Acute Hypoxemic Respiratory Failure with High Clinical Suspicion of COVID-19 Despite Negative PCR: a Case for Empiric Corticosteroids and Role of Serum Antibody in Diagnosis

Excerpt

HN cis a 39-year-old healthy male who worked as an essential worker in a healthcare setting. He first presented to clinic in November 2020 with 3 days of fatigue, myalgias, and chills after a high-risk encounter with a confirmed COVID-19-positive person. Nasopharyngeal samples for COVID-19 and influenza by PCR were collected and both were negative. Eight days after symptom onset, he returned to clinic with additional symptoms of dry cough and diarrhea. Again, his COVID-19 and influenza PCRs were negative. Ten days after symptom onset, the patient was admitted from clinic, at which time his exam was notable for decreased breath sounds at the bases and he had hypoxemia requiring 2 LPM of supplemental oxygen. A chest x-ray showed bilateral patchy infiltrates (Fig. 1). On admission, he had additional symptoms of shortness of breath, sore throat, nausea, and headache. Initial work-up was highly suggestive of COVID-19 pneumonia, with elevated inflammatory markers (D-dimer 317 ng/ml, ferritin 3,562 ng/ml, CRP > 300 mg/l), a white blood cell count of 8.1 k/cmm with normal differential, and a CT pulmonary angiogram that showed bilateral extensive patchy ground glass opacities without pulmonary emboli (Fig. 1). Because of high clinical suspicion of COVID-19, he was given a dose of dexamethasone, but the COVID-19 nasopharyngeal PCR collected in the emergency department was again negative. Pulmonology and infectious disease were consulted. Due to three negative COVID-19 PCRs, a work-up for alternative diagnoses was pursued, with the differential diagnosis including atypical bacterial pneumonia, viral pneumonia, eosinophilic pneumonia, heart failure, acute interstitial pneumonitis, and cryptogenic organizing pneumonia. While awaiting these results, the patient was started on azithromycin and ceftriaxone, but no further corticosteroids were given. Over the next 3 days of hospitalization, his shortness of breath and dry cough worsened. Fourteen days after symptom onset, his oxygen requirement increased from 2 to 5 LPM and a repeat chest x-ray showed worsening bilateral opacities. Thus far, the patient’s work-up was notable for a normal transthoracic echocardiogram, low procalcitonin, negative HIV, negative legionella PCR, negative respiratory viral panel, and a third negative influenza PCR. Due to lack of a diagnosis and worsening respiratory status, he underwent bronchoscopy with bronchoalveolar lavage (BAL) 15 days after symptom onset. On the day of bronchoscopy, his serum COVID-19 antibody that had been collected the previous day was reported to be positive. Although we were unable to be certain as to the chronicity of his infection, the positive serum antibody was believed to support a presumptive diagnosis of severe COVID-19 pneumonia and he was treated with corticosteroids. Cultures and stains of the BAL were negative for bacteria, fungi, mycobacteria, and pneumocystis. However, a PCR for SARS-COV-2 on the BAL came back positive, confirming a diagnosis of COVID-19 pneumonia. Corticosteroids were continued as dexamethasone 6 mg/day for 10 days and he was also given remdesivir. Over the next few days, he rapidly improved and was discharged home on hospital day 11, 21 days after symptom onset.

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