Category   Therapeutic(s)   Trial identifier   Phase   Location (centers)   Patients (n)   Study eligibility   Mechanism of action(s)
NK cell-based products
      Adoptive NK cells  NK cells  NCT04280224  I  Henan, China  30  Pneumatic COVID19+  Adoptive NK cell therapy
CYNK-001  NCT04365101  I/II  New Jersey, USA  86  Mild COVID19+  From human placental CD34+ cells and culture-expanded
NK cells isolated from healthy donor PBMCs  NCT04344548  I/II  Bagota, Colombia  10  NEWS of >4  Isolated NK cells ex vivo stimulated with IL-2 and IL-15
      CAR-NK Cells  NKG2D-ACE2 CAR-NK cell therapy from umbilical cord blood  NCT04324996  I/II  Chongqing, China  90  Within <14 dpi  IL-15 prolongs NK cell lifespan; GM-CSF neutralizing scFV reduces recruitment of inflammatory cells; NKG2D-ACE2 CAR-NK cells can target virally infected cells; ACE2 CAR-NK can act as decoy cell
NK cell immunostimulants
Direct NK cell activation
      IFN-α Therapy  Recombinant human IFN-α ± Thymosin alpha 1  NCT04320238  III  Hubei, China  2,944  Uninfected HCW  IFN-alpha boosts immune system; thymosin alpha 1 activates TLRs in myeloid and pDCs leading to NK cell activation
Recombinant human IFN-α2β  NCT04293887  I  Hubei, China  328  Within <7 dpi  IFN-alpha activates interferon pathway
Abidol Hydrochloride ± IFN atomization (Peg-IFN-α-2b)  NCT04254874  IV  Hubei, China  100  Pneumatic COVID19+
Rintatolimod ± Recombinant IFN-α2β  NCT04379518  I/II  New York, USA  80  Mild to moderate COVID19+
      IFN-β Therapy  Lopinavir/ritonavir ± IFN-β-1a  NCT04315948  III  France (3)  3,100  Moderate/Severe  IFN-beta activates interferon pathway
Base therapy ± IFN-β-1a  NCT04350671  IV  Tehran, Iran  40  Within <10 dpi  Base therapy = Hydropinchloroquine + Lopinavir/Ritonavir
Base therapy ± IFN-β-1b  NCT04276688  II  Hong Kong, HK  127  NEWS of ≥1  Base therapy = Lopinavir/ritonavir/Ribavirin
IFN-β-1a vs. IFN-β-1b (+Base therapy)  NCT04343768  IV  Tehran, Iran  60  Moderate/Severe  Base therapy = Hydropinchloroquine + Lopinavir/Ritonavir
Indirect NK cell activation
      IFN-λ Therapy  Peg-IFN-Lambda-1a  NCT04331899  II  California, USA  120  Early COVID19+  IFN-lambda to boost NK cells indirectly through Monocytes, Macrophages, and pDCs IL-12 secretion
Peg-IFN-Lambda-1a  NCT04343976  II  Boston, USA  40  Early COVID19+
Peg-IFN-Lambda-1a  NCT04354259  II  Toronto, Canada  140  Ambulatory and hospitalized
Peg-IFN-Lambda-1a  NCT04388709  II  New York, USA  66  Non-ICU COVID19+
Peg-IFN-Lambda-1a  NCT04344600  II  Maryland, USA  164  Asymptomatic COVID19+
Immunoregulatory therapies
Immune checkpoint blockade  Anti-PD-1 (vs. Thymosin)  NCT04268537  II  Nanjing, China  120  Respiratory failure within <48h of ICU  Prevent T-cell regulation by blocking PD-1; in COVID19+ advanced or metastatic cancer patients;
Anti-PD-1 (pembrolizumab) + tocilizumab  NCT04335305  II  Nanjing, China  24  Pneumatic COVID19+  Tocilizumab = anti-IL-6R
Anti-PD-1 (nivolumab) vs. GNS651  NCT04333914  II  France (4)  273  Early COVID19+  GNS651 = Chloroquine analog
Non-specific innate immune stimulation
      Heterologous vaccines  BCG  NCT04328441  III  Netherlands (9)  1,500  Uninfected HCW  Trains and primes innate immunity against subsequent non-specific pathogen infection
BCG (Danish strain)  NCT04327206  III  Australia (8)  4,170  Uninfected HCW
BCG (Danish strain)  NCT04350931  III  Egypt  900  Uninfected HCW
BCG (Danish strain)  NCT04379336  III  South Africa  500  HCW
BCG (Tice strain)  NCT04348370  IV  USA (5)  700  Uninfected HCW
BCG  NCT04369794  IV  São Paulo, Brazil  1,000  Early COVID19+
      TLR agonists  PUL-042 (CpG ODN)  NCT04313023  II  Not listed  200  Unifected/asymptomatic  Activates TLR2/6/9 leading to innate immune stimulation
PUL-042 (CpG ODN)  NCT04312997  II  Texas, USA  100  Within <7 dpi
Natural health products and alternative medicines
      Vitamins  Vitamin C  NCT04323514  N/A  Palermo, Italy  500  Pneumatic COVID19+  General immune boosting properties of vitamin C and natural health products
Vitamin C  NCT04264533  II  Hubei, China  140  ICU COVID19+
Vitamin C  NCT03680274  III  Quebec, Canada  800  ICU COVID19+
Vitamin C  NCT04344184  II  Virginia, USA  200  ICU COVID19+
Vitamin C + Zinc  NCT04342728  N/A  Ohio, USA  520  Outpatient COVID19+
Hydroxychloroquine; Azithromycin; Vitamin C, D; and Zinc  NCT04334512  II  California, USA  600  Low risk COVID-19+
Hydroxychloroquine; vitamin C, D; and Zinc  NCT04335084  II  California, USA  600  Uninfected HCW
Vitamin D  NCT04334005  N/A  Spain (2)  200  Non-severe COVID19+  Vitamin D is immunomodulatory and prevents nutritional deficiencies.
Zinc + Vitamin D (cholecalciferol)  NCT04351490  N/A  Lille, France  3,140  Asymptomatic COVID19+  To treat zinc and vitamin D deficiency and reduce inflammation and ARDS
High dose Vitamin D (4X)  NCT04344041  III  France (9)  260  Severe COVID19+