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ACEP COVID-19 Field Guide

Table of Contents

Management of Patients With COVID-19

Treatment

Abstractor: Stephen V. Cantrill, MD, FACEP

This information has been abstracted from the NIH’s “COVID-19 Treatment Guidelines,” last accessed July 24, 2020. Full details and references are available at the NIH website.

General Drug Treatment Statements:

Currently, no FDA-approved drugs exist to specifically treat patients with COVID-19.

  • Remdesivir:
    • Because remdesivir supplies are limited, it is recommended remdesivir be prioritized for use in hospitalized patients with COVID-19 who require supplemental oxygen but who are not on high flow oxygen (through a high flow device), non-invasive ventilation, mechanical ventilation or ECMO (BI1).
    • For patients with COVID-19 on supplemental oxygen but not requiring high flow oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO), remdesivir is recommended for 5 days (AI1).
    • For patients with COVID-19 who require high flow oxygen, non-invasive ventilation, mechanical ventilation or ECMO,  there is uncertainty regarding whether starting remdesivir confers clinical benefit in these groups of patients, therefore a recommendation for or against starting remdesivir cannot be made.
    • Remdesivir is not approved by the Food and Drug Administration (FDA); however, it is available through an FDA Emergency Use Authorization (EUA) for the treatment of hospitalized adults and children with COVID-19.  Remdesivir is also being investigated in clinical trials, and it is available through an emergency access program for children and pregnant patients. 
  • Chloroquine and hydroxychloroquine:
    • Chloroquine or hydroxychloroquine are recommended against in the treatment of COVID-19, except in a clinical trial (AII1).
  • Dexamethasone:
    • Dexamethasone (at a dose of 6 mg per day for up to 10 days) is recommended for the treatment of COVID-19 in patients who are mechanically ventilated (AI1) and in patients who require supplemental oxygen but who are not mechanically ventilated (BI1).
    • Dexamethasone is recommended against in the treatment of COVID-19 in patients who do not require supplemental oxygen (AI1).

Definition of COVID-19 Disease Severity for this Section:

  • Mild: A variety of symptoms (e.g. fever, cough, sore throat, malaise, headache, muscle pain, malaise) without shortness of breath/dyspnea or abnormal chest imaging (if obtained). 
  • Moderate: Evidence of lower respiratory disease by clinical assessment or imaging with SaO2 >94% on room air (sea level).
  • Severe: Having a SaO2 <94% on room air (sea level), respiratory frequency >30 breaths/minute, ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) <300, or lung infiltrates >50%.
  • Critical: Individuals who have respiratory failure, septic shock, and/or multiple organ dysfunction.
  • In pediatric patients, radiographic abnormalities are common and, for the most part, should not be used as the sole criteria to define COVID-19 illness category. Normal values for respiratory rate also vary with age in children, thus hypoxia should be the primary criteria to define severe illness, especially in younger children.

Pre- or Post- Exposure Prophylaxis:

  • Currently no agents are recommended for pre or post exposure prophylaxis

Asymptomatic/Presymptomatic COVID-19 Disease:

  • No additional laboratory testing or specific treatment is recommended for patients who test positive for SARS-CoV-2 but are asymptomatic.
  • These patients should self-isolate.  If they remain asymptomatic for 10 days after the test, they may resume normal activity.  If they become symptomatic, they should contact their primary care provider for further guidance.

Mild COVID-19 Disease:

  • Most cases can be managed in an ambulatory setting or at home through telemedicine or remote visits.
  • Routine antipyretic, hydration and rest instructions should be provided.
  • These patients should be in self-isolation until the following:
    • If no test is to be done: the patient has been afebrile for at least 72 hours without the use of antipyretics AND other symptoms have improved AND at least 7 days have elapsed since symptoms have appeared.
    • If a test can be performed: the patient is afebrile for at least 72 hours without the use of antipyretics AND other symptoms have improved AND there are two negative tests results in a row, 24 hours apart.
  • Currently, there are insufficient data to recommend either for or against any antiviral or immune-based therapy in patients with mild disease (AIII1).
  • These patients, especially those with risk factors for severe disease, should be closely monitored as the clinical course may rapidly worsen.
  • Additional patient information is available at the CDC Resource on What to Do If You Are Sick

Moderate COVID-19 Disease:

  • Since patients with moderate COVID-19 infection can rapidly deteriorate, most of these individuals should be admitted to a healthcare facility for close monitoring.
  • If bacterial pneumonia or sepsis is suspected, appropriate empiric antibiotic treatment should be initiated.
  • Currently, there are insufficient data to recommend either for or against any antiviral or immune-based therapy in patients with moderate disease (AIII1).
  • Other therapeutic options under investigation for COVID-19 are presented with clinical data at the NIH’s “COVID-19 Treatment Guidelines,”.

Severe COVID-19 Disease:

  • Since patients with severe COVID-19 infection can rapidly deteriorate, these individuals should be admitted to a healthcare facility for close monitoring to a single-person negative-pressure room.
  • If bacterial pneumonia or sepsis is suspected, appropriate empiric antibiotic treatment should be initiated.
  • Oxygen therapy should be instituted with a target O2 saturation of > 94% (sea level).
  • Treatment with remdesivir:  See “General Drug Treatment Statements”, above 
  • Treatment with dexamethasone: See “General Drug Treatment Statements”, above
  • Other therapeutic options under investigation for COVID-19 are presented with clinical data at the NIH’s “COVID-19 Treatment Guidelines,”.
  • See below under “Critical COVID-19 Disease” for other recommendations that may apply.

Critical COVID-19 Disease:  

  • Currently, there is no information to suggest that the critical care management of patients with COVID-19 should differ substantially from the management of other critically ill patients.
  • Special caution about environmental contamination by SARS-CoV-2 is warranted.
  • Infection Control
    • For healthcare workers performing aerosol-generating procedures on patients with COVID-19, using fit tested respirator masks (N-95 respirators) or powered air-purifying respirators (PAPRs) is recommended rather than surgical masks, in addition to other personal protective equipment (PPE) (i.e., gloves, gown, and eye protection such as a face shield or safety googles). (AIII1)  These patients should be placed in airborne infection isolation rooms when available.
    • Endotracheal intubation for patients with COVID-19 should be done by healthcare providers with extensive airway management experience, if possible. (AIII1). Intubation should be achieved via video laryngoscopy, if possible. (CIII1)
  • Hemodynamic Support
    • For adults with COVID-19 and shock, dynamic parameters, skin temperature, capillary refilling time, and/or lactate are recommended to be used rather than static parameters to assess fluid responsiveness (BII1).
    • For the acute resuscitation of adults with COVID-19 and shock, buffered/balanced crystalloids are preferred over unbalanced crystalloids (BII1).
    • Norepinephrine is recommended as the first-choice vasopressor. (AII1)  Either vasopressin (up to 0.03 U/min) (BII1) or epinephrine (CII1) should be added to norepinephrine to raise mean arterial pressure to target, or adding vasopressin (up to 0.03 U/min) (CII1) to decrease norepinephrine dosage.
    • Dobutamine is recommended in patients who show evidence of persistent hypoperfusion despite adequate fluid loading and the use of vasopressor agents. (BII1)
    • When norepinephrine is available, using dopamine is recommended against for patients with COVID-19 and shock (AI1).
    •  Low-dose dopamine for renal protection (BII1) is recommended against.
    • For adults with COVID-19 and refractory shock, using low-dose corticosteroid therapy (“shock-reversal”) is suggested over no corticosteroid. (BII1)
  • Ventilatory Support
    • For adults with COVID-19 and acute hypoxemic respiratory failure despite conventional oxygen therapy, high-flow nasal cannula (HFNC) oxygen is recommended over non-invasive positive pressure ventilation (NIPPV). (BI1)
    • For adults with COVID-19 and acute hypoxemic respiratory failure for whom HFNC is not available, in the absence of an indication for endotracheal intubation, a closely monitored trial of NIPPV is recommended. (BIII1)
    • For adults with COVID-19 who are receiving supplemental oxygen, close monitoring for worsening respiratory status is recommended with early intubation by an experienced practitioner in a controlled setting. (Alll1)
    • For patients with persistent hypoxemia despite increasing supplemental oxygen requirements in whom endotracheal intubation is not otherwise indicated, a trial of awake prone positioning to improve oxygenation (CIII1) should be considered.
    •  Awake prone positioning is recommended against as a rescue therapy for refractory hypoxemia to avoid intubation in patients who otherwise require intubation and mechanical ventilation (AIII1).
    • In ventilated adults with COVID-19 and ARDS:
      • Low tidal volume (Vt) ventilation (Vt 4-8 mL/kg of predicted body weight) over higher tidal volumes (Vt>8 mL/kg) is recommended. (AI1)
      • Targeting plateau pressures of <30 cm H2O is recommended (AII1).
      •  A conservative fluid strategy over a liberal fluid strategy (BII1) is recommended.
      • The routine use of inhaled nitric oxide is recommended against (AI).
    • For mechanically ventilated adults with COVID-19 and refractory hypoxemia despite optimizing ventilation, prone ventilation for 12 to 16 hours per day is recommended, over no prone ventilation (BII1).
    • If necessary, a trial of inhaled pulmonary vasodilator as a rescue therapy is recommended; if no rapid improvement in oxygenation is observed, the patient should be tapered off treatment.  (CIII1)
    • There are insufficient data to recommend either for or against the routine use of ECMO for patients with COVID-19 and refractory hypoxemia. (BIII1)
  • Drug Therapy
    • Treatment with remdesivir: See “General Drug Treatment Statements”, above
    • Treatment with dexamethasone: See “General Drug Treatment Statements”, above
    • There are insufficient data to recommend either for or against any immunomodulatory therapy in patients with severe COVID-19 disease (AIII1).
    • There are insufficient data to recommend either for or against routine broad-spectrum antimicrobial therapy to treat COVID-19 patients with severe or critical illness. (AIII1)

As described elsewhere: there are insufficient data to recommend for or against the use of IL-6 antagonists (such as sarilumab, siltuximab, or tocilizumab) for the treatment of COVID-19 (AIII1).

Antithrombotic Therapy in Patients with COVID-19

Laboratory Testing

  • In non-hospitalized patients with COVID-19, there are currently no data to support the measurement of coagulation markers (e.g., D-dimers, prothrombin time, platelet count, fibrinogen) (AIII1).
  • In hospitalized patients with COVID-19, hematologic and coagulation parameters are commonly measured, although there are currently insufficient data to recommend for or against using this data to guide management decisions (BIII1).

Chronic Anticoagulant and Antiplatelet Therapy

  • Patients who are receiving anticoagulant or antiplatelet therapies for underlying conditions should continue these medications if they receive a diagnosis of COVID-19 (AIII1).

Venous Thromboembolism Prophylaxis and Screening

  • For non-hospitalized patients with COVID-19, anticoagulants and antiplatelet therapy should not be initiated for prevention of venous thromboembolism (VTE) or arterial thrombosis unless there are other indications (AIII1).
  • Hospitalized adults with COVID-19 should receive VTE prophylaxis per the standard of care for other hospitalized adults  (AIII1). 
    • A diagnosis of COVID-19 should not influence a pediatrician’s recommendations about  VTE prophylaxis in hospitalized children (BIII1). 
    • Anticoagulant or antiplatelet therapy should not be used to prevent arterial thrombosis outside of the usual standard of care for patients without COVID-19 (AIII1).
  • There are currently insufficient data to recommend for or against the use of thrombolytics or increasing anticoagulant doses for VTE prophylaxis in hospitalized COVID-19 patients outside the setting of a clinical trial (BIII1)
  • Hospitalized patients with COVID-19 should not routinely be discharged on VTE prophylaxis (AIII1). 
    • Using FDA-approved regimens, extended VTE prophylaxis can be considered in patients who are at low risk for bleeding and high risk for VTE as per protocols for patients without COVID-19  (BI1).
  • There are currently insufficient data to recommend for or against routine deep vein thrombosis screening in COVID-19 patients without signs or symptoms of VTE, regardless of the status of their coagulation markers (BIII1).
  • For hospitalized COVID-19 patients, the possibility of thromboembolic disease should be evaluated in the event of rapid deterioration of pulmonary, cardiac, or neurological function, or of sudden, localized loss of peripheral perfusion (AIII1).

Treatment

  • Patients with COVID-19 who experience an incident thromboembolic event, or who are highly suspected to have thromboembolic disease at a time when imaging is not possible, should be managed with therapeutic doses of anticoagulant therapy as per the standard of care for patients without COVID-19 (AIII1).
  • Patients with COVID-19 who require ECMO or continuous renal replacement therapy, or who have thrombosis of catheters or extracorporeal filters, should be treated with antithrombotic therapy per the standard institutional protocols for those without COVID-19 (AIII1).

Special Considerations During Pregnancy and Lactation

  • Management of anticoagulation therapy during labor and delivery requires specialized care and planning and should be managed similarly in pregnant patients with COVID-19 as other conditions that require anticoagulation in pregnancy (AIII1).
  • Unfractionated heparin, low molecular weight heparin, and warfarin do not accumulate in breast milk and do not induce an anticoagulant effect in the newborn; therefore, they can be used in breastfeeding women with or without COVID-19 who require VTE prophylaxis or treatment (AIII1). 
  • Direct-acting oral anticoagulants are not routinely recommended because of a lack of safety data (AIII1).

Additional information can be found on the NIH’s COVID-19 website.

Considerations for certain concomitant medications in patients with COVID-19

The following medications, if prescribed for the treatment of comorbid conditions or prevention of disease should be continued (AIII1) (details at the NIH’s COVID-19 website):

  • Corticosteroids
  • Statins
  • NSAIDs
  • ACE inhibitors, angiotensin receptor blockers

Acute Kidney Injury and Renal Replacement Therapy

  • For critically ill patients with COVID-19 who have acute kidney injury (AKI) and who develop indications for renal replacement therapy (RRT), continuous renal replacement therapy (CRRT) is recommended, if available (BIII1).
  • If CRRT is not available or not possible due to limited resources, prolonged intermittent renal replacement therapy (PIRRT) rather than intermittent hemodialysis (IHD) is recommended (BIII1).

Therapeutic options for COVID-19 currently under investigation (not covered above):

Summary: At present, no drug has been proven to be safe and effective for treating COVID-19. There are no FDA-approved drugs to specifically treat patients with COVID-19.  While reports have appeared in the medical literature and the lay press claiming successful treatment of patients with COVID-19 with a variety of agents, definitive randomized clinical trial data are needed to identify optimal treatment for this disease.  Recommended clinical management of these patients includes infection prevention and control measures and supportive care, including supplementary oxygen and mechanical ventilatory support when indicated.  As always, treatment decisions ultimately reside with the patient and their healthcare provider.  

 

  • Antivirals 

 

    • Lopinavir/ritonavir (AI1) or other HIV protease inhibitors (AIII1), are not recommended because of unfavorable pharmacodynamics and negative clinical trials data.

 

  • Host Modifiers

 

    • There are insufficient data to recommend for or against the use of convalescent plasma or hyperimmune immunoglobulin for the treatment of COVID-19 (AIII1).
    • There are insufficient data to recommend for or against the use of the following agents for the treatment of COVID-19 (AIII1).
      • IL-6 receptor antagonists (such as sarilumab, siltuximab, or tocilizumab)
      • IL-1 inhibitors (such as anakinra) 
  • The use of other immunomodulators is recommended against, except in a clinical trial, such as:
    • Interferons (AIII1), because of lack of efficacy in SARS and MERS and toxicity.
    • JAK inhibitors (such as baricitinib) (AIII1), because of their broad immunosuppressive effects

Other therapeutic options under investigation for COVID-19 are presented with clinical data at the NIH’s “COVID-19 Treatment Guidelines.”

Table 10.2 Recommendation rating scheme.

Recommendation rating scheme

For more information, see the NIH’s “COVID-19 Treatment Guidelines.”


Also refer to the “Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19” published on April 11, 2020.

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