Primary data exist for all figures Abstract Objective Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now a global pandemic. creatinine (CREA) (l), sodium (m), and total bilirubin (n). Gray boxes indicate the standard reference range for each parameter. mmc4_lrg.jpg (931K) GUID:?C54CBF64-82D3-4F85-8959-0E28DA9B7375 Figure S3 Immunological parameters in critically ill COVID19 patients untreated and treated with leronlimab. aCaf, Plasma levels of cytokines and chemokines in critically ill COVID19 patients treated with leronlimab for the cytokine or chemokine listed. mmc5_lrg.jpg (993K) GUID:?56DD94D1-31D7-43FB-92D8-F25E4169D131 Data Availability StatementAll primary data presented in this study are available from the corresponding author upon reasonable request. Primary data exist for all INCB054329 Racemate figures Abstract Objective Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now a global pandemic. Emerging results indicate a dysregulated immune response. Given the Rabbit Polyclonal to Tau role of CCR5 in immune cell migration and inflammation, we investigated the impact of CCR5 blockade via the CCR5-specific antibody leronlimab on clinical, immunological, and virological parameters in severe COVID-19 patients. Methods In March 2020, 10 terminally ill, critical COVID-19 patients received two doses of leronlimab via individual emergency use indication. We analyzed changes in clinical presentation, immune cell populations, inflammation, as well as SARS-CoV-2 plasma viremia before and 14 days after treatment. Results Over the 14-day study period, six patients survived, two were extubated, and one discharged. We observed complete CCR5 receptor occupancy in all donors by day 7. Compared with the baseline, we observed a concomitant statistically significant reduction in plasma IL-6, restoration of the CD4/CD8 ratio, and resolution of SARS-CoV2 plasma viremia (pVL). Furthermore, the increase in the CD8 percentage was inversely correlated with the reduction in pVL (r INCB054329 Racemate = ?0.77, p = 0.0013). Conclusions Our study design precludes clinical efficacy inferences but the results implicate CCR5 as a therapeutic target for COVID-19 and they form the basis for ongoing randomized clinical trials. test We assessed data based on the repeated measure correlation (rmcorr). Results Ten critical COVID-19 patients at the Montefiore Medical Center received leronlimab via FDA-approved EIND requests for individual patient use (Table 1). These confirmed SARS-CoV-2 positive patients had significant pre-existing co-morbidities and were receiving intensive care treatment, including mechanical ventilation or supplemental oxygen for ARDS. Consistent with previous reports of severe COVID-19 disease (Huang et al., 2020), these patients showed evidence of lymphopenia with liver and kidney damage (Supplementary Figure 2) (Akalin et al., 2020). Four of the patients died during the 14-day study period due to a combination of disease complications and severe constraints on medical equipment culminating in medical triage. Although this EIND study lacked a placebo control group for comparison, a recent study of other critically ill COVID-19 patients in the New York City area indicated mortality rates as high as 88% (Richardson et al., 2020). Table 1 Leronlimab-treated critical COVID-19 patient summaries. 0.05, ** 0.01, *** 0.001, **** 0.0001. At study day 0, all 10 critically ill patients received a subcutaneous injection of 700 mg leronlimab following baseline blood collection. Subsequently, the patients received a second subcutaneous injection of 700 mg leronlimab at study day 7. The defining features of severe COVID-19 disease include the plasma IL-6 and INCB054329 Racemate T cell lymphopenia (Huang et al., 2020, Lescure et al., 2020), so we longitudinally monitored these parameters for.