# Frontlinjeinformation om COVID

# CLINICAL GUIDES/GENERAL INFO

# EPIDEMIOLOGY

# Patient Characteristics:

  • Median hospitalized age varies by country and case report, mostly between 40s-70s (Wang et al, Arentz et al)
  • Initial male predominance but less clear as more data appears (Wang et al, Arentz et al)
  • Most patients with comorbidities, esp HTN, DM, CVD, chronic respiratory disease Incubation period: median 5-7 days, 98% within 12 days (Lauer et al, Tian et al) R0: around 2-2.5 in general population (WHO), up to 11 aboard cruise ships (Mizumoto & Chowell) but can be lowered through distancing & public health controls Viral shedding: can be present 1-3 days prior to onset of symptoms, median duration 20 days with durations up to 37 days in recovered patients (Zhou et al)

# Transmission:

  • Transmission via droplet, contact (fomites up to 7hrs on some surfaces); unclear if airborne transmission but may be possible (van Doremalen et al) Asymptomatic transmission appears to occur based on case reports (Bai et al, Rothe et al) and may be the source of a majority of infections based on modeling (Li et al)

# ISOLATION & PPE

  • Current CDC, WHO, SCCM recommendations: contact and droplet for COVID+ and rule out; airborne if aerosolizing procedure
    • In influenza studies, surgical facemasks appear equivalent to N95 in respiratory infection prevention -- though N95 significantly better in vitro, pragmatic benefit unclear (Smith et al, Radonovich et al)
  • All aerosolizing procedures (intubation, NIPPV, HFNC, suctioning, nebs, bronchoscopy, endoscopy, TEE) should be performed in negative pressure rooms (SCCM)
    • HFNC increases droplet spread and should be considered aerosolizing (Ne-Hooi et al)
    • Laparoscopy should be considered a potentially aerosolizing procedure and viral filters should be used, avoid ALL elective procedures (SAGES)
    • Avoid aerosolizing procedures when possible
  • University of Nebraska UV mask decontamination protocol
  • PPE Distribution Sites working to match HCWs needing PPE with people looking to donate: Get Us PPE Project N95 National COVID PPE Clearinghouse MaskMatch

# Creative solutions as supplies run low:

# 3D printing templates (not tested or validated, but likely better than nothing)

# Masks

Masks

N95s > surgical masks >>> homemade cloth masks > nothing against droplet transmission (MacIntyre et al, van der Sande et al)

2015 large, prospective randomized control trial of cloth masks vs clinical masks. Relative risk of 13 for influenza-like illnesses in healthcare workers wearing cloth masks vs. standard clinical masks. (MacIntyre et al)

# CLINICAL FEATURES

# Symptoms

# Adults

Fever (99% over 99F in one study, but up to 40% afebrile on admission in another), fatigue (70%), dry cough (59%), anorexia (40%), myalgias (35%), dyspnea (31%), sputum production (27%) (Wang et al, Leung et al, Arentz et al, Guan et al)

  • Symptoms are highly variable and should generally have high index of suspicion for isolation and testing (Lynch)
  • Look out for “silent hypoxemia” -- profound hypoxemia without respiratory distress (Xie et al)
  • GI symptoms (abd pain, diarrhea, N/V) were rare in some case series but common (49%) in others; often preceded respiratory symptoms (Wang et al, Lei et al)
  • May present with anosmia per European reports, though unable to find original case reports (ENT UK)
  • ARDS present in all intubated patients Arentz et al
  • Cardiomyopathy in ⅓ of patients (Arentz et al, Ruan et al)
  • Presence of shock highly variable (1%-35%) (SCCM)

# Children

More variable -- most common cough (48%), pharyngeal erythema (46%), fever (42%) (Lu et al)

# Pregnancy

Very little known, but very small (15) case series without clear difference in outcomes of mild disease or clear adverse impact on fetus/childbirth (Liu et al)

  • If you have a pregnant patient, please refer for the PRIORITY study to help us learn more about symptoms & outcomes in pregnancy

# Spectrum of disease

81% mild, 14% severe, 5% critical (Wu & McGoogan) Co-infection with other respiratory virus including flu has been described; does not appear common in adults (Ding et al) but may be common in children (Xia et al)

# Course

Average 7 days from symptom onset to hospitalization (Tian et al) Most admitted to ICU within 24hrs of admission (Arentz et al, Wang et al) and appear to have a prolonged ICU course

# LAB FINDINGS

  • Sensitivity of nasopharyngeal RT-PCR debatable and may be low (59-67%) for single PCR, increased with repetition (Fang et al, Wang et al, Tao et al)
    • Increased sensitivity with BAL (93%), sputum (72%) (Wang et al) but unclear if bronchoscopy advisable given aerosolization risk (Bouadma et al)
    • Chest CT may be more sensitive (98%) but less specific (Fang et al, Tao et al), but may not be a good use of resources esp. with disinfection times required if no designated COVID+/COVID rule out CT scanner
    • Serological tests are in the works but not yet in clinical use (Amanat et al)
  • Normal WBC with lymphopenia common (Wang et al, Arentz et al)
  • Elevated inflammatory markers (D-dimer, CRP, IL-6, ferritin, LDH) though notably low ESR (Zhou et al)
    • Elevated D-dimer, PT, LDH, IL6, trop, CRP, myoglobin more common in severe disease (Wang et al, Arentz et al, Zhou et al, Ruan et al)
  • Procal usually negative or indeterminate, may be elevated in superinfection
    • Small case series in children showed most (80%) with procal >0.05, though unclear if due to COVID or coinfection (Xia et al)
  • Seeing some elevation in LFTs but typically not substantial hepatitis
  • Prevalence of AKI unclear but may be more common than initially thought and AKI is an independent risk factor for mortality (Naicker et al)
    • Proteinuria in 44-67%, massive albuminuria in ⅓, elevated Cr in 15-20% (Li et al, Cheng et al)

# IMAGING

Pulm CCM Guide to Lung Imaging in COVID19 Italian Radiology COVID19 Image Database

# Chest X-Ray

CXRs with hazy, bilateral reticular opacities or GGOs; sensitivity appears variable, but increased after 72hrs (Arentz et al)

# CT

Highly sensitive, progression over disease course (Shi et al)

  • Early on (including before symptom onset) may see unilateral, multilobar, peripheral GGOs
  • CT abnormalities prior to laboratory confirmation in 70% (Li & Xia)
  • Progression to bilateral (90%), diffuse (50%) GGOs in most patients (Shi et al)
  • Consolidation with halo sign may be seen in pediatric patients (Xia et al)
  • Lesions predominantly bilateral, lower lobe > upper lobe (Zhao et al)
  • Progression to multifocal consolidation, air bronchograms, traction bronchiectasis, crazy paving appears to be correlated with more severe disease (Zhao et al, Kanne et al)

# Lung Ultrasound

Lung US findings include pleural thickening/irregular pleural lines, B lines, and subpleural consolidations; seems more sensitive than CXR and less than CT but need to capture a lot of lung area (Peng et al, Buonsenso et al) Butterfly Lung US training videos (no paywall)

# OUTCOMES/PREDICTIVE METRICS

  • Case fatality rates vary widely by country and likely inaccurate at this point given limited capture, overall CFR in largest study thus far (China) was 2.3% (Wu & McGoogan)
    • CFRs may be underestimated due to delays between case identification and death, with estimated mortality accounting for this delay leveling off at 5.7% (Baud et al) ...but CFRs may also be overestimated due to lack of capture of asymptomatic cases, with S Korea having much better capture and a much lower rate (1.1%) (KCDC)
  • Increasing age appears to be a significant predictor of severity & mortality with CFR of 15% in patients over 80 years (Wu & McGoogan, Zhou et al, Ruan et al)
    • HCWs appear to get sicker than age would otherwise predict with 14.8% severe or critical cases, higher rates of infection in overwhelmed areas (Wu & McGoogan)
    • Kids appear to do relatively well -- 87% discharged home, 12% stable on medical floor, 0.6% mortality (1 patient) (Lu et al)
    • Very early data with no clear difference in maternal outcomes in pregnancy (Liu et al) but may have a higher rate of preterm delivery (Mullins et al)
  • Comorbidities significantly increase mortality: CVD (CFR 10.5%, OR 21), diabetes (CFR 7.3%), COPD (CFR 6.3%), HTN (CFR 6.0%), cancer (CFR 5.3%) (Wu & McGoogan, Zhou et al)
  • Cause of death: 53% resp failure, 33% resp failure + heart failure, 5% heart failure (Ruan et al)
  • SOFA score correlated with in-hospital mortality (OR 5.65) (Zhou et al)

# Laboratory indicators of severity/mortality

  • Lower mortality with early warning system based on age, lymphocyte count, O2 req, CT scan (thresholds unclear) to triage to BID or continuous monitoring, then early ICU transfer for RR>30, SpO2<93%, or HR>120bpm (Sun et al)
  • D-dimer > 1 (OR 18.42) (Zhou et al), elevated trop, CRP, and myoglobin correlated with poor outcomes (Ruan et al)
  • Overall, patients with more elevated inflammatory markers appear to have worse outcomes
    • D-dimer (threshold 0.28) and IL-6 (threshold 24.3) may be a good combo of markers for severe disease (96% sensitivity, 93% specificity in small cohort) (Gao et al) -- please note, paper does not include case definition of mild vs severe disease
    • Very small case series argues higher platelet to lymphocyte ratio (i.e. platelet count/absolute lymphocyte count) may be predictive of severe disease, with platelet count tracking severity of disease (Qu et al)

# PULMONARY/CRITICAL CARE

SCCM COVID19 Guidelines Highlights: mostly adheres to traditional critical care for shock and ARDS

  • Conservative over liberal fluid resuscitation with typical preference for buffered crystalloids > NS > colloids
  • If pressors required, recommend norepi first line, vaso second line to target MAP 60-65 If cardiac dysfunction despite fluids and norepi, recommend dobutamine Low-dose corticosteroids for refractory shock
  • COVID19 specific: recommend HFNC over NIPPV for patients needing more support than conventional NC O2 (high risk for aerosol production/transmission, may depend on local hospital protocols)
    • If HFNC unavailable and no immediate indication for intubation, can consider short NIPPV trial (high risk for aerosol production/transmission, may depend on local hospital protocols)

Airway algorithm

# From SCCM guidelines

  • COVID19 specific: recommend early intubation if worsening on HFNC or NIPPV with expert performing, minimal staff in room, negative pressure, and contact + droplet + airborne precautions
  • Follow typical ARDS algorithms with LPV (ARDSNet), PEEP (ARDSNet), paralytics (PETAL), proning (PROSEVA) Consider trial of inhaled pulmonary vasodilator as rescue therapy, recommend against inhaled NO Recommend traditional but not staircase recruitment maneuvers
  • As a last resort, consider VV ECMO if available, but resource intensive and essentially no data (reportedly used in China but no outcomes data yet)

ICU algorithm

# Other COVID19-specific notes:

  • Tend to have better response to high PEEP and better compliance than similarly ill ARDS patients (observations from Italian ICU MDs, no published data; discussed in EmCrit)
  • May be possible to share/split vents in crisis, though prior studies/explorations primarily in mass trauma not pandemic (Neyman)
  • Avoid bronch unless suspected alternate etiology or superinfection given super high infxn risk and no other benefit (Bouadma et al) Brigham & Women’s Critical Care Protocols Crit Care MDs COVID respiratory failure algorithm
# Critical care for non-intensivists:

# CARDIOLOGY

ACC/China Meeting Summary COVID-19: Cardiac and Arrhythmic Complications by Christopher Kovach, MD MSc CardioNerds on COVID & Cardiology by Pranoti Hiremath, MD

  • In one case series, 17% of patients with arrhythmia (44% of ICU patients) and 7% with cardiac injury (22% of ICU patients) (Wang et al)
  • Reports of MI, acute onset heart failure, myocarditis, and cardiac arrest (ACC Bulletin); some patients presenting with purely CHF or myocarditis Sx (Zheng et al)
  • Overall seeing a high mortality with CV involvement though pathway (stress CM vs direct viral injury vs cytokine storm) currently unclear (Zheng et al)
  • ACE2 is a functional receptor for SARS-CoV-2 (Zheng et al) which has led to consideration of association between ACE/ARB use and COVID outcomes Patients with HTN, heart disease appear overrepresented in COVID diagnoses and mortality but difficult to interpret without age adjustment or cohort studies (Sparks et al) No clear evidence of causation or worse outcomes with ACE/ARB (Sparks et al), may have some lung protection from ARB in prior SARS studies Professional societies currently recommend continuing ACE/ARB for patients already taking (Sparks et al, ACC Bulletin)

# NEUROLOGY

  • Limited data suggest that hospitalized patients with SARS-CoV-2 with severe infections (>2 organ systems involved) are at significantly elevated risk of stroke/cerebrovascular events (Li et al) and this is a negative prognostic factor
  • Extremely elevated levels of CRP and D-dimer (>6) are likely indicative of severe generalized inflammatory conditions leading to prothrombotic state responsible for these outcomes (Li et al)
  • SARS-CoV-1 and MERS-CoV have previously demonstrated ability to infiltrate CNS, most likely via olfactory bulb neurons and trans-synaptic spread; prior studies have demonstrated viral antigens in the respiratory centers of the medulla raising questions of a potential contributory effect on pulmonary/respiratory compromise (Li et al 2 [different paper])
  • COVID19 may present with anosmia in otherwise asymptomatic individuals, possibly due to olfactory neuron infection based on reports from China, Italy, South Korea, and the UK; note that no formal studies or centralized aggregated data exist on this topic as yet (ENT UK, ENT UK)

# POTENTIAL COVID-TARGETED TREATMENTS

Please remember to check for drug interactions -- all targeted treatments are currently of theoretical benefit, but can cause proven harm

# Investigational

# Remedesivir

Effective in vitro with chloroquine (Wang et al), clinical trials in progress

  • Very limited availability, restrictive inclusion & exclusion criteria typically including multi-organ failure, intubation, and severe liver or kidney impairment
  • Dosing: 200mg loading dose then 100mg daily x 5-10 days (US study protocols, Belgian guidelines)

# Chloroquine/Hydroxychloroquine

Effective in vitro (Wang et al, [Lui et al]); may have clinical efficacy but unclear validity of studies so far (Gao et al (abstract only), Gautret et al (very small, non-randomized, potentially misleading endpoint (nasopharyngeal viral clearance, not clinical outcome), controls not really comparable to experimental group, many lost to follow up, sporadic non-protocolized azithromycin use))

  • Also in trials for infection prevention/PPx (U Minnesota)
  • Dosing:
  • Contraindications: QTc > 500, history of ventricular arrhythmias, retinal disease; may cause cardiomyopathy

# Lopinavir-Ritonavir

Initial observations & RCT without clear efficacy in COVID19 (Young et al, Cao et al), but notably with known increased activity in SARS-CoV-1 when used in conjunction with ribavirin (Chu et al) which was not used in current COVID studies (EmCrit)

  • Dosing: lopinavir/ritonavir 400mg/100mg PO q12hrs x 14 days AND ribavirin 4g PO loading dose + 1.2g q8hrs OR 8mg/kg IV q8hrs (Chu et al)
  • Contraindications: QTC > 500, caution in liver & cardiac disease; many drug-drug interactions; avoid ribavirin in pregnancy, asthma, and COPD

# Tocilizumab

May help cytokine storm, case series of 21 patients in China with clinical improvement and no known adverse events (Xu et al)

# Favilavir

Approved in China per news reports, not available in US, unable to find studies

# Convalescent sera

Theoretically beneficial (Casadevall & Pirofski), reportedly some cases in China but unable to find data, can’t find trials yet; may also be logistically difficult; SCCM currently recommends against use of convalescent plasma or IVIG

# ACE2

undergoing small observational trial in China, no results yet

# Controversial

  • Corticosteroids: may have reduced mortality in COVID-related ARDS (HR 0.38) in single, small, uncontrolled trial (Wu et al) but not recommended due to prior SARS data indicating increased viral shedding (Lee et al); WHO & CDC guidelines currently recommend against use but SCCM guidelines recommend use in patients with ARDS (not in patients without ARDS)
  • May consider in patients with other indications (COPD, vasopressor-resistant shock), if using steroids dexamethasone may be preferable agent due to relative lack of mineralocorticoid activity → similar immunomodulation with less pulmonary edema
  • NSAIDs for symptomatic treatment: WHO initially recommended against, then rescinded; it appears this may have been based off theoretical concern of increasing ACE2 expression and viral entry, unclear if any clinical data of different outcomes

# Ineffective

Neuraminidase inhibitors (e.g., oseltamivir): no in vitro benefit in SARS-CoV-2 (Tan et al) but useful if flu coinfection

# ETHICS/RESOURCE ALLOCATION

AMA Journal of Ethics COVID19 Resource Center A lot of US states are starting to come up with crisis standards of care (WA State here) and plans for triage, but you should look up your own and keep in touch with your hospital leadership as there are many different standards and they are likely to change over the course of the outbreak SCCM Resource Availability for COVID19 -- includes plans for alternate sources of vents and beds, possible team structures if insufficient intensivists

# TALKING WITH PATIENTS/FAMILIES

Guide for discussions with patients and families about COVID by Anthony Back, MD Reportedly planning guide for families soon Vital Talk app with family discussion guides, including for COVID19

# SELF CARE

(note: not company endorsements, just seemed like good resources -- take care of yourselves)

  • NYT on coping with Coronavirus anxiety
  • Headspace meditation app (free for HCW with NPI)
  • VA Mindfulness Coach app
  • Calm meditation app
  • Stop, Breathe, and Think meditation app
  • Leave No Trace recommendations for safely getting outdoors (if allowed in your region)
  • Down Dog yoga app (free until 04/01)
  • Les Mills workouts on demand (currently free)
  • Kansas City Zoo 24hr Penguin Cam
Senast uppdaterad: 3/29/2020, 12:28:16 PM