Most Likely Diagnosis and Initial Management
In a college student with sore throat, swollen lymph nodes, and negative testing for strep, COVID-19, influenza, and mononucleosis, the most likely diagnosis is viral pharyngitis caused by common respiratory viruses such as rhinovirus, adenovirus, or coronavirus. 1, 2
Diagnostic Reasoning
The negative test results effectively rule out the major bacterial and specific viral pathogens that require targeted treatment:
- A negative rapid strep test in adults has ≥95% specificity and is sufficient to exclude Group A Streptococcus without requiring a backup throat culture 1
- The absence of fever and other systemic symptoms makes bacterial pharyngitis even less likely 1, 2
- Rhinovirus is the most frequent cause of acute pharyngitis overall 2
- Other common viral causes include adenovirus, parainfluenza, respiratory syncytial virus, and other coronaviruses 1, 2
The presence of cervical lymphadenopathy alone does not distinguish viral from bacterial causes, as both can produce this finding 3, 4. However, the constellation of negative testing with isolated sore throat and adenopathy strongly favors a self-limited viral process 1, 2.
Initial Management
Antibiotics should be withheld entirely, and only symptomatic therapy should be provided 1:
- Ibuprofen 400–600 mg every 6–8 hours or acetaminophen 650–1000 mg every 6 hours for pain and discomfort 1
- Adequate hydration 1
- Reassurance that symptoms typically resolve within 3–7 days without antibiotics 1, 2
No additional microbiologic testing is indicated at this time 1, 2. The negative rapid strep test is definitive in adults, and routine throat culture after a negative rapid test provides no clinical benefit and wastes resources 1.
Red Flags Requiring Urgent Reassessment
The patient should return immediately if any of the following develop:
- High fever (>101°F/38.3°C) 2
- Severe unilateral throat pain with trismus, suggesting peritonsillar abscess 2
- Difficulty swallowing or breathing 2
- Neck swelling or tenderness with pulmonary symptoms, raising concern for Lemierre syndrome 2
- Persistent or worsening symptoms beyond 7–10 days 1
Common Pitfalls to Avoid
- Do not prescribe antibiotics based on the presence of pharyngeal erythema or lymphadenopathy alone, as these findings occur in both viral and bacterial infections 1
- Do not order additional throat cultures or repeat strep testing unless new symptoms develop or the clinical picture changes significantly 1
- Do not test or treat asymptomatic roommates or close contacts, as up to one-third may be asymptomatic carriers and prophylactic treatment does not reduce subsequent infection rates 1
Expected Clinical Course
Viral pharyngitis is self-limiting and typically resolves within 3–7 days 1, 2. The patient's energy level should guide activity, and enforced bed rest is not necessary 4. If symptoms persist beyond one week or worsen, reassessment for alternative diagnoses or complications is warranted 1, 2.