ACTIV-3b: Therapeutics for Severely Ill Inpatients With COVID-19

Inclusion Criteria: * Signed informed consent. * Requiring admission for inpatient hospital acute medical care for clinical manifestations of COVID-19 (not for purely public health or quarantine purposes). * Current respiratory failure (i.e. receipt of high-flow nasal cannula, non-invasive ventilation, invasive mechanical ventilation, or ECMO used to treat acute hypoxemic respiratory failure). * SARS-CoV-2 (COVID-19) infection, documented by a nucleic acid test (NAT) or equivalent testing with most recent rest within 14 days prior to randomization. * Respiratory failure is believed to be due to SARS-CoV-2 pneumonia. Exclusion Criteria: * Known allergy to investigational agent or vehicle. * More than 4 days since initiation of support for respiratory failure. * Chronic/home mechanical ventilation (invasive or non-invasive) for chronic lung or neuromuscular disease (non-invasive ventilation used solely for sleep-disordered breathing is not an exclusion). * Moribund patient (i.e. not expected to survive 24 hours). * Active use of "comfort care" or other hospice-equivalent SOC. * Expected inability to participate in study procedures. * In the opinion of the investigator, any condition for which, participation would not be in the best interest of the participant or that could limit protocol-specified assessments. * Previous enrollment in TESICO Additional agent-specific criteria also apply, and are listed in the substudy records Substudy H1: Aviptadil for Severely Ill Inpatien…