ABSTRACT
Condition:
Acute Respiratory Distress Syndrome Due to Disease Caused by 2019-nCoVIntervention:
Biological: Cryopreserved Ex Vivo Expanded Polyclonal CD4+CD127lo/-CD25+ T Regulatory CellsPrimary outcome:
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)Criteria:
Inclusion Criteria:
- Diagnosis of ARDS and respiratory failure requiring mechanical ventilation for less
than 72 hours at the time of enrollment
- PaO2/FiO2 < 300 and PEEP > 5
- Male or female, age 18 to 70 years at Screening
- Weight > 40 kg
- Documented diagnosis of infection with SARS-CoV-2 virus by PCR
- Chest imaging (radiograph or CT scan) with abnormalities consistent with COVID-19
pneumonia that could not be explained by effusions, pulmonary collapse, or nodules;
and respiratory failure that could not be explained by cardiac failure or fluid
overload
- Females of childbearing potential and males must use effective contraception practices
from Screening until 28 days after the EOS visit
- Females of childbearing potential must have a negative pregnancy test at Screening and
within 24 hours prior to dosing of study drug
- Able to provide Informed Consent, either by self or by medical proxy
- Willing and able to comply with this protocol for the entire duration of the study
Exclusion Criteria:
- Any history or sign of significant chronic active or recurrent infection or screening
laboratory evidence consistent with a significant chronic active or recurrent
infection requiring treatment with antibiotics, antivirals or antifungals (other than
SARS-CoV-2); ongoing antimicrobial treatments will not be exclusionary if, in the
opinion of the investigator, no active infection is present (other than SARS-CoV-2)
- Receiving extracorporeal membrane oxygenation therapy
- Moribund patients not expected to survive 24 hours after enrollment based on clinical
assessment
- History of significant underlying pulmonary disease (requiring home oxygen), renal
disease (requiring dialysis for chronic kidney disease), hepatic disease (Child-Pugh
score = 7), or known history of cirrhosis.
- Known or suspected immunodeficiency disease
- Positive serology for HBV, HCV, or HIV at Screening
- Abnormal CBC defined by:
- Platelet count < 75,000/mm3
- White blood cell count < 2500/mm3
- Absolute neutrophil count < 500/mm3
- History of bone marrow or stem cell transplantation
- Received any type of live attenuated vaccine < 1 month prior to Screening or is
planning to receive any such live attenuated vaccine over the course of the study
- History of lung cancer or any other malignancy requiring active treatment, except
adequately treated basal cell carcinoma or in situ carcinoma of the uterine cervix
- Any female who is pregnant or breastfeeding, or any female who is planning to become
pregnant during the study and follow-up period
- Any condition that, in the investigator's opinion, may compromise study participation,
present a safety risk to the subject, or may confound the interpretation of the study
results
- A QT duration corrected for heart rate by Fridericia's formula (QTcF) > 450
millisecond (msec) for males or > 470 msec for females, based on either single or
averaged QTcF values of triplicate ECGs obtained over a 3-minute interval
- Currently enrolled in another investigational device or drug study
ABSTRACT
Host immune responses play central roles in controlling SARS-CoV2 infection, yet remain incompletely characterized and understood. Here, we present a comprehensive immune response map spanning 454 proteins and 847 metabolites in plasma integrated with single-cell multi-omic assays of 221,748 PBMCs in which whole transcriptome, 192 surface proteins, and T and B cell receptor sequence were analyzed within the context of clinical measures from 50 COVID19 patient samples. Our study reveals novel cellular subpopulations, such as proliferative exhausted CD8+ and CD4+ T cells, and cytotoxic CD4+ T cells, that may be features of severe COVID-19 infection. We condensed over 1 million immune features into a single immune response axis that independently aligns with many clinical features and is also strongly associated with disease severity. Our study represents an important resource towards understanding the heterogeneous immune responses of COVID-19 patients and may provide key information for informing therapeutic development.