FRONTLINE COVID GUIDE

FRONTLINE COVID-19 GUIDE

Last update 04/22/20, new additions in green. Full reference citations here.

Compiled by Kathryn Bolles, MD; Shawn Cohen, MD; Justin Granstein, MD MPH; Christopher Kovach, MD MSc; Patrick Marcus, MD; Kristen Rogers, MD MPH; Eric Tanenbaum, MD

 

A compilation and synthesis of COVID information created by and for frontline MDs, representing our interpretations of available data and personal experiences; any data should be personally reviewed and considered alongside guidelines and expert advice. Please email at bolleskm@gmail.com to notify of new studies, omissions, or errors. Any views here are our own and do not reflect the views of our employers.

 

Sharing link: http://bit.ly/covidfrontline

 

ONE PAGERS

COVID ICU One Pager by Nick Mark, MD (in slightly longer publication form in Jamil et al)

COVID Hospitalist One Pager by Kristen Rogers, MD MPH

 

CLINICAL GUIDES & GENERAL INFO

UpToDate COVID19 (no paywall)

UW IDEA Program COVID-19 Information & Teaching Resources

EmCrit COVID Review

EB Medicine COVID19 Guide

Evergreen Hospital Lessons Learned (guidance from the first US hospital to handle cases)

Essential Evidence Plus COVID-19 Chapter (no paywall)

ACP Guide to COVID19

Harvard Medical School Med Student Created COVID Curriculum

IDSA COVID19 Resource Center (with info on testing protocols)

EM:RAP COVID-19 chapter

COVID-19 Grand Rounds:

 

MAPS & TRACKING

WHO Pandemic Situation Reports

Johns Hopkins Pandemic Map

The COVID Tracking Project

IHME COVID19 Projections

COVID Tracking by City

HealthMap COVID-19

 

GUIDELINES & PROTOCOLS

Guidelines: CDC, WHO, NIH

Protocols: University of Washington, MGH, UCSF, Mount Sinai, University of Nebraska, Department of Defense, Walter Reed Medical Center, AliBaba/Global MediXchange Handbook

Critical Care-specific: SCCM, ACLS/BLS, Brigham & Women’s, U Michigan airway protocols

 

CONSOLIDATED COVID STUDY REPOSITORIES & DATASETS

Emory Infectious Disease Weekly COVID-19 Literature Round Up

NIH LitCOVID

WHO COVID Research

NEJM, Lancet, Wiley, JAMA COVID articles (no paywall)

CORD-19 COVID19 Open Research Dataset

 

EPIDEMIOLOGY

Incubation period: most estimates between 4-7 days with 98% within 14 days (Lauer et al, Tian et al, Du et al, Zhang et al, Park et al, Sanche et al)

Transmission: droplet, contact (fomites up to 7hrs on some surfaces), likely airborne (1hr half life of aerosolized virus), possibly fecal-oral (RNA but no infectious virus found), and possibly maternal-fetal (van Doremalen et al, Xiao et al, Santarpia et al, Chen et al, Zeng et al, Leung et al, Wölfel et al, Guo et al)

  • Asymptomatic & presymptomatic transmission occurs (Bai et al, Du et al, Qian et al, Kimball et al, Wei et al) and may be the source of a majority of infections based on modeling (Li et al)
  • Isolating asymptomatic infected individuals may significantly improve containment (Day)
  • Nosocomial transmission may be possible but rate estimates vary (Zhang et al, Wong et al)
  • While some have theorized that transmission will decrease as weather warms, relatively rapid infection rates in West Africa argue against this theory (Martinez-Alvarez et al)

R0: ~2.0-3.0 (WHO, Li et al, Park et al, Kucharski et al); some estimate much higher (5.7) and up to 11 aboard cruise ships (Sanche et al, Mizumoto & Chowell); can be lowered significantly through public health controls (Wang et al, Zhang et al, Pan et al)

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, Kai-Wang To et al, Zou et al) but it is unclear how much this represents live virus capable of causing infection versus inactive viral debris; shedding appears longer in male patients and those with more severe disease (Xu et al)

High risk populations: elderly; residents of nursing homes, shelters, assisted living facilities, and psychiatric facilities (Yao et al); healthcare workers (Wu & McGoogan); immunosuppressed patients; refugees (Kluge et al); prisoners (Kinner et al); minority and poor populations (Johnson & Buford, Grantz et al, Lancet); women and children may be relatively lower risk to contract infection (Gudbjartsson et al)

Immunity: seroconversion appears to occur between day 7-14 but levels appear to vary significantly person-to-person; may be protective based on animal studies but no human data yet (Zhao et al, Bao et al, Wölfel et al, Wu et al)

  • There have been reports of patients recovering from clinical illness, testing negative, then subsequently testing positive again (An et al, Lan et al); no patients developed symptoms and discordance may be due to known issues with PCR testing sensitivity (Petherick, Xiao et al)
  • Not all recovered patients show detectable antibody levels in early testing (Wu et al)

 

ISOLATION & PPE

Isolation

  • Contact and droplet for COVID+ and rule out; airborne if aerosolizing procedure (CDC, WHO, SCCM); avoid aerosolizing procedures if possible
    • Aerosolizing procedures include intubation, extubation, NIPPV, HFNC, suctioning, nebs, sputum induction, bronchoscopy, endoscopy, TEE; possibly laparoscopy
      • Limit staff to minimum during aerosolizing procedures and use the most experienced operator available (SCCM, Cook et al)
      • Data is conflicting on whether HFNC is aerosolizing (Ne-Hooi et al, Cook, Iwashnya et al) though many institutions view it as such, consider using surgical mask over HFNC to reduce spread (Vapotherm, UW HFNC protocol)
      • Laparoscopy should be considered a potentially aerosolizing procedure and viral filters should be used, avoid ALL elective procedures (SAGES)
  • Work to cohort patients in COVID-specific wards (or even hospitals) if possible (Anesi et al)
  • Negative pressure rooms if possible, mandatory for all aerosolizing procedures (SCCM)
  • Limit room entry: no visitors, increase telemedicine, no non-essential personnel, minimize lab draws, bring IV and vent controls into the hallway (Ferioli et al, CNN on UW ICUs, Islam)

PPE: at least gown, gloves, mask (surgical vs N95) and goggles or face shield for general care; for aerosolizing procedures add PAPR/CAPR, shroud/neck cover, and consider “aerosol box” to contain secretions (see Critical Care section for further details) (Luo et al)

  • All PPE use should be combined with proper hand hygiene and regular cleaning of commonly used & contaminated surfaces (printers, door knobs, and keyboards) (Ran et al, Guangming et al)
  • Use extreme caution in donning/doffing PPE, especially if re-using, as virus has been detected on surgical masks 7 days after inoculation (Chin et al)
  • N95s surgical masks >>>>> homemade cloth masks > nothing against droplet transmission (MacIntyre et al, Davies et al, van der Sande et al)
    • N95 vs surgical masks: meta-analyses indicate likely pragmatic equivalence (Offeddu et al, Bartozsko et al), while some individual influenza studies show superiority of N95 over surgical face masks this appears to be mostly present in vitro with likely real-world equivalence (Smith et al, MacIntyre et al, Radonovich et al, Loeb et al, Bae et al) possibly due to improper use or lack of fit testing
    • Cloth masks are clearly inferior protection, with HCW wearing cloth masks vs standard clinical masks having RR 13 for contracting ILI (MacIntyre et al) though CDC & Joint Commission have released statements allowing for cloth masks as a last resort
  • The benefit of universal masking may be more to prevent transmission than to protect the wearer (Leung et al, Klompas et al); the CDC and the Joint Commission have now released recommendations supporting community & in-hospital universal masking

Coping with PPE Shortages

  • The CDC has created a PPE burn rate calculator to help institutions calculate needs
  • PPE distribution sites working to match HCWs needing PPE with people looking to donate:
  • Can consider homemade/3D printed face shields (here, here, & here) and face masks for use with changeable filters (here, here, & here; consider trying with vacuum bags/HEPA filters inside); none of these designs are tested or validated but they’re likely better than running out
    • There are even prototypes for printed ventilators (super cool but again, untested)

 

CLINICAL FEATURES

Symptoms: overall highly variable, symptom- & travel-based screening is not effective and may miss many cases, have high index of suspicion for isolation and testing (Lynch, Seattle Chest Grand Rounds)

Special populations:

  • Children: symptoms more variable and less severe, most common cough (48-54%) & fever (42-56%) (Lu et al, CDC, Choi et al); appear more likely to be asymptomatic than adults (Hu et al)
  • Pregnancy: very little known, but small cases series without clear difference in outcomes of mild disease or clear adverse impact on fetus/childbirth (Liu et al, Yu et al, Chen et al); may mount fever less often than other populations (Chen et al)

Co-infection with other respiratory viruses including influenza has been described and may be more common than initially thought (up to 25%), particularly in children (Ding et al, Sommer et al, Xia et al)

Spectrum of disease: 81% mild/moderate, 14% severe, 5% critical (Wu & McGoogan) in adults; 4% asymptomatic, 51% mild, 39% moderate, 6% severe in children (Yuanyuan et al)

Course:

  • Generally begins with mild infection, progressing to pulmonary symptoms with or without hypoxia and hospitalization; unclear if further progression is due to ongoing viral damage or to cytokine storm/hyperinflammation (MGH FLARE); treatment options may benefit from targeting to a particular disease phase (Siddiqi & Mehra) but there is no definitive data to support this
  • Average 4-7 days from symptom onset to hospitalization (Tian et al, Korean CDC)
  • 26-29% of hospitalized patients require ICU admission (indications: ARDS in 60-70% of ICU patients, shock in 30%; multi-organ dysfunction less common) (Wang et al, Cao et al, Phua et al)
  • Most patients who will require ICU are admitted to ICU within 24hrs of admission and appear to have a prolonged ICU course (Arentz et al, Wang et al, Grasselli et al)
  • Long course of severe disease with average 25 days from symptom onset to hospital discharge or 10-18 days from symptom onset to death (Verity et al, Korean CDC)

 

LAB FINDINGS

Viral studies:

  • RT-PCR: sensitivity is variable and appears low (51-67%) for single nasopharyngeal PCR but increases with repetition (Fang et al, Wang et al, Tao et al, Guo), though 21% of patients in one study with positive result after two prior negatives (Xiao et al)
    • Bayesian probability calculators may help you guess post-PCR test probability of COVID-19 more accurately based on your patient’s symptoms and local prevalence
    • Increased sensitivity with BAL (93%), sputum (72%) (Wang et al) but unclear BAL or sputum induction advisable given aerosolization risk (Bouadma et al, NIH) but NIH suggests use of endotracheal aspirate; small study also suggests use of self-collected oropharyngeal wash but will need further investigation (Guo et al)
    • Quantitative monitoring of viral load may correlate with disease progression, but currently unavailable in most areas (Yu et al)
    • Lab specimen preparation methods such as thermal inactivation may impact PCR yield and lead to false negative results, especially in lower viral loads (Pan et al)
  • Serological tests: early studies appear to show antibody titers inversely correlated with viral load and seroconversion ~10 days from symptom onset (Amanat et al, Kai-Wang To et al) but may be delayed in immunosuppressed patients (Zhao et al)
  • Combining PCR with IgM testing can significantly increase detection rate to 98.6% (Guo)

Blood counts

Inflammatory markers

  • Elevated inflammatory markers (D-dimer, CRP, IL-6, ferritin, LDH) common and may be prognostic (Zhou et al)
  • Procalcitonin 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)

Chemistries

  • Prevalence of AKI unclear and controversial with wide range reported (0.5-23%), appears more common in later studies (Arentz et al, Naicker et al, NephJC) and sometimes severe enough to require CRRT and appears to be an independent risk factor for mortality (Li et al, Cheng et al); but some studies argue it may be uncommon (Wang et al)
  • Seeing some elevation in LFTs but typically not substantial hepatitis or liver failure, the pathogenesis is unclear (Zhang et al, Hansheng et al, Musa)

Cardiac markers: elevated trop, CK-MB, BNP, myoglobin and ECG changes (incl. myocarditis w/ ST elevation) especially in severe disease (Zhou et al, Ruan et al, Han et al)

Coagulation: coagulopathy with elevated PT, PTT, thrombocytopenia appears common; DIC and even positive APLS serologies in some patients (Zhang et al)

 

IMAGING

Pulm CCM Guide to Lung Imaging in COVID19

Italian Radiology COVID19 Image Database

 

OUTCOMES & PREDICTIVE METRICS

Case fatality rates (CFR):

  • Overall CFR so far appears to be ~1-3% (Lai et al, Verity et al, Rajgor et al, Park et al), CFR appears very low in children (<0.05%) (Yuanyuan et al); data vary widely by country and quality variable
    • CFRs may be underestimated due to delays between case identification and death, with some estimates of 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 (Wu et al), with S Korea having much better capture and a much lower rate (0.8%) (Korean CDC, Khafaie & Rahim)
    • CFRs vary by average population age and degree to which hospital systems are overwhelmed, which may account for Italy’s CFR ~7% — their rates were approximately the same for patients 0-69yo, but Italy’s was substantially higher for patients >70yo (and these represent ~38% of Italy’s total cases) (Onder et al); high CFR (34%) in the first US long-term care facility cluster seems consistent with this as well (McMichael et al)
  • Cause of death: 53% resp failure, 33% resp failure + heart failure, 5% heart failure (Ruan et al)

Patient/clinical indicators of severity/mortality:

 

  • Environment: mortality appears to increase with long-term air pollution exposure (Wu et al)
  • Social determinants of health: Pre-existing conditions disproportionately impact racial and ethnic minorities and poorer patients due to large pre-existing healthcare disparities, putting them at much greater risk of complications and mortality (Johnson & Buford, Khullar & Chokshi, Grantz et al); these communities are also likely to have much lower access to care 

 

    • Health department data shows huge disparities by race/ethnicity, with high minority mortality (Hispanic 23%, Black 20%, White 10%, Asian 8% in NYC) (NYC, Louisiana)
  • Surgical procedures: surgery on asymptomatic/presymptomatic patients associated with high rates of ICU admission (44%) and mortality (21%) (Lei et al)

Laboratory indicators of severity/mortality: labs indicating an appropriate immune response to a viral infection (e.g., lymphocytosis) are associated with a good prognosis while those indicating an inappropriate or dysregulated response (neutrophilia or lymphocytopenia),  excessive inflammation/cytokine storm, or end-organ damage are associated with a poor prognosis

 

  • LDH: elevated LDH positively correlated with illness severity (Han et al)

 

  •  
  • Blood counts:
    • Lymphocyte count: lymphocyte percentage of total WBC may be predictive of outcome based on a small study, with percentages >20% generally associated with good outcomes and percentages <5% were associated with poor outcomes and death, esp. later in disease course (Li et al, Han et al, Du et al)
      • High neutrophil-to-lymphocyte ratio (3.13) and low lymphocyte-to-CRP ratio have also been proposed markers of severe illness (Liu et al, Lagunas-Rangel)
    • Platelets: platelet count may track severity of disease, higher platelet to lymphocyte ratio (i.e., platelet count/absolute lymphocyte count) may be predictive of severe disease (Qu et al), and thrombocytopenia is associated with severe disease (Lippi et al)
      • Suspect these may not be contradictory but instead indicative of two competing deleterious processes — reactive thrombocytosis from severe inflammation and thrombocytopenia from severe viral illness and DIC
  • Viral load: higher viral loads may be associated with more severe disease and longer viral shedding (Liu et al, Lescure et al), though other studies show no difference in VL between symptomatic and asymptomatic patients (Cereda et al)
  • Troponin: elevated troponin appears to be a predictor of mortality with 69% mortality in patients with CVD history & elevated troponin, 38% mortality in patients w/o CVD but with elevated trop, 13% mortality w/ CVD but w/o elevated trop, and 7.6% mortality w/o CVD or elevated trop (Guo et al, Ruan et al)
  • Hemostasis/DIC: presence of DIC a marker of poor outcome in the Wuhan cohort — 71.4% of non-survivors vs 0.6% of survivors met criteria for DIC per the International Society on Thrombosis and Hemostasis DIC Score (Tang et al); it is unclear if this is reflective of severity of disease or causing worsening disease through micro-/macro-thrombi
  • Liver enzymes: a small, early machine learning case series found elevated ALT, myalgias, and elevated Hgb most predictive of ARDS development (Jiang et al), other studies have found LFT elevation correlated with overall inflammation and was not an independent predictor of outcomes (Zhang et al, Hansheng et al)
  • Renal function: AKI is an independent risk factor for mortality (Naicker et al, NephJC)

 

PULMONARY & CRITICAL CARE

SCCM Surviving Sepsis COVID-19 Guidelines

AHA Interim Guidance for BLS/ACLS in patients with confirmed or suspected COVID-19

University of Washington Critical Care Protocols

Brigham & Women’s Critical Care Protocols

MGH FLARE Fast Critical Care Literature Updates

JAMA COVID Crit Care podcast

 

Resources for critical care for non-intensivists:

 

Respiratory Failure

    • Non-invasive management: may be appropriate in mild ARDS and help prevent intubation in some patients, if used recommend emphasizing PEEP and trial of HFNC over NIPPV for patients needing more support than conventional NC O2; do not delay intubation in patients experiencing rapid decompensation (SCCM, Phua et al, Lyons & Callaghan, McEnery et al)
      • If HFNC unavailable and no immediate indication for intubation, can consider short NIPPV trial, use helmet if available to reduce aerosolization
      • There is some buzz about non-intubated proning but only a very small prior study (Scaravilli et al, EmCrit, Maley), but should not delay intubation if needed
      • Switch nebulizers to metered-dose inhalers to reduce aerosolization risk (Whittle et al)

 

  • Diagnostics: avoid screening CT or bronchoscopic workup unless suspected alternate etiology or superinfection to avoid risks of iatrogenic spread (esp. from bronch given aerosolization) (Hope et al, Bouadma et al)

 

 

  • Early intubation if worsening on HFNC or NIPPV (SCCM, Hardin)
  • Intubation procedures: most experienced staff available performing, minimal staff in room, negative pressure, and contact + droplet + airborne precautions including ideally PAPR/CAPR and shroud (SCCM, NIH, Cook et al, UW Intubation Guidelines)
  • Consider using clear plastic drapes or “aerosol boxes” around patients’ heads to minimize exposures (Matava et al, Canelli et al)
  • Use rapid sequence intubation and video laryngoscopy; work to preserve continuous vent circuit and consider connecting directly to vent as opposed to bagging first to minimize aerosol generation (Mark, Phua et al)

 

    •  
  • Mechanical ventilation: all patients with severe respiratory failure appear to have ARDS and societies recommend following typical ARDS protocols (SCCM, ATS)
    • Lung-protective ventilation with low tidal volumes (4-8cc/kg) and higher PEEP recommended as per traditional ARDS protocols (ARDSNet on LPV & PEEP)
    • Sedation: may need to consider alternative agents given shortages, consider lighter sedation & early mobilization (including while intubated & proned) to combat profound weakness that appears to be a prominent feature (Seattle Chest Grand Rounds)
      • If having difficulty with tachypnea in febrile patients, before increasing sedation consider aggressively treating fever with antipyretics, cooled IVF, and external cooling (Seattle Chest Grand Rounds)
    • Paralytics: consider use to help ameliorate vent dyssynchrony per ARDS protocols but ensure patients are appropriately sedated (SCCM, PETAL)
    • Prone mechanically ventilated with severe hypoxemia early to promote lung recruitment, appears to show recruitment benefit in COVID-related ARDS (SCCM, ATS, PROSEVA, Pan et al)

From SCCM guidelines

  • Recruitment maneuvers: guidelines recommend use of traditional but not staircase recruitment maneuvers to help open up compressed alveoli (SCCM)
  • Tracheostomy: patients appear to have a prolonged need for mechanical ventilation, not much data on tracheostomy yet but recommendations to avoid until stable, 2-3 weeks from intubation, and ideally PCR negative given high aerosolization risk (AAO)
  • Pulmonary vasodilators can be considered as rescue therapy but guidelines recommend against inhaled NO (SCCM), there are discussions of potential similarities to HAPE but altitude medicine experts argue that the process is clearly ARDS and treatment with vasodilators could worsen V/Q mismatch by releasing appropriate, compensatory hypoxic vasoconstriction and perfusing areas with poor ventilation (Luks et al)
  • ECMO can be considered as a last resort if available, but resource intensive and minimal data to support use; initial studies with mortality rate of 82.3% on ECMO (Hong et al, Ñamendys-Silva)
    • If capacity exists, consider VV use in young patients with few/no comorbidities, single organ dysfunction, and P:F ratio < 100 and poor trajectory despite aggressive ARDS management (Badulak, ELSO guidelines); not using VA or E-CPR at this time
  • Limited vent resources: may be able to repurpose other types of vent supports (transport vents, OR vents, home ventilators) to increase ventilatory resources (Seattle Chest Grand Rounds); ASA has created a guide to repurposing anesthesia machines as ICU vents
    • May be possible to share/split vents as a last resort, groups have created protocols for use, though prior studies attempting this were primarily short-term use in mass trauma not long-term use in pandemic (Neyman, Clarke et al)
      • Many of the largest critical care organizations (SCCM, CHEST, ASA, AARC, and others) are recommending against splitting vents due to risk of increasing mortality by providing inadequate care to multiple patients

From SCCM guidelines

Shock

  • Fluid resuscitation: recommend conservative over liberal fluid resuscitation with typical preference for buffered crystalloids > NS > colloids (SCCM, NIH)
  • Pressors: norepi first line, vaso second line to target MAP 60-65 (SCCM)
    • If cardiac dysfunction or rapidly escalating pressor requirements despite fluids and norepi, recommend dobutamine and assessment for cardiomyopathy (SCCM, NIH, Seattle Chest Grand Rounds)
  • Trial of low-dose corticosteroids for refractory shock (SCCM, NIH)

Cardiac arrest:

  • Outcomes are very poor (0.7% survival with good neuro outcome at 30 days), recommend goals of care discussions early and often (Shao et al)
  • Don airborne + contact PPE prior to entering room without exception (AHA)
  • Limit personnel to only absolutely necessary and consider use of mechanical CPR devices to further limit personnel exposure (AHA)
    • Close doors of rooms in which ACLS/BLS is being conducted to reduce spread (AHA)
  • Prioritize early intubation, use passive oxygenation or bag masks with HEPA filter for pre-oxygenation (AHA)
    • Most experienced available provider should intubate using RSI and VL as above, ideally with cuffed ETT (AHA, SCCM, Cook et al, UW Intubation Guidelines)
    • In intubated patients, try to maintain a closed circuit and limit aerosolization by leaving on vent in asynchronous mode (AHA)
    • Attempt to leave proned patients in position unless able to turn without risk of equipment disconnection and aerosolization (AHA)

 

POTENTIAL COVID-TARGETED TREATMENTS

Please remember to check for drug interactions and use caution in prescribing — all targeted treatments are currently of theoretical benefit, but can cause proven harm. Use caution outside of clinical trials and ensure patients understand questionable benefit when consenting.

 

Investigational, some clinical data available:

    • Convalescent sera: may have clinical benefit in multiple small series of critically ill patients with recovery from ARDS, extubation, O2 wean (Shen et al, Casadevall & Pirofski, Duan et al), may be logistically difficult; SCCM currently recommends against use of convalescent plasma or IVIG and IDSA recommends use clinical trial use only
    • Remdesivir: effective in vitro with chloroquine (Wang et al), small case studies and compassionate use cohort trials appear to indicate possible clinical improvements with decreasing O2 requirements and mortality (but no control group in trials so far), clinical trials in progress (Grein et al, Amirian & Levy)
      • Very limited availability, restrictive inclusion & exclusion criteria; now liberalizing

 

 

    •  
    • Tocilizumab: may help cytokine storm in severe disease, multiple very small case series in China with laboratory improvement (Luo et al) and possibly clinical improvement (Xu et al, Zhang et al)
      • IDSA recommends use clinical trial use only

 

  • Adverse reactions: serious infections, HBV reactivation, anaphylaxis, liver damage and hepatic failure, intestinal perforation (IDSA)

 

  • Mesenchymal stem cell infusion: may help cytokine storm response based on prior studies in influenza pneumonias and GVHD, promising small open-label trials (Chen et al, Leng et al) and anecdotal experience (Atluri et al)
  • IVIG: may decrease cytokine storm, very small series (three patients) with rapid improvement in fevers, respiratory status but many confounders and would need further testing to argue for use (Cao et al); please note that IVIG is already on critical shortage in much of the US
  • Anticoagulation: hypercoagulability, thrombi observed likely due to generalized inflammatory state, ARDS, immobility though most studies without control group so relative rate unclear
    • Prophylactic dose: chemoprophylaxis (LMWH preferred) recommended by multiple societies and guidelines (ASH, ISTH, MGH); non-randomized trials may show mortality benefit to prophylactic dose UFH/LMWH in patients with coagulopathy as manifested by severely elevated D-dimer (Tang et al, Yin et al, Tang et al [different paper])
    • Therapeutic dose: being tried at many institutions but unable to find evidence to support benefit at this time (recommended by Lin et al but appears to be based on hypothesis of pathogenesis, not clinical data); no consensus and most recommendations suggest avoiding use unless other clinical evidence suggestive of thrombosis (and ideally confirmatory US/CT imaging) (ASH, MGH)
      • If heparin gtt is required, recommend monitoring with anti-Xa levels instead of PTT due to PTT lability in COVID (MGH)
      • If on prior therapeutic AC, continue but monitor closely for drug interactions (esp. between VKA/anything and DOAC/immunomodulating Rx)

 

Investigational, no clinical data available yet:

  • SARS-CoV-2 vaccination: some early animal data (Kim et al) is promising, no human data yet, clinical trials enrolling; development likely to take time (>12 months)
  • Sarilumab: could theoretically help cytokine storm, clinical trials enrolling
  • Anakinra: could theoretically help cytokine storm, clinical trials enrolling
  • Nitazoxanide: broad antiviral, good in-vitro activity, no clinical data yet (McCreary and Pogue)
  • Ivermectin: antiviral effect in vitro, no clinical data (Caly et al)
  • Favipiravir: approved in China per news reports, not available in US; an early study seemed to show improved clinical recovery vs another antiviral but no control group (Chen et al), another study is widely cited but was subsequently withdrawn
    • Metabolized in liver and may have significant drug-drug interactions, but specific interaction data limited at this time (Du & Chen)
  • Recombinant ACE2: dose-dependent efficacy in vitro at preventing viral entry (Monteil et al) but no clinical data yet, undergoing small observational trial in China, no results yet
  • Angiotensin II: could theoretically help in shock (Chow et al) but no trials yet

 

Controversial:

 

  • Dosing:

 

        • Chloroquine diphosphate (more toxic, second line): 450mg BID x 1 day then 450mg daily x 4 days (Borba et al)

 

  • Screening before start: ECG, G6PD screen, monitor blood sugar

 

        • If patients are on continuous monitoring, consider programming monitor to show QT/QTc to minimize need for ECGs (and therefore exposure/PPE)

 

  • Overdose/Poisoning: hypotension, prolonged QRS/QTc, hypokalemia, apnea, seizures, ventricular arrhythmias (Poison Control); toxicity being seen across the world
  • Management: no specific reversal agents; early intubation, epinephrine superior to norepinephrine for hypotension, Na bicarb for conduction abnormalities, benzodiazepines for seizures (Clemessy et al)

 

      •  
    • Lopinavir-Ritonavir: initial observations & RCT without clear efficacy in severe COVID-19 (Young et al, Cao et al); trend towards benefit in early disease only (consistent with prior improvements in early but not late use in SARS-CoV-1 studies) and not used in conjunction with ribavirin which was used in prior SARS-CoV-1 studies (Chu et al) but is more toxic (Stockman et al, EmCrit)
      • IDSA recommends use clinical trial use only

 

  • 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

 

  •  
  • Corticosteroids: may have reduced mortality in COVID-related ARDS in single, small, uncontrolled trial (Wu et al) and may have reduced fever and improved SpO2 (though FiO2 not reported) and imaging resolution in another small, uncontrolled trial (Wang et al); 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 only in patients with 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
  • ACEi/ARB: ACE2 is a functional receptor for SARS-CoV-2 (Zheng et al) but there is no evidence of worse outcomes; ARB may even show some lung protection in prior SARS studies (clinical trials are enrolling) (Sparks et al, Vaduganathan et al, Guo et al, Bavishi et al, Patel & Verma)
    • Continue ACE/ARB for patients already taking, new initiation for lung protection in patients without other indications not currently recommended (Vaduganathan et al, Sparks et al, ACC)

 

Ineffective/Likely ineffective:

  • IV Vitamin C: could theoretically alter cytokine release, decrease ROS but has previously demonstrated lack of efficacy in sepsis (Kalil) and ARDS (Fowler et al), clinical trials enrolling
    • High dose IV vitamin C can cause spuriously elevated POC glucose readings with certain glucometer brands (Kahn & Lentz)
  • Neuraminidase inhibitors (e.g., oseltamivir): no in vitro benefit in SARS-CoV-2 (Tan et al) but should still use if influenza coinfection

 

ETHICS & RESOURCE ALLOCATION

AMA Journal of Ethics COVID19 Resource Center

NEJM on Fair Allocation of Scarce Medical Resources in the Time of Covid-19

JAMA Framework for Rationing Ventilators and Critical Care Beds During the COVID-19 Pandemic

SCCM Resource Availability for COVID19

SCCM on Acute Surge Planning

  • Standards of care may shift during emergency situations, with three prominent levels (IOM):
    • Conventional: normal levels of staff, supplies; provide conventional care consistent with usual practices & standards
    • Contingency: abnormal staffing, supplies but can be adapted to provide care functionally equivalent to usual patient care; typical standards of care predominantly apply
    • Crisis: staffing, supplies, space cannot be adapted sufficiently to provide typical care due to a catastrophic disaster or emergency (including pandemic), work to provide best possible care to patients given the circumstances and resources available but activation constitutes a significant adjustment to standards of care with focus on community instead of simply individual patients
      • Many US states are starting to come up with crisis standards of care (WA State here) and plans for triage; look up your regional standards and keep in touch with your hospital to ensure appropriate response to changing conditions
      • Do not apply crisis standards of care until level reached and declared by authorities; many communities are currently in contingency but not crisis standards and applying crisis too early may needlessly sacrifice lives
  • Many experts recommend creation of triage panels or officers separate from patient care to ensure any crisis decisions are objective and take pressure off of frontline providers (Emanuel et al, Truog et al, Anesi et al)
  • Protections for caregivers participating in triage from criminal or civil suits are currently piecemeal and leave frontline workers at risk, reform is urgently needed (Cohen et al)

 

PALLIATIVE CARE & TALKING WITH PATIENTS AND FAMILIES

VitalTalk site & app for discussions with families, including a targeted guide for discussions with patients and families about COVID (Back et al) and COVID-specific family discussion videos

San Francisco VA Advanced Care Planning Communication Guidelines

NHS Scotland poster on Difficult Conversations

 

Goals of care:

  • Early & repeated goals of care discussion, trying to focus first on patient’s goals and then their code status (Curtis et al)
    • Consider early Palliative Care consults (even in ER) to help with discussions
    • Be clear about poor prognosis in pre-existing terminal conditions such as dementia as families may not have heard this information before (as one Palliative Care provider put it, “to be clear is to be kind” even if it feels blunt or cruel to deliver bad news)
  • Consider working on informed assent instead of informed consent— making a recommendation regarding code status based on goals and likely outcomes to which a patient/family may agree or disagree rather than asking them what they would like (Curtis et al)
  • Provide specific, objective outcome predictions — thus far, COVID-19 CPR data indicates extremely poor outcomes with only 13.2% ROSC, 2.9% 30-day survival, and 0.7% 30-day survival with good neurologic outcome (Shao et al)
  • The goals of care discussion process may differ depending on level of emergency/standards of care (see Ethics above) — in general, we should adhere to traditional norms of patient autonomy in determining code status and allow for disagreement with our recommendations
    • Medical futility exists in some patients regardless of care conditions, iIf medically appropriate and legal in your region, may still declare a treatment medically futile
    • We should always understand and empathize with the challenge these decisions present
    • If entering crisis standards of care, families may face triage team decisions they do not understand and may hate; triage re-consideration should be based on objective medical information as per crisis guidelines and not on family discomfort with decision

End-of-life care:

  • Work to help patients and families connect via visitation (if permitted — varies significantly by institution and region) or arranging video or audio calls (Etkind et al)
  • Dyspnea/air hunger control appears to be one of the greatest challenges with this disease and may require admission for symptom management (Etkind et al)
  • O2 supplementation should still be via non-aerosolizing means (NC, NRB) if possible (Fausto)
  • Consider early use of opiate & benzodiazepine infusions for end-of-life symptom management as may be able to control symptoms while minimizing PPE use esp. if IV poles are placed outside rooms (Fausto)

 

SELF CARE

Not company endorsements, just seemed like good free resources — take care of yourselves!

Counseling & therapy:

Guides to self-care, coping

Meditation/mindfulness apps:

Exercise:

Moments of zen: