On February of 2020, a 76-year-old woman was referred to our hospital in Matsumoto, Japan, from another hospital in Japan, where she was admitted for sore throat, dry cough, and fever that started on February 7, 2020 (symptom onset day 1; SOD#1). (The term "symptom onset day" is used to illustrate the patient's clinical course, and the term "hospital day" is used to describe treatment measures.) Past medical history was significant for diabetes mellitus, hypertension, and glaucoma, but she was otherwise healthy and did not smoke. The patient, an American living in the United States, was visiting Japan and arrived at Yokohama Harbor aboard the Diamond Princess cruise ship. Due to a COVID-19 outbreak inside the cruise ship, she was kept in the cruise ship and underwent viral testing as part of quarantine inspection. A reverse transcription polymerase chain reaction (RT-PCR) test, performed by the Japan Ministry of Health, Labour and Welfare, produced a positive result for SARS-CoV-2.
One day before admission to our hospital, the patient was started on lopinavir-ritonavir (400 mg/100 mg twice daily orally) and moxifloxacin (400 mg once a daily orally). She was transferred to our hospital on SOD#12 (hospital day 1; HD#1). On admission, her body temperature was 38.3  C, and her oxygen saturation (SpO2) by pulse oximetry was 93% on 8 L/min of supplemental oxygen via mask. Physical examination revealed coarse crackles in the upper chest on the right. Laboratory examination revealed peripheral blood lymphopenia (350/muL) and elevated levels of blood urea nitrogen (BUN, 28.9 mg/dL), creatinine (1.62 mg/dL), C-reactive protein (CRP, 12.90 mg/dL), and lactate dehydrogenase (LDH, 325 U/L) (Table 1).
Chest computed tomography (CT) images showed ground-glass opacities (GGOs) and consolidation (Fig. 1A and B).
Due to possible community-acquired pneumonia caused by bacteria and influenza virus, the patient was treated with piperacillin-tazobactam and peramivir (at a loading dosage of 300 mg, reduced to 150 mg every 24 hours due to renal failure). Her respiratory failure progressed, leading to endotracheal intubation. An endotracheal aspirate obtained through the intubation tube was positive for SARS-CoV-2 on RT-PCR. Laboratory examination revealed a low gamma-globulin level on HD#3 (SOD#14); intravenous immune globulin (IVIG) (at a dosage of 5000 mg every 24 hours intravenously) was administered from HD#3 (SOD#14) to HD#8 (SOD#19).
On HD#8 (SOD#19), the patient's respiratory status progressively deteriorated; she exhibited dyspnea despite fever alleviation. The respirator setting at the time was assist/control (volume-controlled ventilation), tidal volume was 300 ml, positive end-expiratory pressure (PEEP) was 14 cmH2O, and respiratory frequency was 13 per minute. Her hypoxemia was not improved even if we regulated PEEP. We considered whether this deterioration might be due to increased airway dead space caused by pulmonary embolism or acute pulmonary edema; however, these diagnoses could not be confirmed with evidence on chest CT scans, which were unobtainable because there was concern about the risk of infecting other patients in the radiology unit. We conducted a compression ultrasound, but were not able to point out deep vein thrombosis. The patient's respiratory status continued to worsen and, despite optimal ventilator settings, we were unable to maintain her PaO2/FiO2 above 70 torr. Therefore, we decided to proceed to venous-venous extracorporeal membrane oxygenation (V-V ECMO) on HD#8 (SOD#19). For V-V ECMO, venous catheters were placed in the right common femoral vein (for drainage) and right internal jugular vein (for infusion). Her hemodynamics were maintained using vasoactive agents; we were able to normalize her body water with diuretics and stabilize her oxygenation by ECMO. On HD#16 (SOD#27), to prevent bacterial infection related to catheterization, the previous antibiotics were replaced with vancomycin. Her respiratory status gradually improved. On HD#16 (SOD#27), viral testing of an endotracheal aspirate sample showed that SARS-CoV-2 was undetectable using RT-PCR. A tracheotomy was performed on HD#18 (SOD#29); ECMO was discontinued on HD#19 (SOD#30). Intravenous meropenem was administered for ventilator-associated pneumonia (VAP) prophylaxis.
Chest CT scans obtained on HD#22 (SOD#33) showed enlarged abnormal shadows, GGOs, and consolidation in the upper lobe of the right lung, suggesting organizing pneumonia (Fig. 1C and D), which could result in chronic respiratory failure after ECMO cessation. On HD#25 (SOD#36), the patient was started on methylprednisolone 250 mg daily for three days with improvement of her organizing pneumonia on chest x-ray (Fig. 2E and F). On HD#40 (SOD#51), the patient was taken off the respirator, and her condition was stable.
Chest computed tomography (CT) images. (C-D) Images taken on SOD#33. (D) Posterior consolidation with air bronchogram in the posterior segments of the lower lobes of both lungs.