeutic:
• Cr Cl >30 ml/min 1 mg/kg s/c BD enoxaparin
• Cr Cl < 30 and >15 ml/min 1 mg/kg s/c OD enoxaparin
• Cr Cl < 15 ml/min Unfractionated Heparin preferred
• Dialysis Unfractionated Heparin preferred
• Morbid Obesity (BMI ≥ 40kg/m2)
Management
Candidate therapeutics
Remdesivir
Chloroquine
Hydroxychloroquine
Lopinavir/ritonavir
Lopinavir/ritonavir plus interferon beta-1a
Convalescent plasma
Antibodies
Candidates therapeutics updated till 19 June20
ULTOMIRIS (RAVULIZUMAB-CWVZ), COMPLEMENT INHIBITOR
Phase III to start in May 2020
SOLIRIS (ECULIZUMAB), COMPLEMENT INHIBITOR

Phase II recruiting May 2020. Expanded access protocols
MEDI3506, MONOCLONAL ANTIBODY TARGETING INTERLEUKIN 33

ACCORD Phase II trial to start May 2020
REMSIMA (INFLIXIMAB), ANTI-TNF ANTIBODY

Phase II trial to start in June 2020
continue
ANTI-LIGHT MONOCLONAL ANTIBODY
LERONLIMAB (PRO 140), A CCR5 ANTAGONIST
SYLVANT (SILTUXIMAB), INTERLEUKIN-6 TARGETED MONOCLONAL
ANTI-ANGIOPOIETIN 2 (ANG2) ANTIBODY
LENZILUMAB, ANTI-GRANULOCYTE-MACROPHAGE COLONY STIMULATING FACTOR ANTIBODY

TJM2 (TJ003234), ANTI-GRANULOCYTE-MACROPHAGE COLONY STIMULATING FACTOR ANTIBODY
IC14, RECOMBINANT CHIMERIC ANTI-CD14 MONOCLONAL ANTIBODY
ILARIS (CANAKINUMAB), INTERLEUKIN-1BETA BLOCKER
PD-1 BLOCKING ANTIBODY; THYMOSIN
AVASTIN (BEVACIZUMAB), VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITOR
ACTEMRA (TOCILIZUMAB), INTERLEUKIN-6 RECEPTOR ANTAGONIST
KEVZARA (SARILUMAB), INTERLEUKIN-6 RECEPTOR ANTAGONIST
Pre clinical trial
• Antibodies from recovered COVID-19 patients
• Virna Therapeutics/ University of Toronto..Neutralizing
antibodies
• VIR-7831 and VIR-7832, antibodies from recovered SARS
patients
• Purified ovine immunoglobulin from immunized sheep
• Polyclonal hyperimmune globulin (H-IG)
Note that :
• Antibiotics
• Antibiotics should only be used in cases where a bacterial
infection is suspected, for example in cases with an elevated
white cell count (in the absence of steroid) or procalcitonin.
There is no role of prophylactic antibiotics to prevent a
secondary infection.
• Hydroxychloroquine and chloroquine
• These are no longer recommended given recent studies showing
potential harm and lack of clear benefit.
Asymptomatic cases:
• Home isolation OR
• Monitored institutional isolation
• Educate patient
• No specific treatment (including chloroquine
hydroxychloroquine, azithromycin, ivermectin or, famotidine) is
recommended for asymptomatic or mild disease
• Repeat NP-PCR on day 14
– if negative DC isolation.
– If positive repeat after 5 days.
Mild cases:
• Home/ institutional isolation
• Single room/ cohort (minimum 1 meter distance)
• Contact and droplet precautions.
• Cbc, cr, electrolytes CXR.
• Hydration
• Paracetamol
• Avoid Nsaids and ACE inhibitors
Moderate cases:
Moderate disease without CRS
Moderate disease with CRS
Moderate disease without CRS
• • Mainstay of management : oxygen therapy to maintain O2 sat > 94%

• • Alert proning of 12-16 hrs
• • If available : Remdesivir 200mg iv on day-1 , followed by 100mg iv daily on day 2-5
• • Standard VTE prophylaxis
• • If patient was already on an oral anticoagulant for a pre-existing condition e.g AF, continue with
same
• • Do not prescribe steroids
• • Do not prescribe antibiotics until there is evidence or strong suspicion of bacterial infection
( e.g raised TLC in the absence of steroids AND procalcitonin > 1 , positive blood culture for a
known pathogen )
• • Monitor for increasing oxygen requirement and development of CRS .CBC , CRP , Ferritin should
be repeated after 24-48 hrs of baseline to look for increasing trend
Moderate Disease with CRS :
• In addition to all just mentioned:

• steroids : 0.5-1 mg/kg /d of iv methyl prednisone or equivalent
(including oral steroids if doing home management) for 5 days
• Tociluzimab is reserved for patients in whom worsening occurs
despite steroids (e.g rapidly increasing oxygen demand ,
progressive chest infiltrates) AND IL-6 levels are above 3 times
upper limit of normal along with increasing or persistently
elevated CRP/ ferritin despite 24-48 hrs of steroids .
Severe cases:
• Calculate SOFA
• Admit in HDU or ICU .
• Oxygen therapy for respiratory failure .
• Proning of 12-16 hrs helps in improving oxygenation in both non ventilated and ventilated patients .
• 0.5-1 mg/kg /d of iv methyl prednisone or equivalent for 5 days in patients with definite CRS
• Iv Tociluzimab 400mg once ONLY if IL-6 levels are above 3 times upper limit of normal and patient fulfills CRS
criteria AND no contra-indication exists . A repeat dose of 400mg has to be given within 12 hrs of first dose
and will only be given after ID consultation. Avoid giving TCZ in :
• ✓ Patients ventilated on arrival as risk of nosocomial bacterial and fungal infection , already substantial in
ventilated patients , are multiplied many folds for the next 3-4 weeks .
• ✓ Patients already immunocompromised e.g transplant patients on immunosuppressives, leukaemias , those on
chemotherapy , stage-4 HIV
• ✓ Patients with severe co morbids e.g severe heart failure , ESRD especially if combined with high fraility score
or poor quality of life ( FRC 3-4)
Tocilizumab
• Contraindications:
• • Active TB
• • Zoster
• • Sepsis and positive blood culture
• • Suspected GI perforation
• • Multiple Sclerosis
• • Allergy to Tocilizumab
• • ALT > 5 times or Bilirubin > 2
• • ANC <2000 or Thrombocytopenia <50
• • Pregnancy (relative contraindication)
What is the option if there is no response to toci
• 1: IVIG
• 2:C plasma
ARDS
• Onset: Within 1 week of a known clinical insult (i.e. pneumonia) or new or worsening
respiratory symptoms.
• Chest imaging: (X-ray or CT scan): bilateral opacities, not fully explained by volume
overload, lobar or lung collapse, or nodules.
• Origin of pulmonary infiltrates: respiratory failure not fully explained by cardiac failure or
fluid overload. Need objective assessment (e.g. echocardiography) to exclude hydrostatic
cause of infiltrates/edema if no risk factor presents
• Oxygenation impairment in adults
• • Mild ARDS: PaO2/FiO2: >200 mmHg and ≤ 300 mmHg (with PEEP or CPAP ≥ 5 cmH2O).
• • Moderate ARDS: PaO2/FiO2 ≤ 200 mmHg and >100 mmHg (with PEEP≥ 5 cmH2O).
• • Severe ARDS: PaO2/FiO2 ≤ 100 mmHg (with PEEP ≥ 5 cmH2O)
ARDS:
• Consider following:
• IV Remdesivir: 200 mg loading dose then 100 mg daily (pre-clinical data, in US
pts developed liver injury) (CI with HCQ or other Antivirals, pt’s on
vasopressors, ALT > 5 ULN, crcl <30 ml/min)
• IV Tocilizumab: Single 4-8mg/kg upto 800mg (repeat after 12 hours if the
response to first was poor, max 2 cumulative doses)  pt’s who failed to other
thaerapies. (Worsening of respiratory function with evidence of CRS including
elevations of IL-6, fibrinogen, d-dimer, CRP)
• LPV/r: 400mg/100mg BID 14 days.
• Hydrocortisone 100mg 8 hourly: conditional recommendation for severe
sepsis.
Discontinuation of isolation
• In those who are symptomatic, At least 10 days from the start
of symptoms AND at least 3 days after resolution of symptoms
(fever and respiratory symptoms)
• In those who are asymptomatic, Ten days from the date of the
test
• Note: A test to document cure is not required in the above-
mentioned patients.
Repeat testing
• for the following patinets two consecutive negative PCR tests a
minimum of one day apart are required to discontinue isolation
• 1. Immunocompromised patients
• 2. Those living in congregations such as jails, dorms or madrasas
(if going back to the congregation
• 3. Healthcare workers dealing with immunocompromised

patients
Dose of IVIG
• he diagnosis was modified to COVID-19, severe type. High-dose
IVIg was started on January 28 (hospital day 7) at 25 g/d for 5
days (body weight 66 kg)

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Covid-19 management

• Any of the following in the presence of moderate , severe or critical disease :

• There is no role of prophylactic chloroquine or

• If the patient was not on anticoagulation at the time of admission

• Indications for therapeutic anticoagulation (any of the following):

• Dose: Enoxaparin 1mg/kg every 12 hourly

SOLIRIS (ECULIZUMAB), COMPLEMENT INHIBITOR

MEDI3506, MONOCLONAL ANTIBODY TARGETING INTERLEUKIN 33

REMSIMA (INFLIXIMAB), ANTI-TNF ANTIBODY

LERONLIMAB (PRO 140), A CCR5 ANTAGONIST

SYLVANT (SILTUXIMAB), INTERLEUKIN-6 TARGETED MONOCLONAL

ANTI-ANGIOPOIETIN 2 (ANG2) ANTIBODY

LENZILUMAB, ANTI-GRANULOCYTE-MACROPHAGE COLONY STIMULATING FACTOR ANTIBODY

• • Mainstay of management : oxygen therapy to maintain O2 sat > 94%

• In addition to all just mentioned:

• 3. Healthcare workers dealing with immunocompromised

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