According to FDA guidance, what is the recommended isolation duration for COVID‑19 in mild/moderate cases versus severe or immunocompromised cases, and what criteria must be met before ending isolation?

COVID-19 Isolation Guidelines

For most COVID-19 patients, isolation should last a minimum of 5 days from symptom onset or positive test, and can end only when fever-free for 24 hours without antipyretics, symptoms are resolving, and ideally after a negative rapid antigen test, with extended isolation up to 10 days if symptoms persist or testing remains positive. 1, 2, 3

Standard Isolation Duration and Exit Criteria

All three of the following criteria must be met before ending isolation after day 5:

• At least 5 days have passed since symptom onset (or positive test if asymptomatic) 1, 2, 3
• Fever-free for at least 24 hours without using fever-reducing medications 1, 2, 3
• Symptoms are resolving or absent (particularly respiratory symptoms like cough and shortness of breath) 1, 2, 3
• Ideally, a negative rapid antigen test should be obtained before ending isolation 1, 2, 3

If any of these criteria are not met, extend isolation up to 10 days from symptom onset or until all criteria are satisfied. 1, 2, 3

Extended Isolation Scenarios

Continue isolation beyond 5 days (up to 10 days minimum) if:

• Fever persists or recurs 1, 2
• Symptoms worsen or fail to improve 1, 2
• Rapid antigen testing remains positive 1, 2
• The patient has severe COVID-19 or is immunocompromised (see special populations below) 2, 3

Testing Strategy for Ending Isolation

Key testing principles:

• Rapid antigen tests are preferred over PCR for determining isolation end, as they correlate better with infectiousness 1, 2, 4
• Do NOT use repeat PCR testing to guide isolation discontinuation—patients can remain PCR-positive for weeks after they are no longer infectious 2, 3
• A positive antigen test has high specificity and indicates ongoing infectiousness 1, 2
• After 5-9 days of isolation, approximately 54% of patients may still test positive on rapid antigen testing, with declining positivity over time 4

Testing is NOT routinely required to end isolation in most circumstances if clinical criteria are met, though it is ideal when available. 1, 2

Special Populations Requiring Modified Criteria

For immunocompromised patients or those with severe COVID-19:

• Use a case-by-case approach rather than standard 5-day criteria 2, 3
• Consider extending isolation beyond 10 days 2, 3
• May require test-based strategy with consecutive negative tests 2, 3
• Previous infection and vaccination reduce the likelihood of prolonged infectiousness (adjusted OR 0.17 for both) 4

For hospitalized or surgical patients:

• After discharge, maintain isolation for at least 2 weeks from first positive test until negative RT-PCR is obtained 2, 3
• Place in dedicated COVID-19 wards to prevent nosocomial transmission 1

Stricter clearance criteria for healthcare or congregate settings:

• Body temperature normal for more than 3 days without antipyretics 2
• Respiratory symptoms significantly improved 2
• Two consecutive negative RT-PCR tests with at least 1-day interval 2

Isolation Setting Requirements

During active isolation, patients must:

• Stay in well-ventilated single rooms with restricted activity 1, 2, 3
• If single rooms unavailable, maintain at least 1.1 meters (3.5 feet) distance from others 1, 2, 3
• Wear medical masks (N95 preferred) when in the presence of others, including household members 1, 2, 3
• Clean hands immediately after coughing, sneezing, or touching potentially contaminated surfaces 1, 2
• Monitor body temperature and symptoms daily 1

Caregiver and Household Precautions

Caregivers must:

• Wear N95 masks (preferred) or surgical masks when in the same room as the patient 1
• Avoid sharing personal items (toothbrushes, towels, tableware, bed linens) 1
• Monitor their own temperature and symptoms closely 1
• Clean and disinfect frequently touched surfaces daily using 500 mg/L chlorine-containing disinfectant 1
• Avoid direct contact with patient's respiratory secretions 1

Return to Normal Activities

Patients can return to work or normal activities when:

• The 10-day criterion is met (or 5 days with all exit criteria satisfied) 2, 3
• Plus symptom improvement and 24-hour fever resolution without medications 2, 3
• Patients meeting these criteria are unlikely to be infectious 2, 3

After ending isolation, patients should continue to wear well-fitting masks around others through day 10 to minimize residual transmission risk, as asymptomatic and presymptomatic transmission accounts for more than 50% of all COVID-19 transmission. 4, 5, 6

Critical Pitfalls to Avoid

• Never end isolation before day 5 regardless of symptom resolution 2, 3
• Never use repeat PCR testing routinely to determine when to end isolation—patients can remain PCR-positive for weeks without being contagious 2, 3
• Never apply standard 5-day criteria to immunocompromised patients without individualized assessment—they require longer isolation and potentially test-based strategies 2, 3
• Never end isolation based solely on symptom resolution without meeting the minimum 5-day criterion 2, 3
• Never manage suspected COVID-19 patients without full PPE precautions until diagnosis is definitively ruled out 3

Post-Discharge Surveillance

For discharged patients:

• Quarantine for 2 weeks after discharge with follow-up 7
• Perform PCR tests at 2 and 4 weeks after discharge 7
• If RT-PCR reverts from negative to positive (occurs in 14-16% of cases), re-isolate and consider re-hospitalization based on clinical characteristics 7
• For re-positive patients, require three negative RT-PCR tests from sputum and fecal specimens (each ≥24 hours apart, with at least one from fecal test) before ending isolation again 7