COVID 19 DRUG

THERAPY

-DR PRIYANK RASTOGI

ASSOCIATE PROFESSOR
DEPARTMENT OF MEDICINE
OUTLINE
 COVID CLASSIFICATION AS PER SEVERITY
 PHARMACOTHERAPY
 DRUGS WITH ANTIVIRAL ACTION
 ANTIVIRALS
 ANTIVIRAL ANTIBODIES
 CONVALESCENT PLASMA
 INTERFERONS
 IMMUNOMODULATORS/SUPPRESSANTS
 STEROIDS
 OTHER IMMUNOMODULATORY DRUGS
 ANTICOAGULANTS
 SUPPLEMENTS
 INVESTIGATIONAL THERAPIES
 CONSIDERATIONS FOR USING CONCOMITANT MEDICATIONS
 SUMMARY
COVID SEVERITY CLASSIFICATION AS PER
NATIONAL PROTOCOL
 MILD DISEASE: Upper respiratory tract symptoms (&/or fever) WITHOUT
shortness of breath or hypoxia
 MODERATE DISEASE: Any one of:
 1. Respiratory rate > 24/min, breathlessness
 2. SpO2: 90% to < 93% on room air
 SEVERE DISEASE: Any one of:
 1. Respiratory rate >30/min, breathlessness
 2. SpO2 < 90% on room air

AIIMS/ ICMR-COVID-19 National Task Force/ Joint Monitoring Group (Dte.GHS), Ministry of Health & Family Welfare, Government of
India. CLINICAL GUIDANCE FOR MANAGEMENT OF ADULT COVID-19 PATIENTS
POPULATION AT RISK FOR SEVERE
DISEASE
 Age > 60 years
 Cardiovascular disease, hypertension, and CAD
 DM (Diabetes mellitus) and other immunocompromised states
 Chronic lung/kidney/liver disease
 Cerebrovascular disease
 Obesity

AIIMS/ ICMR-COVID-19 National Task Force/ Joint Monitoring Group (Dte.GHS), Ministry of Health & Family Welfare,
Government of India. CLINICAL GUIDANCE FOR MANAGEMENT OF ADULT COVID-19 PATIENTS
ANTIVIRALS

 REMDESIVIR
 Binds to the viral RNA-dependent RNA polymerase and inhibits viral
replication by terminating RNA transcription prematurely.
 Effects seen best in patients with early presentation and requiring low flow
oxygen.
 Dosage:
 For Hospitalized Adults and Children (Aged ≥12 Years and Weighing ≥40 kg): RDV 200
mg IV on Day 1, then RDV 100 mg IV once daily on Days 2–5. Administer RDV IV
infusion over 30–120 minutes

Beigel JH, Tomashek KM, Dodd LE, et al. ACTT-1 trial. Remdesivir for the treatment of COVID-19—final report. N Engl J Med.
2020;383(19):1813-1826.
ANTIVIRALS

 Reduces time to clinical recovery but no mortality benefit

 Remdesivir (EUA) may be considered ONLY in patients with
 Moderate to severe disease (requiring SUPPLEMENTAL OXYGEN), AND
 No renal or hepatic dysfunction (eGFR <30 ml/min/m2; AST/ALT >5 times ULN)
 Who are within 10 days of onset of symptom/s.

AIIMS/ ICMR-COVID-19 National Task Force/ Joint Monitoring Group (Dte.GHS), Ministry of Health & Family Welfare, Government
of India. CLINICAL GUIDANCE FOR MANAGEMENT OF ADULT COVID-19 PATIENTS
ANTIVIRALS

 Lopinavir/Ritonavir
 Protease inhibitors: inhibit viral replication.
 lopinavir/ritonavir did not show efficacy in two large randomized controlled
trials in hospitalized patients with COVID-19
 NIH/CDC: not recommended in any category of covid patients
Antivirals

 Molnupiravir
 Ribonucleoside prodrug.
 Lead to defects in viral RNA genome rendering it noninfectious and unable to
replicate.
 Indicated in non hospitalized adults with mild to moderate disease and having
at least one risk factor for severe covid illness.
 Started within 5 days of symptom onset.
 DOSE: 800 mg BD FOR 5 Days per orally
 US FDA EUA.
 INDIA DGCI EUA
ANTIVIRALS

 Adverse reactions
 Mutagenic and teratogenic
 Affect bone and cartilage growth

 Precautions
 Not to be given in PREGNANCY-individuals of childbearing potential to use effective
contraception consistently for the duration of treatment and for 4 days after the
last dose of molnupiravir
 Not to be given to those with Age less than 18 years
MOVe-OUT Study Group. Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients. NEJM Dec 2021
ANTIVIRALS

 Paxlovid
 It is a combination of two Protease Inhibitor drugs: Ritonavir 100 mg and
Nirmatrelvir 150 mg.
 Inhibits viral replication.
 ‘Paxlovid’ should be administered as soon as possible after diagnosis of Covid-
19 and within 5 days of symptom onset.
 The US FDA has authorized the emergency use of PAXLOVID for the treatment
of mild-to-moderate COVID-19 in adults and children [12 years of age and
older weighing at least 40 kg] who are at high risk for progression to severe
COVID-19, including hospitalization or death, under an EUA.
ANTIVIRALS

 Dose:
 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet)
with all three tablets taken together orally twice daily for 5 days.

EPIC-HR: Study of Oral PF-07321332/Ritonavir Compared With Placebo in Nonhospitalized High Risk Adults With COVID-19
ANTIVIRALS

 Favipiravir
 Within the tissue, the molecule undergoes phosphoribosylation to favipiravir-
RTP, which is the active form of this drug.
 Inhibits the activity of RNA polymerase leading to termination of viral protein
synthesis.
 It has recently been shown that favipiravir induces lethal mutagenesis in vitro
during influenza virus infection, making it a virucidal drug. Whether a similar
activity is demonstrated against SARS-CoV-2 or not is uncertain.
ANTIVIRALS

 DOSE- usual dosage of favipiravir for adults is 1800 mg orally twice daily on
day 1, followed by 800 mg orally twice daily for 14 days.
 US FDA AND DGCI approved as EUA for treatment for mild to moderate COVID
19 patient but not incorporated in treatment guidelines by ICMR-MoHfW and
NIH
ANTIVIRAL ANTIBODIES

 The SARS-CoV-2 genome encodes 4 major structural proteins: spike (S),

envelope (E), membrane (M), and nucleocapsid (N).
 Anti-SARS-CoV-2 monoclonal antibodies (mAbs) that target the spike protein
have been shown to have a clinical benefit in treating SARS-CoV-2 infection.
 For the treatment of mild to moderate COVID-19 in nonhospitalized patients
with laboratory-confirmed SARS-CoV-2 infection who are at high risk for
progressing to severe disease and/or hospitalization.
 3 anti-SARS-CoV-2 mAb products have received Emergency Use Authorizations
(EUAs) from US FDA
 Casirivimab plus imdevimab- Available in India. EUA
 Bamlanivimab plus etesevimab
 Sotrovimab
ANTIVIRAL ANTIBODIES

 DOSE:
 Casirivimab 600 mg plus imdevimab 600 mg administered as an IV infusion or as
subcutaneous (SQ) injections
CONVALESCENT PLASMA

 Mechanism of action- plasma from donors who have recovered from COVID-19
may contain antibodies that could help suppress viral replication
 Current recommendation-
 ICMR (18/05/21)- removed from the treatment guidelines after RECOVERY
trial and PLACID trial in May 2021.
 NIH (16/12/21)- recommend against the use of convalescent plasma for the
treatment of COVID 19 in hospitalised patient without impaired humoral
immunity.
 Insufficient evidence to recommend either for or against the use of plasma
for treatment in non hospitalized and hospitalised patients with impaired
humoral immunity.
INTERFERONS

 Interferons are a family of cytokines with in vitro and in vivo antiviral

properties.
 US FDA/NIH Recommendation:
 Recommends against the use of systemic interferon alfa, lambda OR beta for the
treatment of hospitalized patients with COVID-19.
 Recommends against the use of interferons for the treatment of nonhospitalized
patients with mild or moderate COVID-19, except in a clinical trial.
STEROIDS

 Mitigate the COVID-19-induced systemic inflammatory response that can lead to

lung injury and multisystem organ dysfunction.
 Improve clinical outcomes and reduce mortality in hospitalized patients with
COVID-19 who require supplemental oxygen.
 Dexamethasone in dose of 6mg/day oral or IV for 10 days or till discharge
(whichever is earlier)
 Equivalent dose of methylprednisolone/ prednisolone can be used.
 Monitoring side effect like hyperglycemia is essential.
 No proven role of increasing the dose.
RECOVERY Collaborative Group, Horby P, Lim WS, et al. Dexamethasone in hospitalized patients with COVID-19. N Engl J Med.
2021;384(8):693-704.
STEROIDS

 Systemic corticosteroids are indicated in only moderate to severe disease

category.
 Inhalational Budesonide (at a dose of 800 mcg BD for 5 days) to be given if
symptoms (fever and/or cough) are persistent beyond 5 days of disease onset
(Therapies based on low certainty of evidence)

AIIMS/ ICMR-COVID-19 National Task Force/ Joint Monitoring Group (Dte.GHS), Ministry of Health & Family Welfare, Government of
India. CLINICAL GUIDANCE FOR MANAGEMENT OF ADULT COVID-19 PATIENTS
OTHER IMMUNOMODULATOR DRUGS

 Interleukin-6 Inhibitors
 TOCILIZUMAB: is a recombinant humanized anti-IL-6 receptor mAb.
 Infection by SARS-CoV induces a dose-dependent production of pro
inflammatory cytokine IL-6 from bronchial epithelial cells.
 Tocilizumab, when coadministered with corticosteroids, offers a modest
mortality benefit in certain patients with COVID-19 who are severely ill, have
increasing oxygen needs, and have a significant inflammatory response.
RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled,
open-label, platform trial. Lancet. 2021;397(10285):1637-1645
IMMUNOMODULATOR DRUGS

 Dose: Recommended single dose 4 to 6 mg/kg (400 mg in 60kg adult) in 100

ml NS over 1 hour.
 Tocilizumab (Off-label) may be considered when ALL OF THE BELOW CRITERIA
ARE MET
 Presence of severe disease (preferably within 24 to 48 hours of onset of severe
disease/ICU admission).
 Significantly raised inflammatory markers (CRP &/or IL-6).
 Not improving despite use of steroids.
 No active bacterial/fungal/tubercular infection.

AIIMS/ ICMR-COVID-19 National Task Force/ Joint Monitoring Group (Dte.GHS), Ministry of Health & Family Welfare,
Government of India. CLINICAL GUIDANCE FOR MANAGEMENT OF ADULT COVID-19 PATIENTS
IMMUNOMODULATOR DRUGS

 Janus Kinase (JAK) inhibitors

 These kinase inhibitors are proposed as treatments for COVID-19 because they can
prevent phosphorylation of key proteins involved in the signal transduction that
leads to immune activation and inflammation.
 Indication for use: For hospitalised patients on dexamethasone who have rapidly
increasing oxygen needs and systemic inflammation, add a second
immunomodulatory drug (e.g., tocilizumab or baricitinib)
 2 drugs:
 Baricitinib. Dose 4 mg PO once daily. Baricitinib dose is dependent on eGFR; duration of
therapy is up to 14 days or until hospital discharge.
 Tofacitinib. Dose Tofacitinib 10 mg PO twice daily for up to 14 days or until hospital
discharge. Use as an alternative immunomodulatory drug if baricitinib is not available.
 RISK OF VENOUS THROMBOEMBOLISM.
ANTICOAGULANTS

 COVID-19 has been associated with inflammation and a prothrombotic state.

 Studies have reported varying incidences of thromboembolic events in COVID
19.
 For nonhospitalized patients, anticoagulants should not be initiated for the
prevention of VTE or arterial thrombosis unless the patient has other
indications for the therapy.
 For hospitalized patients with COVID-19, prophylactic dose anticoagulation
should be prescribed unless contraindicated.
 THERAPEUTIC ANTICOAGULATION SHOULD BE RESERVED FOR CONFIRMED
CASES WITH THROMBOEMBOLISM.
COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health.
2022
ANTICOAGULANTS

 Not recommended in mild cases

 Dosage:
 Moderate case: Conventional dose prophylactic UFH/LMWH (weight based e.g.,
enoxaparin 0.5mg/kg per day SC).
 Severe case: Intermediate dose prophylactic UFH/LMWH (e.g., Enoxaparin
0.5mg/kg per dose SC BD). There should be no contraindication or high risk of
bleeding.

AIIMS/ ICMR-COVID-19 National Task Force/ Joint Monitoring Group (Dte.GHS), Ministry of Health & Family Welfare,
Government of India. CLINICAL GUIDANCE FOR MANAGEMENT OF ADULT COVID-19 PATIENTS
SUPPLEMENTS

 VITAMIN C
 It is an antioxidant and free radical scavenger that has anti-inflammatory
properties.
 There is insufficient evidence to recommend either for or against the use of
vitamin C for the treatment of COVID-19 patients.
 High circulating concentrations of vitamin C may affect the accuracy of point-
of-care glucometers.

COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health.
SUPPLEMENTS

 ZINC
 Increased intracellular zinc concentrations efficiently impair replication in a
number of RNA viruses.
 The recommended dietary allowance for elemental zinc is 11 mg daily for
men and 8 mg for nonpregnant women.
 Maximum dose of zinc sulfate 220 mg (50 mg of elemental zinc) twice daily.
 Not been shown to have a clinical benefit and may be harmful.
 There is insufficient evidence to recommend either for or against the use of
zinc for the treatment of COVID-19.
COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health.
SUPPLEMENTS

 VITAMIN D
 The rationale for using vitamin D is based largely on immunomodulatory
effects that could potentially protect against COVID-19 infection or decrease
the severity of illness.
 There is insufficient evidence to recommend either for or against the use of
vitamin D for the prevention or treatment of COVID-19.

COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health.
Considerations for Using Concomitant
Medications
 Patients with COVID-19 who are receiving concomitant medications:
 ACE inhibitors, angiotensin receptor blockers [ARBs],
 HMG-CoA reductase inhibitors [statins],
 systemic or inhaled corticosteroids,
 nonsteroidal anti-inflammatory drugs,
 acid-suppressive therapy)
 for underlying medical conditions should not discontinue these medications
unless otherwise warranted by their clinical condition.

COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health.
DRUGS NOT INDICATED IN TREATMENT

 Hydroxychloroquine
 Ivermectin
 Ritonavir/ lopinavir
UNDER INVESTIGATION

 Mesenchymal Stem Cells

 Mesenchymal stem cells are investigational products that have been studied
extensively for broad clinical applications in regenerative medicine1 and for
their immunomodulatory properties.
 It is hypothesized that mesenchymal stem cells could reduce the acute lung
injury and inhibit the cell-mediated inflammatory response induced by SARS-
CoV-2.
DRUGS FOR PRE EXPOSURE PROPHYLAXIS

 VACCINATION and COVID APPROPRIATE BEHAVIOUR

 Anti-SARS-CoV-2 monoclonal antibodies (mAbs) tixagevimab plus cilgavimab
(Evusheld)
 US Food and Drug Administration (FDA) issued an Emergency Use Authorization
(EUA) on December 8, 2021
 SARS-CoV-2 spike protein-directed attachment inhibitors.
 OFFER PROTECTION UPTO 6 MONTHS.
 For those who are moderately to severely immunocompromised and may have
an inadequate immune response to COVID-19 vaccination or vaccine AE.
US Food and Drug Administration. Fact sheet for healthcare providers: emergency use authorization for Evusheld (tixagevimab co-
packaged with cilgavimab). 2021
NATIONAL TREATMENT ALGORITHM
SUMMARY

 MILD DISEASE
 MOLNUPIRAVIR:
 EUA in USA and India IN THOSE AT HIGH RISK FOR SEVERE DISEASE

 ANTIBODY COCKTAIl
 Casirivimab plus imdevimab- EUA IN USA and India in those at high risk for severe disease
SUMMARY

 MODERATE TO SEVERE DISEASE

 Steroids as per algorithm
 Anticoagulation: as per algorithm
 Remdesivir: as per algorithm
 Tocilizumab: as per algorithm
 Baricitinib : APPROVED IN USA as alternative to Tocilizumab. EUA in India.
THANK YOU