Afebrile Presentation in Swine Flu and COVID-19 Despite Hydroxychloroquine Use
Yes, it is possible for a patient to remain afebrile despite having contracted swine flu and COVID-19 multiple times, even while taking hydroxychloroquine (Plaquenil). 1, 2
Factors Affecting Fever Response in Viral Infections
- Hydroxychloroquine has immunomodulatory properties that can potentially alter the normal inflammatory response, including fever, in patients with viral infections 1, 3
- The drug works by impairing autophagy and interfering with endosome-lysosome system acidification, which can modify the immune response to infections 4
- Hydroxychloroquine can decrease inflammatory cytokine secretion, which may reduce fever as a symptom of infection 3
Evidence Regarding COVID-19 and Fever
- Not all COVID-19 patients present with fever, and some may remain afebrile throughout their illness despite active infection 1
- In clinical trials, patients with confirmed COVID-19 have shown variable presentations, with some remaining afebrile despite laboratory-confirmed infection 2
- A 2023 study demonstrated that some COVID-19 patients remained asymptomatic (including afebrile) throughout their infection course despite having laboratory-confirmed positive tests 2
Hydroxychloroquine's Effect on Symptom Presentation
- Hydroxychloroquine has anti-inflammatory effects that can potentially mask typical symptoms of viral infections, including fever 1, 5
- The drug interferes with Toll-like receptor signaling and cytosolic sensors of nucleic acids, resulting in decreased cellular activation and lower inflammatory cytokine secretion 3
- These immunomodulatory effects may suppress fever response while not necessarily affecting viral replication 4, 3
Clinical Implications
- Absence of fever does not rule out active infection with influenza or COVID-19, particularly in patients taking immunomodulatory medications like hydroxychloroquine 5
- Hydroxychloroquine's variable pharmacokinetics between patients means its effects on symptom presentation can differ significantly between individuals 5
- While hydroxychloroquine was investigated as a potential COVID-19 treatment, current evidence does not support its use for this purpose, with the European Respiratory Society explicitly recommending against it 1
Important Caveats
- Relying on fever as a screening tool for COVID-19 or influenza may miss cases in patients taking hydroxychloroquine 3
- The immunomodulatory effects of hydroxychloroquine might potentially impair host immunity in response to SARS-CoV-2, especially in elderly patients or those with comorbidities 4
- Despite the absence of fever, patients on hydroxychloroquine may still experience other symptoms of viral infection and can transmit the virus to others 1, 2
In summary, the immunomodulatory properties of hydroxychloroquine can potentially suppress fever response in viral infections like COVID-19 and influenza, making it entirely possible for a patient to remain afebrile despite multiple infections 1, 4, 3.