A 46-year-old patient of African ancestry with history of arterial hypertension and obesity (BMI = 36 kg / m2) was admitted to our hospital for hypertensive emergency (189/123 mmHg) and fever. He did not take any medication. Physical examination was normal. SARS-Cov2 PCR on naso-pharyngeal swab was negative (repeated twice), but COVID-19 serology was positive for IgG (80 UA/mL, positive if >12 UA/mL, Immunoassay YHLO iFlash 1800) and negative for IgM. No previous COVID-19 symptoms were reported and no personal treatment, neither self-medication nor toxic intake were noticed to the anamnesis. Thoracoabdomino-pelvic CT scan was unremarkable. First investigations revealed an inflammatory state, anaemia, thrombocytopenia and an acute kidney injury (AKI). Serum creatinine (sCr) level was 169 µmol/L associated with 1g per day proteinuria, aseptic pyuria, no hematuria and low natriuresis (< 20 mmol/L). C-Reactive protein (CRP) level was 312 mg/L and neutrophil count was 18.7 G/L (Table 1). On day 4, the patient presented evanescent facial erythema and developed acute myocardial dysfunction with reduced left ventricular ejection fraction to 40%, pericardial effusion and high sensitive Troponin (hsTroponin) elevation. Taking into account the frequency of vascular thromboses related to Covid-19 disease, a curative anticoagulant treatment with heparin was started. On day 5, neurological impairment appeared with coma leading to intubation and mechanical ventilation. Cerebrospinal fluid analysis was unremarkable. Abnormal supratentorial periventricular MRI signals responsible for a restriction of the diffusion testified to an acute vasculitis. No immunosuppressive treatment was introduced because of concomitant tracheal aspiration positive for Enterobacter Aerogenes treated with Trimethoprim-Sulfamethoxazole. On day 7, myocardial and renal function worsened (sCr 660 µmol/L), requiring initiation of Dobutamine and renal replacement therapy(RRT).
Renal biopsy light microscopy revealed typical lesions of TMA including fibrin thrombi within glomeruli and myxoid intimal alterations of arterioles and small-to-medium sized renal arteries. The remaining glomeruli were normal without hypercellularity. Significant interstitial infiltrate mainly composed of neutrophils responsible for severe tubulitis and moderate acute tubular necrosis were also present (Figure 1A). Immunofluorescence study showed isolated mesangial complement C3c positive deposits without evidence for IgG, IgA, IgM, C1q nor C4d deposits (Figure 1B). Immunochemistry study showed C5b-9 deposits at the same localization (Figure 1C). ADAMTS13 activity was normal (26 %), anticardiolipin, antiβ2GP1, lupus anticoagulant anti-DNA antibodies and Cryoglobulinemia were negative. Complement work-up evaluation found: serum C5b-9 469ng/mL (normal < 420ng/mL), C3 1030mg/L (normal ranges: 660-1250mg/L), C4 69 mg/l (93-380mg/L), CH50 64% (70-130%), no anti-factor H antibodies. Genetic complement studies are ongoing.
On day 8, specific complement inhibition with Eculizumab therapy (900mg) was initiated.
Three days later, cardiac function and neurological impairment improved, urine output increased and blood creatinine decreased, allowing to withdraw Dobutamine, RRT and mechanical ventilation (Table). On day 15, the patient received another course of Eculizumab (900mg). On day 30, patient was discharged from the hospital, sCr was 109µmol/L and cardiac MRI showed no pericardial effusion, no sequelae of segmental hypokinesia and ejection fraction of the left ventricle was evaluated at 50%.
