covid-19 at lhsc · 2020-06-04 · outline •review of covid-19 literature •focus on clinical...
TRANSCRIPT
Covid-19 at LHSC:An ID Physician’s Perspective
Dr. Megan Devlin, MD, FRCPC
Infectious Diseases, Assistant Professor
April 2nd, 2020
Some Notes:
• No Disclosures
• ZOOM Etiquette:• Mute your Microphone• Please save your questions for the end
• ID is piece, Multiple Stakeholders in this outbreak• Disagreement/Differing opinions common• New Data becoming rapidly available
• (April 1st was my cutoff)
• Evolving Guidelines and Shortages
Outline
• Review of Covid-19 literature• Focus on Clinical Course
• Risk Factors/Prognosis
• Therapeutics
• Discussion of ID/ASP plan for therapeutics
• Tips for Admitting, Managing and Discharging COVID+ or Presumed COVID patients
• Review of Clinical Characteristics of Admitted patients at LHSC
Hierarchy of COVID Literature
Basics of SARS-CoV-2
• +RNA virus, BetaCorona• Related to SARS-CoV-1• Transmitted Droplet/Contact, Ability to Aerosolize with specific procedures
• Some asymptomatic or pauci-symptomatic transmission
• To Date Worldwide (as of April 1 afternoon):• 927,986 Cases, 46,491 Deaths
• Canada:• 9,005 Cases, 105 Deaths
• Ontario:• 2,392 Cases, 37 Death (Mar. 31st)
Natural History
• Incubation Period: 5 days (~ 3-7 days)• Onset of Dyspnea: 7-8 days• Onset of symptoms to requiring mechanical
ventilation (12-14 days)• Recovery 2 weeks for mild, 3-6 weeks for
severe
• Viral Shedding:• Typically 10 Days in those recovered (from onset of
illness) (Severe disease ~20 days)• PCR detectable in stool, but unable to culture
(?Viable virus)
Zhou L. NEJM. 2020. Zhou F. Lancet. 2020.
Testing – PCR Based
In House (LHSC):
• E-gene – Envelope gene (more sensitive)
• RdRP-gene - RNA Dependent RNA Polymerase
• Running ~140 tests/day, ?Increased
• On NP, BAL, ET Aspirate, NOT on Stool
• TAT < 24hours
Test Ordered in Community (outside hospital) PHO
• Sensitivity: 70% for NP - Chinese Numbers, (Wang. JAMA. 2020)• Increased Sensitivity for lower respiratory specimens (96% for BAL)
• Specificity
Serologic Studies??
If E-gene positive,RdRP negative = INCONCLUSIVE
Only target being tested at PHO
Mild – Severe – Critical Disease
Mild Disease
• Non-Pneumonia/
• Mild-pneumonia
Severe
• Dyspnea
• RR >30
• Sat < 93%
• P/F < 300
81 % 14 %
Critical
• Respiratory Failure,
• Septic Shock
• MOD
5 %
Wu Z. JAMA. 2020.
Predictors for Severe Disease
Clinical
• Age (>50) OR 2.61 - 95% CI, 2.29-2.98
• Sex (Male) OR 1.34 - 95% CI, 1.195-1.521
• Smoking 1.73 95% CI 1.146-2.626
• Comorbidities• Any OR = 2.635, 95% CI 2.098-3.309
• CKD, OR = 6.017; 95% CI, 2.192-16.514
• COPD, OR = 5.323; 95% CI, 2.613-10.847
• Cerebral Vascular Disease, OR = 3.219; 95% CI, 1.486-6.972
Laboratory
• Lymphopenia
• Thrombocytopenia
• LDH
• CRP
• D-Dimer• *all for P < 0.001
• IL-6 Levels?
Zhou et al. Lancet . 2020.Ma C. PRE-PRINT. 2020, Metanalysis.
Prognostic Factors
• Old age (≥ 60 yrs) RR = 9.45; 95% CI, 8.09-11.04
• Higher qSOFA score (Zhou)
• Cardiovascular disease RR = 6.75; 95% CI, 5.40-8.43
• In Zhou for CAD OR (Univariate) – 21.40 (95% CI
• Hypertension RR = 4.48; 95% CI, 3.69-5.45
• Diabetes RR = 4.43; 95% CI, 3.49-5.61
• * All Independent prognostic factors
• CKD
• Need more data re: Malignancy, Immunocompromised population
Zhou F et al. Lancet . 2020.Ma C. PRE-PRINT. 2020, Meta-analysis.
Comparing CFR: SARS, COVID-19 and Influenza
Ruan, S. Lancet ID. 2020.
Notes on Clinical Characteristics
• 1/3 early GI symptoms?• More end organ disease, longer disease course• Some ONLY had GI symptoms (Han et al. AGJ. 2020)
• Cardiac: 19.7% “cardiac injury” in hospitalized patients, independent risk factor for mortality (51.2% vs 4.5%)
• Hypercoaguable state or DIC?• Those with elevated D-Dimer ?Therapeutic Anticoagulation• ?Improved outcomes if on anticoagulation? (Tang, JTH, 2020)
Tang N et al. Journal Thrombosis & Hemostasis. 2020.
Shi S et al. JAMA Cardiology. 2020.
Han et al. AGJ. 2020
Covid in Pregnancy
• No (?) reports of pregnant women requiring ventilation
• 3 Case reports of vertical transmission (Case series of 33 babies born to Covid + mothers)• Mothers delivered under Negative Pressure/Local Infection Control
Precautions• Neonates developed Pneumonia, NO Deaths
• Neonatal swabs NP and rectal swab + SARS-CoV-2
• ?Increased Preterm Labour
• Breastfeeding: 6 mothers breast milk tested negative
Zeng. JAMA Pediatrics. 2020.
Notes for Clinicians Admitting Presumptive Covid-19 patients
• At Admission:• Record O2 sat at room air• CBC, lytes, Cr, Liver Enzymes (ALT),
LDH, CRP, Troponin• Look for Markers of Severe Disease:
• Lymphopenia, Tropinitis, CRP, LDH• D-Dimer*
• NP Swab for COVID• ECG (if therapy started, monitor QTc)• CXR (Consider CT, US)
• Therapeutics:• Minimal Fluids (unless AKI, Cr)• Continue ACE/ARB if already on
• Consider Non-Covid issues (consider more than one illness)
• Code Status
• Infection Control: Droplet/Contact precautions• Practice your Donning and Doffing
• ?Notifying CCOT
• ?ABG if Sat <95%
?Standard Order Set
Imaging
Thomas, A. CMAJ. 2020.
CT US
Notes for Managing Patients
@leorahorwitzmd
GIM, NYU
Notes for Managing Patients
@leorahorwitzmd
GIM, NYU
Specific Therapeutics for Covid-19
Therapeutics for Consideration
Antivirals
• Anti-Retroviral (Protease Inhibitors):• Lopinavir/ritonavir• Darunavir/ritonair
• RNA Polymerase• Remdesivir
• Ribavirin
Other• Hydroxychloroquine
• (Plus Azithromycin)• (Plus Zinc and Azithromycin)
• Colchicine, Losartan
• Convalescent Plasma
• Anti IL-6 Therapy
Less Access/Experience in Canada
Anti Viral
• Favipravir
• Arbidol
Online as of Mar. 17
NEJM LPV/r in Severe Covid
• Jan. 18 – Feb. 23, 2020• Randomized, Controlled, Open-label trial• Included (n=199):
• SARS-CoV-2 + , Sat <94% at room air or PF <300• Excluded: Allergy, Cirrhosis, major Drug Interaction, HIV, Pregnancy, Cirrhosis
• Intervention: Lopinavir/ritonavir 400/100mg BID x 14 days vs Standard of Care
• End-points: • Primary: Time to Clinical improvement
• (Defined: Discharge from Hospital or 2 point improvement on a ordinal scale)
Cao, B et al. NEJM. 2020.
Cao, B et al. NEJM. 2020.
Caveats/Questions
• Patients received 1 st dose of LPV/r at 14 days
• ?Would Lopinavir/ritonavir given earlier result in a more significant benefit?
• Lopanivir/r: • Adverse Events (Nausea, Vomiting, Diarrhea)
• Drug-Drug interactions (Ritonavir “Booster” – Midazolam)
Cao, B et al. NEJM. 2020.
Hydroxychloroquine
• Rationale:• In vitro activity against SARS-CoV-2
• Especially when combined with Remdesivir
• Anti-Inflammatory Properties
• Chloroquine: Malaria
• Safety:• N&V, Dizziness, Headache, QT prolonging (w/ other agents), retinal disease,
Study Design
• Non-Randomized Controlled Trial in Marseille, France
• n = 26 intervention arm, 16 in control arm (alternate sites)• HCQ used• Azithromycin added at the discretion of the physician (n = 6)
• Endpoint – Viral Clearance (PCR Status at Day 6)• 41% were male, mean age 45
• 6 patients in treatment arm (HCQ) not included in analysis due to stopping therapy:• 3 transferred to ICU, 1 Death, 1 Nausea, 1 left hospital
HCQ Chinese Trial – Preprint (Mar. 31st, 2020)• Study Design:
• Double-blind, randomized parallel-group trial (1:1) • Recruitment: 4 to 28 February 2020• Location: Renmin University Hospital, Wuhan (single-centre)
• Inclusion:• Age ≥18y & CoV-2 confirmed by PCR • Pneumonia confirmed by chest CT • Not severely ill
• Intervention: Hydroxychloroquine 400 mg/d for 5 days (n=31)• Intervention: 200mg/d x 5 day• Control: usual care (n= 31)
• Outcome: • Time to clinical Recovery (body temperature), • CT Chest at D0 and D6
Chen Z, et al. PREPRINT. 2020.
• Intervention Group 2 (HCQ 200mg) missing
• Underpowered
A Note on HCQ OD
• Chloroquine/hydroxychloroquine OD: • Charcoal if <2h - expect rapid CNS/CVS crash;
• Tube early
• Diazepam 2 mg/kg over 30" then 1-2 mg/kg/d
• Epi 0.25 μg/kg/min, titrate to SBP ≥90
• NaHCO₃ or 3% NS for ↑QRS
• Avoid meds that ↑QT
• Watch for ↓K⁺ (shift); don't overcorrect
Ref: WikiTox
#chloroquinegate
Convalescent Plasma
Donors:
• Recovered from SARS-CoV-2
Convalescent Plasma
Shen C. JAMA. 2020
Colchicine
• Colchicine Coronavirus SARS-CoV2 Trial (COLCORONA) (COVID-19)• Montreal Heart Institute, clinicaltrials.gov
• COVID +• Randomized, double-blind, placebo-controlled, multi-center study.
Following signature of the informed consent form, approximately 6000 subjects meeting all inclusion and no exclusion criteria will be randomized to receive either colchicine or placebo (1:1 allocation ratio) for 30 days. Follow-up phone or video assessments will occur at 15 and 30 days following randomization for evaluation of the occurrence of any trial endpoints or other adverse events.
• Goal: 6000 participants
Evolution of ID LHSC Guidelines
• Week of Mar. 16: Document Created: Dr. Shalhoub and Michael Juba (ID pharmacy)• For Severe Cases: Kaletra, HCQ• For ICU: Remdesivir Application• Active work to be involved in RCTs: WHO and CATCO
• Week of Mar. 24:• HCQ alone or Nothing• For ICU: Tocilizumab• Active work to be involved in RCTs: WHO and CATCO
• Week of Mar. 30th:• Discretion of ID Physician• https://intra.lhsc.on.ca/antimicrobial-stewardship/covid-19-resources
https://intra.lhsc.on.ca/antimicrobial-stewardship/covid-19-resources
https://intra.lhsc.on.ca/antimicrobial-stewardship
Summary of Literature for Therapy as of April 1Therapy Level of Available Evidence LHSC Access to drug? RCT Opportunity?
LPV/r Open label RCT in severe COVID - NEJM 2020
Liquid – Very limitedTablets (*If Crushing tablets reduce AUC < 40%)
WHO Solidarity/CATCO
Remdesivir In Vitro Data ?Compassionate Access for Pregnancy and Pediatric?
Closed to centers in Canada
HCQ RCT from Wuhan (PREPRINT) Yes, for now WHO Solidarity/CATCO
PEP Trials forthcoming
HCQ/Azithromycin Open label, non-randomized(n = 26), serious methodological flaws
Yes Join Raoult, Vive La France Libre
IL-6 Inhibitors(Tocilizumab/Sarilumab)
Case Series n=11 (PREPRINT Cost 4,500/vial Being explored
Colchicine N/A Yes Trial in Montreal
Convalescent Plasma JAMA (n=5 Cases Series) Looking into it Help!
Other:Losartan Trial in US
Hot off the Press (This AM)
• LHSC - Will be a WHO SOLIDARITY Site:• 4 arms:
• HCQ• LPV/r• Remdesivir• Control
• Both ICU/Admitted Patients• Ethics Approval Pending
• 2 HCQ as PEP Trials:• 1 for HCW• 1 for LTCF patients
Thanks to Seema, Michael Silverman, Sarah Shalhoub, Geriatric Division (M. Borrie)
ACE-inhibitors and COVID
Vaduganathan M, NEJM. 2020.
My Thoughts on Therapeutics
• Need to be studied in RCT when possible• Like many respiratory viral illness, therapy may be limited value
• Focus on • Control of Community Spread (Public Health Interventions)
• Physical Distancing, Access to Testing• Preventing Nosocomial Spread, Protecting HCW
• ?Testing for Every Admitted patient• Cohorting of Covid+ Patients• PPE SUPPLY• Surge Capacity
Tips on Discharging Patients
• Notify Public Health• Typically already in discussion
• Instructions on how to Self-Isolate• https://www.publichealthontario.ca/-/media/documents/ncov/factsheet-covid-19-how-to-self-
isolate.pdf?la=en• How are they getting home?• What does their home situation look like?
• Community Self-isolation removed:• Symptoms resolved (fever) AND• 14 days from onset of symptoms in community
• To remove from precaution in hospital: Symptoms resolved AND 2 negative swabs 24 hours apart
Resources
• COVID: • Covidprotocols.org
• MLHU Website – Local Data:• Biweekly updates for community physicians (GPs)
• Train yourself in ICU level care:• https://www.quickicutraining.com/
Looking for people to follow on Twitter?
• ID/Aggregation of Published Studies• @mugecevik
• GIM Clinicians:• @FralickMike @DavidJuurlink (Clin
Pharm)
• ASP/IPAC• @ASPPhysician
• Clinical Trials:• @DrToddLee
• Mathematical Modelers• @DFisman @BogochIsaac
Covid-19 @ LHSCA Review of Cases
Clinical Covid at LHSC – 1 (As of 04.01)University Hospital – Mar. 16-27
Case Demographics PresumedLocation ofAcquisition
Therapy Received CRP atadmission
LOS (Days) Outcome
1 24 yo MT2DM
Community HCQ x 5 daysLPV/r x 4 days
72.0 6 Discharged in stable condition
2 74 yo MT2DM, HTN, CKD
Travel(Portugal)
HCQ x 5 daysLPV/r x 5 daysApplied for Remdesivir –DeclinedPipTazo
314.0 10t/f Mar. 18
Deceased (Mar. 27th)Vent on t/f from Strathroy, Requiring Dialysis
3 68 yo M T2DM, NAFLD
Community HCQ x 5 daysLPV/r C
196.8 A Mar. 23 Vent PAD #2,
4 37 yo M Travel (US) HCQ x 5 days 14.0 2 Discharged in stable condition
*(Admitted Patients not HCW)
Both pts attended Teen Challenge MeetingRequired/Requiring ICU level care
Clinical Covid at LHSC - 2University Hospital (~Mar. 25-29)
Case Demographics PresumedLocation ofAcquisition
Therapy Received CRP at admission
LOS (Days) Outcome
5 75 yo M HTN
Travel (Spain) Supportive 36.2 A Mar. 25 Admitted, requiringSupplemental O2
6 53yo M Community Supportive 12.2 4 Discharged in Stable Condition
7 62 yo F Community xx 110.6 A Mar . 27 Admitted, requiringSupplemental O2
8 21 yo F Community(Travel to Toronto)
Supportive 212.8 A Mar. 28 Ventilated x _ days
9 85 yo FParkinson’s Disease
Community (NH – Henley Place)
SupportiveCeftriaxone
120.0 A Mar. 29 Admitted, requiringSupplemental O2
*(Admitted Patients not HCW)
Clinical Covid at LHSC - 3University Hospital (Mar. 29 – present)Case Demographics Presumed
Location ofAcquisition
Therapy Received
CRP at admission
LOS (Days) Outcome
10 73yo F Travel (Philippines) Supportive 180.2 A Mar. 30Presented Mar. 22
Vented PAD 1
11 82yo MHTN, CLL
Community (LRCP volunteer)
Ceftriaxone,Doxycycline
18.7 A Mar. 30 Supplemental O2
12 66 yo F CHF, COPD, HTN, Obesity
Community/ ?Nosocomial(A @ UH Jan. 25-Mar. 18th)
281 A Mar. 30 Vented PAD 0
13 73yo FCHF, T4
Travel (US) Supportive 31.4 A Mar. 31
14 76 yo MStroke, HTN, etc
Travel (US) Supportive 154.9 A Mar. 31
15 91yo FT2DM, HTN, etc
Community(Retirement home)
N/A A Mar. 29 CCU
*(Admitted Patients not HCW)
Married
Clinical Covid at LHSC - 4University Hospital (Mar. 29 – present)Case Demographics Presumed
Location ofAcquisition
Therapy Received
CRP at admission
LOS (Days) Outcome
16 81 y MStroke, HTN
Travel (Brazil) Supportive,Ceftriaxone/Azithromycin
77.6 A Mar. 31 Supplemental O2
17 48 y FNo CM
Community(International students)
Supportive,Ceftriaxone/Azithromycin
131.5 A Mar. 30 Vented PAD 0
*(Admitted Patients not HCW)
Clinical Covid at LHSC - 5Victoria Hospital
Case Demographics Presumed Location ofAcquisition
Therapy Received CRP at admission
LOS (Days) Outcome
1 32 yo F Travel (US) Supportive 15.6 3 Discharged in Stable Condition
2 67 yo FCMML
Community HCQLopinavir/rRemdesivir
96.5 A Mar. 19th
Presented x 1 Mar. 17
Vented PAD 1
3 45 yo FMild Asthma
Travel (St. Maarten)
LPV/rHCQ
N/A A Mar. 22nd Vented, PAD Day 0
4 68 yo MHTN, T2DM, etc
Community (Wife Travel)
Supportive,PTZ/Azithromycin
274.7 t/f Mar. 27 Vented on t/ft/f from South Huron
5 67 yo M Hepatitis B
Community (Works at Loblaws)
Ceftriaxone/Azithromycin
171.3 A Mar. 29th AIRVO as of Mar. 31st
6 56 yo FeGPA, T2DM, CKD, etc
Community Supportive,PTZ
236.1 A Mar. 29th Vented, PAD 0
*(Admitted Patients not HCW)
Clinical Covid at LHSC - 6Victoria HospitalCase Demographics Presumed
Location ofAcquisition
Therapy Received CRP at admission
LOS (Days) Outcome
7 47yo FCervical Cancer
Community N/A A Mar. 24 Requiring Supplemental O2
8 56 yo FHTN
Community Supportive,Ceftriaxone
46.2 A Mar. 30 Requiring High flow O2
9 60 yo MOSA, HTN
Community 61.7 A Mar. 31
*(Admitted Patients not HCW)
Total Confirmed as of April 1st ~3PM Confirmed• Total Number of Cases Admitted
at LHSC: 26• (UH – 17, Vic – 9)
• Male - 12/26
• % Community Acquired: 65%• (17/26)
• % Travel Acquired: 35%
CRP At Admission
• If CRP > 100• 9/12 in ICU – 75%
• CRP < 100:• 2/11 in ICU – 18%
Advocacy• Preventing Community Spread
• PPE Supply: Occurring at Local, Provincial, National Levels• (N95>Surgical/Isolation Masks, Gowns)
• Staff Wellness & Time away
• Administrative/Planning: Surge Planning
COVID Hospital Hierarchy of Needs
Summary
• Increasing Numbers of Patients of LHSC with COVID• ?Mid April Peak?
• Current data to support specific therapies is limited, more forthcoming
• Active work to be involved in RCTs
Thanks &Questions
Up Next:
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