Now I'm going to present our study titled Pulse Methylprednisolone vs. Dexamethasone in COVID-19, a multi-century cohort study. Hello everyone and welcome to the session. I am Atsuyuki Watanabe from Japan. I am working at a university hospital and participating in the internal medicine residency match this year. First of all, we have no conflicts of interest to declare. Corticosteroids have been widely used to treat COVID-19 patients requiring oxygen supplementation. While dexamethasone is the agent of choice, high-dose corticosteroids can be hypothesized to control fulminant immune system flare-ups. In this study, we sought to compare the effect of Pulse Methylprednisolone, MTP-Pulse therapy, to dexamethasone in treating COVID-19. We used a multi-century inpatient claim database involving over 350 acute care hospitals in Japan and identified adults who were hospitalized for COVID-19 between January 2020 and December 2021. Those who received 250 mg per day or more of MTP on admission day or the next day were included in the MTP-Pulse group, while those who received intravenous dexamethasone on admission day or the next day were included in the dexamethasone group. We performed a 1-to-1 propensity score matching using patient characteristics, baseline comorbidities, hospitalized periods, hospital size, and the treatments on the day of admission or the next day. First, we matched the whole cohort, and then at subgroup analysis, we used the same method and matched those who received mechanical ventilation on the day of admission or the next day and those who did not receive mechanical ventilation as well. For outcomes, we measured in-hospital mortality, hyperglycemia defined by insulin administrations on third hospital day or after, fungal infections, and length of hospital stay. Figure 1 shows the flowchart of patient selection. Finally, we included 1,202 patients in the MTP-Pulse group and 7,669 patients in the dexamethasone group. Figure 2 shows the baseline balance before and after matching. The orange dots denote standardized mean differences before matching, and the blue dots denote after matching. After matching, all covariates were well balanced between the two groups. We generated 1,197 propensity score matched pairs in which the median age was 62 years, females consisted of 30%, more than half had diabetes, and one-third had hypertension at baseline. On admission day or the next day, 15% received mechanical ventilation, 1% received ECMO, 44% received unfractionated heparin or low-molecular-weighted heparin, 10% received tocilizumab, and 10% received vasoactive agents such as norepinephrine, epinephrine, vasopressin, dopamine, and dopamine. MTP-Pulse therapy was associated with higher risks of in-hospital mortality, hyperglycemia, and longer hospital stay compared to dexamethasone. In the subgroup analysis, we generated 171 propensity score matched pairs who received mechanical ventilation on admission or the next day. Figure 3 shows that there was no substantial imbalance between the two groups after matching. MTP-Pulse was not associated with improved in-hospital mortality. Patients in the MTP-Pulse group tended to stay longer, though statistically not significant. In contrast, in those who did not receive mechanical ventilation on admission or the next day, MTP-Pulse was associated with higher risks of in-hospital mortality, hyperglycemia, fungal infections, and longer hospital stay. There were 1025 matched pairs with all covariates well-balanced. While MTP is recommended for acute respiratory distress syndrome, the effect of its high-dose therapy on COVID-19 has not been firmly established. Some studies showed improvements in biomarkers in patients receiving MTP-Pulse. The worst outcomes in the MTP-Pulse group in our study may be explained by the increased adverse effects of high-dose corticosteroids. Since it was an observational study, unmeasured confounding remains an issue. Also, our claimed database did not have laboratory data or ventilator settings. Therefore, a causal relationship should be determined with randomized trials. In contrast to the initial hypothesis, MTP-Pulse was not associated with improved mortality of COVID-19 compared to dexamethasone, even in patients on mechanical ventilation. Instead, it was associated with higher risks of mortality and adverse effects in patients not on mechanical ventilation. We conclude that providers should be aware of the potential benefit and risks of the type and dose of corticosteroids.

Atsuyuki Watanabe

Pulse Methylprednisolone

MTP-Pulse therapy

dexamethasone

COVID-19 treatment