Methylprednisolone

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An event is serious (based on the ICH definition) when the patient outcome is:

• * death

• * life-threatening

• * hospitalisation

• * disability

• * congenital anomaly

• * other medically important event

A 49-year-old woman developed worsening of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection during off-label treatment with methylprednisolone for SARS-CoV-2 infection [not all dosages, routes and outcomes stated].

The woman presented with fatigue and fever on 22 January 2020. She had close contact with the SARS-CoV-2 infected patient. A lung CT revealed single ground-glass opacities present in the outer zone of her right lower lobe. At admission, she had received off-label antiviral treatment with oseltamivir 75mg twice daily for 5 days and antibacterial therapy with moxifloxacin 0.4g once daily for 15 days. She also received diclofenac as antipyretic therapy. On 25 January 2020, she developed vomiting and dry cough. On 25 and 27 January 2020, her lung CT showed ground-glass opacities progressively increased in both lobes of lungs. In view of her close contact with her SARS-CoV-2-infected cousin, a nasopharyngeal swab was taken. Subsequently, she started receiving off-label treatment with interferon-α-2b inhalation 5 × 10⁶IU twice daily for 17 days as antiviral, azithromycin 0.5g once daily for 3 days as antibacterial and methylprednisolone 80mg once daily for 13 days as anti-inflammatory therapy. After this treatment regime, she developed a severe cough, high fever and dyspnoea. Her blood gas analysis showed hypoxaemia. On 28 January 2020, she tested positive for SARS-CoV-2 infection.

Hence, the woman was shifted to the airborne-isolation unit. Subsequently, she started receiving off-label treatment with lopinavir/ritonavir 400mg/200mg twice daily for 19 days, along with the continuation of interferon-α-2b and moxifloxacin. She also received ibuprofen for fever. She was initiated on nasal catheter oxygen inhalation therapy. Her body temperature became normal, but dyspnoea and severe cough persisted. She had a further decrease in PaO₂, arterial oxygen saturation (SaO₂) and oxygenation index levels on 01 Feb 2020. On the same day, her oxygen therapy switched to mask for oxygen inhalation, but her hypoxaemia persisted. On 04 Feb 2020, a lung CT scan revealed >75% of her lungs filled with multiple, diffuse ground-glass opacities, along with partial consolidation. Her PaO₂ was 47.1mm Hg, SaO₂ was 86.9% and the oxygenation index was 78.5mm Hg. Therefore, she had received high-flow nasal cannula oxygen therapy with no improvement of hypoxaemia. On 07 February 2020, she also received non-invasive mechanical ventilation therapy with no effect. On 10 February 2020, she was transferred to the ICU, and subsequently, she was intubated and received small tidal volume positive end-expiratory pressure ventilation in VC mode. Additionally, her antibiotic regimen was changed to meropenem and linezolid. She also received off-label antiviral treatment with umifenovir [arbidol] 0.2g thrice daily for 5 days and intravenous immune-globulin 20g once daily for 4 days for immune regulation. Afterwards, she was rolled over in the prone position, but her oxygenation did not improve. Hence, on 12 February 2020, extra-corporeal membrane oxygenation (EMCO) was initiated. Subsequently (by 15 February 2020), her fever subsides and oxygenation improved. On 17 February 2020, a lavage fluid from bronchofiberscopy showed positive results for hyphae and fungal spores. Cultures showed the existence of Candida albicans, which was sensitive to voriconazole. Hence, she started receiving voriconazole on 19 February 2020. On the same day, meropenem was changed to piperacillin/tazobactam. On 26 February 2020, due to concerns of ECMO-related infections, piperacillin-tazobactam was replaced by daptomycin. On 19 and 21 February 2020, she had received plasma 200mL from convalescent COVID-19 patients with neutralising antibody above 1:640. Her nasopharyngeal swab specimens showed negative results for SARS-COV-2 infection. A dynamic chest-x-ray indicated absorption of pulmonary lesions. On 23 February 2020, her ventilator and endotracheal tube were removed. On 26 and 29 February 2020, she had received 100mL of stem cells from umbilical cord blood. At the same time, her heart, kidney and liver function became normal, and symptoms relieved. Her CRP and lymphocyte count returned to normal. On 02 March 2020, ECMO stopped, and on 06 March 2020, antibiotic therapy was discontinued. The lung CT scan showed most of her ground-glass opacities were absorbed, while some lesions changed to fibrosis with bronchial dilatation and traction. She also received psychological counseling with pulmonary rehabilitation exercises and assisted ambulation. Her oxygen saturation was above 95%. On 14 March 2020, she was discharged from the hospital. At follow-up, fibrosis lesions nearly disappeared. On 05 May 2020, her lung functions were normal, and she was able to tolerate her daily activities. It was determined that her therapy with methylprednisolone might have contributed to rapid progression of SARS-CoV-2 infection.