Steroid Pulse Therapy as a Treatment for Patients With COVID-19 Pneumonia at an Intensive Care Unit: A Single-Center Retrospective Observational Study.

BACKGROUND: Evidence supporting the use of steroid pulse therapy in severely ill patients with coronavirus disease 2019 (COVID-19) pneumonia is lacking. Few studies have evaluated the efficacy of high-dose (1000 mg/day) methylprednisolone (mPSL), which is commonly used in Japan. AIM: This study aimed to compare the clinical outcomes with and without steroid pulse therapy (mPSL 1000 or 500 mg/day for three days) in patients with COVID-19 pneumonia, admitted to an intensive care unit (ICU). METHODS: Study design was retrospective observational study. The inclusion criterion was severe to critically ill adult patients with COVID-19 pneumonia requiring ICU admission. The exclusion criteria were as follows: patients (1) with a "Do not attempt to resuscitate" order; (2) with a "Do not intubate" order; or (3) admitted to the ICU owing to other infectious diseases were excluded. Treatment strategy was as follows: Patients were divided into two groups: steroid pulse therapy (Group P) and steroids without pulse therapy (Group NP). Group P received mPSL 1000 or 500 mg/day on ICU days 1-3, and Group NP received dexamethasone 6.6 mg or mPSL 1 or 2 mg/kg/day. The primary outcome was 28-day mortality. RESULTS: We enrolled 82 patients. Out of 70 who met the inclusion criteria, 48 and 22 were included in Groups P and NP, respectively. No difference in 28-day survival was observed between the Groups P and NP (log-rank P=0.11). After adjusting for covariates (age, sex, interleukin-6 level, and acute physiology and chronic health evaluation II score on ICU admission) using a multivariate Cox proportional hazard model, treatment with steroid pulse therapy significantly improved 28-day mortality (hazard ratio, 0.14; 95% confidence interval, 0.02-0.86; P=0.03). CONCLUSION: Steroid pulse therapy may improve the 28-day mortality in patients with COVID-19 pneumonia in the ICU.

Intravenous methylprednisolone pulse therapy and the risk of in-hospital mortality among acute COVID-19 patients: Nationwide clinical cohort study.

BACKGROUND: Steroids are widely used to modulate the inflammatory reactions associated with coronavirus disease 2019 (COVID-19); however, the optimal upper limit dose of steroid use for acute COVID-19 care remains unclear and currently available data may suffer from a time-dependent bias of no effectiveness or reversed causation given the desperate situation of treatment during this pandemic. Accordingly, the aim of this study was to elucidate the impact of intravenous pulse therapy with methylprednisolone (500 mg or greater per day) on the risk of in-hospital mortality among patients with COVID-19 by controlling for time-dependent bias. METHODS: We performed a prospective cohort study with 67,348 hospitalised acute COVID-19 patients at 438 hospitals during 2020-2021 in Japan. The impact of intravenous methylprednisolone pulse therapy on the risk of in-hospital mortality was examined based on hazard ratios (HRs) and 95% confidence intervals (95% CIs), with stratification according to the status of invasive mechanical ventilation (iMV). Time-dependent bias was controlled for in a marginal structural model analysis, with reference to patients without methylprednisolone therapy. RESULTS: During the study period, 2400 patients died. In-hospital mortality rates of iMV-free patients without or with methylprednisolone pulse therapy were 2.3% and 19.5%, and the corresponding values for iMV-receiving patients were 24.7% and 28.6%, respectively. The marginal structural model analysis showed that intravenous pulse therapy with methylprednisolone was associated with a lower risk of in-hospital mortality among patients receiving-iMV (HR 0.59; 95% CI 0.52-0.68). In contrast, pulse therapy with methylprednisolone increased the risk of in-hospital mortality among iMV-free patients (HR 3.38; 95% CI 3.02-3.79). The benefits of pulse therapy for iMV-receiving patients were greater than in those treated with intermediate/higher doses (40-250 mg intravenously) of methylprednisolone (HR 0.80; 95% CI 0.71-0.89). CONCLUSION: The results of our study suggest that intravenous methylprednisolone showed dose-response efficiencies, and pulse therapy may benefit critically ill patients with acute COVID-19, such as those requiring iMV.

Methylprednisolone pulse therapy for critically ill patients with coronavirus disease 2019: A single-center retrospective observational study.

Aim: This study compared the clinical outcomes of critically ill patients with coronavirus disease (COVID-19) pneumonia treated with high-dose methylprednisolone and other steroids. Methods: This retrospective observational study included critically ill COVID-19 pneumonia adult patients with tracheal intubation treated between April 1, 2020, and September 15, 2021. Of the 46 patients who met the inclusion criteria, 36 received steroid pulse therapy (Group P) and 10 received steroids without pulse therapy (Group NP). Subgroup analyses in Group P by methylprednisolone dose of 1000 or 500 mg for 3 days during intensive care unit stay were carried out. The primary and secondary outcomes were 28-day mortality and steroid-associated complications, respectively. Results: In the Kaplan-Meier curve analysis, there was no difference in the 28-day survival between P and NP groups (log-rank P = 0.046). Univariate Cox proportional hazard model also showed that Group P had a decreased 28-day mortality (hazard ratio 0.30; [95% confidence interval, 0.20-0.44]; P < 0.01). After adjusting for covariates (age, sex, remdesivir, baricitinib, and favipiravir), using the multivariate Cox proportional hazards model, Group P had improved 28-day mortality (0.50 [0.30-0.85], P = 0.01). Conclusion: Steroid pulse therapy might improve the 28-day and in-hospital mortality in critically ill patients with COVID-19 pneumonia.

Successful treatment with steroid pulse therapy for a COVID-19 case with progressive respiratory failure during treatment for pleural metastasis of breast cancer.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients are at high risk for developing severe conditions if other comorbidities are present, such as advanced cancer. Although the regulation of immune response is thought to play an important role in the treatment of coronavirus disease 2019 (COVID-19), physicians often have difficulties in selecting the most appropriate treatment. Furthermore, the impact that interrupting breast cancer treatment due to a COVID-19 infection has on patient outcomes is still unknown. Herein we report a case of advanced breast cancer in a patient whose COVID-19 acute respiratory failure was successfully treated with minimal interruption to their anticancer therapy for recurrent breast cancer. CASE PRESENTATION: A 48-year-old woman developed carcinomatous pleurisy after curative surgery for breast cancer. One month after the initiation of targeted therapy with palbociclib and fulvestrant, the pleural effusion decreased, but soon after she developed a COVID-19 infection. Dexamethasone (8 mg/day) was administered due to a prolonged fever, but her respiratory symptoms got worse and pneumonia appeared on a computed tomography (CT) scan 7 days after hospitalization. Thus, steroid pulse therapy (methylprednisolone 1000 mg/day) was administered for 3 days. Her respiratory condition rapidly improved. Two weeks after hospital discharge, complete regression of pneumonia was confirmed on CT scan, and her targeted therapy was resumed at the same dose and strength. More than 6 months later, her metastatic disease remains stable while on the same treatment. Retrospective analysis of the patient's neutralizing antibodies found the neutralizing activity was low in the early stages of infection, but became high after recovery. This suggests the patient acquired an immunity to SARS-CoV-2 through the infection, despite having a mild myelosuppression due to treatment for recurrent breast cancer. CONCLUSIONS: Steroid pulse therapy is available worldwide, and may have an important role in cancer patients who develop severe pneumonia from SARS-CoV-2, by enabling them to avoid any long-term disruption to anticancer therapy. Moreover, it might also be useful when antiviral therapies lose their efficacy due to mutations of the virus, such as the Omicron variant. A critical element in cases such as this one is that treatment decisions are made by a team of specialists, including pulmonologists.

Fulminant myocarditis after the second dose of COVID-19 mRNA vaccination.

Myocarditis is an adverse event associated with coronavirus disease 2019 (COVID-19) mRNA vaccination. A 50-year-old man presented with dyspnea and resting chest pain after receiving the second dose of the COVID-19 mRNA vaccine and developed cardiogenic shock. Fulminant myocarditis was diagnosed by endomyocardial biopsy and treated with intravenous corticosteroids.

A case of effective intravenous methylprednisolone pulse therapy against severe COVID-19 infection after arteriovenous graft surgery.

Perioperative COVID-19 infections in patients suffering from end-stage renal disease (ESRD) are more likely to become severe, with a high mortality rate, than those in other patients. For such patients, corticosteroid therapy is one of the limited number of treatment options. We experienced a case of ESRD in which COVID-19 infection immediately followed arteriovenous graft surgery. Although the respiratory condition deteriorated following dexamethasone administration, requiring invasive mechanical ventilation, intravenous methylprednisolone pulse therapy (pulse therapy) improved it dramatically, suggesting that pulse therapy may be effective against severe COVID-19 infection in patients suffering from ESRD.

Clinical efficacy and safety of combination therapy of tocilizumab and steroid pulse therapy for critical COVID-19 in HD patients.

BACKGROUND: Critical coronavirus disease 2019 (COVID-19) has a high fatality rate, especially in hemodialysis (HD) patients, with this poor prognosis being caused by systemic hyperinflammation; cytokine storms. Steroid pulse therapy or tocilizumab (TCZ) have insufficient inhibitory effects against cytokine storms in critical cases. This study evaluated the clinical effects and safety of combining steroid pulse therapy and TCZ. METHODS: From September 2020 to May 2021, 201 patients with COVID-19 were admitted to our hospital. Before February 2021, patients with an oxygen demand exceeding 8 L/min were intubated and treated with standard therapy (dexamethasone and antiviral therapy). After February 2021, patients underwent high-flow nasal cannula oxygen therapy and were treated with TCZ (8 mg/kg) and methylprednisolone (mPSL) (500 mg/day [≤ 75 kg], 1000 mg/day [> 75 kg]) for 3 days. We compared background characteristics, laboratory findings, and prognosis between non-HD and HD patients and between patients who received and did not receive TCZ and mPSL pulse therapy. RESULTS: Among non-HD patients, the TCZ + mPSL pulse group had significantly higher survival rates and lower secondary infection rates (p < 0.05), than the standard therapy group. All HD patients in the standard therapy group with oxygen demand exceeding 8 L/min died. Contrastingly, all patients in the TCZ + mPSL pulse group survived, with their oxygen demand decreasing to 0-1 L/min within 3 weeks post-administration. CONCLUSION: TCZ combined with mPSL pulse therapy improved the survival rate without significant adverse events in critical HD and non-HD patients with COVID-19 by strongly suppressing systemic hyperinflammation.

Successful treatment with methyl-prednisolone pulses for the late phase of COVID-19 with respiratory failure: A single-center case series.

Although some prospective studies provided the evidence of corticosteroids for critically ill patients with COVID-19, the optimal dosage or timing of corticosteroids is still unknown. This is a case series of four patients on methyl-prednisolone pulses for the late phase of Coronavirus disease 2019 (COVID-19) with respiratory failure in our hospital. All patients needed invasive mechanical ventilation and had bimodal worseness of their respiratory status with consolidation and volume loss after intubation. All cases could successfully discontinue oxygen therapy without any severe adverse events after this pulse therapy in the late phase of COVID-19. This therapy is believed to be effective on some optimal patients. Hence, further studies to explore this efficacy and safety were needed.