Case Report
In April 2020, a 69yearold man with a history of type 2 diabetes and high blood pressure presented with five days of dry cough and fever. A polymerase chain reaction (PCR) test for SARSCoV2 on nasal swabs was positive, and the patient was diagnosed with COVID19. On the eighth day after onset, he was admitted to the COVID19 ward of our hospital.
On admission, he presented with a body temperature of 37.6°C, and 2 L/min oxygen via nasal cannula was started because his oxygen saturation (SpO2) was 89% on room air. Computed tomography (CT) scan of the chest revealed bilateral patchy groundglass opacity (GGO) consistent with COVID19 pneumonia (Fig. ). Laboratory tests showed a white blood cell count (WBC) of 3700/μL (lymphocyte 1010/μL), and Creactive protein (CRP) was 8.7 mg/dL, ferritin was 4000.0 ng/mL, and ddimer was 1.17 μg/mL. Antiviral therapy with favipiravir was started on hospital day 1 (eighth day after symptom onset), with a firstday dose of 1800 mg twice, and then 800 mg twice a day for two weeks.
On day 4 (11th day after symptom onset), sudden dyspnoea and oxygen saturation drop required an oxygen supplementation increase up to 8 L/min using a face mask. Laboratory tests showed an elevation of inflammatory markers: CRP was 21.5 mg/dL, ferritin was 7735.0 ng/mL, and ddimer was 1.81 μg/mL. Xray revealed bilateral deterioration with GGO (Fig. ). Highdose corticosteroid (methylprednisolone 1 g/day for three days) and ceftriaxone antibiotics were administered. Nevertheless, the patient's clinical condition, including oxygenation, worsened despite a slight decrease in CRP. On day 6 (13th day after symptom onset), 5 h of PMXDHP therapy was initiated to address the hyperinflammation. Post PMXDHP, the oxygenation and blood inflammation markers, including serum ferritin, were significantly improved. The progression to ARDS was halted and the need for intubation and mechanical ventilation was avoided. Serum ferritin levels promptly decreased to 2132 ng/mL after PMXDHP. Chest Xray showed that the bilateral infiltration gradually improved after PMXDHP (Fig. ). No supplementary oxygen was required on day 19 (26th day of onset). The patient fully recovered from COVID19 symptoms and was discharged home after a 30day hospitalization.
COVID19 causes a spectrum of diseases ranging from mild symptoms (~80%) to respiratory failure (~20%), ARDS, and multiple organ failures. The leading causes of death are cytokine storm syndrome and ARDS, and 50% of patients with cytokine storm syndrome subsequently develop ARDS. Although the precise pathogenesis of severe COVID19induced ARDS remains unclear, hyperferritinaemia, which is categorized as hyperinflammation, is associated with severity and poor outcomes in COVID19 [1, 2]. Hyperinflammation is defined as follows: CRP concentration greater than 15 mg/dL; a doubling of CRP concentration within 24 h from a concentration of greater than 5 mg/dL; or a ferritin concentration of greater than 1500 ng/dL [1]. Ferritin levels at admission in COVID19 nonsurvivors were reported to be around 1400 ng/mL [3]. In the present case, even when concomitant treatment with an antiviral agent and highdose corticosteroid were administered, serum ferritin levels were elevated (up to 7735 ng/dL) and no improvement in oxygenation was observed. We speculated that COVID19associated hyperinflammation or hypercytokinaemia induced severe respiratory failure, which could progress to ARDS. Next, we introduced DHP with PMX in order to remove inflammatory cytokines or mediators. Oxygenation and hyperferritinaemia were improved immediately after PMXDHP therapy. PMX was originally developed for the removal of endotoxins and is used to treat endotoxaemia. Recent reports have demonstrated the beneficial effect of PMX in severe influenza pneumonia, including both 2009pH1N1 and H5N1 [4, 5]. Hypercytokinaemia induced by 2009pH1N1 influenza was reported to be successfully treated with PMX, suggesting the potential efficacy of PMX to address hyperinflammation [4]. The removal of inflammatory mediators by PMX appears to be a promising treatment in patients at risk of developing ARDS due to COVID19.
In conclusion, we report the first case of COVID19induced hyperferritinaemia and severe respiratory failure successfully treated with PMX, which decreased the inflammatory markers and improved oxygenation. As a result, the patient's progression to ARDS was halted and the need for mechanical ventilation was avoided. Further studies are needed to determine the optimal timing of PMX in the disease course and its indication based on clinical parameters including hyperferritinaemia.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604553/