This document summarizes treatment guidelines for COVID-19 based on disease severity and stage: - Monoclonal antibodies like Sotrovimab and Bebtelovimab can reduce hospitalization when given early for mild-moderate cases. Antiviral pills Paxlovid and Molnupiravir may also be options. - For hospitalized patients, remdesivir, corticosteroids like dexamethasone, and IL-6 inhibitors like tocilizumab are recommended. Baricitinib may also help reduce mortality. Remdesivir works best early in hospitalization while corticosteroids are preferred later for patients with ARDS. - Guidelines discuss optimal dosing of cort

1. TAHSEEN J SIDDIQUI, MD, MRCPI
INFECTIOUS DISEASE SPECIALIST
FEB, 12, 2022

2. COVID-19 VARIANT PROPORTIONS IN USA

4. https://www.nejm.org/doi/full/10.1056/NEJMe2034982
https://www.nejm.org/doi/full/10.1056/NEJMe2034982#article
Efficacy of Covid-19 Therapies, According to Clinical Course &
Disease Severity.
Modified from NIAID National Institute of Allergy and Infectious Diseases

5. Early Infection: mild upper respiratory tract sx.
During this stage, the viral load of SARS-CoV-2 peaks
After 7 or 8 days, in 20% of patients the disease progresses to bilateral
pneumonia.
This second stage is characterized by a massive immune response, with
subsequent worsening of the lung damage, respiratory failure often requiring
invasive mechanical ventilation, and other organ dysfunction

8. • SARS-CoV-2 neutralizing monoclonal antibodies (mAbs) can reduce the risk
of hospitalization and death when administered early- (70%-85%)
• To date, Sotrovimab (May,2021) and Bebtelovimab (Feb,2022) are the only
two monoclonal antibodies authorized by FDA for COVID-19 treatment.
• Antibody cocktail of bamlanivimab and etesevimab was banned by the FDA
because it was shown to be ineffective against omicron. Regeneron’s
antibody, REGEN-COV, also was grounded for the same reason.

9. SOTROVIMAB (XEVUDY®)

10. SOTROVIMAB (XEVUDY®)

11. SOTROVIMAB (XEVUDY®)

12. BEBTELOVIMAB -BLAZE-4 CLINICAL TRIAL
• A new monoclonal antibody for the treatment of COVID-19 that retains activity against both the
omicron variant and the BA.2 omicron subvariant.
• a highly potent SARS-CoV-2 spike glycoprotein receptor binding domain (RBD)-specific antibody
• It is a neutralizing IgG1 monoclonal antibody that binds to an epitope within the receptor
binding domain of the spike protein of SARS-CoV-2.
• FDA granted EUA (February 11, 2022) for the for the treatment of 1) non-hospitalized mild to
moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40
kilograms) 2) with a positive COVID-19 test, and 3) who are at high risk for progression to severe
COVID-19, including hospitalization or death and 4) for whom alternative COVID-19 treatment
options approved or authorized by FDA are not accessible or clinically appropriate.
• The authorized dose of bebtelovimab is 175 mg given as an intravenous injection over at least 30
seconds.
• Bebtelovimab is not authorized for patients who are hospitalized due to COVID-19 or require oxygen
therapy or mechanical ventilation due to COVID-19.
•

13. BEBTELOVIMAB
• Side effects of bebtelovimab include itching, rash, infusion-related reactions, nausea
and vomiting.
• Serious and unexpected adverse events including hypersensitivity, anaphylaxis and
infusion-related reactions
• It may only be administered in settings in which health care providers have
immediate access to medications to treat a severe infusion reaction
• clinical worsening following administration of other SARS-CoV-2 monoclonal
antibody treatment has been reported and therefore is possible with bebtelovimab.
• Bebtelovimab should only be used during pregnancy if the potential benefit
outweighs the potential risk for the mother and the fetus

14. PAXLOVID

15. PAXLOVID
• Pregnancy/Breastfeeding: There is no experience treating pregnant women or breastfeeding mothers with PAXLOVID. For
a mother and unborn baby, the benefit of taking PAXLOVID may be greater than the risk from the treatment.
• It is recommended that you use effective barrier contraception or do not have sexual activity while taking PAXLOVID.
• Resistance to HIV Medicines. If you have untreated HIV infection, PAXLOVID may lead to some HIV medicines not
working as well in the future.

16. PAXLOVID

17. MOLNUPIRAVIR
• Molnupiravir is a nucleoside analogue that inhibits SARS-CoV-2 replication by
viral mutagenesis.
• FDA issue an Emergency Use Authorization (EUA) for the emergency use of
molnupiravir for the treatment of non-hospitalized patients with mild-to-
moderate COVID-19 who are at high risk for progression to severe COVID-19,
including hospitalization or death and for whom alternative COVID-19 treatment
options authorized by FDA are not accessible or clinically appropriate
• Molnupiravir should be administered as soon as possible after a diagnosis of COVID-19 has been
made, and within five days of symptom onset. The recommended dose for molnupiravir is 800 mg
(four 200 mg capsules) taken orally every 12 hours for five days, with or without food.
• NOT recommended for patients who are: • Pregnant • Breastfeeding • Children
• Most common side effects: • diarrhea • nausea • dizziness

18. MOLNUPIRAVIR
• Limitations on Authorized Use •
• Molnupiravir is not authorized for use in patients who are less than 18 years of age.
• Molnupiravir is not authorized for initiation of treatment in patients requiring hospitalization due
to COVID
• Molnupiravir is not authorized for use for longer than 5 consecutive days.
• Molnupiravir is not authorized for use as pre-exposure or as post-exposure prophylaxis for
prevention of COVID-19.
• Recent data shows that Molnupiravir decreased the risk of hospitalization from COVID-19 by 30% —
down from a 50% reduction observed early in the trial.
• Potential for emergence of viral mutations! (mutagenic)

19. REMDESIVIR (VEKLURY)
• Remdesivir is a nucleotide prodrug of an adenosine analog. It binds to the viral RNA-dependent RNA polymerase and inhibits viral replication
by terminating RNA transcription prematurely.
• In Hospitalized:
• FDA approved for the treatment of COVID-19 in hospitalized adult and pediatric patients (aged ≥12 years and weighing ≥40 kg).
• Dosing • 200 mg IV loading dose, followed by 100 mg IV daily for a total 5‐day duration (Extended to 10-day Tx in Vent patients)
• Infusion time 30‐120 minutes – If tolerated, shorter infusion times (30‐60 minutes) are preferred
• If the patient progresses to more severe illness, complete the course of RDV.
• In Non-Hospitalized:
• FDA recently approved its use in adults and pediatric patients (12 years of age and older who weigh at least 40 kilograms) with positive results
of direct SARS-CoV-2 viral testing, and who are not hospitalized and have mild-to-moderate COVID-19, and are at high risk for progression to
severe COVID-19, including hospitalization or death.
• EUA for treatment of pediatric patients weighing 3.5 kilograms to less than 40 kilograms or pediatric patients less than 12 years of age
weighing at least 3.5 kilograms, with positive results of direct SARS-CoV-2 viral testing, and who are not hospitalized and have mild-to-
moderate COVID-19, and are at high risk for progression
• Intravenous infusion for a total of three days for the treatment of mild-to-moderate COVID-19 disease.
• Possible side effects include increased levels of liver enzymes, which may be a sign of liver injury; and allergic reactions, which may include
changes in blood pressure and heart rate, low blood oxygen level, fever, shortness of breath, wheezing, swelling (e.g., lips, around eyes, under
the skin), rash, nausea, sweating or shivering.
• Remdesivir should not be withheld from pregnant patients if it is otherwise indicated.

20. REMDESIVIR (VEKLURY)

21. © 2021 American Society of Health-System Pharmacists, Inc. All rights

22. CORTICOSTEROIDS (ANTI-INFLAMMATORY)
Hospitalized Patients:
• Multiple randomized trials indicate that systemic corticosteroid therapy improves
clinical outcomes and reduces mortality in hospitalized patients with COVID-19
who require supplemental oxygen (RECOVERY trial)
• There is no observed benefit of systemic corticosteroids in hospitalized patients
with COVID-19 who do not require supplemental oxygen.
• Dose: DEXAMETHASONE 6 mg IV or PO once daily for up to 10 days or until
hospital discharge.
• If DEX is not available, an equivalent dose of another corticosteroid may be
used.
Non-hospitalized Patients:
• No data to support the use of systemic corticosteroids in non-hospitalized
patients with COVID-19
• Early use of corticosteroids blunt the immune response in COVID-19 patients

23. CORTICOSTEROIDS- OPTIMAL DOSING
• The optimal dosing and duration of corticosteroid therapy in COVID-19 remains unclear
• If dexamethasone is not available, other corticosteroids may be substituted at equivalent daily doses :
• Dexamethasone 6 mg (oral or IV) : Long half-life 36 to 72 hours, administer once daily.
• Prednisone 40 mg once daily or in 2 divided doses daily
• Hydrocortisone 160 mg in 2 to 4 divided doses daily (Short half-life 8 to 12 hours
• Methylprednisolone 32 mg once daily or in 2 divided doses daily - Intermediate half-life 12 to 36 hours
• High dose of methylprednisolone of 250 to 500 mg every day for three days with a subsequent change to oral
prednisone 50 mg every day for 14 days compared with 6 mg dexamethasone for 7 to 10 days, statistically
significantly decreased the recovery time in patients with severe COVID-PNA outside the ICU
(https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252057/Kaohsuing Medical University Hospital,
TAIWAN)
• Compared with 6 mg of dexamethasone, 12 mg of dexamethasone did not statistically significantly increase the
number of days alive without life support at 28 days. (JAMA. 2020;324(13):1307-1316.)
• In hospitalized patients with COVID-19-related ARDS, high-dose dexamethasone (20 mg daily for 5 days,
followed by 10 mg daily for 5 days)) rapidly improves the clinical status and decreases inflammatory biomarkers.
Italian study- https://pubmed.ncbi.nlm.nih.gov/34275096/

24. • Systemic corticosteroids used in combination with other agents, including other immunomodulators (tocilizumab
or baricitinib) have demonstrated clinical benefit in subsets of hospitalized patients with COVID-19, especially
those with early critical illness and/or with signs of systemic inflammation
• There is insufficient evidence to recommend either for or against the use of inhaled corticosteroids for the
treatment of COVID-19.
• Adverse effects (e.g., hyperglycemia, secondary infections, psychiatric effects, avascular necrosis)
• Early use of corticosteroids blunt the immune response in COVID-19 patients not yet seriously ill may be
counterproductive
• Risk of opportunistic fungal infections (e.g., Mucormycosis, Aspergillosis) and reactivation of latent infections
(e.g., hepatitis B virus infection, herpesvirus infections, strongyloidiasis, tuberculosis)
• Pregnancy: NIH Panel recommends using dexamethasone in hospitalized pregnant patients with COVID-19
who are mechanically ventilated or who require supplemental oxygen but are not mechanically ventilated.
• In pregnancy or breastfeeding women, prednisolone 40 mg administered by mouth (or intravenous
hydrocortisone 80 mg twice daily) should be used instead of dexamethasone. (WHO)
CORTICOSTEROIDS

26. TOCILIZUMAB (ACTEMRA®)
FDA has issued an EUA for the emergency use of
ACTEMRA for the treatment of coronavirus
disease 2019 (COVID-19) in hospitalized adults
and pediatric patients (2 years of age and older)
who are receiving systemic corticosteroids and
require supplemental oxygen, non-invasive or
invasive mechanical ventilation, or extracorporeal
membrane oxygenation (ECMO).
Tocilizumab is a recombinant humanized
anti-human interleukin 6 (IL-6) receptor
monoclonal antibody of the immunoglobulin
IgG1κ (gamma 1, kappa) subclass with a
typical H2L2 polypeptide structure.
Tocilizumab binds specifically to both soluble
and membrane-bound IL-6 receptors (sIL-6R
and mIL6R), and has been shown to inhibit
IL-6-mediated signaling through these
receptors.

27. TOCILIZUMAB (ACTEMRA®)
Can be concomitantly
used with dexa
/Remdeisivir

28. BARICITINIB (OLUMIANT)
• Baricitinib acts through the inhibition of JAK1 and JAK2 and consequently blocks the immune cascade
and reduces viral replication.
• Baricitinib may play a role in management of COVID 19 through its inhibition of the pro-inflammatory
response seen in patients with moderate to severe disease
• Baricitinib has postulated antiviral effects by blocking SARS-CoV-2 from entering and infecting lung cells.
• Standard-of-care for late-stage patients on ventilators, as it reduces the risk of death by 46%
• Common side effects reported with baricitinib use in RA include upper respiratory tract infections,
increased risk for opportunistic infections, reactivation of herpes zoster virus (HZV), decreased
hemoglobin levels neutrophil counts and lymphocyte counts, and elevations in liver enzymes and serum
creatinine.
• serious infections (including tuberculosis or other bacterial, invasive fungal, and viral infections),
malignancy, and thrombosis (including DVT, PE, and arterial thrombosis due to hypercoagulable state
leading to risk for thromboembolic events.
• Baricitinib should only be used during pregnancy if the potential benefit justifies the potential risk for the
mother and the fetus

29. BARICITINIB (OLUMIANT)

30. BARICITINIB (OLUMIANT)

31. THERAPEUTIC MANAGEMENT OF HOSPITALIZED ADULTS WITH
COVID-19

33. CLINICAL
PATHWAY

34. LAST UPDATED: DECEMBER 16, 2021

35. THERAPEUTIC MANAGEMENT OF HOSPITALIZED ADULTS WITH
COVID-19
• On the basis of this evidence, remdesivir is likely to be most effective in early Covid-19 (ordinal score of 4 or 5), whereas
dexamethasone is likely to be most effective later in the disease course (ARDS).Randomized Evaluation of Covid-19 Therapy (RECOVERY)
.