What is the diagnosis and treatment for a patient with cough, low-grade fever, fatigue, and body aches, but no headache, with negative home test results for COVID-19 (Coronavirus Disease 2019) and influenza, and no pre-existing medical conditions?

Diagnosis and Management of Viral Upper Respiratory Infection

This patient most likely has an uncomplicated viral upper respiratory infection (URI) and should be managed with symptomatic treatment including guaifenesin for cough, adequate hydration, and monitoring for red flags that would indicate bacterial superinfection or pneumonia. 1

Clinical Reasoning

The constellation of cough, low-grade fever, fatigue, and body aches with negative COVID-19 and influenza testing is consistent with a common viral URI caused by one of many circulating respiratory viruses. 1 While COVID-19 and influenza share overlapping symptoms with other viral URIs, the negative home tests make these diagnoses less likely, though not completely excluded given test limitations. 2

Key Diagnostic Considerations

The typical viral URI follows a predictable course: fever occurs early (first 24-48 hours) and resolves before respiratory symptoms, which peak at days 3-6 and then improve over 5-7 days total. 1 This patient's presentation fits this pattern.

Important distinguishing features from COVID-19:

• COVID-19 patients typically report longer symptom duration (median 7 days vs. 3 days for other viral URIs) 3
• COVID-19 more commonly presents with fever (82% vs. 44%), fatigue (85% vs. 50%), and myalgias (61% vs. 27%) compared to other acute respiratory illnesses 3
• The absence of headache is notable, as headache can be a feature of COVID-19, though its absence does not rule out the diagnosis 2

Regarding test accuracy: Home antigen tests have lower sensitivity than laboratory-based NAAT testing, particularly early in illness or with low viral loads. 2 However, a negative antigen test in a symptomatic patient without alternative diagnosis warrants consideration of repeat testing with standard NAAT if clinical suspicion remains high. 2

Recommended Management

Symptomatic Treatment

For cough management:

• Guaifenesin to help loosen phlegm and thin bronchial secretions, making productive cough more effective 1
• Honey for cough suppression if not contraindicated 1

For supportive care:

• Adequate hydration (up to 2 liters per day) to thin mucus secretions and support natural clearance mechanisms 1, 4
• Saline nasal spray if nasal congestion persists, to prevent crusting and facilitate mechanical removal of mucus 1
• Acetaminophen 500-1000mg every 4-6 hours as needed for fever control, targeting temperature reduction below 38°C 4

What NOT to do:

• Do not prescribe antibiotics at this stage, as they are not indicated for uncomplicated viral URIs and may cause adverse effects without benefit 1
• Avoid decongestants if the patient has cardiovascular disease 1
• Do not obtain imaging studies (chest X-ray, CT) unless red flags develop 1

Critical Red Flags Requiring Immediate Re-evaluation

Monitor closely and instruct the patient to seek immediate medical attention if any of the following develop:

Temporal red flags:

• Symptoms persisting beyond 7-10 days without improvement or worsening after initial improvement (may indicate bacterial superinfection or pneumonia) 1
• Fever persisting beyond 3-5 days or recurrence of fever after initial resolution (may indicate bacterial superinfection) 1

Respiratory red flags:

• Development of shortness of breath or respiratory distress 1, 4
• Respiratory rate ≥30/min 4
• New chest pain or pleuritic symptoms 1

Other concerning features:

• Severe or worsening headache with facial pain suggesting bacterial sinusitis 1
• Altered mental status or severe headache 4
• Inability to maintain oral hydration 4
• Persistent high fever despite antipyretics 4

Common Pitfall to Avoid

Do not assume negative COVID-19 test completely rules out COVID-19 involvement—false negatives occur, particularly with home antigen tests, and clinical suspicion should guide management. 2, 4 If symptoms worsen or persist beyond expected viral URI course, consider repeat testing with standard NAAT (laboratory-based PCR). 2

When to Consider Bacterial Superinfection

Laboratory markers that can help distinguish bacterial superinfection from prolonged viral symptoms:

• Elevated C-reactive protein and procalcitonin 1
• These should be measured if red flags develop, as approximately 40% of viral respiratory infections requiring hospitalization have bacterial coinfection 4

If bacterial superinfection is suspected, do not delay antibiotics—the high rate of bacterial coinfection in severe viral respiratory infections necessitates prompt treatment. 4