What is the appropriate management for an 18-year-old female presenting with headache, thirst, chills, body aches, nausea, and sweats, with negative influenza (flu) and coronavirus disease 2019 (COVID-19) tests?

Management of Acute Febrile Illness with Negative Flu and COVID-19 Testing

This 18-year-old female with systemic symptoms (headache, thirst, chills, body aches, nausea, sweats) and negative flu/COVID-19 tests should receive symptomatic management with antipyretics, hydration support, and close monitoring for development of severe symptoms or alternative diagnoses.

Immediate Assessment and Symptomatic Treatment

Fever Management

• Use paracetamol (acetaminophen) as first-line antipyretic for temperatures above 38.5°C, administered orally at 0.2 g per dose every 4-6 hours as needed (maximum 4 times in 24 hours) 1
• Paracetamol is preferred over NSAIDs (like ibuprofen) when viral illness is suspected, even with negative testing 1
• Target temperature reduction to below 38°C is acceptable; excessive temperature reduction is not necessary and may interfere with immune response 1

Hydration Support

• Advise regular fluid intake to prevent dehydration, but limit to no more than 2 liters per day 1
• The complaint of "thirst" suggests possible dehydration requiring active rehydration 1
• Monitor for signs of adequate hydration (urine output, mucous membrane moisture)

Nausea Management

• Optimize anti-emetic therapy with careful attention to QTc prolongation risk 1
• Consider H2 receptor antagonists or proton pump inhibitors if gastrointestinal symptoms persist 1
• Ensure adequate caloric intake despite nausea 1

Differential Diagnosis Considerations

Consider Alternative Viral Pathogens

Despite negative flu and COVID-19 testing, this presentation is consistent with viral illness. The symptom constellation (fever, myalgia, headache, chills, sweats, nausea) occurs in multiple viral infections 1, 2.

Key differential diagnoses include:

• Other respiratory viruses (parainfluenza, adenovirus, respiratory syncytial virus, metapneumovirus) 1
• Infectious mononucleosis (Epstein-Barr virus)
• Acute viral gastroenteritis
• Early bacterial infection (though less likely without localizing signs)

Important Clinical Caveats

• GI symptoms (nausea) can precede respiratory symptoms in COVID-19 by several days 1, so a single negative test does not definitively exclude COVID-19 if tested very early
• COVID-19 testing has variable sensitivity depending on timing and specimen collection technique 1
• Consider repeat COVID-19 testing if symptoms persist beyond 7-10 days or worsen 1

Monitoring and Red Flags

Monitor for Progression to Severe Illness

Instruct the patient to seek immediate medical attention if she develops:

• Dyspnea or shortness of breath 1
• Respiratory rate ≥30/min 1
• Persistent high fever despite antipyretics
• Altered mental status or severe headache 1
• Inability to maintain oral hydration 1
• Chest pain or pressure
• Worsening symptoms after initial improvement

Follow-up Timeline

• Symptoms should improve within 5-7 days for most viral illnesses 1
• If symptoms persist beyond 7-10 days or worsen, consider:
  • Repeat COVID-19 testing (PCR on second sample with proper technique) 1
  • COVID-19 serology if symptoms present ≥7-10 days 1
  • Chest imaging if respiratory symptoms develop 1
  • Laboratory evaluation including complete blood count, inflammatory markers 1

Supportive Care Measures

Rest and Activity

• Bed rest with monitoring of vital signs (heart rate, oxygen saturation, respiratory rate, blood pressure) 1
• Avoid overexertion during acute illness 1

Nutrition

• Ensure adequate energy intake with balanced nutrition 1
• Protein-rich foods (eggs, fish, lean meat, dairy) and carbohydrates 1
• Target energy intake of 25-30 kcal/kg/day 1

Lifestyle Modifications During Illness

• Regular sleep schedule 1
• Avoid alcohol and smoking 1
• Self-quarantine until symptoms resolve to prevent potential transmission of unidentified pathogen 1

When to Escalate Care

Obtain additional testing if:

• Symptoms persist beyond 7-10 days without improvement 1
• Development of respiratory symptoms (cough, dyspnea) 1
• Signs of dehydration despite oral intake 1
• Severe or worsening headache suggesting possible meningitis 1
• Any red flag symptoms listed above develop

The majority of young, previously healthy patients with acute viral syndromes recover with supportive care alone 1. However, vigilance for deterioration and consideration of alternative diagnoses remains essential, particularly given the ongoing circulation of multiple respiratory pathogens 3, 4.