current covid 19 management and treatment recommendations

9/30/2021

1

CurrentCOVID‐19ManagementandTreatmentRecommendations

CoreyYeates,D.O.Internal Medicine, PGY-2

Oklahoma State University Medical Center

OSHP Fall MeetingOctober 22, 2021

FinancialDisclosureandResolution

Under guidelines established under the Standards for Integrity and Independence in Accredited Continuing Education, disclosure must be made regarding relevant financial

relationships with ineligible companies within the last 24 months.

Ihavenorelevantfinancialrelationshipswithineligiblecompaniestodisclose.

9/30/2021

2

Iwillbediscussingexperimentaloroff‐labeldrugs,therapiesand/ordevicesthathavenotbeenapprovedbytheFDA.

ExperimentalorOff‐LabelDrug/Therapy/DeviceDisclosure

ProfessionalPracticeGap

• As SARS-CoV-2 continues to evolve and researchers learn more about the virus and COVID-19, treatment strategies are updated as new data becomes available

• Review of recent guidelines for management and prevention of COVID-19 infection can help guide pharmacotherapy for infected patients

9/30/2021

3

LearningObjectives

At the completion of this activity, pharmacists will be able to:1. Describe the clinical spectrum of SARS-CoV-2 infection2. Summarize evidence for the use of various pharmacologic treatments for COVID-193. State the indications, contraindications, adverse reactions and monitoring

parameters of approved pharmacologic agents for COVID-194. Identify strategies to mitigate further spread of SARS-CoV-2

At the completion of this activity, pharmacy technicians will be able to:1. List the clinical symptoms of SARS-CoV-2 infection2. Identify strategies to mitigate further spread of SARS-CoV-2

Pre‐AssessmentQuestion1

What is currently considered the standard of care for treatment of COVID-19?

A. Baricitinib

B. Corticosteroids

C. Remdesivir

D. Supplemental oxygen

9/30/2021

4


Which of the following is a reason or contraindication to withhold or discontinue remdesivir?

A. ALT >10x ULN

B. GFR <30 mL/min

C. Not requiring supplemental O2 to maintain >94% O2

D. All of the above


Which neutralizing antibody or combination is currently recommended for post-exposure prophylaxis to individuals at high risk of progression to COVID-19?

A. Bamlanivimab

B. Bamlanivimab + etesevimabC. Casirivimab + imdevimabD. Sotrovimab

E. B and C

9/30/2021

5

Outline

• Overview of COVID-19• Recommended treatments• Other therapies• Treatments under investigation• Pediatric considerations• Preventative measures

OverviewofCOVID‐19Virus transmission• Spreads via respiratory droplets/particles• Infectious period is 10-20 days from symptom onsetClinical presentation• Average incubation period is 4-5 days, estimated up to 14 days• Presentation can vary• Fever, cough, shortness of breath, myalgias, headache• Diarrhea, anosmia, dizziness, sore throat, abdominal pain,

vomiting

9/30/2021

6

COVIDProgression

OverviewofCOVID‐19

Disease severity• Non-severe illness: SpO2 > 94% not requiring supplemental O2

• Severe illness: SpO2 ≤ 94% on RA or requiring supplemental O2

• Critical illness: Mechanically ventilated or ECMO, including end-organ dysfunction (ARDS), sepsis, septic shock

9/30/2021

7

DiseaseSeverity

IDSA Guidelines on the Treatment and Management of Patients with COVID-19.Clinical Spectrum of SARS-CoV-2 Infection. National Institutes of Health.

NIH IDSA WHO

• Mild: Signs/symptoms orabnormal chest imaging

• Moderate: Evidence of lower respiratory disease clinically or on imaging, SpO2 >94% O2 on RA

• Severe: SpO2 <94% O2 on RA, PaO2/FiO2 <300, RR >30, or >50% lung infiltrates

• Critical: Respiratory failure, septic shock, multiple organ dysfunction

• Non-severe: SpO2 >94% not requiring supplemental O2

• Severe: SpO2 </= 94% on RA or requiring supplemental O2

• Critical: Mechanically ventilated or ECMO, including end-organ dysfunction (ARDS), sepsis, septic shock

• Non-severe: Not meeting criteria for severe or critical

• Severe: SpO2 <90% on RA, RR >30, signs of severe respiratory distress

• Critical: ARDS, sepsis, septic shock, or other conditions requiring life-sustaining therapy

OverviewofCOVID‐19

9/30/2021

8

RecommendedTreatments

• Corticosteroids• Remdesivir• Tocilizumab• Baricitinib• Tofacitinib• Neutralizing antibodies• Specific combinations of above medications

Corticosteroids

• Recommended for severe or critical illness (NOT for non-severe illness) based on RECOVERY trial

• Decreased mortality, patients were more likely to be discharged from the hospital

• Considered the standard of care

Mortalityat28DaysinAllPatientsandAccordingtoRespiratorySupportatRandomization

9/30/2021

9

Corticosteroids

• Dose: 6 mg IV or PO x10 days daily or until discharge• If dexamethasone unavailable, another glucocorticoid at

equivalent dose can be used• Dexamethasone 6 mg = methylprednisolone 32 mg =

prednisone 40 mg• Adverse effects: hyperglycemia, neurologic (agitation/confusion),

adrenal suppression, risk of infections (bacterial, fungal)

Remdesivir (Veklury)FDA approved: October 22, 2020• Mechanism of action: Prodrug,

nucleoside analog, inhibits SARS-CoV-2 RNA-dependent RNA polymerase preventing viral replication

• Dose: 200 mg IV x 1 load, then 100 mg IV daily x 4 days

• Renal Adjustment: Recommended not to use for GFR <30 ml/min

• Accumulation of the excipient SBECD, can lead to hepatic and renal toxicity

9/30/2021

10

Remdesivir• Drug Interactions:

• Risk of reduced antiviral activity when co-administered with chloroquine or hydroxychloroquine

• Adverse Events:• Hypersensitivity (infusion) reactions, rash, transaminase elevation, seizure (less common)

• Monitoring parameters:• Hepatic testing prior to initiation and as clinically appropriate

• Consider discontinuing if ALT > 10x ULN or ALT elevation with accompanying symptoms of liver inflammation

• Contraindications:• Hypersensitivity reaction to remdesivir or its components

RemdesivirStudy N Comparator OxygenStatus Results/Endpoint

SIMPLEsevere

397• Remdesivir x5 days• Remdesivir x10 days

• SpO2 <94% on RA• Supplemental O2

Similar clinical status at day 14

SIMPLEmoderate

584

• Remdesivir x5 days• Remdesivir x10 days• Standard of care (SOC)

x10 days

• Pulmonary infiltrates• RA >94% O2

Clinical status observed at day 11• 5-day remdesivir group had better

clinical status• 10-day remdesivir and SOC not

statistically significant• No difference in 28-day mortality

ACTT-1 1062• Remdesivir x5 days• Placebo

• RR ≥24• SpO2 <94% on RA• Supplemental O2

Shortened time to recovery

SOLIDARITY 11,330

• Remdesivir• HCQ• Lopinavir ± interferon• Placebo

VariableLittle to no effect on mortality, initiation

of ventilation, or duration of hospital stay

9/30/2021

11

Remdesivir Summary

• Benefit: clinical improvement, no reduction in mortality• Recommended 5-day treatment in severe illness versus no

antiviral treatment in addition to steroids• Not recommended in non-severe or critically ill• More information is needed for immunocompromised patients or

effect on viral load

Tocilizumab (Actemra)NOT FDA approved: EUA June 24, 2021 • MOA: Anti-IL-6-receptor blocking

antibody• Dose: 8 mg/kg actual body weight (up

to 800 mg) as a single IV dose• 2nd dose may be given 8 hours later

• Warnings and Precautions:

• ALT >10x ULN, high risk for gastric perforation, ANC <1000, platelets <50k, concurrent active infection including localized infection

Fu, B., Xu, X. & Wei, H. (2020). https://doi.org/10.1186/s12967-020-02339-3.

9/30/2021

12

Tocilizumab• Renal and hepatic impairment: no dosage adjustment, minimal data• Drug interactions:• IL-6 inhibition may lead to increased metabolism of drugs that are CYP450

substrates• Adverse Events:• Gastrointestinal perforations, increased infection risk (chronically),

thrombocytopenia, neutropenia, transaminitis, diverticulitis• Monitoring parameters:• CRP, signs and symptoms of infection during and after therapy, LFT, CBC,

abdominal symptoms

TocilizumabStudy N Comparator OxygenStatus Results/Endpoint

COVACTA 452• Tocilizumab• Placebo

• SpO2 <93% on RA• Supplemental O2• PaO2/FiO2 <300

• Higher median number of ventilator-free days

• Shorter time to clinical improvement• No difference in clinical status

RECOVERY 4116• Tocilizumab• Standard of care

• SpO2 <92% on RA• CRP ≥75 mg/dL Reduced 28-day mortality

REMAP CAP 584• Tocilizumab• Sarilumab• Standard of care

• ICU admission• Respiratory organ

support (invasive or non-invasive ventilation)

• Improved morality (28-day and 90-day)• More organ support-free days

EMPACTA 389• Tocilizumab + SOC• Placebo + SOC

• Not on mechanical ventilation

• Reduced progression to mechanical ventilation

• Did not improve survival

9/30/2021

13

Tocilizumab Summary

• Benefits: reduced mortality, reduction in inflammatory markers, slowed/prevented progression to critical illness

• Recommended for severe or critical illness in addition to steroids• Studied in patients with elevated inflammatory markers: CRP ≥75

mg/L• More beneficial if initiated early, may reduce progression of severe to

mechanical ventilation/ECMO• No available data for oncologic or other immunosuppressed patients

Baricitinib (Olumiant)NOT FDA approved: EUA July 28, 2021 • MOA: Selective JAK1 and JAK2

inhibitor• Dose: 4 mg PO daily x 14 days or

until hospital discharge• Warnings and Precautions:

• Known active tuberculosis, thrombosis, ANC <1000, hemoglobin <8 g/dL

• Prophylaxis for VTE is recommended unless contraindicated Stanford Medicine. https://medicine.stanford.edu/news/current-news/standard-news/baricitinib-

approved-for-emergency-use.html.

9/30/2021

14

Baricitinib• Renal adjustment:

• eGFR 30 to ≤60 mL/min/1.73 m2: 2 mg PO daily

• eGFR 15 to ≤30 mL/min/1.73 m2 : 1 mg PO daily

• No hepatic adjustment, consider discontinuing with hepatic impairment• Adverse Events:

• Increased risk for infections*, thrombosis*, malignancies (lymphoma)*, anemia, elevated liver enzymes, elevated CK

• Monitoring parameters:• Screen for viral hepatitis and tuberculosis prior to initiation

• Liver/kidney function monitoring as clinically indicated

*Black box warning

Baricitinib

Study N Comparator OxygenStatus Results/Endpoint

COV-BARRIER 1525• Baricitinib up to 14 days

± steroids• Placebo ± steroids

• Less than HFNC

• No significant difference in progression to death or need for ventilation

• Reduction in 28-day mortality

ACTT-2 1033• Remdesivir + placebo• Remdesivir + baricitinib

• High-flow O2• Non-invasive

ventilation

Remdesivir + baricitinib was superior in reducing recovery

time

9/30/2021

15

Baricitinib Summary

• Recommended for severe illness with elevated inflammatory markers (CRP, d-dimer, LDH)• Most beneficial for HFNC or other non-invasive ventilation• To be used in addition to steroids

• Not to be given with tocilizumab or other IL-6 inhibitors• More likely to see serious adverse reactions with chronic use• Recommended in combination with remdesivir for severe illness for those

with a contraindication to steroids

Tofacitinib (Xeljanz)

NOT FDA approved, NO EUA• Mechanism of action: Preferentially inhibits JAK1 and JAK3 with activity against

other JAK isoforms• Dose: 10 mg PO q12H up to 14 days• Renal adjustment:

• eGFR <60: 5 mg PO q12H daily

• No hepatic adjustment, consider discontinuing with hepatic impairment

9/30/2021

16

Tofacitinib

• Monitoring parameters:• CBC, liver enzymes, lipids

• Adverse Events:• Thrombosis, serious infections including TB/fungal/bacterial/viral,

lymphoma and other malignancies, increased mortality• Allblackboxwarnings

Tofacitinib

Study N Comparator OxygenStatus Results/Endpoint

STOP-COVID 289• Tofacitinib up to 14

days ± steroids• Placebo ± steroids

• Maximum HFNC

• Lower risk of death• Lower risk of respiratory

failure (progression to mechanical ventilation)

COV-BARRIER 1525• Baricitinib up to 14

days ± steroids• Placebo ± steroids

• Less than HFNC

• No significant difference in progression to death or need for ventilation

• Reduction in 28-day mortality

9/30/2021

17

Tofacitinib Summary• Recommended for severe illness (supplemental or HFNC) in addition to

steroids• Use as an alternative if baricitinib unavailable• Should not be co-administered another IL-6 inhibitor or tocilizumab• Patients should be on DVT prophylaxis at minimum while on this drug• Immunocompromised patients have no been evaluated

NeutralizingAntibodies

• Casirivimab + Imdevimab• Bamlanivimab + Etesevimab• Sotrovimab

9/30/2021

18

NeutralizingAntibodies• Directed at the receptor-binding domain of SARS-CoV-2 spike protein• GOAL: Decrease progression of disease (hospitalization)• FDA EUA for treatment with certain criteria:• Mild to moderate disease, positive direct SARS-CoV-2 viral testing• Age 12+, weight 40 kg+• Within 10 days of symptom onset• High risk for progression: age ≥ 65, obesity/overweight, pregnancy, CKD,

DM, immunosuppression, cardiovascular disease, HTN, chronic lung disease, sickle cell, neurodevelopmental disorders, medical-related technology dependence (trach, gastrostomy)


• Limitations of authorization:• Hospitalized due to COVID-19• Require oxygen therapy due to COVID-19• Require an increase in baseline oxygen flow rate due to COVID-

19 (in those on chronic oxygen therapy due to underlying non-COVID-19 related comorbidity)

9/30/2021

19

NeutralizingAntibodiesPost-exposure prophylaxis• Recommended for persons exposed to COVID-19 infection who are at high

risk of progression to severe illness• Casirivimab + imdevimab or bamlanivimab + etesevimab

• High risk individuals:• Not fully vaccinated OR not expected to mount an adequate immune

response to their vaccination AND exposure to infected person OR high risk of exposure to infected individuals

• Can reduce symptomatic infection or shorter duration of symptoms


• Dose: • Bamlanivimab 700 mg + etesevimab 1400 mg IV once• Casirivimab 600 mg + imdevimab 600 mg IV or SQ once• Sotrovimab 500 mg IV once

9/30/2021

20


Casirivimab + imdevimab• Combination shown to have

activity against all variants• Casirivimab alone has reduced

activity against beta, gamma, and delta variants


Bamlanivimab + etesevimab• Significant reduction in activity

seen against beta, gamma, “delta plus,” and mu variants

• Less likely to be effective with these variants

9/30/2021

21


• Sotrovimab• Activity against variants or

either undetermined at this time


• Goal is reduce progression of disease, aimed at high-risk populations

• Specific criteria and limitations for use• Casirivimab + imdevimab or bamlanivimab + etesevimab have

EUA for post-exposure prophylaxis in certain populations• Current evidence against variants is from pseudotyped virus

particles

9/30/2021

22

OtherTherapies

• Convalescent plasma• Ivermectin• Hydroxychloroquine/Azithromycin• Lopinavir/ritonavir• Famotidine

ConvalescentPlasma

• Not recommended for hospitalized patients• Only recommended in the context of a clinical trial for

mild/moderately ill ambulatory patients• More information is needed to determine if there is a benefit at

milder severity, and if so what dose (antibody titer)• Most benefit may be when given earlier in the course of disease

(within first 3 days of diagnosis)

9/30/2021

23

Ivermectin

• Anti-parasitic, in vitro activity against some viruses including SARS-CoV-2

• Not recommended in ambulatory or hospitalized patients with COVID-19

• Currently only FDA-approved for onchocerciasis and strongyloidiasis, used off label for other parasitic infections

• Current studies show no benefit on mortality in hospitalized patients

HydroxychloroquineAzithromycin

• Hydroxychloroquine (HCQ): 4-aminoquinoline used to treat malaria, autoimmune disorders due to immunomodulatory effects on IL-1 and IL-6

• Azithromycin (AZ): macrolide used for treatment of bacterial infections, unknown antiviral MOA

• Neither HCQ or HCQ + AZ is recommended for treatment of COVID-19• High concerns for toxicity (increased QT prolongation) especially with the

addition of AZ• Trend towards higher mortality in those treated with HCQ

9/30/2021

24

Lopinavir‐Ritonavir

• Protease inhibitors used to treat HIV• Not recommended for treatment of COVID-19• Failed to show or exclude benefit on mortality or

worsening of illness

Famotidine

• H2 receptor antagonist used to treat acid reflux and peptic ulcer disease

• Not recommended for the sole purpose of treating COVID-19• One small study showed that people on famotidine versus PPI had

improved survival• Small study with multiple types of bias

9/30/2021

25

TreatmentsUnderEvaluation

• Lopinavir-ritonavir combinations• Convalescent plasma for prophylaxis• Ribavirin• Oseltamivir• Intravenous Immunoglobulin• NSAIDs• ACE inhibitors, ARBs• Antibacterials, antifungals• Favipiravir• Immunomodulatory agents

TreatmentsUndergoingEvaluation

Lopinavir-ritonavir (L-R) combined with interferon beta or other antivirals• Shown to have in vitro activity against SARS-CoV and MERS-CoV• When combined with ribavirin, reduced mortality in SARS patients• Interferons have some in vitro activity against SARS-CoV and MERS-CoV• Triple therapy with L-R, interferon, and ribavirin is being investigated

9/30/2021

26


Convalescent plasma for prophylaxis• Currently undergoing trials for patients at high-risk exposure but without

disease• No current data on safety or efficacy yet available

Ribavirin• Only in vitro data against SARS-CoV-2 available• Patients with MERS-CoV infection: ribavirin combined with interferon, no

improvement in mortality or RNA clearance


Oseltamivir• Neuraminidase inhibitor used for prophylaxis and treatment of influenza• Being explored as a combination agent for treatment of COVID-19, not as

monotherapy• Unsure of MOA against COVID-19

IVIG• Current studies include co-administration of other treatments (steroids,

remdesivir, CCP)• Unsure of its utility at this time

9/30/2021

27

TreatmentsUndergoingEvaluationNSAIDs

• Early concerns: NSAIDs may impair recruitment of PMNs, leading to a delayed inflammatory response and resolution of infection

• RCTs are underway to determine the safety of NSAID use in COVID-19

ACE inhibitors, ARBs• ACE2 is the entry receptor for SARS-CoV-2 on human cells

• Observational studies have suggested no increased risk of acquiring COVID-19 or progression to severe disease

• Possible increased risk of renal dysfunction in COVID-19

• Currently recommended by most to continue if already on them for other medical conditions


Antibacterials/antifungals• Many patients receive broad-spectrum antimicrobials for coverage of

superimposed bacterial/fungal infections• Minimal data available on co-infection with COVID-19

Favipiravir• Purine analong that inhibits the RNA-dependent RNA polymerase of influenza

and other RNA viruses (approved for influenza in Japan)• In vitro activity against SARS-CoV-2, unsure if adequate drug levels are

achievable in vivo• Ongoing clinical trials

9/30/2021

28


Immunomodulatory agents• IL-1 inhibitors: anakinra, canakinumab• Janus kinase inhibitors: baricitinib• Being compared to remdesivir and other treatments

• GM-CSF inhibitors: mavrilimumab• May disrupt the downstream signaling of proinflammatory cytokines,

decreasing the inflammatory response seen with COVID-19• Complement inhibitors: eculizumab, ravulizumab• Complement activation has a role in the pathogenesis of ARDS

PediatricConsiderations

• Children generally have a milder illness• Has been associated with a severe

inflammatory syndrome known as multisystem inflammatory syndrome in children (MIS-C)

• Most clinical trials for treatments have been focused on the adult population

• Remdesivir and neutralizing antibodies have EUA for children age 12+

9/30/2021

29

PreventativeMeasures

• Masking, handwashing, social distancing

• Vaccinations• Recommended for all patients 12 or

older• Booster shot is recommended for

certain populations• Recommended before/during/after

pregnancy and breastfeeding• No evidence of fertility issues

ConclusionsandClinicalPearls• SARS-CoV-2 causes varying degrees of illness from asymptomatic to critical

illness that can be classified based on oxygen requirements• Multiple treatments are currently available for the treatment of COVID-19 but

many are under investigation for efficacy, mortality benefit, and use in combination with other agents

• Standard of care for COVID-19 is corticosteroids• Other therapies to consider include antivirals, monoclonal antibodies, and

janus kinase inhibitors• Vaccination, basic hand hygiene, and social distancing are crucial to prevent

the spread of COVID-19

9/30/2021

30

Post‐AssessmentQuestion1

What is currently considered the standard of care for treatment of COVID-19?

A. Baricitinib

B. Corticosteroids

C. Remdesivir

D. Supplemental oxygen


Which of the following is a reason or contraindication to withhold or discontinue remdesivir?

A. ALT >10x ULN

B. eGFR <30 mL/min

C. Not requiring supplemental O2 to maintain >94% O2

D. All of the above

9/30/2021

31


Which neutralizing antibody or combination is currently recommended for post-exposure prophylaxis to individuals at high risk of progression to COVID-19?

A. Bamlanivimab

B. Bamlanivimab + etesevimabC. Casirivimab + imdevimabD. Sotrovimab

E. B and C

ReferencesActemra (tocilizumab). Genentech. Accessed September 22, 2021. https://www.actemra.com/.

After Clinical Trial, Baricitinib Approved for Emergency Use. Stanford Medicine. Accessed September 20, 2021. https://medicine.stanford.edu/news/current-news/standard-news/baricitinib-approved-for-emergency-use.html.

Agrawal U, Raju R, Udwadia ZF. Favipiravir: A new and emerging antiviral option in COVID-19. MedJArmedForcesIndia. 2020;76(4):370-376. doi:10.1016/j.mjafi.2020.08.004.

Clinical Spectrum of SARS-CoV-2 Infection. National Institutes of Health. Updated April 21, 2021. Accessed September 6, 2021. https://www.covid19treatmentguidelines.nih.gov/overview/clinical-spectrum/.

COVID-19 Vaccines While Pregnant or Breastfeeding. Center for Diseases Control and Prevention. Updated August 11, 2021. Accessed September 20, 2021. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/pregnancy.html.

Ending Isolation and Precautions for People with COVID-19: Interim Guidance. Centers for Disease Control and Prevention. Updated September 14, 2021. https://www.cdc.gov/coronavirus/2019-ncov/hcp/duration-isolation.html.

Fact Sheet for Health Care Providers for Emergency Use Authorization (EUA) of Bamlanivimab and Etesevimab. Eli Lilly and Company. Revised September 16, 2021. Accessed September 24, 2021. https://www.fda.gov/media/145802/download.

Fact Sheet for Health Care Providers Emergency Use Authorization (EUA) of REGEN-COV (casirivimab and imdevimab). Regeneron. Revised September 2021. Accessed September 24, 2021. https://www.regeneron.com/downloads/treatment-covid19-eua-fact-sheet-for-hcp.pdf .

Fact Sheet for Health Care Providers for Emergency Use Authorization (EUA) of Sotrovimab. GlaxoSmithKline. Revised September 2021. Accessed September 24, 2021. https://www.fda.gov/media/149534/download.

9/30/2021

32

ReferencesFu, B., Xu, X. & Wei, H. Why tocilizumab could be an effective treatment for severe COVID-19?. JTransl Med 18, 164 (2020). Accessed September 24, 2021. https://doi.org/10.1186/s12967-020-02339-3.

IDSA Guidelines on the Treatment and Management of Patients with COVID-19. Infectious Diseases Society of America. Updated September 14, 2021. Accessed September 6, 2021. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/.

Immunomodulators. COVID-19 Real-Time Learning Network. Reviewed September 10, 2021. Accessed September 10, 2021. https://www.idsociety.org/covid-19-real-time-learning-network/therapeutics-and-interventions/immunomodulators/.

Immunomodulators. National Institute of Health. Updated September 24, 2021. Accessed September 10, 2021. https://www.covid19treatmentguidelines.nih.gov/therapies/immunomodulators/interleukin-6-inhibitors/.

Interleukin-6 inhibitors. National Institute of Health. Updated April 21, 2021. Accessed September 10, 2021. https://www.covid19treatmentguidelines.nih.gov/therapies/immunomodulators/interleukin-6-inhibitors/.

Malin JJ, Suárez I, Priesner V, Fätkenheuer G, Rybniker J. Remdesivir against COVID-19 and Other Viral Diseases. Clin Microbiol Rev. 2020;34(1):e00162-20. Published 2020 Oct 14. Accessed September 24, 2021. doi:10.1128/CMR.00162-20.

Olumiant (baricitinib). Eli Lilly and Company. Revised July 2020. Accessed September 22, 2021. https://uspl.lilly.com/olumiant/olumiant.html#pi

Remdesivir. COVID-19 Real Time Learning Network. Updated June 14, 2021. Accessed September 20, 2021. https://www.idsociety.org/covid-19-real-time-learning-network/therapeutics-and-interventions/remdesivir/#guidelines.

ReferencesSiddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: A clinical-therapeutic staging proposal. J Heart Lung Transplant. 2020 May;39(5):405-407. doi: 10.1016/j.healun.2020.03.012. Epub 2020 Mar 20. Accessed September 24, 2021. PMID: 32362390; PMCID: PMC7118652.

Symptoms of COVID-19. Centers for Disease Control and Prevention. Updated February 22, 2021. Accessed September 6, 2021. https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html.

Therapeutics and COVID-19: living guideline. World Health Organization. Updated July 6, 2021. Accessed September 20, 2021. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2021.2.

Therapeutic Management of of Hospitalized Adults with COVID-19. National Institutes of Health. Updated August 25, 2021. Accessed September 7, 2021. https://www.covid19treatmentguidelines.nih.gov/management/clinical-management/hospitalized-adults--therapeutic-management/.

Tocilizumab. Dosing and Uses. Medscape. Accessed September 22, 2021. https://reference.medscape.com/drug/actemra-tocilizumab-999419.

Variant Proportions. COVID Data Tracker. Center for Disease Control and Prevention. Updated September 21, 2021. Accessed September 20, 2021. https://covid.cdc.gov/covid-data-tracker/#variant-proportions.

Veklury (remdesivir) EUA Fact Sheet for Healthcare Providers. Revised October 2020. Accessed September 22, 2021. https://www.fda.gov/media/137566/download.

Xeljanz (tofacitinib). Pfizer. Revised October 2020. Accessed September 22, 2021. http://labeling.pfizer.com/ShowLabeling.aspx?id=959.

9/30/2021

33

AdditionalResourcesRECOVERY (Steroids): RECOVERY Collaborative Group, Horby P, Lim WS, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17. PMID: 32678530; PMCID: PMC7383595.

SIMPLE Severe: Goldman JD, Lye DCB, et al. Remdesivir for 5 or 10 Days in Patients with Severe Covid-19. N Engl J Med. 2020 Nov 5;383(19):1827-1837. doi: 10.1056/NEJMoa2015301. Epub 2020 May 27. PMID: 32459919; PMCID: PMC7377062.

SIMPLE Moderate: Spinner CD, Gottlieb RL, Criner GJ, et al. Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19: A Randomized Clinical Trial. JAMA. 2020;324(11):1048–1057. doi:10.1001/jama.2020.16349.

ACTT-1: Beigel JH, Tomashek KM, et al. Remdesivir for the Treatment of Covid-19 - Final Report. N Engl J Med. 2020 Nov 5;383(19):1813-1826. doi: 10.1056/NEJMoa2007764. Epub 2020 Oct 8. PMID: 32445440; PMCID: PMC7262788.

ACTT-2: Baricitinib plus remdesivir for hospitalized adults with Covid-19Kalil A.C., Patterson T.F., Mehta A.K., TomashekK.M., Wolfe C.R., Ghazaryan V., Marconi V.C., (...), ACTT-2 Study Group Members (2021) NewEnglandJournalofMedicine, 384 (9), pp. 795-807. https://www.nejm.org/doi/full/10.1056/nejmoa2031994.

SOLIDARITY: WHO Solidarity Trial Consortium. The New England Journal of Medicine; Boston. Vol. 384, Iss. 6, (Feb 11, 2021): 497-511. DOI:10.1056/NEJMoa2023184. https://www.nejm.org/doi/full/10.1056/nejmoa2023184.

AdditionalResourcesCOVACTA: Rosas IO, Bräu N, Waters M, et al. Tocilizumab in Hospitalized Patients With Severe Covid-19 Pneumonia. NEnglJMed 2021;Feb 25:[Epub ahead of print]. https://www.nejm.org/doi/full/10.1056/NEJMoa2028700.

RECOVERY (tocilizumab): RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2021 May 1;397(10285):1637-1645. doi: 10.1016/S0140-6736(21)00676-0. PMID: 33933206; PMCID: PMC8084355.

REMAP CAP: The REMAP-CAP Investigators. Interleukin-6 Receptor Antagonists in Critically Ill Patients With Covid-19. NEngl JMed 2021;Feb 25:[Epub ahead of print]. https://www.nejm.org/doi/full/10.1056/NEJMoa2100433.

EMPACTA: Salama C, Mohan SV. Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia. Reply. N Engl J Med. 2021 Apr 15;384(15):1473-1474. doi: 10.1056/NEJMc2100217. Epub 2021 Mar 3. PMID: 33657287.

STOP-COVID: Guimaraes, PO; Quirk, D; et al. Tofacitinib in Patients Hospitalized with Covid-19 Pneumonia. July 29, 2021. N Engl J Med 2021; 385:406-415. DOI: 10.1056/NEJMoa2101643.

COV-BARRIER: Marconi, VC; Ramanan, AV; et al. Baricitinib plus Standard of Care for Hospitalized Adults with COVID-19. https://doi.org/10.1101/2021.04.30.21255934.

9/30/2021

34

CurrentCOVID‐19ManagementandTreatmentRecommendations

CoreyYeates,D.O.Internal Medicine, PGY-2

Oklahoma State University Medical Center

OSHP Fall MeetingOctober 22, 2021

current covid 19 management and treatment recommendations

Documents