This report describes a 26-year-old Caucasian female with no known past medical history who presented to the Piedmont Columbus Regional Midtown emergency department with a chief complaint of worsening shortness of breath and dyspnea on exertion. The patient was found to be positive for COVID-19 around 25 days before this admission. The patient reported that she had isolated herself for ten days during that time and that her symptoms had improved. However, one week before the current admission, she started experiencing worsening shortness of breath and cough with hemoptysis. These symptoms prompted her visit to an emergency department, where she was subsequently diagnosed with atypical pneumonia and discharged on doxycycline [100 mg orally every 12 hours for five days].
The patient continued to worsen and was subsequently found to have generalized malaise, severe fatigue, non-productive cough, myalgias, fever, decreased appetite, and hemoptysis in the current admission. The patient had no family history of bleeding disorders. Her vital signs on admission were the following: temperature, 100.8°F (38.2°C); blood pressure, 128/72 mmHg; heart rate, 122 beats per minute; respiratory rate, 35 breaths per minute; and oxygen (O2) saturation, 90% on room air, for which she required a 100% nonrebreather for oxygen support. An arterial blood gas (ABG) panel was performed and revealed the following: pH of 7.43; pCO2 of 32.9 mmHg; pO2 of 73.6 mmHg; HCO3 of 21.9 mmol/L. The patient had an elevated white blood cell (WBC) count of 11,200 cells/mcL [normal range, 4000–10500 cells/mcL], severe anemia with hemoglobin of 6.9 g/dL [normal range, 12.0–16 g/dL], hematocrit of 20.6% [normal range, 36.0–48.0%], and a platelet count of 432 103/mcL [normal range, 130–400 103/mcL]. The repeat COVID-19 test during this admission using the Xpert® Xpress SARS-CoV-2/Flu/RSV test (Cepheid®, Sunnyvale, California, United States) and the SARS-COV-2 Immunoglobulin G (IgG) antibody were positive, which indicated that she was in the late stage of the infection.
The chest computed tomography (CT) scan was negative for pulmonary embolism (PE). However, it revealed extensive bilateral ground-glass opacities with confluent densities suggestive of multifocal pneumonia. Consequently, pulmonology and infectious diseases were consulted for evaluation and management. The patient was started on community-acquired pneumonia (CAP) treatment with ceftriaxone [1 g intravenously (IV) every 24 hours for five days] and azithromycin [500 mg IV every 24 hours for three days]. Additionally, there was strong suspicion for diffuse alveolar hemorrhage (DAH), most likely due to a COVID-19-associated vasculitis process, for which methylprednisolone [250 mg IV four times per day] was started.
A series of serologic tests were ordered to investigate the cause of DAH. The patient was found to be positive for perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA) [1:40 Titer; normal range, < 1:20 Titer]. She was also found to be negative for antinuclear antibody (ANA), anti-double-stranded deoxyribonucleic acid (anti-dsDNA), and cyclic citrullinated peptide (CCP) antibodies. Additionally, her total complement (CH50) was 49 U/mL [normal range, 31–60 U/mL], her C3 complement was 141 mg/dL [normal range, 90–180 mg/dL], and her C4 complement was 16 mg/dL [normal range, 10–40 mg/dL]. Based on these serologic findings, the patient was thought to have microscopic polyangiitis.
At the time of discharge, the patient had an oxygen saturation of 96% on room air and a respiratory rate of 18 breaths per minute with no evidence of ongoing hypoxia. The patient was prescribed a tapering course of prednisone [40 mg orally twice daily for five days, then 30 mg orally twice daily for five days, then 20 mg orally twice daily for five days, then 10 mg orally twice daily for five days, then 10 mg orally once daily for five days] and advised to follow up with both pulmonology and her primary care physician.
Three days after discharge, the anti-glomerular basement membrane (anti-GBM) antibodies were found to be positive [4.5 AI; normal range, < 1.0 AI]. In addition, the urinalysis (UA) obtained during admission confirmed the presence of blood and protein. The patient was informed about the positive results and advised to schedule an appointment with a nephrologist for further assessment.
A renal biopsy was obtained during her visit with the nephrologist. The renal parenchyma available for light microscopic examination was represented by approximately 90% cortex and 10% medulla. Forty-eight glomeruli were present, none of which were globally sclerotic. Two glomeruli showed segmental rupture of the capillary loops associated with fibrinoid necrosis of the glomerular tuft and cellular crescent formation. Twenty-six additional glomeruli showed areas of segmental glomerulosclerosis, eleven of which were associated with fibro-cellular crescents and fifteen with fibrous crescents. The twenty uninvolved glomeruli showed no mesangial or endocapillary hypercellularity. The findings of the light microscopy can be seen in Fig. 1a and Fig. 1b.
The renal parenchyma available for immunofluorescence studies was entirely represented by cortex and contained nine glomeruli, none of which were globally sclerotic. The sections were stained for IgG, IgM, IgA, C3, complement 1q (C1q), albumin, fibrinogen, kappa, and lambda light chains. In addition, there was focal intense fibrinogen staining within the glomerular tuft. Additionally, there was mild mesangial finely granular staining for IgA (trace), IgG (2+), kappa (2+), and lambda (1+). All other stains were negative within the glomeruli. The findings of the immunofluorescence studies can be seen in Fig. 2a and Fig. 2b.
Based on the serology results mentioned above and the renal biopsy findings, the patient was determined to be having ANCA-associated vasculitis with glomerulonephritis and was started on methylprednisolone [500 mg IV daily for three days], followed by rituximab [375 mg/m2 IV once weekly for four weeks].