COVID-19: Pandemic Perspectives for Primary Care

SARS CoV-2: A Global Pandemic

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

https://coronavirus.jhu.edu/data/hubei-timeline

Campions League Football: Atalanta and Spanish team Valencia on 19 February in Milan, Italy

• Patient zero in Wuhan, China likely early December 2019

• Super-spreader events across Europe contributed to the spread

• Serologic evidence indicates that COVID came to the Eastern U.S. from Europe

https://coronavirus.jhu.edu/data/cumulative-cases 9/20.2020

• Case fatality rate in Wuhan >10% in early outbreak

• Case fatality rate in Italy > 10%

• Case fatality rate in Germany <2%• Case fatality rate in U.S. 2-3%

Rodents: Hantavirus, Lassa

Monkeys: Yellow Fever, Herpes B

Chimpanzees: HIV-1

Bats: dominate as the species of choice for zoonosis: Hendra, Marburg, SARS, Nipah, Rabies, Ebola and Covid-19

COVID-19 is transmitted by respiratory droplets primarily

Slide adapted courtesy of Esclid Petersen, M.D.

Viral Phase

Time Course

Seve

rity

of il

lnes

s

Stage IEarly Infection

Stage IIPulmonary Phase

Stage IIIHyperinflammation

Phase

Inflammatory Response Phase

15%

5%

80%

Zhu et al. J Med Virol. 2020. Apr 10 DOI: 10.1002/jmv.25884

Guan et al. NEJM. DOI: 10.1056/NEJMoa2002032

Diagnostic Testing Nasopharyngeal or oropharyngeal swab for RT-PCR testing

Test for other respiratory viruses when indicated

Tracheal aspirate in intubated patients is more sensitive

Sputum induction and bronchoscopy are NOT recommended

PFT are NOT recommended

AJRCCM 2020. 201; 19-22NEJM 2020 DOI: 10.1056/NEJMc2016359

N Engl J Med 2020; 383:e38DOI: 10.1056/NEJMp2015897

• The sensitivity of nasopharynealswab for COVID 19 has varied between 70-80%

• Re-test a patient if needed if early in the symptomatic phase OR high pretest probability

• Serologic antibody testing is not recommended to determine active infection or immunity (only exposure)

• CXR may be normal in 63% of patients with COVID-19, especially in early stages

• Ground glass opacity is most common and bilateral

• Sensitivity is 50-59%

• Should not replace COVID testing where quick turn around results are available

Cleverley et al. BMJ 2020; 370 DOI: 10.1136/mbmj.m2426

Day 0 Admission Day 8

Pretest Probability

Typical Pattern in COVID + Patient

Indeterminate Pattern in a COVID + PatientAtypical Pattern in a COVID - Patient

• Typical Pattern of COVID on CT sensitivity of 72% and specificity 92% with PPV 88% for COVID+ patients

• Atypical or Negative Pattern PPV of 89% for non-COVID patients

• Indeterminate pattern showed sensitivity of 17% and PPV of 36% for COVID patients

Chest CT in the Diagnosis of Suspected COVID 19

Ciccarese et al. Radiology: Cardiothoracic Imaging 2020 DOI: 10.1148/ryct.2020200312

Risk stratification of patients admitted to hospital with covid-19

using the ISARIC WHO Clinical Characterization Protocol:

development and validation of the 4C Mortality Score. BMJ2020;370:m3339 Available at: https://isaric4c.net/risk/

General Management Recommendations

Adhere to isolation and infection control procedures for confirmed or suspected cases

World Health Organization has recommended against NSAIDS

Nebulizers should be converted to MDI’s

Anticoagulation prophylaxis strongly considered in all inpatients

Patient with Suspected or

Confirmed COVID

SpO2 ≤92%

Yes

Low-Dose Oxygen• Face Mask 6-12 LPM preferred

Improvement

YesContinue Low-Dose

Oxygen

NoTransfer to Higher

Level of Care

HFNC (High Flow Nasal Cannula)

• Flow >50LPM with FiO2 > 60%• Self proning• Negative Pressure Room• Staff in full PPE

SpO2 ≤92%

NoContinue HFNC

CPAP or NIV Helmet

Yes

SpO2 ≤92%

No Continue CPAP or NIV Helmet

YesEndotracheal Intubation

• 670 COVID patients and 369 health care workers in Italy

• HFNC, CPAP were similar in efficacy by reducing need for intubation

• 11.4 % of health care workers infected with COVID 19

Franco et al. ERJ 2020 DOI: 10.1183/13993.02130-2020

Type L• Low Elastance (i.e. High Compliance)• Low V/Q ratio• Low Recruitability

Type H• High Elastance (i.e. Low Compliance)• High Right to Left Shunt• High Recruitability

Gattinoni et al. Intensive Care Med DOI: 10.1007/s00134-020-06033-2

• Inflammation results in platelet and fibrinogen dysregulation

• Both macrothrombosis (A) and microthrombosis (B and C) are present

• Higher dead space is more highly associated with PaO2/FiO2 than is lung compliance

• High d-dimer levels have associated with higher mortality

Petal et al AJRCCM 2020 202; 690Zhou F, Lancet 2020

Lung Protective Ventilation

P/F* < 150

• Early (within 72 hours of intubation)

• 16 hours prone initially , then cycles of > 12 hours

• Continue until P/F > 150 with PEEP < 10 for at least 4 hours after supineProne Positioning

Yes

P/F 80-100** PaCO2 > 60

pH <7.25

YesRefer for ECMO if

eligible

*P/F = partial pressure of O2 (from ABG) to inhaled oxygen fraction**inhaled nitric oxide may be attempted but limited evidence

Viral Phase

Time Course

Seve

rity

of il

lnes

s

Stage IEarly Infection

Stage IIPulmonary Phase

Stage IIIHyperinflammation

Phase

Inflammatory Response Phase

Antivirals?

Immune-Modulatory Drugs?

Anticoagulation?

Bikdeli et al. JACC 2020 DOI: 10.1016/j.jack.2020.04.031Paranjpe et al. JACC DOI: 10.1016/j.jack.2020.05.001Nadkarni et al. JACC 2020 DOI: 10.1016/j.jack.2020.08.041

• The prevalence of DVT/PE is approximately 30% in COVID ICU patients

• D-dimer >3.0 µg/mL (3000 ng/mL)associated with thrombosis

• Non-randomized trials have shown both prophylactic and therapeutic anticoagulation are associated with reduced mortality

Patients with Moderate COVID 19-Inpatient

Management

Patients with Severe COVID 19-ICU Management

Therapeutic Anticoagulation

D-dimer > 3,000 ng/mLSymptoms of possible DVT/PE

or micro –thrombosis*

Yes

No

BMI>30D-dimer > 1.5 ng/mL

Need for supplemental O2

No

Yes

Prophylactic Anticoagulation: High DoseProphylactic Anticoagulation:

Low Dose

• Therapeutic Anticoagulation-Enoxaparin 1 mg/kg q 12

• Prophylactic High Dose-40 mg q 12

• Prophylactic Low Dose-40 mg q 24

*micro-thrombosis: livedo racemosa or reticularis, SVT, etc.

Demonstrate EfficacyRemdesivir

Demonstrate Lack of EfficacyHydroxychloroquineLopinavir/ritonavir

Beigel et al. NEJM 2020 DOI: 10.1056/NEJMoa2007764

• Remdesivir is associated with improved rate of recovery most apparent in hospitalized patients on or off oxygen

• Rate of recovery or mortality was not different those on HFNC or mechanical ventilation

• 5 days is adequate

• Dexamethasone 6 mg q 24 for 10 days reduced 28-day mortality due to COVID 19

• The main effect was seen in patients severely ill patients especially those mechanically ventilated

The RECOVERY Collaborative Group-Preliminary Report (Oxford, England)

• The first randomized trial showed no benefit in clinical improvement or mortality

• There may a therapeutic improvement in more severe disease

Ling et al. JAMA 2020 DOI: 10.1001/jama.2020.10044

Equipoise: Balancing the benefit of new medical information when uncertainty exists with the rights and interests of research subjects.

JAMA. 2020;324(6):603-605. doi:10.1001/jama.2020.12603Journal of Medical Virology, First published: 30 July 2020, DOI: (10.1002/jmv.26368)

• Hospitalized COVID patients studied 2 months after symptom onset

• Acute Phase: 72% had pneumonia; 15% received NFNC; 5% mechanical ventilation; hospital stay 13.5 ± 10 days

• Only 12 % symptom free

• Symptoms of PTSD, anxiety/depression and difficulty concentrating were present in many patients

Post COVID Pulmonary Fibrosis• Early analysis indicates that >30% of patients

on hospital discharge will have fibrotic changes on CT

• 47% of patients will have impaired DLCO and 25% will have reduced total lung capacity

• This is worse in more severe disease.

• There are no data on the use of corticosteroids, pirfenidone, or nintedanib in the treatment of post-COVID fibrosis

Mo X et al. Eur Resp Journal 55:2001217, 2020

• 26 college athletes with COVID, 27% mild symptoms otherwise asymptomatic

• Troponin normal• Clinical significance unknown

Rajpal et al. JAMA Cardiol 2020. DOI: 10.1001/jamacardio.2020.4916JAMA Cardiol. Published online July 27, 2020. doi:10.1001/jamacardio.2020.3557

• 100 patients recently recovered from COVID• 78% had ongoing myocardial inflammation

and reduced LVEF• Clinical significance is unknown

Pediatrics: Consensus Statement on the Paediatricinflammatory multisystem syndrome The Lancet: Child and Adolescent Health DOI: 10.106/S2352-4642

• Pregnancy: ACOG guidelines-https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2020/03/novel-coronavirus-2019

• more likely to be admitted to ICU and require mechanical ventilation

COVID-19 has produced unprecedented change

Heer-Stavert, S BMJ 2020 DOI: 10.1136/bmj.m2532