the world of coronaviruses: sars, mers, and …...• 58 (30%) hypertension, 36 (19%) diabetes, 15...

The World of Coronaviruses: SARS, MERS, and COVID-19

Meagan Deming MD, PhD

Wilbur H. Chen, MD, MS, FACP, FIDSA

18-Mar-2020

Confidential. ©2020 University of Maryland School of Medicine.

Respiratory Viruses

• Influenza

• Parainfluenza

• RSV

• Rhinovirus

• Adenovirus

• Human Coronavirus

• Enteroviruses (Coxsackie, Echo)

• Human Parechovirus (1999)

• Human Metapneumovirus (2001)

• Bocavirus (2005)

• Zoonotic agents:Hendra virus (1994), Nipah virus (1998), SARS (2003), MERS (2013)

Responsible for 15-40% of all common cold-like infections


Coronaviruses

• Single-stranded positive-sense RNA viruses

• 4 seasonal human coronaviruses (HCoV): 229E, NL63, OC43, HKU1

• endemic in bats – risk of zoonotic infection to humans


3 Novel Coronaviruses emerged in the last 18 years

SARS-CoV (2002)Severe Acute Respiratory Syndrome-associated coronavirus• 8098 cases w/774

deaths, ~10% CFR • 30 countries affected• Economic loss ~$80-

100 billion• Nov 2002 – July 2003

MERS-CoV (2012)Middle East Respiratory Syndrome-associated coronavirus• 2499 cases w/861

deaths, ~35% CFR • 27 countries affected• Economic loss? • April 2012 – present

COVID-19SARS-CoV-2

• 60,363 cases w/1,370 deaths, ~1-2% CFR

• 28 countries affected

• Economic loss?

• Dec 2019 – present


Recent History of Other Zoonotic Infections (Emerging & Re-emerging Diseases)

H5N1

SARS

West Nile

Nipah

Dengue

H3N2v

MERSH7N9

EbolaChikungunya

Zika

Hendra

H1N1pdm

2019-nCoV

Hendra 1994H5N1 1997Nipah 1998West Nile (Americas) 1999SARS 2003H1N1pdm 2009H3N2v 2011MERS-CoV 2012H7N9 2013Chikungunya 2013Ebola 2014Zika (Americas) 2015Dengue (Americas) 2016Ebola (Central Africa) 2018

nCoV 2019

Ebola


Nat Rev Micro 2014; 12:822-31

U.N. Food and Agriculture Organization

Science 2008; 320: 340-6

Flyways of migratory birds

WHO Surveillance of circulating influenza viruses

Predicting Zoonotic Threats(lessons from Pandemic Influenza)

Coronavirus or COVID-19 or SARS-CoV-2 or Wuhan or novel coronavirus or…

https://xkcd.com/2275/

What’s in a name?

The disease:CoronaVirus Infectious Disease 2019 (COVID-19)


What’s in a name?

The disease:CoronaVirus Infectious Disease 2019

(COVID-19)

The virus: Severe Acute Respiratory Syndrome Coronavirus 2

(SARS-CoV-2)


What’s in a name?

The disease:CoronaVirus Infectious Disease 2019

(COVID-19)

The virus: Severe Acute Respiratory Syndrome Coronavirus 2

(SARS-CoV-2)

80% sequence identity to SARS-CoV

Gorbalenya AE, Baker SC, Baric RS, Groot RJ De, Gulyaeva AA, Haagmans BL, et al. Severe acute respiratory syndrome-related coronavirus: The species and its viruses – a statement of the Coronavirus Study Group. BioRxiv 2020. https://doi.org/10.1101/2020.02.07.937862.Wrapp D, Wang N, Corbett K, Goldsmith J, Hsieh C-L, Abiona O, et al. Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation. Science (80- ) 2020:1–9.

Emergent Coronaviruses

Sheahan, T. Preparing for future pandemics, today with broad-spectrum antivirals. Commentary (Jan 2020) https://naturemicrobiologycommunity.nature.com/users/341687-timothy-sheahan/posts/58125-preparing-for-future-pandemics-today-with-broad-spectrum-antivirals

2002, China: ~8437 infected worldwide, 774 deaths.(10% CFR) • Severe atypical pneumonia

CoV outbreaks: Severe Acute Respiratory Syndrome

1. Lin Y, et al. (2004) Antivir Ther (Lond) 9: 287–289.2. Ksiazek TG et al. (2003) N Engl J Med 348: 1953–1966.

3. Peiris J et al.(2004) Nat Med 10: S88–S97.4. https://www.who.int/csr/sars/epicurve/epiindex/en/index2.html

SARS Coronavirus

1 2

4


• Single spillover - controlled by public health measure alone



SARS Coronavirus

1 2


4


• Single spillover - controlled by public health measure alone

• Progressive age-dependent mortality

Age Mortality3

0-24 0%

25-44 6%

45-65 15%

65+ 52%



SARS Coronavirus

1 2


CoV outbreaks: Middle East Respiratory Syndrome

MERS situation update, November 2019. WHO. http://www.emro.who.int/health-topics/mers-cov/mers-outbreaks.html (Accessed 3/2/20)

2012, Saudi Arabia: 2494 cases (lab-confirmed), 858 deaths. (35% CFR)• Severe atypical pneumonia


• Ongoing primary infections (camels)

CoronaVirus Infectious Disease 2019 (COVID-19)

1/1

3/2

0

12

/31

/19

1/2

0/2

0

2/1

3/2

0

2/2

0/2

0

2/2

9/2

0

2/2

7/2

0

1/3

0/2

0

in China

outside China

12/31/2019 atypical pneumonia identified in Wuhan, China1/13/2020 Case in Thailand1/20/2020 1st Case in Washington State, US1/30/2020 WHO declared Public Health Emergency of

International Concern2/27/2020 updated global risk to High Risk2/29/2020 1st US death

1/1

3/2

0

https://www.ecdc.europa.eu/en/geographical-distribution-2019-ncov-cases


https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6

100,330 infections; 3408 deaths (crude CFR 3.4%)• Severe atypical pneumonia


• Single spillover event (probably)



200K infections; 8008 deaths (crude CFR 4%)• Severe atypical pneumonia


• Single spillover event (probably)



200K infections; 8008 deaths (crude CFR 4%)• Severe atypical pneumonia

COVID-19 diagnosis

• 90% of patients with COVID-19 are febrile at some point during hospitalization, but only 44% were febrile on admission

• 80-100% of hospitalized patients with imaging abnormalities• Usually bilateral, ground glass progressing to consolidation, peripheral and

posterior

• Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China. JAMA 2020 (In press).• Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020;6736:1–7.• Song F, Shi N, Shan F, Zhang Z, Shen J, Lu H, et al. Emerging Coronavirus 2019-nCoV Pneumonia. Radiology 2020 (In press).

Admission Day +5

COVID-19 diagnosis

• Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China. JAMA 2020 (In press).• Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020;6736:1–7.• Song F, Shi N, Shan F, Zhang Z, Shen J, Lu H, et al. Emerging Coronavirus 2019-nCoV Pneumonia. Radiology 2020 (In press).

Admission

Day +5

Day +3

Nonspecific CT findings:• GGO • Consolidations• Crazy paving• Rarely nodular• Occasional pleural effusions

COVID-19 diagnosis

• 90% of patients with COVID-19 are febrile at some point during hospitalization, but only 44% were febrile on admission

• 80-100% of hospitalized patients with imaging abnormalities• Usually bilateral, GGO progressing to consolidation, peripheral and posterior

• Sensitivity 97%, Specificity 25% (in a time of pandemic)

• Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China. JAMA 2020 (In press).• Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020;6736:1–7.• Ai T, Yang Z, Hou H, Zhan C, Chen C, Lv W, et al. Correlation of Chest CT and RT-PCR Testing in Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases. Radiology 2020;2019:200642.

Spectrum of Illness

• ~80% mild-moderate

• 13.8% severe• dyspnea, RR ≥30/minute, O2 sat

≤93%, PaO2/FiO2 ratio <300, and/or lung infiltrates >50% of the lung field within 24-48 hours

• 6.1% are critical • respiratory failure, septic shock,

and/or multiple organ dysfunction/failure

• Crude CFR 1.4-4%

Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19).Wu, Z. et al. 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. Feb 24, 2020.

Spectrum of Illness

• ~80% mild-moderate

• 13.8% severe• dyspnea, RR ≥30/minute, O2 sat

≤93%, PaO2/FiO2 ratio <300, and/or lung infiltrates >50% of the lung field within 24-48 hours

• 6.1% are critical • respiratory failure, septic shock,

and/or multiple organ dysfunction/failure

• Crude CFR 1.4-4%

0 20 40 60 80

0

20

40

60

80

Mortality by age

Age group

Perc

en

t M

ort

ality COVID-19

MERS

SARS

Wu, Z. et al. 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. Feb 24, 2020.

Chan-yeung M, Xu R. SARS: epidemiology. Respirology 2003;8:S9–S14.MERS mortality by age curtesy of Vineet Menachery (personal communication)

Clinical Course

Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;6736:1–9.

191 patients in 2 hospitals in Wuhan, China• 137 discharged, 54 died (28%)

Clinical Course

• 191 patients in 2 hospitals in Wuhan, China• 137 discharged, 54 died (28%)

• 48% had comorbidity: • 58 (30%) hypertension, 36 (19%) diabetes, 15 (8%) coronary artery disease

Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;6736:1–9.Wu, Z. et al. 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. Feb 24, 2020

0 5 10 15

Case fatality rate

% cases

Hypertension 12.8

Diabetes 5.3

Cardiovascular disease 4.2

Chronic respiratory disease 2.4

Cancer (any) 0.5

none 74

data missing 53

10.5%

7.3%

6%

6.3%

5.6%

In Children?

Retrospective study of 366 children with respiratory infections admitted to hospitals in Wuhan

• 23 (6.3%) Influenza A

• 20 (5.5%) Influenza B

• 6 (1.6%) SARS-CoV-2

• No deaths

[1] Liu W, Zhang Q, Chen J, Xiang R, Song H, Shu S, et al. Detection of Covid-19 in Children in Early January 2020 in Wuhan, China. N Engl J Med 2020:2019–21.[2] Wei M, Yuan J, Liu Y, Fu T, Yu X, Zhang Z-J. Novel Coronavirus Infection in Hospitalized Infants Under 1 Year of Age in China. JAMA 2020.

All hospitalized infants (28d to 1 year) diagnosed with COVID-19 Dec through Feb 6 in China:

9 infants (7 female)

• All presumed from a family member• 4 with fever, 2 mild URI, 1 asymptomatic,

2 unknown

In pregnancy?

• All 3rd trimester

• 1 ICU admission (5%)

• 8 (42%) pre-term deliveries • none spontaneous

• 1 neonatal death

• No evidence of virtual transmission

19 women in published or pre-published studies, delivering 20 babies

Mullins E, Evans D, Viner R, O’Brien P, Morris E. Coronavirus in Pregnancy and Delivery: Rapid Review and Expert Consensus. MedRxiv 2020;preprint.

COVID-19 treatment options?

Remdesivir

*not to scale**educated guesswork

Convalescent sera

Suspected efficacy?**

Harmless

Harmful*

Lopinavir

Mair-Jenkins J, et al. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: A systematic review and exploratory meta-analysis. J Infect Dis. 2015;211(1):80–90.

Steroids

Chloroquine

SARS convalescent sera associated with reduction in mortality:• Absolute reduction ranged from 7% (95%

CI, −2.39 to 18.68) to 23% (95% CI, 5.59–42.02) (2 studies, +risk of bias)

• 4 noncomparative studies – CFR 0 to 12%


Remdesivir


Convalescent sera


Harmless

Harmful*

Lopinavir

SARS convalescent sera associated with reduction in mortality:• Absolute reduction ranged from 7% (95%

CI, −2.39 to 18.68) to 23% (95% CI, 5.59–42.02) (2 studies, +risk of bias)

• 4 noncomparative studies – CFR 0 to 12%

Mair-Jenkins J, et al. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: A systematic review and exploratory meta-analysis. J Infect Dis. 2015;211(1):80–90. Lv H, Wu NC, Tsang OT, Yuan M, Perera M, Leung WS, et al. Cross-reactive antibody response between SARS-CoV-2 and SARS-CoV infections. BioRxiv 2020;prerprint:1–20.

Steroids

Chloroquine


Remdesivir


Convalescent sera


Harmless

Harmful*

Lopinavir

Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020:2019–21.

Steroids

Chloroquine

“Ineffective”

Robustly inhibits SARS-CoV-2 in cell culture


Remdesivir


Convalescent sera


Harmless

Harmful*

Lopinavir

Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020:2019–21.Guangdong Provincial Science and Technology Department and Guangdong Provincial Health and Health Commission's Multicenter Collaboration Group on Chloroquine Phosphate for New Coronavirus Pneumonia. Expert Consensus on Chloroquine Phosphate for New Coronavirus Pneumonia. Chinese Journal of Tuberculosis and Respiratory Medicine, 2020,43 (2020-02-20) .

Steroids

Chloroquine Chloroquine:• Robustly inhibits SARS-CoV-2 in cell culture• Ongoing study(ies) – may improve clinical

outcomes• Available, known safety and dosing profile


Remdesivir


Convalescent sera


Harmless

Harmful*

Lopinavir

Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020:2019–21.Guangdong Provincial Science and Technology Department and Guangdong Provincial Health and Health Commission's Multicenter Collaboration Group on Chloroquine Phosphate for New Coronavirus Pneumonia. Expert Consensus on Chloroquine Phosphate for New Coronavirus Pneumonia. Chinese Journal of Tuberculosis and Respiratory Medicine, 2020,43 (2020-02-20) .

Steroids

Chloroquine


Remdesivir


Convalescent sera


Harmless

Harmful*

Lopinavir

Sheahan TP, Sims AC, Leist SR, Schäfer A, Won J, Brown AJ, et al. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun. 2020;11(1).

Steroids

Chloroquine


Remdesivir


Convalescent sera


Harmless

Harmful*

Lopinavir

Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020:2019–21.

Steroids

Chloroquine

Robustly inhibits SARS-CoV-2 in cell culture


1. Agostini ML, et al. Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. MBio. 2018;9(2):1–15. 2. Sheahan TP, Sims AC, Leist SR, Schäfer A, Won J, Brown AJ, et al. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun.

2020;11(1).

Remdesivir


Convalescent sera


Harmless

Harmful*Steroids

ChloroquineLopinavir


1. Agostini ML, et al. Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. MBio. 2018;9(2):1–15. 2. Sheahan TP, Sims AC, Leist SR, Schäfer A, Won J, Brown AJ, et al. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun.

2020;11(1).

Remdesivir


Convalescent sera


Harmless

Harmful*Steroids

ChloroquineLopinavir

Lopinavir/ritonavir:Not recommended. No plausible mechanism and ineffective in animal models.Targets the HIV protease (aspartyl protease) - quite different from the CoV proteases: PLpro (serine protease) or Mpro(cysteine protease)

RemdesivirPlausible, in vitro activity & animal models. − Adverse effects in phase 1 clinical trials

included: constipation, heartburn, itching, dizziness, loss of appetite, nausea, vomiting

− LFT abnormalities (AST 70s to 290s; ALTs 60s to 250)

Available through compassionate use and (soon) clinical trial.


Zumla A, Chan JFW, Azhar EI, Hui DSC, Yuen KY. Coronaviruses-drug discovery and therapeutic options. Nat Rev Drug Discov 2016;15:327–47.

Corticosteroid use for SARS patients • Higher plasma RNA levels at weeks 2-3 into

illness (likely prolonged viremia) • Increased 30-day mortality

(adjusted OR 26, 95% CI 4.4-154.8).

Remdesivir


Convalescent sera


Harmless

Harmful*

Lopinavir

Steroids* *Not for treatment. Use may be required for related illness eg. Refractory shock, asthma, COPD, organ transplant.

Chloroquine

COVID-19 vaccine?

Bolles M, et al. A Double-Inactivated Severe Acute Respiratory Syndrome Coronavirus Vaccine Provides Incomplete Protection in Mice and Induces Increased Eosinophilic Proinflammatory Pulmonary Response upon Challenge. J Virol 2011;85(23):12201–15.

Unvaccinated VRP-N vaccinated

Nucleocapsid specific responses (likely cell mediated)increase immunopathology

Vaccine-induced immunopathology after challenge

Mo

ck V

acci

ne

Kill

ed V

acci

ne

What happens next?

• Seasonal coronaviruses?

• Durable immunity?• Common coronaviruses (229E) show

declining immunity after 1 year

[1] Callow KA, Parry HF, Sergeant M, Tyrrell DAJ. The time course of the immune response to experimental coronavirus infection of man. Epidemiol Infect 1990;105:435–46.[2] Kissler SM, Tedijanto C, Goldstein EM, Grad YH, Lipsitch M. Projecting the transmission dynamics of SARS-CoV-2 through the post-pandemic period. MedRxiv 2020;preprint:1–30.

Fold change in neutralizing antibody titers

What happens next?

• Warm weather hypothesis?• cold and dry (low absolute humidity) environments

facilitate survival of respiratory viral diseases

[1] Sajadi MM, Habibzadeh P, Vintzileos A, Miralles-wilhelm F, Amoroso A. Temperature and latitude analysis to predict potential spread and seasonality for COVID-19. SSRN n.d.;preprint:6–7.

Circled cities with significant community transmission as of 6-Mar

What happens next?

• Warm weather hypothesis?• cold and dry (low absolute humidity) environments

facilitate survival of respiratory viral diseases

[1] Luo W, Majumder MS, Liu D, Poirier C, Mandl KD, Lipsitch M, et al. The role of absolute humidity on transmission rates of the COVID-19 outbreak 2020:1–7.

Seasonal variations in absolute humidity may be insufficient to

prevent widespread transmission

What happens next?

• Warm weather hypothesis?• cold and dry (low absolute humidity)

environments facilitate survival of respiratory viral diseases

• Seasonal variations in absolute humidity may be insufficient to prevent widespread transmission

• Duration of immunity• Short term (40 weeks) annual

• longer biennial

Short term immunity (40 weeks)

Longer immunity (104 weeks)

Kissler SM, Tedijanto C, Goldstein EM, Grad YH, Lipsitch M. Projecting the transmission dynamics of SARS-CoV-2 through the post-pandemic period. MedRxiv 2020;preprint:1–30.


Don’t be a “Patient A”Patient A, stayed at Hotel M:

Feb 15, symptoms began in Guandong, China

Feb 21, traveled to HK to visit family, stayed at Hotel M (9th Floor)

Feb 22, admitted to hospital 2

Feb 23, patient A died

MMWR 2003

Patient A directly resulted in 12 infections at Hotel M, 4 HCW infections & 2 Family member infections

Indirectly associated with 268 cases


Don’t be a superspreader

Defined as spread to ≥ 8 other patients

Superspreadermean age 56

75% mortality

No. close contacts 36

AR close contacts 43%

Non-superspreadermean age 44

16% mortality

No. close contacts 0.37

AR close contact 18.5%

EID 2004

Index patient lead to 4 generations of spread including 76 case-patients


Importance of Non-Pharmaceutical Interventions

CDC Interim Pre-pandemic Planning Guidance Feb 2007

NPIs (Community Mitigation):• Isolation (of known cases)• Quarantine (potential contacts)• Social Distancing

o Closure of schools, businesseso Travel restrictionso Cancellation of mass gatherings

• Infection Control


Recent Modeling of the Potential Impact of NPIs

Imperial College COVID-19 Response Team, 16 Mar 2020DOI: https://doi.org/10.25561/77482

Necessary to layer multiple interventions


Potentially Very Protracted Situation

Imperial College COVID-19 Response Team, 16 Mar 2020DOI: https://doi.org/10.25561/77482


Local Projection, using a model

Assume:Population of Maryland 6.043M

N=60 current infections6 days for doubling of infections5% hospitalization rate2% ICU rate1% ventilation rate

Hospital length of stay 10 daysICU length of stay 7 daysVent length of 5 days

Penn Medicine, Predictive Healthcare team toolhttp://penn-chime.phl.io/

http://penn-chime.phl.io/


Tips for Staying Safe During COVID-19 (or the next emerging infection)

Personal Hygiene & Practices

Handwashing/Hand sanitizer

Cough/Sneeze etiquette

Stay home when sick

Avoid sick contacts

Seek medical assistance

Public Health Authorities

Isolation/Quarantine

Control mass gatherings/travel

Hospitalize– Contact/Droplet Precautions– PPE– ICU, mech vent support

Clear & Fast Communication– Prevent public panic

Vaccines

Therapeutics

Diagnostics

http://www.sesamestreet.org/video_player?p_p_lifecycle=0&p_p_id=videoPlayer_WAR_sesameportlets4369&p_p_videoListId=1783

http://www.sesamestreet.org/video_player?p_p_lifecycle=0&p_p_id=videoPlayer_WAR_sesameportlets4369&p_p_videoListId=1782

http://www.cdc.gov/sesame.html?s_cid=healthyHabits_001

Thank You

Institue of Human Virology & Center for Vaccine Development and Global HealthUniversity of Maryland School of Medicine

[email protected]

53

Funding: T32AI007524


• Host targeted therapeutics• Tocilizumab – calm cytokine storm

• Tmprss2 – co-receptor SARS-CoV-2 Camostat mesylate

• ACEi ? Assoc with hypertension?

the world of coronaviruses: sars, mers, and …...• 58 (30%) hypertension, 36 (19%) diabetes, 15...

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