A total of 49 patients had a positive COVID-19 test during this period. In the outbreak described here which occurred in a non-urban area at the height of the Omicron surge, no additional acute care capacity was available in the vicinity after the first two patients were transferred, which necessitated management of the additional patients on site. At the time, the Japanese government had just included short-course remdesivir as a treatment option in its COVID-19 management guideline. Since remdesivir was the only COVID-19 agent that was readily available without restrictions, patients were treated with this agent as soon as they developed symptoms consistent with COVID-19 and the diagnosis was confirmed by a positive test. Thirty-four of them were on the rehabilitation ward, and 15 of them were on the palliative care/internal medicine ward. Three of them did not receive remdesivir and were excluded from the analysis. The reasons for not receiving remdesivir were immediate transfer to an acute care hospital (2 patients) and impaired renal function (1 patient). The remaining 46 patients who received at least one dose of remdesivir constituted the cohort for this study. The demographics and remdesivir therapy administered are described in Table 1 . The median age was 75, and 41 had received at least one dose of mRNA vaccine. While the timing of vaccination was unknown, most of them likely received the doses more than six months earlier, since the age group (60 years old and greater) was largely vaccinated by the end of July 2022 in Japan. However, none had received the third dose. The median Charlson comorbidity index was 6, which corresponds to an estimated background 10-year survival of 2%. Documented COVID-19-related symptoms included fever (39 patients), sore throat (17 patients), cough (17 patients), headache (5 patients) and fatigue (2 patients). Based on the COVID-19 severity classification system adopted in Japan, 34 patients had mild disease (i.e. not requiring supplemental oxygen), 12 patients had moderate disease (i.e. requiring supplemental oxygen), and none had severe disease (i.e. requiring mechanical ventilation). Only one patient was asymptomatic. In all except one patient, remdesivir was started within 2 days from the symptom onset (positive test in the case of the one asymptomatic patient) and administered for a median of 3 days.
The median time from onset to resolution of symptoms was 4 days (IQR, 2-7). Two patients were discharged prior to 14 days, and an additional 3 patients were discharged prior to 28 days. Of the patients followed up to 14 and 28 days from onset, 41/44 (95.3%) and 35/41(85.4%) were alive, respectively. All 6 deaths occurred among patients on the palliative care/internal medicine ward who had advanced malignancy (lung cancer [2], pancreatic cancer [2], colon cancer [1], renal cancer [1]). Additionally, two and one patients had history of diabetes and stroke, respectively. They all developed moderate disease, with SpO2 at room air ranging between 86 and 94%. Two of these deaths were possibly related to COVID-19, where one patient had cardiac arrest of undetermined cause and the other patient expired from respiratory failure. The remaining 4 deaths were deemed to have been due to underlying illnesses and unrelated to COVID-19. Specifically, all patients who died were both age 70 or greater and had malignancy (Fig. 1 ). While information is limited in the literature, COVID-19 in inpatient palliative care settings has been associated with extremely high mortality. In contrast, all patients on the rehabilitation ward were alive at 28 days.
Even when these vulnerable patients survive COVID-19, cognitive and functional decline is commonly observed. In this cohort, the median performance status score was 3 at onset, 14 days and 28 days (Table 2 ). Most patients maintained the same performance score over the course of 28 days, and none of the surviving patients had a decline in the performance status score of greater than one. This suggests that the negative impact on the functional levels of those who survived the infection was minimal.
In terms of safety, short-course remdesivir was generally well tolerated. Three patients developed transient liver function test abnormalities, one patient developed transient renal function abnormality, and one patient had itching at the infusion site.
Institutional outbreaks in non-acute care settings have accounted for a significant portion of morbidity and mortality over the course of the COVID-19 pandemic thus far, including in Japan. Vaccination has dramatically reduced the risk of severe disease and deaths across age groups, but waning protection over time has been recognized as a major concern especially among the elderly, and the advent of the Omicron variant has further compromised the efficacy conferred by two doses of vaccines. In this context, uncertainties remain over the risk of severe disease and death for vulnerable patients hospitalized in non-acute care settings. We acknowledge that a major limitation of our study is the lack of untreated patients as this was not a controlled clinical study, and we were not able to find such data in the literature, either. Though not directly comparable, a study from the U.K. in the Omicron period reported a 28-day mortality rate of 5.48% among long-term care facility residents with COVID-19, the majority of whom were either previously infected or received a booster vaccination, down from 10.75% in the pre-Omicron era.
During surges of infection, transferring patients from non-acute care settings to acute care hospitals can be challenging when the latter are also overwhelmed with excessive demand. The approach described here, where high-risk COVID-19 patients are identified and treated expeditiously, may represent the most effective and realistic COVID-19 care in non-acute care settings during such periods especially among those who have not received a booster vaccination. While remdesivir is available only as an intravenous infusion, future advent of safe and potent oral antiviral agents may make this approach more generalizable.