Background Casirivimab-imdevimab has been developed to neutralize SARS-CoV-2. The global clinical trials in outpatients documented several adverse effects (AE), which mandate caution in Japan where part of patients return home. To investigate post-infusion clinical events and their risk factors, we attempted a retrospective study. Main body Subjects were a consecutive series of inpatients with COVID-19 undergoing an infusion of casirivimab-imdevimab in our institute. The criteria for administration were in accordance with previous clinical trials, e.g., exclusion of patients necessitating oxygen supply. In Japan, however, SARS-CoV-2 vaccinees were eligible. Methods were review of background factors of status, imaging, and laboratory findings for the outcome of post-infusion events such as temperature increase (Temp+), pulse oximetry below 94%, and other events. Also, we documented the drug efficacy. Of a total of 96 patients with a median follow-up of 54 days, one (1.0%) died who alone was an exception demanding oxygen supply. Other 95 patients (99.0%) recovered from fever and hypoxia by Day 4 and later had no worsening of COVID-19. Median increase of body temperature was 1.0 degrees Celsius, which was used for computation of Temp+. Multivariate analysis showed that for Temp+ (n = 47), white blood cell counts more than 4.3 × 103/microliter (Odds Ratio [OR] 2.593, 95% Confidence Interval [CI] 1.060–6.338, P = 0.037) was at risk, whereas 2-time vaccination for SARS-CoV-2 (OR 0.128, 95% CI 0.026–0.636, P = 0.012) was a preventing factor. Likewise for lowered oximetry (n = 21), CT showing bilateral ground glass attenuation (OR 5.544, CI 1.599–19.228, P = 0.007) was a significant risk factor. Two patients (2.1%) showed bradycardia (asymptomatic, intervention not indicated) on Day 3 and recovery on Day 5. Limitations for this study included the difficulty distinguishing AE from worsening of COVID-19, thus we documented as clinical events. Conclusions For 24 h after infusion of casirivimab-imdevimab, COVID-19 patients with increased white blood cell counts may be predisposed to temperature elevation more than 1.0 degrees centigrade, as may bilateral ground glass opacity to lowered oximetry. Thus, patients with leukocytosis and bilateral ground glass attenuation may need precaution for transient fever and hypoxia, respectively.

Background Sotrovimab has been developed to neutralize SARS-CoV-2 which remained effective at the advent of B.1 lineage of the Omicron variant. To investigate post-infusion clinical events and their risk factors, we performed a retrospective study.Methods Subjects were a consecutive series of inpatients with COVID-19 undergoing an infusion of sotrovimab in our institute. In accordance with previous clinical trials, we included patients at risk but permitted SARS-CoV-2 vaccinees. For statistical analyses, we reviewed background factors of demographics, imaging, and laboratory findings for the outcome of post-infusion events such as temperature over 38 degrees Celsius (Temp38) and pulse oximetry below 94%.Results Of a total of 136 patients, the median follow-up was 47 days. Among 110 fully vaccinated patients (80.9%) for SARS-CoV-2, 2-time vaccinees accounted for 88 while 3-time vaccinees were 22. Three patients (2.2%) showed worsening of COVID-19; one developed hypoxia and two died. For the outcome of Temp38 (N=41), multivariate analysis showed that factors at risk were younger age (<66.5) (Odds Ratio [OR] 4.364, 95% Confidence Interval [CI] 1.562 – 12.194, P=0.005) and pre-infusion temperature more than 36.7 degrees Celsius (OR 7.256, 95% CI 2.695 – 21.455, P<0.001). For post-infusion reduced oximetry (N=17), symptomatic days (>2) (OR 8.657, 95% CI 1.030 – 72.786, P=0.047) and pulse oximetry (<96.5%) (OR 7.160, 95% CI 2.071 – 24.751, P=0.002) were at risk. Oxygen was supplied for a median of 1.5 days (range, 1 - 5). We observed vomiting (N=1) and elevated aminotransferase levels (N=1). Conclusions With fully vaccinated patients predominant, antibody-dependent enhancement may have brought about post-infusion fever in the younger population prone to increase antibody titers. Likewise, patients undergoing delayed infusion after symptom onset may have produced antibody, leading into respiratory distress or lowered oximetry. Limitations for this study included inherent difficulty in distinguishing AE from worsening of COVID-19. Thus for 24 hours after infusion of sotrovimab, COVID-19 patients younger than 66.5 years may have temperature elevation, indicating the need for preparation of post-infusion fever. Those undergoing infusion after 3 symptomatic days or more may develop an oximetry decrease, thus demanding pulse oximetry monitoring.

Objectives: The incidence of remdesivir-induced renal dysfunction has not been investigated until now. The present study explored the clinical factors and laboratory data that predict remdesivir-induced renal dysfunction. The subjects were COVID-19 patients and we determined the endpoint as dialysis or death within 29 days. Background status parameters included (1) estimated glomerular filtration rate < 30 ml/min/1.73 m2, (2) serum creatinine (SCr) ratios to baseline > 1.5, (3) SCr ratios to upper limits > 1.5, (4) alanine aminotransferase ratios to upper limits > 5, (5) administration days, (6) sex, (7) age, (8) height, (9) weight, (10) dexamethasone use, and (11) SARS-CoV-2 vaccination. Results: In a total of 490 patients, a multivariate analysis showed that status (2) (odds ratio [OR] 8.342, 95% confidence interval [CI] 1.589-43.788, P=0.012) and status (7) (OR 7.620, CI 1.181-49.169, P=0.033) at 72 years or more were significant factors for remdesivir-induced renal dysfunction. To monitor renal function after remdesivir administration in COVID-19 patients, SCr ratios to baseline may work better than those to the upper limits.

Background Sotrovimab neutralizing SARS-CoV-2 remained effective at the advent of B.1 lineage of the Omicron variant in outpatients. Primarily for hospitalized patients, however, the Japanese government regulated to administer this antibody agent. As this regulation enabled close monitoring in inpatients to investigate post-infusion adverse events (AEs) and efficacy, we attempted a retrospective study while the Omicron BA.1 lineage was dominant regionally. Methods Subjects were inpatients with COVID-19 who received infusion of sotrovimab in our institute. In line with previous clinical trials, we included patients at risk of COVID-19 worsening and SARS-CoV-2 vaccinees, who were hospitalized as directed by the government. For statistical analyses, we reviewed background factors of demographics, imaging, and laboratory findings for the outcome infusion-related reactions including post-infusion pyrexia over 38 degrees Celsius and/or pulse oximetry below 94%. Results In a total of 139 patients, the follow-up period had a median of 200 days (range, 154–248 days). Among 119 patients (85.6%) fully vaccinated for SARS-CoV-2, 86 (61.9% of all) underwent 2 doses while 33 (23.7% of all) received 3 doses. For the outcome of pyrexia and/or dyspnea (N = 40, 28.8%), multivariate analysis showed that significant risk factors were pre-infusion lowered oximetry below 96.5% (Odds Ratio [OR] 0.344, 95% Confidence Interval [CI] 0.139–0.851, P = 0.021) and pre-infusion temperature more than 36.7 degrees Celsius (OR 4.056, 95% CI 1.696–9.701, P = 0.002). Infusion-related reactions included vomiting immediately after infusion, chill/shivering, dizziness, rash, pruritus, pyrexia, and dyspnea. The number of patients with any of these events was 44 (31.6%). Three patients (2.2%) showed worsening of COVID-19; one developed hypoxia and two died. Limitations for this study included no genome typing whether BA.1 or BA.2 lineage of the Omicron variant but the local epidemiology indicated the prevalence of BA.1. Another was sotrovimab administration for inpatients that allow precise detection of post-infusion events, confounding previous exacerbation definition including hospitalization. Conclusions For 24 h after infusion of sotrovimab, COVID-19 patients showing pre-infusion lowered oximetry below 96.5% and/or temperature more than 36.7 degrees Celsius may have temperature elevation or dyspnea, warranting close monitoring for these risk factors.

Background: To see how the COVID-19 pandemic influenced the 3-year use of parenteral antimicrobials, we attempted a historical control study. Main body: Materials were the electronic medical record on the use of a total of 33 antimicrobials. We compared antimicrobial use density (AUD) of pre-pandemic 1 year (PreY), the first pandemic year (Pan1Y), and the second pandemic year (Pan2Y). Our antimicrobial team monitored all in-patients and COVID-19 patients underwent clinical pathways with antivirals. Results: showed that in a total of 20,013 patients (7,534, 6,146, and 6,333 for PreY, Pan1Y, and Pan2Y), sepsis-3 was diagnosed in 152, 132, and 283 patients while Clostridioides difficile toxin tests were positive in 17, 5, and 7 patients, respectively. Among patients with COVID-19 (N=622) at a median age of 58 (range, 1-99), 11 (1.8%) died; parenteral antimicrobials were given in 59 patients (9.5%) preceded by bacteriological tests in 48 (81.4%). Comparing before and during the pandemic, parametric analyses showed that the means of total AUD decreased from 16.767 (PreY) to 15.62 (Pan1Y+Pan2Y) (P=0.034). Likewise, the means of carbapenems’ AUD showed decrease from 0.773 (PreY) to 0.462 (Pan1Y) but increase into 0.777 (Pan2Y) (P=0.001).The non-parametric comparison between COVID-19 and other wards showed that the medians of AUD in the COVID-19 wards were significantly (P<0.05) less in 22 out of 33 antimicrobials (66.7%) and in the total AUD. Conclusion: The COVID-19 pandemic stewardship decreased the total AUD and may have contributed to decrease ESBL-producing microbes and C. difficile infection. The burden of sepsis-3 may have fluctuated the carbapenems’ use.