COVID-19 (Coronavirus Disease 2019)

Medical Therapy
 COMMONLY USED DRUGS THAT ARE LIKELY TO BE BENEFICIAL
Drug Mechanism Dose Comments
Methyl- Glucocorticoid – downregulates pro- 1 mg/kg/day IV for 5-10 days is acceptable. ***Proven to be beneficial only in patients who require
prednisolone inflammatory cytokine production Higher doses (500mg/d x 3 doses) need supplemental O2/ mechanical ventilation. Should not be
further research used for mild/asymptomatic cases – may be potentially
harmful if used in this group
Dexamethasone Glucocorticoid– downregulates pro- 6mg/d PO/IV for 5-10 days (based on data
inflammatory cytokine production from RECOVERY trial)
Enoxaparin LMWH – Anticoagulant Prophylactic – 40mg s.c OD Can be tried in moderately ill & critically ill patients (for
Therapeutic - 1mg/kg s.c BID (or) standard DVT prophylaxis) and may be beneficial in
1.5mg/kg/day patients with D-dimer > 1 μg/L/ elevations > 6x ULN.
Dose is controversial. Prophylactic dose vs therapeutic
Fondaparinux Factor Xa inhibitor - anticoagulant Prophylactic –2.5mg s.c OD dose – debate is STILL ON. Therapeutic doses in the
Therapeutic -5-10mg s.c OD (based on absence of VTE can increase bleeding risk !
weight) Dose adjustments needed in elderly and those with renal
failure. Safe in pregnancy and breast feeding.
If heparins are C/I – Intermittent Pneumatic compression
devices are an alternative.
Remdesivir Adenosine nucleotide analogue, a 200mg IV on D1 & then 100mg/day IV till Need more research. Early studies demonstrated a small
prodrug D5 (or D10) benefits in terms of speed of recovery. Benefit may be
Inhibits RNA polymerase (hence viral (Till D10 in case patient is on mechanical larger in patients who are NOT on mechanical ventilation
RNA synthesis) ventilation) Use in renal & liver dysfunction/ pregnancy & breast
feeding has NOT been established
Tocilizumab Anti – IL6 receptor 400mg IV x 2 doses – 12h apart ? Benefit in patients with ARDS + elevated IL6 +
(Alternatively 6mg/kg IV x 2 doses – 12h elevated CRP (≥ 75) . Uncertainties in the right dosing as
apart) well as the timing of dose. May increase the risk of
secondary infections
***RECOVERY TRIAL: Dexamethasone resulted in lower mortality for patients on ventilators (reduced by ∼ 33%) and those requiring oxygen (reduced by ∼ 20%)
 COMMONLY USED DRUGS THAT ARE LIKELY TO BE BENEFICIAL
Drug Mechanism Dose Comments
Casirivimab and mAb that specifically binds to spike 1200mg + 1200mg as a single Reduce disease progression in high risk** outpatients with mild
imdevimab (Roche) protein receptor binding domain (RBD) IV infusion disease. Combination therapy is recommended to prevent
of SARS-CoV-2, and thereby block development of escape mutants and resistance.
binding to the human ACE2 receptor
Bamlanivimab (+/- mAb against ‘S’ protein and prevents Bamlanivimab – 700mg +/- Used only in mild cases who are at high risk** of progression to
etesevimab) EUA - its engagement with ACE2 receptor etesevimab – 1400mg as single severe disease. Combination with estesevimab is recommended to
Nov 9, 2020 IV infusion prevent development of escape mutants and subsequent resistance.
Baricitinib JAK inhibitor 4mg/day x 14 days. Use along Use in hospitalized patients who require supplemental oxygen,
with remdesivir. Currently use invasive mechanical ventilation, or extracorporeal membrane
without remdesivir is NOT oxygenation (ECMO). Use along with steroids – NOT
recommended. recommended. Use in patients where steroids cannot be used (or)
C/I. Overall no mortality benefit with baricitinib at present.
Convalescent Confers passive immunity 4-13 mL/kg (usually 200 mL Poor evidence for use in hospitalized patients (no benefit). Can be
plasma over ≥ 2 hours) uses in high risk elderly contacts to confer passive immunity.
Benefits may be greater with high antibody titer (≥ 1:640) and if
treated within the first 3 days of diagnosis
**High-riskdefined as meeting at least 1 of these criteria - BMI ≥35, CKD, Diabetes, Immunosuppressed state, Age ≥65 years, Age ≥55 years and have CV disease,
hypertension, or COPD/chronic respiratory disease. Administer as soon as possible after positive viral test for SARS-CoV-2 and within 10 days of symptom onset. These
drugs are NOT beneficial in patients hospitalized due to COVID-19 and data demonstrates an unfavorable risk/benefit profile in that population.
NO PRE/POST – EXPOSURE PROPHYLAXIS IS RECOMMENDED TIL DATE FOR SARS-COV2 !!
ACEi/ARB’s, NSAID’s, Pioglitazone – No special guidelines (or) precautions required in patients with COVID19.
ADJUNCTIVE THERAPIES
ü Empiric antibiotic therapy: Consider in patients @ risk for HAI (especially those receiving strong immunosuppression)
ü Cytokine adsorbers (e.g., Cytosorb) – Extra-corporeal removal of cytokines (to reduce inflammatory injury to lungs). Only for use In ICU patients with severe COVID19
Pneumonia (with shock and significantly elevated inflammatory markers like IL6)
ü Vitamin C & Zinc: Downgrades cytokine mediated inflammatory response in experimental animals but NO evidence for its recommendation with regards to COVID19
ü Inhaled/nebulized corticosteroids: Postulated to reduce local inflammation but NO proven benefit in COVID19 and use outside patients with reactive airway disease is
controversial.
ü Vitamin D: Vitamin D has shown to downregulate inflammatory response in experimental models. Vitamin D deficiency has been postulated to result in serious disease
but NO evidence exists for the same
 INVESTIGATIONAL DRUGS THAT ARE POTENTIALLY BENEFICIAL/ EXPERIMENTAL
Drug Mechanism
Favipiravir Inhibits RNA dependent RNA
polymerase. It is a nucleoside
analog
Molnupiravir Oral antiviral prodrug of N4-
hydroxycytidine, which blocks
replication of some RNA viruses
by introducing copying errors
during replication
Ivermectin Inhibits nuclear import protein
IMPα/β1 (heterodimer)
Dipyridamole Binds to a SARS-CoV-2 protease
and can suppress viral replication
in vitro
Sitagliptin May reduce SARS-CoV-2 entry
into human cells by inhibiting viral
binding to DPP-4
Dose
1800mg PO x 2 doses on D1 &
then 800mg/d PO till 14
Unknown
Not established.
In trials: 200μg/kg/day PO
(empty stomach) x 6 days
(If used - can consider a dose of
12mg/d PO)
100mg/day
100mg/day if eGFR > 45. (If
eGFR < 45 à 50mg/day.
Avoided if eGFR < 30)
Comments
Doubtful benefit (only in moderate cases). Unlikely
to be beneficial in mild/asymptomatic patients and
those requiring mechanical ventilation.
Experimental/ under clinical trial
Active area of research. Initial studies from
Bangladesh established a small benefit in clinical
outcome. Often used in combination with
Nitazoxanide (under trial) or doxycycline (under
trial)
Experimental/ under clinical trial
Experimental/ under clinical trial. Can be tried in
patients with DM + COVID19
 INVESTIGATIONAL DRUGS THAT ARE POTENTIALLY BENEFICIAL/ EXPERIMENTAL

Drug Mechanism Dose Comments

Bevacizumab Anti-VEGF
Doxycycline ? inhibits microbial protein
synthesis by binding to the 16S
rRNA
Nitazoxanide Interference with host-regulated
pathways involved in viral
replication, amplifying
cytoplasmic RNA sensing and
type I IFN pathways
Famotidine H2 receptor blocker –beneficial
effects maybe mediated by
blocking effects of histamine,
released by dysfunctional mast
cells in COVID19
ü Others: Camostat (protease inhibitor), Umifenovir (fusion inhibitor), Baloxavir marboxil (cap dependent endonuclease inhibitor in influenza virus) ,
Recombinant ACE2 (rhACE2, APN01), Itolizumab (Anti CD6), Ibrutinib, acalabrutinib, Leflunomide and lenalidomide.
400mg IV single dose
200mg PO STAT on D1 and
then 100mg BID PO from D2-5
500mg PO BID x 6 days
Not established. 40-80mg PO
TID x 14 days.
Ongoing trial done with a dose
of 140mg IV TID
Likely beneficial. Most likely to get upgraded in the
near future. Trials are on-going and and early results
seen promising especially if given at the beginning
of clinical decompensation & early ARDS. Based on
the autopsy evidence of florid endothelial
proliferation in COVID19 patients.
Ongoing trial in combination with Ivermectin. Early
reports from Bangladesh trials showed a marginal
benefit in clinical outcomes
Often used along with Ivermectin in trials
Benefit unknown. Currently under trial. Initial
reports from experts suggested a marginal reduction
in mortality and reduced need for ventilators and
increased speed of recovery from illness.
 DRUGS THAT ARE NOT LIKELY TO BE BENEFICIAL/ DANGEROUS
Drug Mechanism
Hydroxychloroquine Increases endosomal pH required for
virus/cell fusion, as well as interfering
with the glycosylation of ACE-2
Chloroquine
Azithromycin ? Immunomodulator (acts as a
acidotropic lipophilic weak base which
modulate the pH of endosomes and
trans-Golgi network)
Lopinavir/Ritonavir Viral protease inhibitor (3CL protease
and papain like protease)
Darunavir/Ritonavir Viral protease inhibitor (3CL protease
and papain like protease)
Ribavirin Multiple – most important being
inhibition of RNA polymerase
Oseltamivir Neuraminidase inhibitor
Dose Comments
400mg PO x 2 doses on D1 More research needed. FDA currently revoked the
& then 400mg/d PO till D5 emergency use authorization given initially to treat
COVID19 and determined that hydroxychloroquine
500mg PO BID for 5-10
is unlikely to be effective in treating COVID19.
days
500mg PO on D1 and then Combination with HCQ/chloroquine can result in
250mg PO BID till D5 clinically significant QT prolongation and fatal
cardiac arrhythmias. Early reports show no benefit
compared to standard care.
400/100mg PO BID for 14 No benefit/dangerous
days
600/100mg PO BID for 14 No benefit/dangerous
days
400mg PO BID for 14 days Often used in combination with a protease inhibitor
(e.g., Lopinavir/ritonavir). No benefit observed in
early clinical trials
75mg PO BID for 5 days No benefit observed in early clinical trials