tetano
Editor, Senior Moderator
Basic Res Cardiol. 2020 May 12;115(4):36. doi: 10.1007/s00395-020-0795-1.
Allogeneic cardiosphere-derived cells (CAP-1002) in critically ill COVID-19 patients: compassionate-use case series.
Singh S[SUP]1[/SUP], Chakravarty T[SUP]1[/SUP], Chen P[SUP]2[/SUP], Akhmerov A[SUP]1[/SUP], Falk J[SUP]2[/SUP], Friedman O[SUP]1,[/SUP][SUP]2[/SUP], Zaman T[SUP]2[/SUP], Ebinger JE[SUP]1[/SUP], Gheorghiu M[SUP]1[/SUP], Marb?n L[SUP]3[/SUP], Marb?n E[SUP]1[/SUP], Makkar RR[SUP]4[/SUP].
Author information
Abstract
There are no definitive therapies for patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Therefore, new therapeutic strategies are needed to improve clinical outcomes, particularly in patients with severe disease. This case series explores the safety and effectiveness of intravenous allogeneic cardiosphere-derived cells (CDCs), formulated as CAP-1002, in critically ill patients with confirmed coronavirus disease 2019 (COVID-19). Adverse reactions to CAP-1002, clinical status on the World Health Organization (WHO) ordinal scale, and changes in pro-inflammatory biomarkers and leukocyte counts were analyzed. All patients (n = 6; age range 19-75 years, 1 female) required ventilatory support (invasive mechanical ventilation, n = 5) with PaO[SUB]2[/SUB]/FiO[SUB]2[/SUB] ranging from 69 to 198. No adverse events related to CAP-1002 administration were observed. Four patients (67%) were weaned from respiratory support and discharged from the hospital. One patient remains mechanically ventilated as of April 28th, 2020; all survive. A contemporaneous control group of critically ill COVID-19 patients (n = 34) at our institution showed 18% overall mortality at a similar stage of hospitalization. Ferritin was elevated in all patients at baseline (range of all patients 605.43-2991.52 ng/ml) and decreased in 5/6 patients (range of all patients 252.89-1029.90 ng/ml). Absolute lymphocyte counts were low in 5/6 patients at baseline (range 0.26-0.82 ? 10[SUP]3[/SUP]/?l) but had increased in three of these five patients at last follow-up (range 0.23-1.02 ? 10[SUP]3[/SUP]/?l). In this series of six critically ill COVID-19 patients, intravenous infusion of CAP-1002 was well tolerated and associated with resolution of critical illness in 4 patients. This series demonstrates the apparent safety of CAP-1002 in COVID-19. While this initial experience is promising, efficacy will need to be further assessed in a randomized controlled trial.
KEYWORDS:
Cell therapy; Coronavirus; Cytokine storm; Hyperinflammation
PMID:32399655DOI:10.1007/s00395-020-0795-1
[Indexed for MEDLINE]Free PMC Article
Allogeneic cardiosphere-derived cells (CAP-1002) in critically ill COVID-19 patients: compassionate-use case series.
Singh S[SUP]1[/SUP], Chakravarty T[SUP]1[/SUP], Chen P[SUP]2[/SUP], Akhmerov A[SUP]1[/SUP], Falk J[SUP]2[/SUP], Friedman O[SUP]1,[/SUP][SUP]2[/SUP], Zaman T[SUP]2[/SUP], Ebinger JE[SUP]1[/SUP], Gheorghiu M[SUP]1[/SUP], Marb?n L[SUP]3[/SUP], Marb?n E[SUP]1[/SUP], Makkar RR[SUP]4[/SUP].
Author information
Abstract
There are no definitive therapies for patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Therefore, new therapeutic strategies are needed to improve clinical outcomes, particularly in patients with severe disease. This case series explores the safety and effectiveness of intravenous allogeneic cardiosphere-derived cells (CDCs), formulated as CAP-1002, in critically ill patients with confirmed coronavirus disease 2019 (COVID-19). Adverse reactions to CAP-1002, clinical status on the World Health Organization (WHO) ordinal scale, and changes in pro-inflammatory biomarkers and leukocyte counts were analyzed. All patients (n = 6; age range 19-75 years, 1 female) required ventilatory support (invasive mechanical ventilation, n = 5) with PaO[SUB]2[/SUB]/FiO[SUB]2[/SUB] ranging from 69 to 198. No adverse events related to CAP-1002 administration were observed. Four patients (67%) were weaned from respiratory support and discharged from the hospital. One patient remains mechanically ventilated as of April 28th, 2020; all survive. A contemporaneous control group of critically ill COVID-19 patients (n = 34) at our institution showed 18% overall mortality at a similar stage of hospitalization. Ferritin was elevated in all patients at baseline (range of all patients 605.43-2991.52 ng/ml) and decreased in 5/6 patients (range of all patients 252.89-1029.90 ng/ml). Absolute lymphocyte counts were low in 5/6 patients at baseline (range 0.26-0.82 ? 10[SUP]3[/SUP]/?l) but had increased in three of these five patients at last follow-up (range 0.23-1.02 ? 10[SUP]3[/SUP]/?l). In this series of six critically ill COVID-19 patients, intravenous infusion of CAP-1002 was well tolerated and associated with resolution of critical illness in 4 patients. This series demonstrates the apparent safety of CAP-1002 in COVID-19. While this initial experience is promising, efficacy will need to be further assessed in a randomized controlled trial.
KEYWORDS:
Cell therapy; Coronavirus; Cytokine storm; Hyperinflammation
PMID:32399655DOI:10.1007/s00395-020-0795-1
[Indexed for MEDLINE]Free PMC Article