Infectious Diseases
COVID-19 (Coronavirus Disease 2019): Therapeutics
Management is based on illness severity
Asymptomatic or presymptomatic infections and most with mild illness can self-isolate at home
- Home Care
- Appropriate for patients who can adequately isolate at home
- Steps to implement during home care
- Avoid public settings; stay home except to get medical care
- Separate from other people and animals in the household
- Monitor for clinical deterioration
- Seek immediate medical care if showing any COVID-19 emergency warning signs
- Wear a facemask when in the same room/vehicle as other people
- Frequently wash hands and disinfect touched surfaces
- CDC Guidelines for Discontinuation of Home Isolation (sxms and severity-based strategy for discontinuing isolation and precautions as opposed to testing based strategies)
- Isolation
- For most pts, isolation can be discontinued 5 days after symptom onset, resolution of fever for ≥ 24 hrs (without antipyretics), and improvement in other symptoms
- Continue wearing well-fitting mask around others (home & public) for 5 additional days; if unable to wear mask, continue isolation through day 10
- Avoid contact with high-risk populations until after day 10
- Pts with severe disease or severe immunosuppression, recommend waiting 10-20 days after symptom onset to discontinue isolation
- Quarantine
- CDC guidance states individuals with suspected or confirmed COVID-19 exposure are not required to quarantine if they meet following criteria:
- Are up to date with COVID-19 vaccines, OR
- Had confirmed COVID-19 within last 90 days
- Wear well-fitted mask for 10 days; obtain test 5 days post-exposure (not required if confirmed COVID-19 within last 90 days)
- COVID-19 Vaccines
Mildly ill patients with risk factors for severe disease and moderately ill patients should be closely monitored
Severe and critically ill patients should be hospitalized
- Inpatient Care
- Separate triage of patient with respiratory conditions
- Immediately apply surgical mask on all patients with respiratory conditions
- Consider
- If COVID-19 suspected after triage
- Immediate isolation
- Transfer to negative pressure room
- Healthcare personnel use full protective gear and precautions (i.e., contact precautions, airborne precautions, eye protection)
- If COVID-19 is diagnosed
- Notify infection control within institution
- Maintain list of all hospital personnel who may have been in contact
- Notify County Health Department per local protocol
- Consult Infectious Disease and Pulmonology services early
- Supportive therapy
- IV fluids PRN, Antipyretics PRN, O2 PRN, Monitors
- Noninvasive ventilatory support as necessary
- Prevent venous thromboembolism
- LMWH (contraindications: active bleeding, severe thrombocytopenia)
- Unknown whether anticoagulation (prophylactic or therapeutic) has any impact on the outcome of COVID-19
- If undergoing aerosol producing procedures (sputum production, intubation, HFNO, BiPAP/CPAP, etc.)
- Isolate: single private negative pressure isolation room with HEPA filter
- If no isolation room available: be cautious when applying airway devices that deliver ≥ 6 L/min O2 (if not intubated) - may generate aerosols
- High flow nasal oxygen can give fraction of inspired oxygen (FiO2) up to 100% and reduces the need for intubation
- Apply airborne precautions
- BiPAP and CPAP should be avoided if possible
- Use with caution if necessary
- If private room not possible: keep ≥ 2 ft distance between patients
- If concomitant asthma or COPD
- Bronchodilators: use metered dose inhalers with a spacer instead of nebulizers (risk of aerosolization)
- If severe asthma/COPD: consider epinephrine, early intubation and rapid sequence induction
- Secondary infections (especially in severely ill and critically ill patients)
- Occurs in patients in ICU (13-44%)
- Bacterial or fungal (especially Aspergillus)
- Often 'nosocomial' pathogens (ESBL, P.aeruginosa, Aspergillus spp)
- Median time from onset of symptoms:10-17 days
- Factors to consider (mostly China, NY hospital reports)
- Frequent antibacterial use received in 80-100%
- Antifungals in 7.5-15%
- Steroids in 25-80% of seriously ill patients
- Inpatient care revolves around supportive management of the most common complications of severe COVID-19
- Sepsis
- Empiric antibiotics (CAP vs HCAP) within 1 hr of recognition of sepsis, then work-up source of infection
- Septic shock
- Volume support and pressors:
- Norepinephrine (first line)
- Vasopressin (second line)
- Dopamine NOT recommended
- If flu season or suspect flu
- ARDS/Respiratory failure (hypercarbic or hypoxic)
- Strongly consider advanced ventilatory support/intubation
- DO NOT share ventilators
- If refractory hypoxemia even with advanced ventilatory support
- Consider extracorporeal membrane oxygenation (ECMO) if available
- Hypercoagulability and COVID-19
- The pathogenesis for COVID-19-associated hypercoagulability remains unknown
- Hypoxia and systemic inflammation secondary to COVID-19 may lead to high levels of inflammatory cytokines and activation of the coagulation pathway
- Limited data available to inform clinical management of venous thromboembolism in COVID-19 patients
- Many institutions adopted an intermediate-intensity (i.e., administering the usual daily LMWH dose BID) or a therapeutic-intensity dose strategy for thromboprophylaxis
- International Society of Thrombosis and Hemostasis Interim Guidance:
- LMWH should be considered in all patients (including non‐critically ill) who require hospital admission for COVID‐19, if not contraindicated
- American Society of Hematology:
- All hospitalized adults with COVID-19 should receive pharmacologic thromboprophylaxis with LMWH over unfractionated heparin, if not contraindicated
- Medical/Pharmaceutical
- Many types of drugs are under investigation including antivirals (protease inhibitors, influenza drugs, nucleoside analogs), immunomodulators, and surface protein antagonists such as lecithin.
- Dexamethasone
- Results from the RECOVERY trial showed dexamethasone 6 mg PO or IV daily for up to 10 days reduced 28-day mortality in certain groups of hospitalized COVID-19 patients: recommended for patients with severe COVID-19 (requiring oxygen) including those on mechanical ventilation by the NIH and IDSA
- Other corticosteroids shown to also be potentially beneficial in other trials and meta-analyses had a summary OR 0.66 on 28d all-cause mortality
- Recommend
- Dexamethasone (6mg/day IV/PO for 10 days) in patients with COVID-19 who are mechanically ventilated or
- Dexamethasone (6mg/day IV/PO for 10 days) in COVID-19 patients who require supplemental oxygen but are not mechanically ventilated
- Recommend against
- Dexamethasone in COVID-19 patients who do not require supplemental O2
- Remdesivir
- Based on the Adaptive Covid-19 Treatment Trial (ACTT), RDV appears most beneficial if given for severe COVID-19 before mechanical ventilation, reduces the length of hospital stay.
- Investigators concluded that benefit was accrued to patients prior to the need for mechanical ventilation, highly suggestive that this antiviral yield greater benefit the earlier it is initiated
- NIH has suggested that this drug will be standard for comparison in adaptive clinical research trials.
- Recommendations for Hospitalized Patients with Severe COVID-19 (consider concomitant baricitinib):
- Remdesivir is recommended for treatment of COVID-19 patients hospitalized with SpO2 ≤94% on room air or those who require supplemental O2
- Remdesivir is recommended for treatment of COVID-19 patients who are on mechanical ventilation or ECMO
- Remdesivir appears to demonstrate the most benefit in those with severe COVID-19 on supplemental oxygen rather than in patients on mechanical ventilation or ECMO.
- Recommendation for Duration of Therapy in Patients with Severe COVID-19 Who Are Not Intubated:
- Hospitalized patients with severe COVID-19 who are not intubated are recommended to receive 5 days of remdesivir
- Recommendation for Duration of Therapy for Mechanically Ventilated Patients, Patients on ECMO, or Patients Who Have Not Shown Adequate Improvement After 5 Days of Therapy:
- Insufficient data on optimal duration of therapy for these patients
- Some experts extend the total remdesivir treatment duration to up to 10 days for these patients
- Recommended for patients with Mild or Moderate COVID-19:
- 200 mg IV on day 1, then 100 mg IV daily for days 2 & 3
- Must be initiated ≤7 days of S/S onset
- Baricitinib
- FDA approved for monoTx (consider concomitant remdesivir and/or corticosteroids)
- Severe pts: 4 mg PO qD x14 days or hospital D/C (whichever is first)
- Avoid concomitant use with tocilizumab
- Administration:
- May be given with/without food
- If unable to swallow tabs, consider alternative admin:
- Oral dispersion
- Gastrostomy tube (G tube)
- Nasogastric tube (NG tube) or orogastric tube (OG tube)
- Tocilizumab
- ≥ 30 kg: 8 mg/kg IV x single dose over 60 mins
- < 30 kg: 12 mg/kg IV x single dose over 60 mins
- If no improvement of S/S: may repeat dose once, ≥8 hrs later
- NMT 800 mg/dose
- SC admin not authorized
- Avoid concomitant use with baricitinib
- Nirmatrelvir/ritonavir
- FDA approved for COVID-19
- Dosing based on renal fxn
- eGFR > 60 mL/min
- 300 mg/100 mg (nirmatrelvir/ritonavir, co-admin) PO q12hr x5 days
- eGFR ≤ 60 mL/min and ≥ 30 mL/min
- 150 mg/100 mg (nirmatrelvir/ritonavir, co-admin) PO q12hr x5 days
- eGFR < 30 mL/min
- If hospitalization occurs during Tx course
- May complete Tx per providers discretion
- Administration:
- Take with/without food
- Co-admin nirmatrelvir and ritonavir tabs
- Swallow whole; do not crush, chew, split tabs
- Missed dose: if ≤ 8 hrs take dose, otherwise skip
- IDSA recommendation
- Recommended for use in ambulatory pts w/ mild-to-moderate COVID-19 at high-risk for
- Progression to severe disease
- Nirmatrelvir/ritonavir should be initiated w/in 5 days of symptom onset
- Rather than no tx w/ nirmatrelvir/ritonavir
- Molnupiravir
- FDA EUA for COVID-19
- 800 mg PO q12h x5 days
- Initiate within 5 days of S/S onset
- Safety/efficacy of >5 days Tx not established
- If hospitalization occurs during Tx course
- May complete Tx per providers discretion
- Administration:
- Take with/without food
- Swallow whole; do not open, crush, chew
- Missed dose: take asap if ≤10 hrs since missed, otherwise skip
- Anti-SARS-CoV-2 monoclonal antibodies
- Bebtelovimab (not currently authorized in any US region; not effective against BQ.1 and BQ.1.1 variants)
- FDA EUA for COVID-19
- 175 mg IV x1
- Admin ASAP after positive results and ≤7 days of S/S onset
- Administration:
- Admin as single IV injection for ≥30 sec in healthcare setting
- Monitor for IRRs for ≥1 hr after infusion
- Authorized for mild-to-moderate COVID-19 in
- Adults
- Children (12 years and weighing at least 40 kg)
- Used to prevent progression to severe COVID-19 and
- Do not have access or clinically inappropriate for other treatments
- No longer authorized due to ineffective neutralization of Omicron BA2 subvariant
- Convalescent Plasma
- Definition
- Has been used as passive immunotherapy for infections for > 100 years
- In recent years, studies derived from people who had recovered from specific infections showed encouraging results
- However, these studies were typically small, non-randomized and largely descriptive
- Transfusion of COVID-19 virus antibody-rich plasma
- IDSA recommendation
- Against the use of COVID-19 convalescent plasma
- For ambulatory patients w/ mild-to-moderate COVID-19 at high risk for progression
- To severe disease and who have no other treatment options
- Suggests the use of FDA-qualified high-titer COVID-19 convalescent plasma
- Within 8 days of symptom onset, rather than not given
- For immunocompromised patients hospitalized w/ COVID-19
- Pre-Exposure Prophylaxis
- Cilgavimab/Tixagevimab (EUA)
- Pre-Exposure Prophylaxis
- Cilgavimab/Tixagevimab (not effective against current dominant variants)
- Pemivibart (EUA; Premgrada)
- Adults and adolescents (12 y/o and older weighing at least ~ 88 lbs (40 kgs))
- Pts who are not currently infected with SARS-CoV-2
- Pts who have not had a known recent exposure to an individual infected with SARS-CoV-2
- Moderate-to-severe immune compromise: illness or d/t medications
- Post-Exposure Prophylaxis
- COVID-19 Investigational Therapies: (safety and efficacy not yet established)
- Interferon 1b
- RCT from Hong Kong found when used with lopinavir/ritonavir and ribavirin (triple therapy) versus LPV/RTV alone, the triple therapy yielded quicker clinical improvement and reduced viral shedding.
- Suspect most of the benefits derived from interferon; however, many hesitant to use since it tends to make people feel terrible
- Phase II inhaled formulation trial yielded favorable results.
- Other potential drugs under discussion or study; some use anecdotally reported:
- Sarilumab (anti-IL6R)
- Siltuximab (anti-IL6)
- 11 mg/kg IV x single dose
- Anakinra (anti-IL1)
- IDSA guideline panel suggests against routine use in hospitalized patients w/ severe COVID-19
- anti-GM-CSF
- GM-CSF
- Concomitant Therapy Considerations
- Dexamethasone
- Results from the RECOVERY trial showed dexamethasone 6 mg PO or IV daily for up to 10 days reduced 28-day mortality in certain groups of hospitalized COVID-19 patients: recommended for patients with severe COVID-19 (requiring oxygen) including those on mechanical ventilation by the NIH and IDSA.
- Recommended for patients with severe COVID-19 (requiring oxygen) including those on mechanical ventilation by the NIH and IDSA
- Supplemental stress-dose steroids may be indicated on a case-by-case basis
- Patients on chronic corticosteroids (PO or inhaled) for other underlying conditions (e.g., adrenal insufficiency, asthma/COPD) should not discontinue its use
- In patients w/ severe disease on corticosteroids
- IDSA suggests baricitinib to be added, rather than no baricitinib
- Baricitinib 4 mg/day (or appropriate renal dosing)
- Up to 14 days or until discharge
- Shows most benefit in pts w/
- Severe COVID-19 on high-flow O2/non-invasive ventilation
- Pregnancy Considerations:
- Since betamethasone and dexamethasone are known to cross the placenta, consider using an equivalent systemic steroid when possible
- Use of steroids that cross the placenta may be individualized, weighing the neonatal and maternal benefits with the risks
- ACE inhibitors/ARBs
- Despite ACE2 being a receptor for SARS-CoV-2, patients taking ACE inhibitors and ARBs for other conditions should continue taking these agents
- NIH recommends against use of ACE inhibitors or ARBs for treatment of COVID-19 outside of a clinical trial
- Statins
- Continue statins in hospitalized patients with COVID-19 who are already taking them
- Many severe COVID-19 patients have underlying cardiovascular disease, diabetes mellitus, and other indications for use of statins
- Also, statins are indicated because acute cardiac injury is a reported complication of COVID-19
- Whether statins could impact the course of SARS-CoV-2 infection is not clear
- Immunomodulators
- Immunocompromised patients with COVID-19 are at increased risk for severe disease
- Decision to terminate immunomodulators must be determined on a case-by-case basis
- For individuals who require treatment with these agents and DO NOT have COVID-19 infection, there is NO evidence supporting routine discontinuation of the drugs
- AGA Recommendations for Immunomodulator use in IBD for COVID-19
- IBD patients with symptomatic COVID-19 (e.g., fever, respiratory symptoms, GI symptoms, etc.) should stop medications after consultation with GI or primary care physicians
- Drugs to be temporarily discontinued include thiopurines, methotrexate, tofacitinib, and anti-TNFs (i.e., ustekinumab and vedolizumab)
- However, some drugs may still be continued for IBD (i.e., aminosalicylates, topical rectal therapy, dietary management, oral budesonide and antibiotics)
- NSAIDs
- FDA and WHO indicate current epidemiologic evidence is not sufficient to advise against NSAIDs in COVID-19 patients
- WHO retracted earlier warning against the use of ibuprofen
- Warning was due to theoretical mechanism suggesting NSAIDs increase expression of ACE2, the receptor by which the coronavirus enters host cells
- It was unclear whether harm was associated with intermediate or prolonged use of NSAIDs
- Currently, discontinuation of chronic ibuprofen use is not advised
- WHO and NHS suggest acetaminophen is preferred to treat pain and fever until there is more evidence
- Stronger evidence is needed to deduce causation of harmful effect of ibuprofen in COVID-19 patients
- Avoid nebulized medications
- Avoid the risk of aerosolization of SARS-CoV-2 through nebulization
- Use metered dose inhaler for inhaled medications
- Use appropriate infection control measures
- Critical Care Guidelines for Adults with COVID-19
- Infection Control
- For health care workers who are performing aerosol-generating procedures on COVID-19 patients:
- Recommended use of N95 masks or powered air-purifying respirators rather than surgical masks
- Recommended use of PPE (i.e., disposable gloves, gown, and eye protection such as face shield or goggles)
- Endotracheal intubation should be performed by providers with extensive airway management experience, if possible
- Intubation should be achieved by video laryngoscopy, if possible
- Hemodynamic Support
- Norepinephrine as first-line vasopressor
- For adults with refractory shock, use low-dose corticosteroid therapy over no corticosteroid
- Ventilatory Support
- The following are recommendations for adults with COVID-19 and acute hypoxemic respiratory failure
- If respiratory failure persists despite conventional O2 therapy:
- If no indication for endotracheal intubation:
- Use a trial of NIPPV if HFNC is not available
- If hypoxemia persists despite increasing supplemental O2 and in whom endotracheal intubation is not indicated:
- Consider a trial of awake prone positioning
- The panel recommends against awake prone positioning as a rescue therapy for refractory hypoxemia to avoid intubation
- For mechanically ventilated adults with ARDS:
- Low tidal volume ventilation (VT 4-8 mL/kg of predicted BW) is recommended over higher tidal volumes (VT>8 mL/kg)
- For mechanically ventilated adults with refractory hypoxemia:
- Prone ventilation for 12-16 hrs/day is recommended over no prone ventilation
- For mechanically ventilated adults with severe ARDS and hypoxemia despite optimal care:
- Use an inhaled pulmonary vasodilator as a rescue therapy
- If no rapid improvement in oxygenation, treatment should be tapered off
- Insufficient data to recommend for or against routine use of ECMO for COVID-19 patients with refractory hypoxemia
- Intubation Considerations
- COVID-19 may cause hypoxemia even in the setting of little respiratory distress
- May be profoundly hypoxemic without dyspnea (patients may "look" fine)
- Work of breathing cannot be relied upon to detect patients who are failing on high flow nasal cannula
- Consider a lower threshold for intubation indications
- Patients can develop worsening "silent" atelectasis and decline quickly and abruptly without lots of symptoms
- Oxygenation techniques to maintain saturation during intubation may increase virus aerosolization (e.g., mask ventilation)
- "Pure" rapid sequence intubation without bagging is preferred
- Consider viral filter to BMV
- This will be safer if the patient is starting out with more oxygenation reserve
- Consider semi-elective intubation over crash intubation (decreases prep time)
- Intubation procedure can place healthcare workers at risk of acquiring the virus
- Endotracheal tube confirmation could pose inoculation risk to practitioner
- Pulmonary complications by COVID-19
- Atelectasis (consider PEEP, APRV, ARDS)
- Alveolar fluid filling (drain fluid- prone positioning with ventilation, APRV, coughing or "dumping" breaths to help clear lungs)
- WHEN TO INTUBATE?
- Physician clinical decision
- Consider if
- Progressively rising FiO2 requirements (e.g., > 75% FiO2 - again, based on patient's status)
- High flow cannula does not improve oxygenation
- Comorbid conditions (e.g., COPD, asthma, cardiovascular disease, etc.)
- AKI and Renal Replacement Therapy
- For critically ill COVID-19 patients with AKI and indications for RRT:
- Give continuous RRT, if available
- If not available, prolong intermittent RRT rather than intermittent hemodialysis
Special Populations
- Immunity and Reinfection Risk
- Individuals who have been infected are normally induced with antibodies
- Preliminary studies suggest some of the antibodies are protective
- Evidence is not confirmed
- Unknown whether immunity in previously infected patients is sufficient for protective purposes and how long immunity will last
- NOTE: FDA has granted EUA for tests that qualitatively identify antibodies against SARS-CoV-2 in serum or plasma
- Pregnant Women and Breast Feeding
- Minimal information available
- Intrauterine or perinatal transmission has not been identified
- Pregnant women may be at increased risk for severe illness from COVID-19
- There may be increased risk of adverse pregnancy outcomes (e.g., preterm birth) among pregnant women with COVID-19
- Clinical guidelines for pregnant women with suspected COVID-19 should be similar to that in nonpregnant individuals
- ACOG: decision to separate patients with known or suspected COVID-19 from their infants should be made on a case-by-case basis
- Breast feeding
- Unknown whether the virus can be transmitted through breast milk
- Droplet transmission could occur through close contact during breastfeeding
- Therefore, breast feeding mothers should use appropriate hand hygiene and a facemask
- Suspected or confirmed maternal COVID-19 is not a contraindication to breast feeding
- MIS-C ASSOCIATED WITH COVID-19 in the Pediatric Population
- Multi-system inflammatory syndrome in children associated with COVID-19 Criteria:
- An individual aged <21 years of age presenting with:
- Fever (Fever >38.0°C for ≥24 hours, or report of subjective fever lasting ≥24 hours)
- Laboratory evidence of inflammation (Including, but not limited to, one or more of the following: an elevated (CRP), (ESR), fibrinogen, procalcitonin, d-dimer, ferritin, lactic acid dehydrogenase (LDH), or interleukin 6 (IL-6), elevated neutrophils, reduced lymphocytes and low albumin
- and evidence of clinically severe illness requiring hospitalization, with multisystem (>2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological); AND
- No alternative plausible diagnoses; AND
- Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or exposure to a suspected or confirmed COVID-19 case within the 4 weeks prior to the onset of symptoms
- Some individuals may fulfill full or partial criteria for Kawasaki disease but should be reported if they meet the case definition for MIS-C
- Consider MIS-C in any pediatric death with evidence of SARS-CoV-2 infection.
- Clinical presentation includes:
- Fever
- Red eyes/Red cracked lips
- Abdominal pain
- vomiting
- Diarrhea
- Skin rash
- musculocutaneous lesion
- Swollen Hands and Feet
- Hypotension, shock (severe cases)
- Other evaluations include:
- Echo
- EKG
- Cardiac enzymes and troponin testing
- BNP, NT-proBNP
- Treatment
- Fluid Resuscitation
- Inotropic support
- Respiratory support
- Anti-inflammatory measures (Steroids/IVIG)
Related Topics
References
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Contributor(s)
- Wedro, Benjamin, MD
- Cox, Takema, DO, MBS
- Ho, Nghia, MD
- Cherian, Geo, MD
- Tom, Jubil, MD
- Singh, Ajaydeep, MD
- Ausi, Michael, MD, MPH
Updated/Reviewed: June 2025