COVID-19 TELE-EDUCATION SERIES FOR HEALTHCARE PROVIDERS IN LMICS - - PowerPoint PPT Presentation

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COVID-19 TELE-EDUCATION SERIES FOR HEALTHCARE PROVIDERS IN LMICS - - PowerPoint PPT Presentation

Aug 14, 2022 300 likes •685 views

COVID-19 TELE-EDUCATION SERIES FOR HEALTHCARE PROVIDERS IN LMICS PROJECT ECHO ETIQUETTE v Foundation of love and respect (Respond kindly rather than react if you disagree) v It is everybodys responsibility to keep ECHO a safe space v Test your

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COVID-19 TELE-EDUCATION SERIES FOR HEALTHCARE PROVIDERS IN LMICS

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PROJECT ECHO ETIQUETTE

v Foundation of love and respect (Respond kindly rather than react if you disagree) v It is everybody’s responsibility to keep ECHO a safe space v Test your equipment ahead of time (both audio and video) v Introduce yourself before speaking v Avoid making noise (i.e. potato chips, shuffling papers, whispering, cell phones, loud bags, etc.) v For questions during Q&A session use the chat box v Mute microphone when not speaking (Left bottom corner of your screen) v If you are to speak, speak remember to unmute before speaking and speak close to the microphone v Position webcam effectively to show your face if alone or to capture the whole group v Have a light source from the front (Avoid being backlit) v IT issues? Send a message through chat/email

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What’s New in COVID-19? Treatment and Research Updates

COVID-19 TELE-EDUCATION SERIES FOR HEALTHCARE PROVIDERS IN LMICS

Yuri van der Heijden, MD, MPH Vanderbilt University Medical Center The Aurum Institute May 12 & 13, 2020

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DISCLOSURES

  • I have no significant financial conflicts of interest to disclose
  • I receive support from the National Institutes of Health to

Vanderbilt University Medical Center for research activities

  • Off-label therapies will be discussed but not recommended
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LEARNING OBJECTIVES

  • General SARS-CoV-2 updates
  • Remdesivir
  • Treatment candidates
  • Additional research
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GLOBAL PANDEMIC

We Think We Know We Don’t Know Epidemiology 2 major types (L & S) Sex differences Further evolution Clinical significance Transmission Respiratory droplets Lingers on surfaces Natural aerosols Viability post-infection & type of specimen Immunity Antibodies are induced Relationship of antibody detection & risk of reinfection

Tang X, et al. National Science Review. 3 March 2020 van Doremalen N, et al. NEJM. 16 April 2020 Wölfel R, et al. Nature. 1 April 2020 Wu F, et al. medRxiv (PREPRINT - NOT IN PEER-REVIEWED PUBLICATION). 20 April 2020

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https://informationisbeautiful.net/visualizations/covid-19-coronavirus-infographic- datapack/ http://www.stoptb.org/assets/documents/news/Modeling%20Report_1%20May%2 02020_FINAL.pdf

  • Disruption to programs and service delivery
  • Other infectious diseases
  • Non-communicable diseases
  • Disease prevention efforts
  • COVID-19 impact on tuberculosis - model
  • 3-month lockdown, 10-month restoration
  • Additional 6.3 million TB cases 2020-2025
  • Additional 1.4 million TB deaths
  • Setback of 5-8 years in global TB fight

GLOBAL PANDEMIC

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NO APPROVED SPECIFIC TREATMENT

Don’t forget basics

  • Public health messaging
  • Infection control & prevention in healthcare settings

Do not abandon principles of evidence-based care

  • Example: ICU
  • Low tidal volume ventilation
  • Conservative fluid management after shock
  • Daily awakening & spontaneous breathing trials
  • Care bundles and checklists

Rice T, Janz D. Annals ATS. 22 April 2020

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TREATMENT TARGETS

Sanders J, et al. JAMA. 13 April 2020

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Siddiqi H, et al. Journal Heart Lung Transplant. 20 March 2020

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REMDESIVIR, GS-5734

  • Prodrug, metabolized to adenosine nucleotide analogue
  • Inhibits viral RNA-dependent RNA polymerase
  • Efficacy against SARS-CoV-1, MERS-CoV, and Ebola virus in vitro & animal

studies

  • Efficacy against SARS-CoV-2 in vitro

Wang M, et al. Cell Research. 4 February 2020

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REMDESIVIR

Wang Y, et al. Lancet. 29 April 2020

  • Randomized, double-blind, placebo-controlled,

10 hospitals in Hubei Province, China

  • 200mg IV day 1, 100mg daily days 2-10
  • Outcome: time to clinical improvement
  • Symptom duration ≤ 10 days before remdesivir
  • HR 1.52 (0.95-2.43)
  • Stopped early (control of outbreak in Wuhan)
  • Pointed to need for larger studies
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REMDESIVIR

https://www.gilead.com/news-and-press/press-room/press-releases/2020/4/gilead-announces-results-from-phase-3-trial-of-investigational-antiviral-remdesivir- in-patients-with-severe-covid-19 (NOT IN PEER-REVIEWED PUBLICATION)

  • Gilead announcement 29 April 2020
  • SIMPLE trial
  • Phase 3, open-label
  • Compared 5-day & 10-day dosing
  • Hospitalized, severe disease
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REMDESIVIR

29 April 2020 NIH NIAID press release

  • Interim analysis of Adaptive COVID-19 Treatment Trial (ACTT) sponsored by NIAID
  • Randomized, placebo-controlled trial, began February 21, 2020
  • 1063 patients, 68 sites (47 U.S.; 21 countries in Europe & Asia)
  • Median time to recovery 11 days remdesivir vs 15 days placebo (p<0.001)
  • Mortality rate 8.0% remdesivir vs 11.6% placebo (p=0.059)

https://www.niaid.nih.gov/news-events/nih-clinical-trial-shows-remdesivir-accelerates-recovery-advanced-covid-19 (NOT IN PEER-REVIEWED PUBLICATION)

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REMDESIVIR EUA

FDA Emergency Use Authorization (EUA) 1 May 2020

  • Treatment of suspected or lab confirmed COVID-19
  • Adults and children hospitalized with severe disease (any of the following):
  • Oxygen saturation ≤ 94% on room air
  • Require supplemental oxygen
  • Require mechanical ventilation
  • Require extracorporeal menbrane oxygenation (ECMO)

https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-issues-emergency-use-authorization-potential-covid-19-treatment https://www.fda.gov/media/137566/download

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https://www.fda.gov/media/137566/download

TREATMENT CONSIDERATIONS

  • Caution in pregnancy (assess risk/benefit)
  • Not recommended eGFR < 30 mL/min
  • Caution with hepatic impairment
  • Aseptic technique in preparation
  • No preservative or bacteriostatic agent
  • Lyophilized powder + sterile water + saline
  • Store prepared solution
  • Up to 4 hours 20ºC - 25ºC
  • Up to 24 hours 2ºC - 8ºC
  • Must review & provide “Fact Sheet for

Patients and Parents/Caregivers”

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REMDESIVIR ADVERSE EFFECTS

  • Infusion reaction (hypotension, nausea, vomiting, diaphoresis, shivering)
  • Liver enzyme elevation (Also noted in COVID-19 patients)
  • ↑ ALT observed in majority of healthy volunteers during clinical development
  • Check liver tests before starting & daily while receiving remdesivir
  • Do not start remdesivir if ALT ≥ 5 times upper limit of normal ( x ULN)
  • Stop if ALT ≥ 5 x ULN during treatment, may restart when ALT < 5 x ULN
  • Stop if ↑ ALT with signs/symptoms liver inflammation or ↑ bilirubin, alk phos, INR
  • Mandatory reporting of adverse events or medication errors

https://www.fda.gov/media/137566/download

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HYDROXYCHLOROQUINE & CHLOROQUINE

  • 4-aminoquinolines
  • Treatment of malaria, lupus, rheumatoid arthritis
  • Possible antiviral mechanisms
  • Alkalanize endosome & inhibit autophagosome-lysosome fusion
  • Inactivate enzymes needed for viral replication
  • Alter glycosylation of angiotensin converting enzyme-2

Ferner R, Aronson J. BMJ. 8 April 2020 Devaux C, et al. IJAA. 12 March 2020

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HYDROXYCHLOROQUINE & CHLOROQUINE

28 March 2020

  • FDA Emergency Use

Authorization 24 April 2020

  • FDA cautions

against use

https://www.fda.gov/media/136534/download https://www.fda.gov/drugs/drug-safety-and-availability/fda-cautions-against-use-hydroxychloroquine-or-chloroquine-covid-19-outside-hospital-setting-or

Reference Study Description Comment Gautret P . IJAA. 20 March 2020 Open-label, non-randomized clinical trial hydroxychloroquine ± azithromycin n=36, day 6 viral load reduction Borba M. JAMA. 24 April 2020 Phase IIb randomized clinical trial high vs low dose chloroquine (azithromycin for all) – stopped at interval analysis n=81, higher dose group with ↑ mortality & QTc interval prolongation Geleris J. NEJM. 7 May 2020 Observational comparing hydroxychloroquine to none n=1376, no difference intubation or death

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HIV PROTEASE INHIBITORS

Cao B, et al. NEJM. 7 May 2020 https://www.nejm.org/doi/pdf/10.1056/NEJMc2008043?listPDF=true

  • Randomized, controlled, open-label trial
  • Hospitalized, low oxygen
  • Lopinavir-ritonavir x 14 days vs standard care
  • Primary outcome
  • Time to clinical improvement
  • HR 1.31; 95% CI 0.95,1.80
  • Letters to Editor:
  • Underpowered
  • Randomized late into course (13 days)
  • Secondary signals
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Hung I, et al. Lancet. 8 May 2020

  • Patients randomized (2:1) to 14-day combination of
  • lopinavir 400 mg / ritonavir 100 mg every 12 h
  • ribavirin 400 mg every 12 h
  • interferon beta-1b 8 million IUs, alternate days x 3 days (n=86)
  • Combination group shorter median time from treatment to negative NP swab
  • 7 days (IQR 5,11) vs 12 days (IQR 8,15); HR 4.37; 95% CI 1.86, 10.24; p=0.001
  • Note that subgroup (n=34) of combination group omitted interferon beta-1b
  • Implications: Early treatment with triple antiviral may shorten duration of virus shedding, alleviate

symptoms, and facilitate discharge of patients with mild to moderate COVID-19

  • 14-days

lopinavir/ritonavir alone (n=41) vs

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IMMUNE MODULATORS

  • May reduce cytokine impact (“cytokine storm”) triggered by viral infection
  • Interleukin (IL)-1, IL-6, TNF, interferon 𝛅, and JAK inhibition proposed as

potential targets

  • Anecdotal reports of use with good outcomes
  • Trials studying tocilizumab, sarilumab, siltuximab, baracitinib, and ruxolitinib all

proposed or currently in trials

  • COLCORONA – colchicine phase 3, multi-center, randomized, double-blind,

placebo-controlled trial

Feldmann M, et al. Lancet. 2 May 2020 https://www.smartpatients.com/trials/NCT04322682

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CONVALESCENT PLASMA

  • Passive antibody transfer from patients who previously recovered from infection
  • Previously utilized for H1N1 influenza, H5N1 avian influenza, SARS-CoV-1,

MERS-CoV, and Ebola virus

  • Administration associated with reduced viral load, serum cytokine response, and

mortality for patients with H1N1 influenza

  • Faster discharge for patients with SARS-CoV-1
  • Case series of 5 severely-ill COVID-19 patients in China with improvement

Shen C, et al. JAMA. 27 March 2020

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EIDD-1931 AND EIDD-2801

EIDD-1931

  • β-D-N4-hydroxycytidine (NHC)
  • Ribonucleoside analog

EIDD-2801

  • NHC prodrug
  • Lethal viral mutagenesis

Treatment & prevention? Human trials pending

29 April 2020

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OTHER CONSIDERATIONS - UNPROVEN

  • Nitazoxanide
  • Ivermectin
  • Vitamin C, vitamin D, zinc
  • Mpro inhibitors
  • Vaccines
  • Others

Rossignol JF. J Inf Public Health. May-June 2016 Caly L, et al. Antiviral Research. June 2020 Jin Z, et al. Nature. 9 April 2020 Le T, et al. Nature Reviews. 9 April 2020

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BENEFITS AND RISKS OF NEW TREATMENTS

Possible Benefits Possible Risks Decreased viral activity Adverse effects (known & unknown) Decreased disease progression Costs (direct & indirect) Cure Obfuscation of true efficacy of treatment Decreased transmission Delay in defining most appropriate care for future patients Lack of available medications for other medical conditions

Bauchner H, Fontanarosa P . JAMA. 4 May 2020 Kalil A. JAMA. 24 March 2020

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CAUTION

“Indiscriminate promotion and widespread use of CQ/HCQ have led to extensive shortages, self-treatment, and fatal overdoses. Shortages and increased market prices leave all countries vulnerable to substandard and falsified medical products, and safety issues are especially concerning for Africa because of its healthcare system limitations.”

Abena P , et al. Am J Trop Med Hyg. 22 April 2020

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ETHICS

  • Equity of access
  • Within communities: amplification of disparities
  • Global context: geopolitical leaders leverage political, economic power to procure

supplies and interventions

  • Rationing of scarce resources
  • Conducting research in LMICs
  • Interventions should be affordable, available, and adaptable to populations in need

Kavanagh M, et al. Lancet. 7 May 2020 Emanuel E, et al. NEJM. 23 March 2020 COVID-19 Clinical Research Coalition. Lancet. 2 April 2020

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OTHER UPDATES

Arons M, et al. NEJM. 24 April 2020

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Kai D, et al. arXiv (PREPRINT - NOT IN PEER-REVIEWED PUBLICATION). 22 April 2020

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KEY POINTS

  • Don’t forget basics for prevention and treatment
  • Emerging therapies (new and old) have plausible but unproven efficacy against the

SARS-CoV-2 virus and COVID-19 disease

  • Well-designed studies are necessary to evaluate treatment candidates
  • Consider potential consequences of unproven therapies
  • Thoughtful leadership & wisdom needed – ethical distribution of new treatments,

development of public health policy

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REFERENCES

Maps & Aggregated Epidemiologic Data

  • Johns Hopkins Coronavirus Resource Center Map

https://coronavirus.jhu.edu/map.html

  • WHO COVID-19 Dashboard https://covid19.who.int

Guidelines

  • WHO Country & T

echnical Guidance https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical- guidance

  • Infectious Diseases Society of America Guidelines on the Treatment and

Management of Patients with COVID-1, published April 11, 2020, updated periodically https://www.idsociety.org/COVID19guidelines

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REFERENCES

U.S. FDA Releases on Remdesivir

  • Summary of FDA Emergency Use Authorization: https://www.fda.gov/news-

events/press-announcements/coronavirus-covid-19-update-fda-issues- emergency-use-authorization-potential-covid-19-treatment

  • Fact sheet for healthcare providers.

https://www.fda.gov/media/137566/download

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THANK YOU

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QUESTIONS?

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WhatsApp Chat

If you have more questions following this session, we have created a WhatsApp chat group for sharing relevant information about caring for COVID-19 patients. A link has been sent to your email with the registration link. Please reach out to ECHO@assistinternational.org with any other questions.

JOIN OUR WHATSAPP GROUP!