Oct 4 2020 Thomas M File Jr MD MSc MACP FIDSA FCCP Chair Infectious Disease Division CoDirector Antimicrobial Stewardship Program Summa Health Professor of Internal Medicine Chair ID Section ID: 1038264
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1. UPDATE COVID-19: What have we learned?Oct 4, 2020Thomas M File Jr. MD, MSc, MACP, FIDSA, FCCPChair, Infectious Disease DivisionCo-Director, Antimicrobial Stewardship Program; Summa Health; Professor of Internal Medicine, Chair ID Section, Master Teacher NEOMED;President Infectious Diseases Society of AmericaCOVID-19 is the greatest social, health, and economic threat of our generation
2. Unprecedented response by general population and medical providers/systemsRapid development of information (?Evidence)COVID-19 specificallyTransmission (-2 to day 5); droplets and aerosolsContagionAsymptomatic spreadersMitigation (Masks, etc.)ManifestationsPathophysiology‘long-term’ effectsTherapeutics (evidence vs opinion)Antivirals; antibodies; anti-inflammatoriesControl (Vaccine)What have we Learned: selected thoughts2
3. Incubation 2-14 days (Mean 5)Respiratory dropletHigher transmission rate than endemic Coronavirus, Influenza R naught 2-4 (seasonal influenza approx 1)Transmission from 2-3 days prior to symptomsLess by touching surfacesRole of airborne?Oral-FecalSpread from Asymptomatic personsCongregate settings .COVID 19: Transmission3Cruise ship Japan687 +
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5. Droplets vs AerosolsNew CDC Guidance: How COVID-19 Spreads (10/5)Most commonly from close contact via respiratory dropletsCan sometimes be spread by airborne transmission under certain conditions (e.g. enclosed areas, inadequate ventilation)“Available data indicate that it is much more common for the virus that causes COVID-19 to spread through close contact with a person who has COVID-19 than through airborne transmission.”Less commonly via contact with contaminated surfaces5Morawska et al. It is Time to Address Airborne Transmission of COVID-19. Clin Infect Dis. 2020
6. Associated SymptomsInitial: Cough; Dyspnea; FeverSubsequent: Fever, Chills, Repeated chills, Muscle pain, Headache, Sore Throat; New loss of taste or smell; GI symptoms; RashAsymptomatic infection (? prevalence)Associated LabsLymphopenia; Elevated LFTs, LDH, CreatinineElevated inflammatory markers (CRP, D-dimer, troponin)Course: Most mild; May be Biphasic-initial symptoms(virologic phase) followed by ‘cytokine’ storm (immune inflammatory phase)Clinical Characteristics6
7. COVID-19: Syndromes/MechanismsMultiple Organs/SyndromesRESPIRATORY (Pulmonary)OTHER ORGANSCardiacNeurologicKidneyLiverCoagulationCutaneousMultiple Inflammatory Syndrome-Children (MIS-C)Mental HealthMechanisms:Direct viral infectionHypoxemiaCoagulopathyInflammatory response Cytokine effect
8. TherapeuticsEarly attempted treatments: Influenza/HIV medications Hydroxychloroquine (+/- Azithromycin) Vit C, D; Zinc; Famotidine BUT ? evidence Results of randomized Clinical Trials (Positive effect): Remdesivir DexamethasoneNeed to treat based on scientific evidence 8Study with many limitationsInter J Antimicrob Agents. Feb 2020Hydroxychloroquine +/- Azithromycin
9. 9MOST patients 80+% General WardICUSupportive CareAntiviralsAnti Inflammatory agentsAnti coagulationViral StageInflammatory StageCOVID-19: TherapyAntibody therapy (Conv Plasma)Modified from Gandhi Clinc Infect Dis 2020
10. TherapyIDSA (GRADE level)1*NIH2HydroxychloroquineRecommend Against (Strong)Recommend Against (AI)Conv Plasma**Rec in clinical trialInsuff data; not standard of careRemdesivir**Rec for severe (conditional); not if no O2 required (cond)Rec for hospitalized, reqireing 02 (BI)Dexamethasone**Suggests for critical (strong); severe (cond); against if O2 not requiredRec if O2 required (BI); not if O2 not required (AI)IL-6 inhibitors Suggests against routine use of tocilizumab* (cond)Rec Against except in trial (BI)Vit CNot Assessed (NA)Insuff DataVit DNAInsuff DataZincNAInsuff data; recommends against using above the recommended dietary allowance, except in a clinical trial (BIII). FamotidineSuggests against outside clin trial (cond)NAEvidence-Based Guidelines1. Infectious Diseases Society of America Guidelines. Available at: http://www.idsociety.org/covid19guidelines2. COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Available at https://www.covid19treatmentguidelines.nih.gov/. ACCESSED Oct 4, 2020*“It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations.”** have FDA designated Emergence Use Authorization
11. COVID-19 Symptoms can Linger for Months (Years?)Post-Acute Care Study (Rome)187.4% of 143 hospitalized patients had at least one persistent symptom after onsetSymptoms:Fatigue 53%Dyspnea 43%Arthralgia 27%Chest pain 22%44% Worse quality of life Asymptomatic patientsAbnormal lung findings2Abnormal Heart findings3Heart damageAnxiety/Depression4 1. Carfi A. et al. 2020. jamanetwork.com/journals/Jama/fullarticle/2768351;2. Medicine 2020; Ann Intern Med 2020 3. Puntmann V et al. JAMA Cardiology July 27, 20204. Prescott HC et a l. JAMA 2020
12. PatientDuration Symptomatic Patients (symptom strategy) preferred by CDC10 days after start of symptoms if afebrile*Symptomatic Patients (testing strategy) not recommendedFor use to reduce duration compared to above (e.g.,test at 5-7 days; if negative end isolation)Asymptomatic + patients10 days after + testAt risk contact to positive patient**14 days after contact (10 days after initial symptom if becomes symptomatic) Duration viable virus and of Isolation (Quarantine) 06.01.2016Summa Health Sample Preso12*Up to 20 days if severe or critical illness or severely immunocompromised** Within 6 feet without mask for 15-30 minutes; if test do so at day 5-7Duration of viable virus in patient: For most patiens-10 day from start of symptoms Up to 20 days if critical illness or severely immunosuppressed
13. Containment (to prevent infection into a population)Travel restrictionTest; Contact tracingQuarantineMitigation (Reduce sprea) Good Infection ControlPhysical distancing avoid gatheringsMasksHand HygieneDisinfectionCOVID 19: Control13
14. 14“MASKS SAVE LIVES” Francis Collins, Director NIH 1,2[1] Face mask use in the general population and optimal resource allocation during the COVID-19 pandemic. Worby CJ, Chang HH. Nat Commun. 2020 Aug 13;11(1):4049.[2] Masks Do More Than Protect Others During COVID-19: Reducing the Inoculum of SARS-CoV-2 to Protect the Wearer . Gandhi M, Beyrer C, Goosby E. J Gen Intern Med. 2020 Jul 31.Face Masks to Prevent COVID-19: meta-analysisChu et l. Lancet 2020
15. 15US: 10/1CharacterristicsModernaPfizerAztraZenecaJ&JTechnologymRNA*mRNA* Adenovirus vector Adenovirus vector TargetSpike proteinSpike proteinSpike proteinSpike proteinDoses2221Cold-chainFrozen -20 C-70 C----Paused 2nd AE*New technology-based on carrying the genetic material that instructs the host cell to make the antigen-Spike Protein VACCINE STATUS
16. Other COVID-19 Specific Treatment OptionsFall/Winter surgeEffect of Schools ‘reopening’Effect of Influenza (? Co-circulating)Vaccine trial resultsImmunityDurationHerdLong-term clinical effectsLong-term viral presenceViral Load??Level of Cytokines assoc with mortalityCOVID-19: Future, Unknowns
17. 17Loss of smell or taste
18. “What is a vaccine for SARS-CoV-2 and when will we have it?”Angelo DeLucia, PhDDepartment of Integrative Medical Sciences10/7/2020College of Medicine at Northeast Ohio Medical University18
19. 10/7/202019Immunologists have been on the hunt for the antibodies (and B cells and T cells) that help to defeat SARS-CoV-2 in the body.
20. Public health messageAs a scientist and now witnessing ongoing phase III trials, praise on the sophisticated and innovative technologies being used will need to be replaced by actions and messages that will foster trust among clinicians and the public Three concernsWhen will we have confidence that available vaccines are safe and effective?When will such vaccines be available to the people?When will vaccine uptake be high enough to return to normal?10/7/2020College of Medicine at Northeast Ohio Medical University20
21. 10/7/2020College of Medicine at Northeast Ohio Medical University21A. Sariol and S. Perlman, Immunity 53, August 18, 2020
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23. 10/7/2020College of Medicine at Northeast Ohio Medical University23D. Van Riel and E. de Witt, Nature Materials VOL 19 August 2020 p.810–820
24. 10/7/2020College of Medicine at Northeast Ohio Medical University24Vrabet et al. 910 Immunity 52, June 16, 2020 Elsevier Inc.
25. 10/7/2020College of Medicine at Northeast Ohio Medical University25Huang et al. Nature Communications volume 11, Article number: 4704 published 17 September 2020
26. 10/7/2020College of Medicine at Northeast Ohio Medical University26