Breakthrough of False Negative: A Case of Protracted H1N1 Influenza with Chest Pain Onset Implications for The Diagnosis and Treatment of Encapsulated Empyema

<p>Background: Influenza A (H1N1) infection usually has a self-limiting course (5–7 days), but some patients may progress to severe pneumonia or complications, resulting in a significantly prolonged course of the disease. This case reports a special case of protracted H1N1 infection lasting more than one month. The patient presented with persistent chest pain (>1 month) as the initial symptom. The preliminary diagnosis was "encapsulated empyema." The results of multiple PCR tests on respiratory samples (swabs from the throat and sputum) in the early stage of fever were negative, masking the existence of the disease, and secondary bacterial mixed infections occurred. Through targeted next-generation sequencing (tNGS) of bronchoalveolar lavage fluid (BALF), it was finally confirmed as H1N1 virus infection. This highlights the crucial diagnostic value of lower respiratory tract sample testing in overcoming false negatives in upper respiratory tract testing. Further analysis revealed that the patient's weakened immunity might be a new risk factor for protracted influenza, providing clinical implications for the delayed initiation of antiviral treatment and the management of encapsulated empyema.<br>Case Presentation: This article reports a 49-year-old male patient who had a history of gastric perforation surgery and appendicitis surgery. He was admitted to the hospital with chest pain for more than 1 month and fever for 2 days. The final diagnosis was influenza A (H1N1) combined with purulent pleural effusion caused by Fusobacterium nucleatum and Klebsiella pneumoniae infection. The patient initially presented with a large amount of encapsulated pleural effusion on the right side. Empirical use of "ceftriaxone" for 5 days of anti-infection treatment was ineffective. The pleural fluid tNGS indicated "Fusobacterium nucleatum sequence number 9, relative abundance 49.9%." Subsequently, the treatment was adjusted to "piperacillin-tazobactam" for 3 days. The patient no longer had fever, but on the 18th day of treatment, the patient had a fever again. The re-examination of nasopharyngeal swabs for influenza A and B antigens was all "negative." The treatment continued with "piperacillin-tazobactam." On the 21st day, the patient still had a fever. Bronchoalveolar lavage fluid tNGS indicated "influenza A virus H1N1 sequence number 1344, relative abundance 76.2%, Klebsiella pneumoniae sequence number 50, relative abundance 0.3%." On the 22nd day, oseltamivir was added for antiviral treatment for 1 day. The fever was controlled, and the patient's condition improved and was discharged. On the 29th day of follow-up after discharge, the patient's pulmonary infection and pleural effusion had significantly absorbed.<br>Conclusion: This case suggests that for patients with refractory pleural effusion and repeated fever, the possibility of mixed viral and bacterial infection should be considered. When traditional respiratory tract tests are negative, molecular techniques such as BALF tNGS should be actively adopted to clarify the etiological diagnosis and guide precise treatment.</p>