Case Presentation: This is a 50-year-old woman with a history of Rheumatoid Arthritis on Rituxan and methylprednisolone, COVID-19, MGUS, and recent admissions for bacterial pneumonia and fever of unknown origin who presented with fevers, rigors, and dizziness. Of note, she had tested positive for COVID-19 on 4/2020 via a nasopharyngeal swab, and states fevers began thereafter. All subsequent COVID-19 PCR testing was negative. Prior workup was negative for infectious etiology and CT Chest (from 06/2020) showed ground glass opacities with no source for infection. Further, bone marrow biopsy had no hematological neoplasm and rheumatological evaluations showed no rheumatoid arthritis flare.She was admitted for fever of unknown origin (FUO). The patient presented with spiking fevers to 101-103˚F. Physical exam was notable for clear lung with no rales or rhonchi. Lab results showed elevation of Ferritin to 800s and Erythrocyte Sedimentation Rate to 120. Other inflammatory markers (D-dimer, LDH, and CRP) were within normal limits. Urinalysis was positive for moderate leukocyte esterase. Transthoracic echocardiogram showed no vegetations and blood cultures were negative. CT Chest revealed interval increase in the bilateral ground-glass opacities. Per rheumatology recommendations, the patient was empirically started on methylprednisolone 12 mg twice daily for possible rheumatoid arthritis flare. However, she was not clinically improving and continued to require supplemental oxygen. Bronchoscopy with Bronchoalveolar lavage (BAL) was subsequently performed and was positive for COVID-19. She was started on a 5-day course of Remdesivir and received two doses of convalescent plasma. The patient stopped spiking fevers on hospital day 8. Treatment with methylprednisolone was tapered to 8 mg AM and 6 mg PM, with a plan to continue taper outpatient. Patient was discharged with outpatient follow up with rheumatology.
Discussion: Hospitalists frequently encounter febrile illnesses without a primary source of infection. FUO can be divided into several sources, including infectious, neoplastic, and non-infectious inflammatory [1]. It is defined as a T ≥38.3°C on at least two occasions and a duration of ≥3 weeks or multiple febrile episodes in this time [1]. Other causes are nosocomial, neutropenic, and HIV-associated, and treatment depends on the underlying pathology [1].Our patient demonstrates COVID-19 as a novel source of infectious FUO. Despite negative nasopharyngeal testing, hospitalists should be cognizant for the possibility of latent infection and/or colonization of COVID19 in the respiratory tract [2]. Due to atypical pulmonary symptoms and imaging, BAL was considered in our patient as the virus can present in the lower respiratory tract [3]. This allowed for diagnosis of COVID-19, which developed since antibodies were not produced to the initial infection likely due to immunosuppression [4]. Our patient clinically improved and remained afebrile after being treated with Remdesivir and convalescent plasma.
Conclusions: This case highlights the clinical significance of COVID-19 as a unique cause of FUO despite repeatedly testing negative with COVID19 PCR. For hospitalists who manage patients with atypical respiratory symptoms, it is crucial to consider re-infection with COVID-19 and/or respiratory tract colonization in the immunocompromised population despite negative PCR test results. Early recognition and prompt management with Remdesivir and convalescent plasma can be lifesaving.