SARS CoV-2: Rising to the Testing Challenge in the United States - - PowerPoint PPT Presentation

SARS CoV-2:

Rising to the Testing Challenge in the United States

Steven E. Cagas, PhD

Supported by:

• M. Laura Parnas,

PhD, DABCC, FAACC

Speakers:

SA RS CoV - 2 :

R i s i n g t o t h e Te s t i n g C h a l l e n g e i n t h e U n i t e d S t a t e s

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Steven E. Cagas, PhD

• M. Laura Parnas, PhD, DABCC, FAACC

Medical and Scientific Affairs Roche Diagnostics April 29, 2020

• Dr. Cagas and Dr. Parnas are employees of Roche Diagnostics Corporation functioning as a Scientific Affairs

Managers within the non-commercial division of Medical & Scientific Affairs. Data presented is intended for educational use to provide the participant with scientific, evidence-based information in compliance with FDA guidelines. All trademarks, trade names, images, or logos mentioned or used herein are the property of their respective owners and are not used for purposes of promotion or as an indication of affiliation with the provider of any particular good or service.

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Information presented herein is current as of April 18, 2020.

Disclosures

• Background
• Epidemiology
• Tracking SARS-CoV-2 and COVID-19
• Testing Modalities
• Testing Hurdles
• Biomarkers and Serology
• Potential Therapeutic Approaches
• Questions and Answers

Agenda

History

• World Health Organization (WHO) informed of

cases of pneumonia of unknown origin in Wuhan City, Hubei Province, on 31-Dec-2019.

• WHO declares coronavirus a global emergency on

31-Jan-2020.

The Virus

• A novel coronavirus (SARS-CoV-2) was officially

announced as the causative agent by Chinese authorities on 07-Jan-2020.

• The resulting disease has been named COVID-19.

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SARS-CoV-2: A Novel Coronavirus

1.World Health Organization (WHO). Coronavirus. Geneva: WHO; 2020 Available from: [Accessed 26 Jan 2020]. 2.World Health Organization (WHO). Coronavirus Disease Outbreak: [Accessed 26 Jan 2020]. 3.Novel Coronavirus(2019-nCoV) Situation Report – 7. Available from: [Accessed 26 Jan 2020]. 4.Lu R, Zhao X, Li J, et al. Genomic characterization and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding ]The Lancet. Published online January 29

• Coronaviruses are large (HBV – 3kbp; CoV – 30 kb), enveloped RNA

viruses

• Coronaviruses are zoonotic, meaning they are transmitted between

animals and people.

• Animal reservoirs are ecologically diverse with the widest variety seen in

bats, which are the reservoirs for many of these viruses.

• Mammals may serve as intermediate hosts, facilitating recombination

and mutation events with expansion of genetic diversity.

• Not all coronaviruses are pandemic strains - endemic human coronavirus

are responsible for approximately 5–10% of all upper and lower respiratory tract infections.

• Two previous outbreaks:

– Severe acute respiratory syndrome - SARS-CoV (2002) - China – Middle East respiratory syndrome - MERS-CoV (2012) - Saudi Arabia

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What are Coronaviruses?

1.Peiris, J., Guan, Y. & Yuen, K. Severe acute respiratory syndrome. Nat Med 10, S88–S97 (2004). https://doi.org/10.1038/nm1143

SARS-CoV MERS-CoV

Focus of Outbreak China (2002) Saudi Arabia (2012), South Korea (2015) Animal source of human infection Civet cats Camels Infected people 8000 2494 % severe cases/mechanical ventilation 35 % 50-89% Deaths (mortality rate) 774 (<10%) 858 (34%) Distribution 29 countries 27 countries Global economy costs 30-120 billion (USD) 30-100 billion (USD) *SARS - Severe acute respiratory syndrome **MERS – Middle East respiratory syndrome

• 1. Center for Disease and Control Prevention. Evaluating and testing persons for Coronavirus disease 2019(COVID-19). (March 24, 2020).Retrieved from: https://www.cdc.gov/coronavirus/2019-nCoV/hcp/clinical-

criteria.html?fbclid=IwAR30Pu8d3PT6vAR90E8xu93WryY5F5EIpSaJm6dAFcBAuHhdXi2K52SLGpw.Accesed on March 26, 2020. 2. Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA (2020).doi:10.1001/jama.2020.2648 3. Burrell C, Howard C & Murphy F. Chapter 31 – Coronavirus. In: Fenner and White’s Medical Virology. (2017) 437-446.

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SARS* and MERS** - Brief History

• In December 2019, a cluster of pneumonia cases

related to exposure to a live animal market emerged in Wuhan City, China.

• Viral genome sequences identified novel

coronavirus as causative agent (originally named 2019-nCoV)

• On February 11, 2020, the World Health

Organization (WHO) announced the official name

• f the novel coronavirus, SARS-CoV-2, and the
• fficial name of the respiratory disease caused by

the virus, COVID-19.

• 1. Xu Y. Unveiling the Origin and Transmission of 2019-nCoV.Trends Microbiol. (2020)Apr;28(4):239-240.doi: 10.1016/j.tim.2020.02.001.

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SARS-CoV-2:

Relationship between SARS-CoV and SARS-CoV-2

1 Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395:507-13. PMID: 32007143. 2. Holshue ML, DeBolt C, Lindquist S, et al. First Case of 2019 Novel Coronavirus in the United States. N Engl J Med. 2020. PMID: 32004427. 3. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497-506. PMID: 31986264. 4. Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020. PMID: 32031570. 5. Centers for Disease Control and Prevention. Coronavirus Disease 2019 (COVID-19)–Evaluating and Reporting Persons Under Investigation (PUI). Accessed March 4, 2020. 6. Joseph T Wu*, Kathy Leung*, Gabriel M Leung, Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study Lancet 2020.

Symptoms

Fever, respiratory symptoms, abdominal pain, diarrhea, vomiting, headache, myalgia

Clinical presentation

Asymptomatic infection, mild illness, or fatal disease

Transmission

Person-to-person via respiratory secretions

Incubation

Range of 2-14 days (median – 5 days)

Clinical progression

Can cause severe respiratory disease

SARS-CoV-2

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COVID-19

Signs and Symptoms

Mild

• The clinical symptoms are mild, and there was no sign of

pneumonia on chest imaging Moderate

• These patients had fever and respiratory symptoms.

Radiologic assessments found signs of pneumonia. Severe

• Adults meet any of the following criteria:
• Shortness of breath, RR ≥30 times/min
• Oxygen saturation ≤93% at rest
• Alveolar PaO2 / FiO2 ≤300 mmHg (1 mmHg = 0.133

kPa).* Patients whose pulmonary imaging showed significant progression of lesion >50% within 24–48 hours should be treated as severe

• Children meet any of the following criteria:
• Shortness of breath (<2 months old, RR ≥60 beats/min; 2 to

12 months old, RR ≥50 beats/min; 1 to 5 years old, RR ≥40 beats/min; >5 years old, RR ≥30 beats/min), excluding the effects of fever and crying

• Oxygen saturation is ≤92% in the resting state
• Assisted breathing (groaning, wing flaps, tri-retraction sign),

cyanosis, intermittent apnea

• Lethargy and convulsions
• Refuse to feed, and have signs of dehydration

Critically Severe

• Patients meet any of the following conditions:
• Respiratory failure requiring mechanical ventilation
• Shock
• Patients combined with other organ failure needed ICU

monitoring and treatment

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* At high altitudes (>1000 m), PaO2 / FiO2 should be corrected according to the following formula: PaO2 / FiO2 x [Atmospheric pressure (mmHg)/760]. PaO2 / FiO2, oxygen partial pressure / fraction of inspiration O2.. The Chinese Clinical Guidance for COVID-19 Pneumonia Diagnosis and Treatment (7th Edition) http://kjfy.meetingchina.org/msite/news/show/cn/3337.html

Clinical Classification of COVID-19

The Chinese Clinical Guidance for COVID-19 Pneumonia Diagnosis and Treatment (7th Edition)

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Source: https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6 (Accessed 01/27/20)

COVID-19 Global Cases

27 January 2020

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COVID-19 Global Cases

23 February 2020

https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6 Accessed 02/23/20

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https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6 (Accessed 04/18/20)

COVID-19 Global Cases

18 April 2020

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https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6 (Accessed 04/18/20)

COVID-19 Global Cases

18 April 2020

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Other Resources

https://covid19.healthdata.org/united-states-of-america(Accessed 04/18/20) https://nextstrain.org/ncov/global (Accessed 4/18/20)

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Other Resources

https://usafacts.org/visualizations/coronavirus-covid-19-spread-map/(Accessed 04/18/20) https://www.google.com/covid19/mobility/(Accessed 4/18/20)

• Community-level measures are needed

when containment is no longer feasible in order to delay the peak of the epidemic and decrease the peak magnitude to protect healthcare capacity

• Social distancing measures can

significantly reduce transmission if consistently performed by the population

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Why do we need to “Flatten The Curve?”

Community Level Measures: The Reason Behind Social Distancing

• 1. Anderson R, Heesterbeek H, Klinkenberg D, et al. How will country-based mitigation measures influence the course of the COVID-19 epidemic? Lancet (2020) Mar 21;395,10228:931-934.

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Current Assumptions for SARS-CoV-2 Infection

Graph constructed using BCG report as of 20-mar-2020 and data from: [1] Cai et al. 2020 [2] Okba et al. 2020 [3] Long et al. 2020 [4] Amanat et al. 2020 [5] Haveri et al. 2020 [6] Woelfel et al. 2020 [7] Kissler et al. 2020 [8] Li et al. 2020

Dec Jan Feb March

Cluster of unknown pneumonia reported to WHO New Coronavirus Identified . Wuhan city shut down WHO declares coronavirus a public health emergency of international concern Daily new cases

• utside China

exceeds China numbers WHO declares COVID-19 a pandemic FDA releases Guidance on EUA Procedure for labs First commercially Available real-time PCR RUO assay (US) First commercially available real-time PCR EUA assay (US) FCDC 2019-nCoV EUA assay available (US) WHO testing guidance released Corman, et al. publication on 2019-nCoV real time PCR

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COVID-19 and Testing Timelines

The FDA provides guidance to manufacturers and labs on requirements needed for approval for EUA

*CBRN- Chemical, Biological, Radiological or Nuclear *MCM-Medical Countermeasures

The Emergency Use Authorization (EUA) authority allows FDA to help strengthen the nation’s public health protections against CBRN threats by facilitating the availability and use of MCMs needed during public health emergencies. Under section 564 of the Federal Food, Drug, and Cosmetic Act (FD&C Act), the FDA Commissioner may allow unapproved medical products or unapproved uses of approved medical products to be used in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions caused by CBRN threat agents when there are no adequate, approved, and available alternatives

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Emergency Use Authorization (EUA)

What Does this Mean?

https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization

Validation Study Recommendations for Molecular Diagnostic Assays*

• 1. Limit of Detection
• 2. Clinical Evaluation
• 3. Inclusivity
• 4. Cross-Reactivity

*-Not intended to be fully inclusive; Please read full guidance for all assay development

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FDA EUA Policies: Molecular

https://www.fda.gov/media/135659/download

Criteria to Guide Evaluation and Laboratory Testing for COVID-19 Laboratory Testing Strategy Recommendations for COVID-19 In Summary:

• Nucleic Acid Amplification Test (NAAT) for diagnosis
• Testing is needed to inform clinical decision making and public health policy
• Prioritization of testing is needed when the availability of testing is limited

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COVID-19 Testing Recommendations

• 1. Criteria to Guide Evaluation and Laboratory Testing for COVID-19. Available at: https://www.cdc.gov/coronavirus/2019-nCoV/hcp/clinical-criteria.html (Accessed 22-Mar-2020)

• Priority 1
• Inpatients
• Healthcare Workers w/Symptoms
• Priority 2
• LTCF w/symptoms
• 65+ w/symptoms
• Underlying conditions w/symptoms
• First Responders w/symptoms
• Priority 3
• Critical workers w/symptoms
• Any individual w/symptoms
• Healthcare workers and First Responders
• Individuals in “hot spots” w/mild symptoms
• Non-Priority
• Individuals without symptoms

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Testing Prioritization for Laboratories

Collection Materials PPE Testing Medical Personnel

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Testing Resource Limitations

https://www.copanusa.com/sample-collection-transport-processing/utm-viral-transport/ https://www.nejm.org/doi/full/10.1056/NEJMvcm1412105?query=featured_ebola https://usafacts.org/visualizations/coronavirus-covid-19-spread-map https://pointofview.net/viewpoints/exploiting-medical-professionals/

High Throughput Molecular Systems Rapid Lateral Flow Immunoassay

*Instruments and Devices shown here are only representatives of the category. As of April 18, 2020 a total of 39 assays have been granted EUA authorization. See FDA website link: https://www.fda.gov/medical-devices/emergency-situations-medical-devices/emergency-use-authorizations#covid19ivd

Point of Care Molecular

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SARS-CoV-2 EUAs

Technologies Currently Available (4/18/2020)

https://www.alere.com/en/home/product-details/id-now-covid-19.html https://cellexcovid.com/

Clinical Stages of COVID-19

Symptoms, Biomarkers and Potential Therapies

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• 1. Siddiqi H & Mehra M. COVID-19Illness in Native and Immunosuppressed States: A Clinical-Therapeutic Staging Proposal, J Heart Lung Transp (2020).In press. doi: https://doi.org/10.1016/j.healun.2020.03.012

Biomarker Utility in COVID-19 Levels

Lymphocyte count (CBC) Immunological response to virus

↓

D-Dimer Activation of blood coagulation and/or disseminated coagulopathy

↑

Lactate Dehydrogenase (LDH) LDH levels may be useful to predict disease severity. May indicate organ damage

↑

Stage I

Mild changes in biomarkers – Non-specific

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• 2. Lippi G & Plebani M. The critical role of laboratory medicine during coronavirus disease 2019 (COVID-19) and other viral outbreaks (2020)In press

Biomarker Utility in COVID-19 Levels

AST and ALT Monitoring of liver function. Indicate liver injury. Potential prognostic indicators

↑

Procalcitonin Marker of bacterial infection Can be elevated if bacterial co-infection present

N or ↑

CRP Marker of inflammation/response to infection

N or ↑

Ferritin Acute phase protein

N or ↑

Lactate Marker of tissue hypoperfusion. Indicates organ damage

↑

Mild-moderate changes in biomarkers Inflammatory state

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• 2. Lippi G & Plebani M. The critical role of laboratory medicine during coronavirus disease 2019 (COVID-19) and other viral outbreaks (2020)In press

Stage II

Biomarker Utility in COVID-19 Levels

CRP Marker of inflammation/severe response to infection

↑↑

Ferritin Acute phase protein. Potential prognosis for disease severity and progression

↑↑

IL-6 Marker of inflammation. Potential prognosis for disease severity and

• progression. Potential link to treatment

↑↑

Procalcitonin Marker of bacterial infection Can be elevated if bacterial co-infection present and sepsis develops

N or ↑↑

TnT-hs Diagnosis of AMI, risk stratification for ACS. Indicates cardiac injury

↑

NT-Pro BNP Diagnosis of HF in acute and non acute setting

↑

Lactate Marker of tissue hypoperfusion. Indicates widespread organ damage

↑↑

Hyperinflammatory host response

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• 2. Lippi G & Plebani M. The critical role of laboratory medicine during coronavirus disease 2019 (COVID-19) and other viral outbreaks (2020)In press

Stage III

Inflammatory Biomarkers as Warning Signals

IL-6 and CRP are Recommended as Markers of Severe and Critical COVID-19

The Chinese Clinical Guidance for COVID-19 Pneumonia Diagnosis and Treatment (7th Edition):

• Progressive increase in the levels of peripheral

inflammatory biomarkers, such as IL-6 and CRP is included as a warning signal for severe and critically severe COVID-19 disease types

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CRP, C-reactive protein; IL-6, interleukin-6. The Chinese Clinical Guidance for COVID-19 Pneumonia Diagnosis and Treatment (7th Edition) http://kjfy.meetingchina.org/msite/news/show/cn/3337.html

• Retrospective multicenter study of 150

hospitalized patients with confirmed COVID-19 (died n=68; discharged n=82)

• cTn, myoglobin, CRP, and IL-6 were significantly

greater in patients that died compared to discharged patients (p<0.001 for all)

Laboratory parameters for patients with COVID-19 by

• utcome (n=150)

CRP (mg/L) IL-6 (ng/mL) cTn (pg/mL) Myoglobin (ng/mL) p<0.001 p<0.001 p<0.001 p<0.001 400 350 300 250 200 150 100 50 600 500 400 300 200 100 300 250 200 150 100 50 30 25 20 15 10 5 Died Discharged

Inflammatory Biomarkers and COVID-19 Mortality

IL-6 and CRP were Significantly Higher in Patients Who Died

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CRP, C-reactive protein; cTn, cardiac troponin; IL-6, interleukin-6.

• 1. Ruan Q, et al. Intensive Care Med. (2020). doi: 10.1007/s00134-020-05991-x.

p://kjfy.meetingchina.org/msite/news/show/cn/3337.html

• Studies suggest that a subgroup of patients with severe COVID-19 may develop a cytokine storm1
• A cytokine storm involves the overproduction of proinflammatory cytokines, such as IL-6, and is

associated with a variety of infectious diseases2

– A cytokine storm is also a common treatment-related toxicity associated with CAR-T cell therapy3,4

• Research is ongoing to determine whether cytokines can be used to predict cytokine storm severity3
• Tocilizumab, an antibody against the IL-6 receptor, is a standard cytokine storm treatment4

CAR-T, chimeric antigen receptor T cell.

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Cytokine Storm

• 1. Mehta P, et al. Lancet. (2020). doi: 10.1016/S0140-6736(20)30628-0
• 2. Tisoncik JR, et al. Microbiol Mol Biol Rev. (2012). doi: 10.1128/MMBR.05015-11
• 3. Wang Z & Han W. Biomarker Res. (2018). doi: 10.1186/s40364-018-0116-0
• 4. Frey N & Porter D. Biol Blood Marrow Transpl. (2019). doi: 10.1016/j.bbmt.2018.12.756.

Immune Response to SARS-CoV

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Current Assumptions for SARS-CoV-2 Infection

Graph constructed using BCG report as of 20-mar-2020 and data from: [1] Cai et al. 2020 [2] Okba et al. 2020 [3] Long et al. 2020 [4] Amanat et al. 2020 [5] Haveri et al. 2020 [6] Woelfel et al. 2020 [7] Kissler et al. 2020 [8] Li et al. 2020

• Most patients have rising IgG and IgM antibody titers 10

days after symptom onset1

• IgA antibody titers have been shown to increase

at a similar time period2

• Serum IgG amounts can rise at the same time or earlier

than those of IgM against SARS-CoV-21

• For 16/23 patients with serum specimens available for 14

days or longer after symptom onset, the rate of seropositivity was 94% for anti-NP IgG, 88% for anti-NP IgM, 100% for anti-RBD IgG, and 94% for anti-RBD IgM1

• Serum antibody levels were not correlated with

clinical severity1

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Serum Antibody Responses in SARS-CoV-2 Infection

An Observational Cohort Study

• 1. To KKW, et al. Lancet Infect Dis 2020; DOI:10.1016/ S1473-3099(20)30196-1; 2. Okba NMA, Emerg Infect Dis 2020; doi: https://doi.org/10.3201/eid2607.200841

Tests for SARS–CoV-2/COVID-19 and Potential Uses

Type of test Measure Value Beneficiary

Nucleic acid amplification test for viral RNA

(Nasopharyngeal swab,

• ropharyngeal swab,

sputum, bronchoalveolar lavage fluid, others)

Direct detection of infection i.e. Current infection with SARS-CoV-2

Inform individual of infections status so they can anticipate course of illness and take action to prevent transmission Individual Inform patient management and actions needed to prevent transmission Healthcare or long term care facility Inform actions needed to prevent transmission Public health

Antibody detection Detection of immune response i.e. Past exposure to SARS-CoV-2

Detect susceptible individuals (antibody negative) and those previously infected Identify those potentially immune to SARS-CoV-2 (if tests can detect protective immunity individuals could return to work Identify individuals with neutralizing antibodies Healthcare facilities: experimental therapy Facilitate contact tracing and surveillance Public health

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Robin Patel et al. mBio 2020; doi:10.1128/mBio.00722-20

Potential Uses of Serology Assays

• Determine exposure to SARS-CoV-2

– Seroprevalence studies

• Community screening
• Contact tracing
• Epidemiological studies
• Immunity
• “Back to Work”

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Robin Patel et al. mBio 2020; doi:10.1128/mBio.00722-20

Uses of Serology Assays

What we don’t know

• Is the immunological response protective?
• Does the presence of antibodies indicate immunity?
• How long does the immunity last?
• What kind of antibodies will a safe and effective vaccine generate? How fast will this happen?

– How long will the vaccine be protective for?

• How long will it take to reach “herd” immunity?
• How many times will an individual need to be tested?

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Device Pathway and Specifics FDA Notification Type/Distribution

Serology (IgM, IgG)

• Fastest Path
• No Emergency Use Authorization Required
• Cannot claim test is “sole basis to diagnose or

inform infection status”

• 4 disclaimers need to be included on test

reports (therefore built into the method sheet) Email Notice of Distribution to FDA. Start distributing immediately. Serology (IgM, IgG) EUA* Pre-EUA EUA Antigen (detects SARS-CoV-2 antigens directly from clinical specimens) EUA* Pre-EUA EUA

*EUA products can be distributed prior to EUA authorization after validation of the test and while the EUA request is being prepared. After notification of validation, FDA feels 15 business days is a reasonable timeframe for submitting the EUA. As with non-EUA path, the manufacturer should notify FDA of intent to distribute. FDA doesn’t have a formal EUA clock (i.e. can’t state how long it will take to grant authorization of EUA).

Regulatory Pathways for Serology Assays

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Source: FDA Guidance-Policy for Diagnostic Tests for Coronavirus Disease-2019 during the Public Health Emergency (16-March-2020)

Regulatory Pathways for Serology Assays

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Source: FDA Guidance-Policy for Diagnostic Tests for Coronavirus Disease-2019 during the Public Health Emergency (16-March-2020)

Device Minimum Validation Studies Recommended by FDA Notes

Serology (IgM, IgG)

• Cross-reactivity/Analytical Specificity
• Class Specificity
• Clinical Agreement Study
• Sample Type/Matrix Equivalency (this was

not listed in the 16 March guidance, but has been communicated by FDA as an additional requirement) FDA recommends that clinical accuracy should be established on human specimens from patients with microbiologically confirmed COVID-19 infection. Antigen

• Limit of Detection/Analytical Sensitivity
• Cross-reactivity/Analytical Specificity
• Microbial Interference
• Clinical Agreement Study

For devices claiming multiple clinical matrices, the most challenging matrix should be used in your validation studies.

For both, Clinical Agreement Studies are intended to establish the performance characteristics (e.g., sensitivity/PPA, specificity/NPA) of the test.

Drug name Manufacturer Mechanism of Action Preliminary antiviral evidence

Repurposed agents Kaletra (Ritonavir+ Lopinavir) Abbvie HIV protease inhibitors Approved for HIV treatment. No strong evidence from China but used

• nly in severe cases.

(https://www.nejm.org/doi/full/10.1056/NEJMoa2001282) Chloroquine / Hydroxychloroquine Many Endosomal acidification fusion inhibitor Approved for malaria. In vitro studies showed encouraging

• results. (https://doi.org/10.1016/j.ijantimicag.2020.105949)

Arbidol (Umifenovir) S protein/ACE2, membrane fusion inhibitor Investigational agents Remdesivir Gilead Sciences RNA polymerase inhibitor Originally intended for Ebola but not effective, preliminary effectiveness against MERS. Data from China

• pending. (https://www.pnas.org/content/early/2020/02/12/1922083117)

Favipiravir Toyama Chemical of Japan inhibits RdRp https://www.ncbi.nlm.nih.gov/pubmed/28769016 Adjunctive therapies Actemra (Tocilizumab) Roche IL-6 inhibitor (immuno-modulator) Approved for rheumatoid arthritis. Encouraging evidence from China. (https://www.roche.com/media/releases/med-cor-2020-03-19.htm) Deferoxamine Regenerative Medicine Research Center, Iran Iron chelator (Desferal) https://www.nature.com/articles/nrmicro1930

Therapeutics Being Evaluated for COVID-19

Experimental – Only to be used in the context of clinical trials

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Sanders JM, et. al. JAMA. Published online April 13, 2020. doi:10.1001/jama.2020.6019

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Sanders JM, et. al. JAMA. Published online April 13, 2020. doi:10.1001/jama.2020.6019

Therapeutics Being Evaluated for COVID-19

Experimental – Only to be used in the context of clinical trials

Questions?

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Doing now what patients need next

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SARS CoV-2: Rising to the Testing Challenge in the United States

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