This is a randomized, double-blind placebo-controlled trial to investigate the efficacy and safety of tradipitant 85 mg orally given twice daily to treat inflammatory lung injury associated with severe or critical COVID-19 infection.

On evaluation for enrollment, participant will need to meet all inclusion and exclusion criteria. If participant consents, they will be randomized 1:1 to treatment with either tradipitant 85 mg PO BID or placebo in addition to standard of care for COVID-19 infection as per the protocol at the treating hospital. NEWS 2 will be assessed at screening and daily following randomization. Inflammatory lab markers as detailed should be collected once per day in the morning, preferably at the same time every morning. All enrolled participants will have whole blood collected for whole genome sequencing.

Inclusion Criteria:

• Adults aged 18-90
• Confirmed laboratory COVID-19 infection by RT-PCR
• Meeting severe or critical criteria of COVID-19 infection as defined at treating hospital
• Confirmed pneumonia by chest radiograph or computed tomography
• Fever defined as temperature ≥ 36.6 °C armpit, ≥ 37.2 °C oral, or ≥ 37.8 °C rectal
• Oxygen saturation less than 92%

Exclusion Criteria:

• Recent use of illicit drugs or alcohol abuse
• Known allergy to tradipitant or other neurokinin-1 antagonists
• Pregnancy
• Known HIV, HBV, or HCV infection
• Malignant tumor, other serious systemic diseases
• Inability to provide informed consent or to have an authorized relative or designated person provide informed consent, or to comply with the protocol requirements