General Management of Non-hospitalized Patients With Acute COVID-19
This section of the Guidelines is intended to provide information to health care providers who are caring for Non-hospitalized patients with COVID-19. The COVID-19 Treatment Guidelines Panel’s (the Panel) recommendations for pharmacologic management can be found in Therapeutic Management of Non-hospitalized Adults With COVID-19. The Panel recognizes that the distinction between outpatient and inpatient care may be less clear during the COVID-19 pandemic. Patients with COVID-19 may receive care outside traditional ambulatory care or hospital settings if there is a shortage of hospital beds, staff, or resources. Settings such as field hospitals and ambulatory surgical centers and programs such as Acute Hospital Care at Home have been implemented to alleviate hospital bed and staffing shortages.1 Patients may enter an Acute Hospital Care at Home program from either an emergency department (ED) or an inpatient hospital setting. Health care providers should use their judgment when deciding whether the guidance offered in this section applies to individual patients.
Managing Patients With COVID-19 in an Ambulatory Care Setting
Approximately 80% of patients with COVID-19 have mild illness that does not warrant medical intervention or hospitalization. Most patients with mild COVID-19 (defined as the absence of viral pneumonia and hypoxemia) can be managed in an ambulatory care setting or at home. Patients with moderate COVID-19 (those with viral pneumonia but without hypoxemia) or severe COVID-19 (those with dyspnea, hypoxemia, or lung infiltrates >50%) need in-person evaluation and close monitoring, as pulmonary disease can progress rapidly and require hospitalization.
Health care providers should identify patients who may be at high risk for progression to severe COVID-19; these patients may be candidates for anti-SARS-CoV-2 monoclonal antibody treatment (see Figure 1 in Therapeutic Management of Non-hospitalized Adults with COVID-19). Management of COVID-19 patients in the outpatient setting should focus on providing supportive care, taking steps to reduce the risk of SARS-CoV-2 transmission (e.g., wearing a mask, isolating the patient), and advising patients on when to seek in-person evaluation. Supportive care includes managing symptoms (as described below), ensuring that patients are receiving the proper nutrition, and paying attention to the risks of social isolation, particularly in older adults. Other unique aspects of care for geriatric patients with COVID-19 include considerations related to cognitive impairment, frailty, fall risk, and polypharmacy. Older patients and those with chronic medical conditions have a higher risk for hospitalization and death; however, SARS-CoV-2 infection may cause severe disease and death in patients of any age, even in the absence of any risk factors. The decision to monitor a patient in the outpatient setting should be made on a case-by-case basis.
Assessing the Need for In-Person Evaluation
When possible, patients with suspected or laboratory-confirmed COVID-19 should be triaged via telehealth visits before they receive an in-person evaluation. Outpatient management may include the use of patient self-assessment tools. During initial triage, clinic staff should determine which patients are eligible to receive supportive care at home and which patients warrant an in-person evaluation.8 Local emergency medical services, if called by the patient, may also be of help in deciding whether an in-person evaluation is indicated. Patient management plans should be based on the patient’s vital signs, physical exam findings, risk factors for progression to severe illness, and the availability of health care resources (AIII).
All patients with dyspnea, oxygen saturation (SpO2) ≤94% on room air at sea level (if this information is available), or symptoms that suggest higher acuity (e.g., chest pain or tightness, dizziness, confusion or other mental status changes) should be referred for an in-person evaluation by a health care provider. The criteria used to determine the appropriate clinical setting for an in-person evaluation may vary by location and institution; it may also change over time as new data and treatment options emerge. There should be a low threshold for in-person evaluation of older persons and those with medical conditions associated with risk of progression to severe COVID-19. The individual who performs the initial triage should use their clinical judgement to determine whether a patient requires ambulance transport. There are unique considerations for residents of nursing homes and other long-term care facilities who develop acute COVID-19. Decisions about transferring these patients for an in-person evaluation should be a collaborative effort between the resident (or their health care decision maker), a hospital-based specialist (e.g., an emergency physician or geriatrician), and the clinical manager of the facility.
In some settings where clinical evaluation is challenged by geography, health care provider home visits may be used to evaluate patients. Patients who are homeless should be provided with housing where they can adequately self-isolate. Providers should be aware of the potential adverse effects of prolonged social isolation, including depression and anxiety. All outpatients should receive instructions regarding self-care, isolation, and follow-up, and should be advised to contact a health care provider or a local ED for any worsening symptoms. Guidance for implementing home care and isolation of outpatients with COVID-19 is provided by the U.S. Centers for Disease Control and Prevention.
Clinical Considerations When Managing Patients in an Ambulatory Care Setting
Persons who have symptoms that are compatible with COVID-19 should undergo diagnostic SARS-CoV-2 testing (see Prevention and Prophylaxis of SARS-CoV-2 Infection). Patients with SARS-CoV-2 infection may be asymptomatic or experience symptoms that are indistinguishable from other acute viral or bacterial infections (e.g., fever, cough, sore throat, malaise, muscle pain, headache, gastrointestinal symptoms). It is important to consider other possible etiologies of symptoms, including other respiratory viral infections (e.g., influenza), community-acquired pneumonia, congestive heart failure, asthma or chronic obstructive pulmonary disease exacerbations, and streptococcal pharyngitis.
In most adult patients, if dyspnea develops, it tends to occur between 4 and 8 days after symptom onset, although it can also occur after 10 days.13 While mild dyspnea is common, worsening dyspnea and severe chest pain/tightness suggest the development or progression of pulmonary involvement. In studies of patients who developed acute respiratory distress syndrome, progression occurred a median of 2.5 days after the onset of dyspnea. Adult outpatients with dyspnea should be followed closely with telehealth or in-person monitoring, particularly during the first few days following the onset of dyspnea, to monitor for worsening respiratory status (AIII).
If an adult patient has access to a pulse oximeter at home, SpO2 measurements can be used to help assess overall clinical status. Patients should be advised to use pulse oximeters on warm fingers rather than cold fingers for better accuracy. Patients should inform their health care provider if the value is repeatedly below 95% on room air at sea level. Pulse oximetry may not accurately detect occult hypoxemia, especially in Black patients.3,17,18 Additionally, SpO2 readings obtained through a mobile phone application may not be accurate enough for clinical use. Importantly, oximetry should only be interpreted within the context of a patient’s entire clinical presentation (i.e., results should be disregarded if a patient is complaining of increasing dyspnea).
Counseling Regarding the Need for Follow-Up
Health care providers should identify patients who are at high risk for disease progression. These patients may be candidates for anti-SARS-CoV-2 monoclonal antibody treatments, and clinicians should ensure that these patients receive adequate medical follow-up. The frequency and duration of follow-up will depend on the risk for severe disease, the severity of symptoms, and the patient’s ability to self-report worsening symptoms. Health care providers should determine whether a patient has access to a phone, computer, or tablet for telehealth; whether they have adequate transportation for clinic visits; and whether they have regular access to food. The clinician should also confirm that the patient has a caregiver who can assist with daily activities if needed.
All patients and/or their family members or caregivers should be counseled about the warning symptoms that should prompt re-evaluation through a telehealth visit or an in-person evaluation in an ambulatory care setting or ED. These symptoms include new onset of dyspnea; worsening dyspnea (particularly if dyspnea occurs while resting or if it interferes with daily activities); dizziness; and mental status changes, such as confusion. Patients should be educated about the time course of these symptoms and the possible respiratory decline that may occur, on average, 1 week after the onset of illness.
Managing Adults With COVID-19 Following Discharge from the Emergency Department
There are no fixed criteria for admitting patients with COVID-19 to the hospital; criteria may vary by region and hospital facilities. Patients with severe disease are typically admitted to the hospital, but some patients with severe disease may not be admitted due to a high prevalence of infection and limited hospital resources. In addition, patients who could receive appropriate care at home but are unable to be adequately managed in their usual residential setting are candidates for temporary shelter in supervised facilities, such as a COVID-19 alternative care facility.22 For example, patients who are living in multigenerational households or who are homeless may not be able to self-isolate and should be provided resources such as dedicated housing units or hotel rooms, when available. Unfortunately, dedicated residential care facilities for COVID-19 patients are not widely available, and community-based solutions for self-care and isolation should be explored
Treatment with an anti-SARS-CoV-2 monoclonal antibody is recommended for patients with mild to moderate COVID-19 who are not on supplemental oxygen and who have been discharged from the ED but who are at high risk for clinical progression (see Therapeutic Management of Non-hospitalized Adults With COVID-19).
In the cases where institutional resources (e.g., inpatient beds, staff members) are scarce, it may be necessary to discharge an adult patient and provide an advanced level of home care, including supplemental oxygen (if indicated), pulse oximetry, and close follow-up. Although early discharge of those with severe disease is not generally recommended by the Panel, it is recognized that these management strategies are sometimes necessary. In these situations, some institutions are providing frequent telemedicine follow-up visits for these patients or providing a hotline for patients to speak with a clinician when necessary. Home resources should be assessed before a patient is discharged from the ED; outpatients should have a caregiver and access to a device that is suitable for telehealth. Patients and/or their family members or caregivers should be counseled about the warning symptoms that should prompt re-evaluation by a health care provider. Special consideration may be given to using certain therapeutics (e.g., dexamethasone) in this setting. For more information, see Therapeutic Management of Non-hospitalized Adults With COVID-19.
Anticoagulants and antiplatelet therapy should not be initiated in the ED for the prevention of venous thromboembolism (VTE) or arterial thrombosis if the patient is not being admitted to the hospital, unless the patient has other indications for the therapy or is participating in a clinical trial (AIII). For more information, see Antithrombotic Therapy in Patients With COVID-19. Patients should be encouraged to ambulate, and activity should be increased according to the patient’s tolerance.
Managing Adults With COVID-19 Following Hospital Discharge
Most patients who are discharged from the hospital setting should have a follow-up visit with a health care provider soon after discharge. Whether an in-person or a telehealth visit is most appropriate depends on the clinical and social situation. In some cases, adult patients are deemed to be stable for discharge from the inpatient setting even though they still require supplemental oxygen. Special consideration may be given to using certain therapeutics (e.g., dexamethasone) in this setting. For more information, see Therapeutic Management of Non-hospitalized Adults With COVID-19. When possible, these individuals should receive oximetry monitoring and close follow-up through telehealth visits, visiting nurse services, or in-person clinic visits.
Hospitalized patients with COVID-19 should not be routinely discharged while receiving VTE prophylaxis, unless they have another indication or are participating in a clinical trial (AIII). For more information, see Antithrombotic Therapy in Patients With COVID-19. Patients should be encouraged to ambulate, and activity should be increased according to the patient’s tolerance.
Considerations in Pregnancy
Managing pregnant outpatients with COVID-19 is similar to managing nonpregnant patients (see Special Considerations in Pregnancy). Clinicians should offer supportive care, take steps to reduce the risk of SARS-CoV-2 transmission, and provide guidance on when to seek an in-person evaluation. The American College of Obstetricians and Gynecologists (ACOG) has developed an algorithm to aid the practitioner in evaluating and managing pregnant outpatients with laboratory-confirmed or suspected COVID-19.23 ACOG has also published recommendations on how to use telehealth for prenatal care and how to modify routine prenatal care when necessary to decrease the risk of SARS-CoV-2 transmission to patients, caregivers, and staff.
In pregnant patients, SpO2 should be maintained at 95% or above on room air at sea level; therefore, the threshold for monitoring pregnant patients in an inpatient setting may be lower than in nonpregnant patients.24 In general, there are no changes to fetal monitoring recommendations in the outpatient setting, and fetal management should be similar to the fetal management used for other pregnant patients with medical illness.25 However, these monitoring strategies can be discussed on a case-by-case basis with an obstetrician. Pregnant and lactating patients should be given the opportunity to participate in clinical trials of outpatients with COVID-19 to help inform decision-making in this population.
Considerations in Children
Children and adolescents with acute COVID-19 are less likely than adults to require medical intervention or hospitalization, and most can be managed in an ambulatory care setting or at home. In general, the need for ED evaluation or hospitalization should be based on the patient’s vital signs, physical exam findings (e.g., dyspnea), and risk factors for progression to severe illness. Certain groups, including young infants, children with risk factors, and those with presentations that overlap with multisystem inflammatory syndrome in children (MIS-C), may require hospitalization for more intensive monitoring. However, this should be determined on a case-by-case basis.
Most children with mild or moderate COVID-19, even those with risk factors, will not progress to more severe illness and will recover without specific therapy (see Special Considerations in Children). There is insufficient evidence for the Panel to recommend either for or against the use of anti-SARS-CoV-2 monoclonal antibody products in Non-hospitalized children with COVID-19 who have risk factors for severe disease. The available efficacy data for adults suggests that anti-SARS-CoV-2 monoclonal antibody products may be considered for use in children who meet the Food and Drug Administration Emergency Use Authorization (EUA) criteria, especially those who have more than one risk factor. The decision to use these products in children should be made on a case-by-case basis in consultation with a pediatric infectious disease specialist. The risk factors that predict progression to severe disease in adults can be used to determine the risk of progression in children aged ≥16 years (see the Panel’s statement on the EUAs for anti-SARS-CoV-2 monoclonal antibodies).
In general, pediatric patients should not continue receiving remdesivir, dexamethasone, or other COVID-19-directed therapies following discharge from an ED or an inpatient setting. Clinicians should refer to Special Considerations in Children for more information on the management of children with COVID-19.
Therapeutic Management of Non-hospitalized Adults With COVID-19
Last Updated: July 8, 2021
Figure 1 outlines the COVID-19 Treatment Guidelines Panel’s (the Panel) recommendations for using therapeutic interventions outside the hospital inpatient setting. These recommendations differ depending on the patient’s disposition.
Symptomatic treatment includes using over-the-counter antipyretics, analgesics, or antitussives for fever, headache, myalgias, and cough. Patients with dyspnea may benefit from resting in the prone position rather than the supine position.1 Health care providers should consider educating patients about breathing exercises, as severe breathlessness may cause anxiety. Patients should be advised to drink fluids regularly to avoid dehydration. Rest is recommended as needed during the acute phase of COVID-19, and ambulation and other forms of activity should be increased according to the patient’s tolerance. Patients should be educated about the variability in time to symptom resolution and complete recovery.
Rationale for the Use of Specific Agents Listed in Figure 1
Anti-SARS-CoV-2 Monoclonal Antibodies
Two combination anti-SARS-CoV-2 monoclonal antibody products (bamlanivimab plus etesevimab and casirivimab plus imdevimab) and a single monoclonal antibody (sotrovimab) have been shown to reduce the risk of hospitalization and death in the outpatient setting in those with mild to moderate COVID-19 symptoms and certain risk factors for disease progression. As a result, these products have received Emergency Use Authorizations (EUAs) from the Food and Drug Administration (FDA) for the treatment of COVID-19 in these individuals, as well as in those with other risk factors for progression that have been identified in population-based studies. There are no comparative data to determine whether there are differences in clinical efficacy or safety between these products.
The Panel recommends using one of the following anti-SARS-CoV-2 monoclonal antibodies to treat outpatients with mild to moderate COVID-19 who are at high risk of clinical progression, as defined by the EUA criteria and the Panel’s statement about the EUAs (treatments are listed in alphabetical order):
Casirivimab plus imdevimab; or
At this time, the Panel recommends against the use of bamlanivimab plus etesevimab (AIII) because of the increase in the proportion of the variants of concern Gamma (P.1) and Beta (B.1.351), which have reduced susceptibility to both bamlanivimab and etesevimab. See the Centers for Disease Control and Prevention COVID-19 Data Tracker website for the latest information regarding variant proportions by region in the United States. Casirivimab plus imdevimab and sotrovimab remain active against these variants.
Treatment should be started as soon as possible after the patient receives a positive result on a SARS-CoV-2 antigen test or a nucleic acid amplification test (NAAT) and within 10 days of symptom onset. For more details on the available clinical trial data for these antibodies, see Anti-SARS-CoV-2 Monoclonal Antibodies and the Panel’s statement on the EUAs for anti-SARS-CoV-2 monoclonal antibodies.
Receipt of a COVID-19 vaccine should be deferred for at least 90 days in those who have received anti-SARS-CoV-2 monoclonal antibodies. This is a precautionary measure, as the antibody treatment may interfere with vaccine-induced immune responses. In people who are vaccinated and then develop COVID-19, prior receipt of a vaccine should not affect treatment decisions, including the use of and timing of treatment with monoclonal antibodies.
The Panel recommends against the use of dexamethasone or other systemic glucocorticoids to treat outpatients with mild to moderate COVID-19 who do not require hospitalization or supplemental oxygen (AIII). There is currently a lack of safety and efficacy data on the use of these agents, and systemic glucocorticoids may cause harm in these patients. Patients who are receiving dexamethasone or another corticosteroid for other indications should continue therapy for their underlying conditions as directed by their health care providers (AIII).
In RECOVERY, dexamethasone was shown to reduce mortality in hospitalized patients with COVID-19 who required supplemental oxygen. There was no observed benefit of dexamethasone in hospitalized patients who did not receive oxygen support. Non-hospitalized patients who did not require supplemental oxygen were not included in this trial; thus, the safety and efficacy of corticosteroids in this population have not been established. Therefore, the Panel recommends against the use of dexamethasone or other systemic glucocorticoids in this population, as there are no clinical trial data to support their use (AIII). Moreover, the use of corticosteroids can lead to adverse events (e.g., hyperglycemia, neuropsychiatric symptoms, secondary infections), which may be difficult to detect and monitor in an outpatient setting.
Dexamethasone was stopped at the time of hospital discharge during RECOVERY. For hospitalized patients with COVID-19 who do not require supplemental oxygen after discharge, the Panel recommends against the continuation of dexamethasone (AIIa).
In some cases, adult patients are deemed to be stable enough to be discharged from the inpatient setting even though they still require supplemental oxygen. The practice of discharging inpatients who still require oxygen was likely uncommon during RECOVERY; therefore, there is insufficient evidence to recommend either for or against the continued use of dexamethasone after hospital discharge in patients who require supplemental oxygen. The data supporting the use of corticosteroids after discharge in such cases are limited, with the main concerns being the lack of monitoring for toxicities, including, but not limited to, blood glucose control and neuropsychiatric impairment. If a patient continues to receive corticosteroids after discharge, consider continuing corticosteroids for the duration of supplemental oxygen. However, the total duration of corticosteroid use should not exceed 10 days (including days during hospitalization). Only patients who showed good tolerance to this therapy prior to discharge should continue to receive corticosteroids after discharge, and these patients should be carefully monitored for adverse events. These individuals should receive oximetry monitoring and close follow-up through telehealth, visiting nurse services, or in-person clinic visits.
In rare cases, patients with COVID-19 who require supplemental oxygen and hospital admission may need to be discharged from the emergency department (ED) due to scarce resources (e.g., in cases where hospital beds or staff are not available). For these patients, the Panel recommends using dexamethasone 6 mg PO once daily for the duration of supplemental oxygen (dexamethasone use should not exceed 10 days) with careful monitoring for adverse events (BIII). These patients should receive oximetry monitoring and close follow-up through telehealth, visiting nurse services, or in-person clinic visits.
Remdesivir is currently the only drug that is approved by the FDA for the treatment of COVID-19. It is recommended for use in hospitalized patients who require supplemental oxygen. The clinical trials that evaluated the safety and efficacy of remdesivir stopped this treatment at the time of discharge from the hospital.5-7 The Panel recommends against the continuation of remdesivir (AIIa) in hospitalized patients with COVID-19 who are stable enough for discharge and who do not require supplemental oxygen.
In some cases, adult patients are deemed to be stable enough to be discharged from the inpatient setting even though they still require supplemental oxygen. There is insufficient evidence to recommend either for or against the continued use of remdesivir after hospital discharge in patients who require supplemental oxygen. Since remdesivir can only be administered by intravenous infusion, there may be logistical issues with providing remdesivir to outpatients. If remdesivir is provided, it should only be administered in health care settings that can provide a similar level of care to an inpatient hospital. These individuals should receive oximetry monitoring and close follow-up through telehealth, visiting nurse services, or in-person clinic visits.
In rare cases, patients with COVID-19 who require supplemental oxygen and hospital admission may need to be discharged from the ED due to scarce resources (i.e., a hospital bed or staff may not be available). There is insufficient evidence to recommend either for or against the routine use of remdesivir in this setting. If remdesivir is provided, it should only be administered in health care settings that can provide a similar level of care to an inpatient hospital. These individuals should receive oximetry monitoring and close follow-up through telehealth, visiting nurse services, or in-person clinic visits.
The pivotal safety and efficacy trials for baricitinib enrolled hospitalized patients with COVID-19, and treatment was stopped at the time of hospital discharge. The Panel recommends against the continuation of baricitinib (AIIa) in hospitalized patients with COVID-19 who are stable enough for discharge and who do not require supplemental oxygen.
There is insufficient evidence to recommend either for or against the continued use of baricitinib after hospital discharge in patients who have been discharged from the inpatient setting but who still require supplemental oxygen.
There are currently no data that assess the safety and efficacy of using baricitinib in patients who require supplemental oxygen and hospital admission, but who have been discharged from the ED due to scarce resources. Therefore, the Panel recommends against the use of baricitinib in these patients, except in a clinical trial (AIII).
Other Agents That Have Been Studied or Are Under Investigation for Use in the Outpatient Management of COVID-19
The Panel recommends against the use of chloroquine or hydroxychloroquine with or without azithromycin (AI), lopinavir/ritonavir, and other HIV protease inhibitors (AIII) for outpatient treatment of COVID-19.
The Panel recommends against the use of antibacterial therapy (e.g., azithromycin, doxycycline) for outpatient treatment of COVID-19 in the absence of another indication (AIII).
Other agents have undergone or are currently undergoing investigation in the outpatient setting. For more information, please refer to the sections of the Guidelines that address:
Antiviral agents, such as ivermectin and nitazoxanide
Immunomodulators, such as colchicine and fluvoxamine
Supplements, such as vitamin C, vitamin D, and zinc
Anticoagulants and antiplatelet therapy should not be initiated in the outpatient setting for the prevention of venous thromboembolism or arterial thrombosis unless the patient has other indications for the therapy or is participating in a clinical trial (AIII). For more information, see Antithrombotic Therapy in Patients With COVID-19.
Health care providers should provide information about ongoing clinical trials of investigational therapies to eligible outpatients with COVID-19 so they can make informed decisions about participating in clinical trials (AIII).
Concomitant Medication Management
In general, a patient’s usual medication and/or supplement regimen should be continued after the diagnosis of COVID-19 (see Considerations for Certain Concomitant Medications in Patients With COVID-19). Angiotensin-converting enzyme inhibitors, statin therapy, nonsteroidal anti-inflammatory drugs, and oral, inhaled, and intranasal corticosteroids that are prescribed for comorbid conditions should be continued as directed (AIII). Patients should be advised to avoid the use of nebulized medications in the presence of others to avoid potential aerosolization of SARS-CoV-2.10 In patients with HIV, antiretroviral therapy should not be switched or adjusted for the purpose of preventing or treating SARS-CoV-2 infection (AIII). For more information, see Special Considerations in People With HIV.
When a patient is receiving an immunomodulating medication, the prescribing clinician should be consulted about the risks and benefits that are associated with a temporary dose reduction or discontinuation; these risks and benefits will depend on the medication’s indication and the severity of the underlying condition.
Patients who use a continuous positive airway pressure (CPAP) device or a bilevel positive airway pressure (BiPAP) device to manage obstructive sleep apnea may continue to use their machine. As with nebulizers, patients should be advised to use the device only when they are isolated from others.