Cayuga Health System (CHS)
Cayuga Medical Center/Schuyler Hospital

COVID-19 Clinical Management Guidelines

Reviewed: 04/28/2020 Version 4
Author: Dr. de Lima

Disclaimer: This document is intended as a resource for clinicians caring for non-critically-ill as well as critically ill COVID-19 patients, based on available evidence and recommendations of governing bodies. These recommendations do not replace clinical judgment or the need for individualized patient care plans. While we attempt to keep this document up-to-date, the literature on COVID-19 is rapidly evolving, and we suggest that practitioners search for the most up-to-date literature on any specific topic.

Introduction

SARS-CoV-2 is a non-segmented, positive sense RNA virus that causes COVID-19. The virus binds itself via the angiotensin-converting enzyme 2 (ACE2) receptor located on type II alveolar cells and intestinal epithelia, causing significant respiratory symptoms, as well as GI. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis.

Transmission

Large droplets and fomites COVID-19—New Insights on a Rapidly Changing Epidemic
Viral particles survive <24h on cardboard, <72h on plastic or steel – Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1
Aerosols (droplet nuclei, < 5 µm), estimated < 4h
Incubation period: median 4 days, common range 2-7 days, up to 24 days Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia
Symptomatic and asymptomatic patients can transmit the virus, though symptoms are likely associated with increased frequency of transmission Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany
Nasopharyngeal viral load peaks within days of symptom onset followed by decline Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore
There is evidence of presymptomatic and asymptomatic transmission Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility Asymptomatic Transmission, the Achilles’ Heel of Current Strategies to Control Covid-19 .
A study proposed infectiousness peaked on or before symptom onset and estimated that 44% of transmission could occur before first symptoms of the index. Temporal dynamics in viral shedding and transmissibility of COVID-19
SNF study showed 23 days after first diagnosed case 64% of residents tested positive; 56% asymptomatic at the time of positive testing.

Presentation

Fever (98%), fatigue (70%), dry cough (60%), myalgia (34%), SOB (31%), diarrhea/N/V Clinical Characteristics of Patients With 2019 Novel Coronavirus (2019-nCoV)–Infected Pneumonia in Wuhan, China
81% have mild to moderate symptoms (mild symptoms to mild pneumonia)
14% have severe symptoms (hypoxemia, or >50% lung involvement)
5% have critical symptoms (respiratory failure, shock, multiorgan dysfunction) The Coronavirus Disease 2019 (COVID-19) Outbreak in China—Summary of a China CDC Report
10-20% develop bacterial superinfection
2-25% have respiratory viral co-infection Precautions are Needed for COVID-19 Patients with Coinfection of Common Respiratory Pathogens; Shah N, Medium, 2020 unpublished data)
20% develop ARDS
5% develop renal injury requiring renal replacement therapy
25% require ICU, 10% require MV https://jamanetwork.com/journals/jama/article-abstract/2762510
Those requiring critical care, median age 60 yo, 40% with comorbid condition (DM/cardiac disease) Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study
Respiratory failure is common: Behaves like and should be treated like ARDS essentially
Some have “silent” hypoxemia (without dyspnea) initially and then deteriorate quickly
Can cause septic shock, cardiomyopathy (CHF, Arrhythmias, ACI), viral rhabdomyolysis/AKI, bone marrow suppression (leukopenia, thrombocytopenia), mild transaminitis, but fulminant hepatitis not reported
CNS symptoms (headache, dizziness, CVA, ataxia) and peripheral NS manifestations (taste and smell impairment) are reported Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China

PPE

CHS PPE Guidelines COVID

Discontinuation of isolation

ALL cases must be discussed with Infection Prevention & Control prior to discontinuing Transmission Precautions.
Interim Guidance for Discontinuing Transmission-Based Precautions for Hospitalized Patients with Confirmed COVID-19 April 23 2020.pdf

Testing criteria

CHS COVID-19 Testing Criteria

HCP exposure

Staff Community Exposure Protocol

CHS CHP Exposure guidelines

Laboratory

RT-PCR NP swab sensitivity ~70% Essentials for Radiologists on COVID-19: An Update—Radiology Scientific Expert Panel Radiology Correlation of Chest CT and RT-PCR Testing in Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases
In inpatients with high pre test probability, we recommend repeat RT-PCR on the second day hospital stay
Serology (flow immunoassay IgM/IgG) being developed – sensitivity 88.66% and specificity 90.63% – not available at this time https://www.ncbi.nlm.nih.gov/pubmed?term=32104917
IgG testing (ELISA assay) is now available with provider order through our reference lab (Mayo Clinic).
Test validation demonstrated a specificity of 99.3% upon testing normal donor sera and specificity of 95.7% when tested against a panel of similar pathogens (cross reactivity panel).
- Patients must not currently or recently (within the past 14 days unless previous COVID-19 PCR positive) have fever, cough, dyspnea, or myalgia. Patients must not have exposure to known COVID-19 patient without PPE in the previous 14 days. If any of these conditions are met, IgG testing is not appropriate and PCR swab test should be performed instead.
- Priority of testing is known recovered COVID-19 patients for potential plasma donor selection followed by other asymptomatic persons.
CBC with diff: lymphopenia with normal WBC. Neutrophil-to-Lymphocyte Ratio (NLR) ≥ 3.13 predicts severity Neutrophil-to-Lymphocyte Ratio Predicts Severe Illness Patients with 2019 Novel Coronavirus in the Early Stage
Lower lymphocyte count associated with increased mortality Neutrophil-to-Lymphocyte Ratio Predicts Severe Illness Patients with 2019 Novel Coronavirus in the Early Stage
Severe lymphopenia, elevated troponin, elevated creatinine, elevated LDH, elevated CRP, elevated D-dimer are all poor prognosis indicators
CMP (BMP + LFTs): Severe hypokalemia common, AKI. Mild transaminitis later in disease
CPK: Frequent rhabdomyolysis
Troponin/EKG: Trend to monitor for NICM/myocarditis. Formal echo if it’s going to change management
Ferritin, LDH, D-dimer, CRP as inflammatory markers
QuantiFERON if tocilizumab is being considered
Pregnancy test if female & reproductive age
Consider cytokine storm: CRP (very high at start), LDH, Ferritin, D-Dimer with Hemophagocytic lymphohistiocytosis (HLH) picture COVID-19: consider cytokine storm syndromes and immunosuppression

Imaging

CXR: Hazy, bilateral, peripheral opacities, basilar predominant. Initially low sensitivity
Lung US on POCUS (ED and ICU only): more sensitive than CXR and may precede deterioration – Patchy B-lines w/ subpleural consolidation
Chest CT: Only if result will change management (eg: considering alternate diagnosis: complex PTX, PE)
- Max lung involved at 10 days from onset. 4 stages of lung CT: Stage 1 (0 – 4 days): ground glass opacities(GGO); Stage 2 (5 – 8 days): increased crazy-paving pattern; Stage 3 (9 – 13 days): consolidation; Stage 4 (≥ 14 days): gradual resolution Time Course of Lung Changes On Chest CT During Recovery From 2019 Novel Coronavirus (COVID-19) Pneumonia | Radiology
- The hallmarks on imaging are bilateral and peripheral ground-glass and consolidative pulmonary opacities. 56% early patients had a normal CT Chest CT Findings in Coronavirus Disease-19 (COVID-19): Relationship to Duration of Infection | Radiology
TTE: RV strain (TAPSE <1.8), follow for viral cardiomyopathy (LV or BiV failure)

Clinical Course

Mild (10.0%), moderate (72.8%) and severe/critical (17.2%) Epidemiological and clinical features of 291 cases with coronavirus disease 2019 in areas adjacent to Hubei, China: a double-center observational study
Median hospital LOS in severe cases 13 days vs 11 days in non-severe Clinical Characteristics of Coronavirus Disease 2019 in China
Expect rapid deterioration (NC to ETT in < 24h) at ~7-10 days from onset
Timing of complications from illness onset:
- Sepsis ~9 days
- ARDS ~12 days, duration between symptom onset and ventilation ranges from 3-12.5 days
- Acute cardiac injury ~15 days
- AKI ~15 days
- Secondary infection ~ 17 days
- Time from initiation of invasive ventilation to VAP occurrence ~ 8 days Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study
Duration of viral shedding in survivors unknown. Repeat testing & prolonged isolation may be required

Patients at risk for poor outcomes

Increased age correlates with more severe disease and increased mortality Acute Respiratory Distress Syndrome and Death in Patients With COVID-19 in Wuhan, China Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study Dysregulation of immune response in patients with COVID-19 in Wuhan, China
Age ≥60, male, pulmonary disease, CKD, transplant, DM, HTN, cardiovascular disease, cardiomyopathy, biologic immune modulators, malignancy, immunosuppressive medications (chronic corticosteroid use equivalent to prednisone ≥20 mg daily), detectable HIV viral load or CD4 <200 cells/m3
Pregnancy: Likely only postpartum transmission. Severity unknown in newborns. Consult pharmacy for pregnancy drug classes

Indications for ICU admission/transfer

Usual ICU admission indications, but with lower threshold due to concern for rapid deterioration and advantages of early intubation. Examples:
- Provider concern
- Respiratory distress: Need O2 > 6 LPM to maintain SpO2 > 92 or PaO2 > 65, rapid escalation of oxygen requirement, significant work of breathing.
- Hemodynamic instability after initial conservative fluid resuscitation with SBP < 90, Mean arterial pressure < 65, or Heart rate > 120.
- Acidosis: ABG with pH < 7.3 or PCO2 > 50 or above patient’s baseline; lactate > 2.
- Need for intensive nursing care or frequent laboratory draws requiring arterial line.
- Severe comorbid illness / high risk for deterioration.

Management

Discuss code status early and regularly. CPR is unlikely to help with respiratory disease.
Management is largely supportive
Volume status: Limit fluids, balanced solutions preferred (LR). Hypokalemia may limit ability to diurese
NSAIDS: Reports from France indicated possible increase in mortality with ibuprofen in COVID-19 infection, but these reports have not been corroborated Covid-19: ibuprofen should not be used for managing symptoms, say doctors and scientists. WHO does not recommend avoiding NSAIDs (03/18/2020). Consider acetaminophen instead of NSAIDs if possible; risk / benefit should be discussed with patients
Acetaminophen 975mg PO q8h PRN. Preferred for symptomatic treatment of pain and fever
Steroids: There is no clinical evidence of net benefit from steroids in SARS-CoV, MERS-CoV or influenza infection, and observational data show increased mortality, more secondary infections, impaired viral clearance and more adverse effects in survivors Effects of early corticosteroid treatment on plasma SARS-associated Coronavirus RNA concentrations in adult patients; Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected. However, a new retrospective cohort (201 patients, 84 [42%] of whom developed ARDS) demonstrated that among patients with ARDS, methylprednisolone decreased risk of death (HR, 0.38; 95% CI, 0.20-0.72) Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. May use corticosteroids if required for other indications and use the lowest dose for the shortest duration:
- Asthma or COPD exacerbation: 40mg prednisone PO or 30mg methylprednisolone IV, once daily x 3-5 days
- Shock with history of chronic steroid use > 10mg prednisone daily: 50mg hydrocortisone IV Q6H until improvement in shock
- Multipressor shock without history of chronic steroid use: 50mg hydrocortisone IV Q6H until improvement in shock
- Inhaled steroids – if asthmatic patients are already on it, they should be continued COVID-19 and Asthma: What Patients Need to Know
ACEI/ARB: ACC/AHA/HFSA Joint Statement (3/17/20): “The HFSA, ACC, and AHA recommend continuation of RAAS antagonists for those patients who are currently prescribed such agents for indications for which these agents are known to be beneficial, such as heart failure, hypertension, or ischemic heart disease. In the event patients with cardiovascular disease are diagnosed with COVID-19, individualized treatment decisions should be made according to each patient’s hemodynamic status and clinical presentation. Therefore, be advised not to add or remove any RAAS-related treatments, beyond actions based on standard clinical practice.” HFSA/ACC/AHA Statement Addresses Concerns Re: Using RAAS Antagonists in COVID-19
Bronchodilators: Insert link to CHS COVID-19 MDI guidelines
- COVID-19 positive / PUI & non-intubated patient: Albuterol MDI – ideally with spacer
- COVID-19 positive / PUI intubated patient: Albuterol nebulizer through Aerogen (closed circuit)
- Non COVID-19 / non PUI patient with bronchospasm: Albuterol/Duoneb via nebulizer
- Patients on inhalers as outpatient should be encouraged to bring their own medication.
OSA: Patients with OSA should continue to wear their own CPAP/BiPAP (or hospital provided) overnight and be on airborne precautions while on it
Statins: Continue statins if already prescribed. If no contraindication, and for those who have a guideline indication for a statin, consider starting Atorvastatin 40mg daily. Cardiovascular disease is a major risk factor for COVID-19 disease severity. Additionally, statins may help promote antiviral innate immune response.
Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review | Clinical Pharmacy and Pharmacology | JAMA
Antiviral and immune-modulating therapies are investigational – we recommend hydroxychloroquine to patients with moderate or severe disease (patients with at least one Category 1 and one Category 2/3 feature admitted to the floor or any patients in ICU or with progressive disease)

*Epidemiological – Category 1*	*Vital Signs – Category 2*	*Labs – Category 3*
Age >55	Respiratory rate > 24	D-dimer > 1000 ng/mL
Pre-existing pulmonary disease	HR > 125	CPK > twice upper limit of normal
CKD	SpO2<90% on RA	CRP > 100
DM with A1c>7.6		LDH > 245 U/L
HTN		Elevated troponin
Cardiovascular disease		Admission absolute lymphocyte count < 0.8
Use of biologics		Ferritin > 300 ug/L
Transplant or other immunosuppression
HIV CD4<200 or unknown

NYS approved, FDA authorized clinical study for symptomatic COVID-19 patients with hydroxychloroquine (400mg PO BID on day one, 400mg daily day 2-5, subject to change at NYSDOH discretion) and azithromycin
- Marseille study – Hydroxychloroquine for 10 days – 70% negative PCR day 6. Azithromycin added to 6 patients to prevent bacterial superinfection – 100% negative PCR day 6 Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial
- We recommend azithromycin use for suspect secondary bacterial infection at this time
- A continuation of the Marseille study including 80 in-patients receiving a combination of hydroxychloroquine and azithromycin noted a clinical improvement in all but two patients. COVID-IHU #2
- Another study from France with a control branch showed no evidence of clinical efficacy of hydroxychloroquine No evidence of clinical efficacy of hydroxychloroquine in patients hospitalized for COVID-19 infection with oxygen requirement: results of a study using routinely collected data to emulate a target trial
Chloroquine 500mg PO BID for 10 days – may become available [Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia].
Recent literature suggests hydroxychloroquine did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure after high-risk or moderate-risk exposure to Covid-19.
Remdesivir – an NIH press release from April 29, 2020 commented on a randomized, placebo-controlled trial at 68 sites evaluating 1063 patients. Full details are not yet published, but remdesivir was reported to result in a median time to recovery of 11 days vs. 15 days in the placebo group (31% reduction, p<0.001) and a mortality rate of 8% in the remdesivir arm vs. 11.6% in the placebo arm (p=0.059). A full publication is expected shortly.NIH Clinical Trial Shows Remdesivir Accelerates Recovery from Advanced COVID-19
Remdesivir now available at CMC – it will require discussion with Pharmacist when ordered. FDA Emergency use authorization (EUA) on May 1st, 2020
IL-6 agents – Tocilizumab, Sarilumab, Siltuximab.IL-6 levels are reported to correlate with severe COVID-19 and although lymphopenia is present, BAL is usually lymphocytic. CRS/severe disease (Mechanical ventilation with PaO2/FiO2 ≤300mmHg, shock requiring vasopressor support, radiographic infiltrates by CXR/CT, any of the following lab results: Ferritin >300 ug/L with doubling within 24h, Ferritin >600 ug/L at presentation AND current LDH >250 IU/L, D-dimer >1 mg/L – consult Pharmacist
IL-1 agents – Anakinra, Canakinumab, Rilonacept – undergoing clinical trials
Convalescent plasma – limited preliminary data is promising.Treatment of Critically Ill Patients With COVID-19 With Convalescent Plasma Treatment with convalescent plasma for critically ill patients with SARS-CoV-2 infection The feasibility of convalescent plasma therapy in severe COVID-19 patients: a pilot study\
We are now enrolled on a Mayo clinic clinical trial for convalescent plasma. You need to register yourself as a physician in order to enroll a patient at this address https://redcap2.mayo.edu/redcap/surveys/?s=N44T8M9PED
The address for study documents including consent protocol, information is Convalescent Plasma COVID-19 (Coronavirus) Treatment – Mayo Clinic
- Mayo clinic clinical trial criteria:
  - 18+ years of age
  - Laboratory-confirmed diagnosis of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19
  - Admitted to an acute care facility for the treatment of COVID-19 complications
  - Severe or life-threatening COVID-19, or judged by the treating provider to be at high risk of progression to severe or life-threatening disease
  - Informed consent provided by the patient or health care proxy
  - Severe COVID-19 is defined by one or more of the following:
    - Shortness of breath (dyspnea)
    - Respiratory frequency ≥ 30/min
    - Blood oxygen saturation ≤ 93%
    - Partial pressure of arterial oxygen to fraction of inspired oxygen ratio < 300
    - Lung infiltrates > 50% within 24 to 48 hours
  - Life-threatening COVID-19 is defined as one or more of the following:
    - Respiratory failure
    - Septic shock
    - Multiple organ dysfunction or failure

Steroids

There is no clinical evidence of net benefit from steroids in SARS-CoV, MERS-CoV or influenza infection, and observational data show increased mortality, more secondary infections, impaired viral clearance and more adverse effects in survivors Effects of early corticosteroid treatment on plasma SARS-associated Coronavirus RNA concentrations in adult patients; Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected.
However, a new retrospective cohort (201 patients, 84 [42%] of whom developed ARDS) demonstrated that among patients with ARDS, methylprednisolone decreased risk of death (HR, 0.38; 95% CI, 0.20-0.72) Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China.
In the setting of an excess inflammatory response, corticosteroids could be beneficial, in modulating lung injury. The data are most firm for patients with severe illness, where in the setting of severe CAP, corticosteroids have been helpful for those with evidence of a high inflammatory response, and for those with ARDS of all causes. Acute Respiratory Distress Syndrome and Death in Patients With COVID-19 in Wuhan, China Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China
Patients intubated in ARDS within 7-14 days of the onset of COVID symptoms, consider corticosteroids at 0.5 mg/kg methylprednisolone every 12 hours in consultation with infectious disease and pulmonary and critical care medicine, for 5-7 days.
Patients not intubated
- P/F < 200 ( or a saturation < 93% on a non-rebreather mask) , that is sustained or worsening for 6- 12 hours, in spite of prone positioning in bed (if proning is safe and tolerated).
- Radiographic pneumonia, especially if bilateral
- At least 2 of: CRP > 15 mg/dL., Ferritin > 1000 ng/ml , D-dimer > 1,000 ng/L
- Has received or is receiving hydroxychloroquine and remdesivir
- If PCT elevated > 1, patients should be on systemic antibiotic therapy for pneumonia or any other documented infection
- Exceptions : Careful consideration if other immune suppression (including anakinra, tocilizumab), steroid therapy required for an alternate indication, documented uncontrolled bacterial or viral infection, uncontrolled hyperglycemia or history of corticosteroid intolerance, actively participating in a clinical trial that excludes corticosteroid therapy If non-response or transient benefit, consider alternative therapy per institutional clinical practice strategy.
- Follow biomarkers of CRP, Ferritin, D-dimer daily and monitor daily for infection.
Inhaled steroids – if asthmatic patients are already on it, they should be continued COVID-19 and Asthma: What Patients Need to Know

Anticoagulation

There is emerging data that COVID-19 + confirmed patients who are critically ill may suffer from a hypercoagulable state and in extreme cases, Disseminated Intravascular Coagulation (DIC). Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy
Data from Weill Cornell Medicine and Lower Manhattan Hospital from March 5-27, 2020 showed an incidence of VTE (DVT or PE) of 3.3% but increased to 8.4% in patients requiring mechanical ventilation.
Recommend checking daily D-dimers. If D-dimer continues to increase, call Hematology Consult Service to discuss management.
Heparin binds tightly to COVID-19 spike proteins Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites, downregulates IL-6 and directly dampens immune activation Characterization of the Heparin-Binding Properties of IL-6
DOACs do not appear to have these anti-inflammatory properties
Recent French case series showed DVT was found in 65% at admission to ICU and in 79% when the US performed 48 hours after ICU admission were included. 53% had bilateral thrombosis, and 26% had proximal thrombosis.

VTE prophylaxis for ICU patients

Indication

CrCl

AKI/HD

CRRT

VTE prophylaxis

≥30 ml/min

Enoxaparin 0.5mg/kg SQ q12h

<30 ml/min and ≥10ml/min

UFH 5,000 units SQ q8h

HIT or suspected HIT

Fondaparinux 2.5mg SQ daily

Fondaparinux 2.5mg SQ daily (requires Hematology consult)

Requires Hematology consult

VTE treatment for ICU patient

Indication

CrCl

AKI

CRRT

DVT/PE

≥30 ml/min

Enoxaparin 1mg/kg SQ q12h

UFH IV continuous infusion

HIT or suspected HIT

Fondaparinux

>100kg 10mg SQ daily

50-100kg 7.5mg SQ daily

<50kg 5mg SQ daily

Argatroban infusion (Requires Hematology consult)

VTE prophylaxis for non-ICU patients

Indication

CrCl

AKI/HD

CRRT

VTE prophylaxis

≥30 ml/min

Enoxaparin 0.5mg/kg SQ q12h

<30 ml/min and ≥10ml/min

UFH 5,000 units SQ q8h

HIT or suspected HIT

Fondaparinux 2.5mg SQ daily

Fondaparinux 2.5mg SQ daily (requires Hematology consult)

Requires Hematology consult

Thromboprophylaxis at discharge

VTE risk factor	VTE risk score
Previous VTE	3
Known thrombophilia	2
Current limb paralysis of paresis	2
History of cancer	2
ICU/CCU stay	1
Complete immobilization ≥ 1 day	1
Age ≥ 60	1
Elevated d-dimer > 2 ULN	2

Score ≥4 or a score of 2-3 plus elevated d-dimer
Duration: at least 2 weeks AND until fully ambulatory
Options:
- Apixaban 2.5mg PO q12h
- Rivaroxaban 10mg PO daily
- Rivaroxaban 10mg daily x 5 days followed by Aspirin 81mg PO daily for patients with no insurance coverage
- If oral intake unreliable due to nausea and vomiting:
  - Enoxaparin 40mg SQ daily BMI <30
  - Enoxaparin 30mg SQ q12h BMI ≥30 and <40
  - Enoxaparin 40mg SQ q12h BMI ≥ 40

Respiratory support and intubation

Optimize utilization and capacity of negative pressure environments Interim Guidance on Performing Aerosol-Generating Procedures on Patients with Suspected or Confirmed COVID-19 in Non-Negative Pressure Environments%.pdf
Consider continuous pulse oxymeter monitoring if available
Avoid oscillating positive expiratory pressure devices (Acapella) and cough assist devices, due to aerosolization risk and unclear benefit in COVID-19.
Patients with COVID-related lung disease have significantly higher compliance than is typical for their shunt fraction, indicating this may be a very different phenotype than typical ARDS Covid-19 Does Not Lead to a “Typical” Acute Respiratory Distress Syndrome
Recent studies suggest complement related vascular injury has a role in COVID ARDS Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases
Management of hypoxia:

- Humidified nasal cannula (NC) 1 to 8 LPM for target SpO2 92-96% (88-94% in oxygen-dependent COPD)
- If a patient requires > 8 LPM NC, initiate dry oxy mask (non-humidified to reduce aerosolization risk)
  - Start oxy mask at 9 LPM and FiO2 28%
  - Up-titrate FiO2 to goal SpO2 of 92-96% (not exceeding FiO2 35%)
  - If FiO2 > 35% then increase flow to 12 LPM
- Change to HFNC at flow rate less than 30L
  - Use surgical mask over the high flow cannula TRANSMISSION ASSESSMENT REPORT:

- Awake proning:
  - This involves a non-intubated patient on nasal cannula who prone themselves by lying on their belly.
  - Can be combined with simultaneous use of any other noninvasive support device (e.g. low-flow nasal cannula, high-flow nasal cannula, BiPAP, or CPAP).
  - Requires cooperative patients with intact mentation.
  - Could be useful especially in situations where access to invasive ventilation is limited.
  - Encourage proning as much as is tolerated (ideally ~12-18 hours/day, but this may be difficult for some patients).
  - Follow oxygenation and FiO2 requirements. Ideally an improvement in oxygenation should be seen within a few hours. If no change in oxygenation is observed, ongoing pronation may have less merit.
- Non invasive ventilation:
  - More recent experience suggests early intubation may not be recommended as much as before.
  - There is widespread concern that using HFNC could increase the risk of viral transmission. This doesn’t appear to be evidence-based.
  - Multiple sources support HFNC use with appropriate PPE ANZICS – COVID-19 Guidelines Version 1 Intensive Care Medicine Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Diseas Yang et al.
  - Atelectasis leading to hypoxemia seems to be a major problem among these patients. CPAP can provide the greatest amount of mean airway pressure, and thus most effective recruitment.It doesn’t augment tidal volumes, so this could facilitate more lung-protective ventilation.
- Intubation:
Case reports from China suggest high failure rates for non-invasive ventilation, including high-flow nasal oxygen (Zuo et al., Chin Med Sci J, 2020)
For patients on NC 6 liters and SpO2<92% – initiate arrangements for “elective” intubation
For patients maintained on oxy mask, once FiO2=60% and SpO2 < 92%, or RR>30, AMS, paradoxical respiration, or increasing WOB, call for intubation if patient is a candidate for mechanical ventilation
Standard, contact, airborne precautions: N95 or PAPR, gown, eye protection, gloves. PPE Guidelines COVID
All ABC alerts will be attended by essential personnel only (one provider, two BLS trained compressor, respiratory therapist, ICU RN, ED RN, 4S RN [recorder]). House supervisor and pharmacist will attend but not enter room. House supervisor will call additional resources if needed. Back up support personnel outside only (see picture below). ABC FLYER

Consensus statement: Safe Airway Society principles of airway management and tracheal intubation specific to the COVID-19 adult patient group

“Closed” pre oxygenation with oxymask and viral filter on BMV before start. Apneic Oxygenation with NC with flush flow
Avoid bag-masks due to risk of aerosolization, always use a viral filter. If absolutely needed, use small tidal volumes + 2 person technique to ensure tight seal
Most skilled non trainee operator available. First pass success keeps the team safe
True RSI (succinylcholine and etomidate), no BMV, with paralytic (Rocuronium) + VL (Glidescope)
Backup supplies kept outside of room with personnel outside to provide supplies
Proning: Good clinical response per reports from China and Italy. Resource burden recognized Proning guidelines
Avoid the following unless absolutely necessary:
- Nebulizer treatments (Bronchodilators, Hypertonic saline), chest PT of any kind; induced sputum samples
- Bronchoscopy: Very limited role, to be essentially avoided. Need ICU attending approval.

Mechanical ventilation

CHS Guidelines for management of ARDS and COVID

Guidelines for discharge

Guidlines for Discharging Inpatients with COVID 19.docx

Complication/Prognosis

Hypokalemia: can be severe/refractory, use IV + oral supps. Especially life threatening if NICM. Consider spironolactone/eplerenone if BP/GFR stable.
Hypoalbuminemia can be severe and require supplementation
Median hospital LOS in severe patients 13 days (11.5 – 17.0). Mortality rate unclear, likely <1 – 2%
Cardiac:
- Acute cardiac injury: troponin elevation, EKG or echo changes, non-specific, but poor prognosis (59% in non survivors vs 1% in survivors) Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.
- Arrhythmias: Afib/Vtach 17% of hospitalized patients with COVID-19, with higher rate in ICU patients (44%) compared to non-ICU patients Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China.
Septic shock
- Goal MAP > 65mmHg
- Start Norepinephrine while determining the etiology of undifferentiated shock
- We do not recommend conventional 30cc/kg resuscitation: Give 250-500cc IVF and assess in 15-30 minutes for increase > 2 in CVP, increase in MAP or decrease in pressor requirement. Use isotonic crystalloids; Lactated Ringer’s solution is preferred where possible. Avoid hypotonic fluids, starches, or colloids
- Unless new evidence emerges, standard choices for distributive shock (e., norepinephrine then vasopressin) are recommended.
Cardiogenic shock
- May present late in the course of illness even after improvement of respiratory symptoms, and manifest as a precipitous clinical deterioration in the setting of an acute decline in LVEF
- Norepinephrine gtt for goal MAP 65-75
- Diuretic therapy for CVP > 14, PCWP >18, PAD > 25
- Inotropic support with Dobutamine gtt for SCvO2 < 60%, CI < 2.2 and MAP > 65. Start at 2mcg/kg/min. Up-titrate by 1-2mcg/kg/min every 30-60 minutes for goal parameters. Alternative strategies should be considered once dose exceeds 5mcg/kg/min. Maximum dose is 10mcg/kg/min.
- Ensure negative inotropes such as beta blockers, calcium channel blockers and antihypertensives are discontinued.
Cytokine Activation Syndrome
- Subgroup of patients with severe COVID-19 may have cytokine storm syndrome and secondary HLH. Patients who had cytokine storm developed rapid progression to ARDS, shock, and multiorgan failure COVID-19: consider cytokine storm syndromes and immunosuppression
- IVIG, steroids, cytokine blockade (IL-6 and IL-1)may be useful. While steroids have been implicated with worse lung injury and outcomes, they may be beneficial in the hyperinflammatory state.