Other substances

NK cells

Natural Killer cell therapy as an universal COVID-19 treatment strategy

Phase of research

Potential treatment - theoretical effect

How it helps

Antiviral

Drug status

Used to treat other disease

Supporting references

Contradictory references

AI-suggested references

Clinical trials

General information

Both innate and adaptive immune responses are essential to control viral infections. Natural killer (NK) cells, as a part of the innate immune system, play an important role during acute viral infection. Due to the loss of NK cells in COVID-19 patients, it is straightforward to assume that the restoration of the number of NK cells by infusing ex vivo expanded NK cells into patients can reinstate immune capacity and increase chances of recovery. If adequately treated, NK cells could well suit adoptive cell transfer due to the low risk of graft-versus-host disease (Ahmed et al., 2020).

NK cells on Wikipedia.

On August 10, 2020, Novocellbio has confirmed that its autologous NK cell treatment agent Novo-NK is effective in killing SARS-CoV-2. In the experiment, monkey kidney cells (Vero E6) infected with SARS-CoV-2 were treated with Novo-NK cells. The analysis showed that the therapy successfully decreased the virus's effects in various controlled time periods and effectively killed the virus within six hours. The treatment has also been shown to increase immunity by reducing the risk of reinfection from virus or cancer cell mutation.

Synonyms

Natural Killer cells, NK

Supporting references

Link	Tested on	Impact factor	Notes	Publication date
Natural killer cells associated with SARS-CoV-2 viral RNA shedding, antibody response and mortality in COVID-19 patients Cell-based therapy	Theory only	2.92	This study suggests the potential value of allo-Natural Killer cell therapy as an universal COVID-19 treatment strategy.	Jan/27/2021
Can Natural Killer Cells Be a Principal Player in Anti-SARS-CoV-2 Immunity? Cell-based therapy Adoptive cell therapy	Theory only	6.43	Due to the reduced frequencies of NK cells found in COVID-19 patients and the well-known antiviral role of NK cells, it is tempting to speculate that the restoration of NK cells and their function would be a plausible solution for COVID-19 patients.	Dec/07/2020
Harnessing Memory NK Cell to Protect Against COVID-19 Cell-based therapy Adoptive cell therapy	Theory only	3.86	NK cell-mediated antiviral activity may offer important new tools in COVID-19 treatment	Aug/20/2020
Identifying SARS-CoV-2 ‘memory’ NK cells from COVID-19 convalescent donors for adoptive cell therapy Cell-based therapy Adoptive cell therapy In vitro Mixed substance	in vitro; COVID-19-recovered patients' peripheral blood (source)	7.40	CD57+ NKG2C+ NK cells responding to SARS-CoV-2 peptides were identified in the peripheral blood of COVID-19 convalescent donors. Their further use for COVID-19 treatment was hypothesized.	Nov/14/2021
Glycoprotein Targeted CAR-NK Cells for the Treatment of SARS-CoV-2 Infection Spike protein Cell-based therapy Adoptive cell therapy In vitro Mixed substance	hACE2-expressing 293T cells; (HIV) SARS-CoV-2 Spike (WH1)-pseudotyped virus	7.56	H84T-Banana Lectin (BanLec) CAR-NK cells are modified and expanded NK cells. They stably express SARS-CoV-2 glycan binding moiety on their surface. In vitro, the modified NK cells reduced SARS-CoV-2 Spike pseudoviral infection.	Dec/23/2021
CAR-NK Cells Effectively Target SARS-CoV-2-Spike-Expressing Cell Lines In Vitro Spike protein Spike variant Cell-based therapy In vitro Mixed substance	293T-hACE2-RBD cells; A549-Spike cells; (lentiviral) SARS-CoV-2 Spike-pseudotyped viruses (D614G, N501Y and E484K mutants)	7.56	Expanded NK cells carrying a chimeric antigenic receptor based on S309 antibody specifically bound to SARS-CoV-2 Spike (D614G, N501Y and E484K mutants)-pseudotyped virus and killed Spike-expressing cells in vitro.	Jul/23/2021

AI-suggested references

Link	Publication date
MEK inhibitors reduce cellular expression of ACE2, pERK, pRb while stimulating NK-mediated cytotoxicity and attenuating inflammatory cytokines relevant to SARS-CoV-2 infection.	Aug/25/2021
Restoring NK cells functionality via cytokine activation enhances cetuximab-mediated NK-cell ADCC: A promising therapeutic tool for HCC patients.	Oct/30/2021
Efficacy of the BNT162b2 mRNA COVID-19 Vaccine in Patients with Chronic Lymphocytic Leukemia: A Serologic and Cellular Study	Dec/06/2021
Efficacy of diammonium glycyrrhizinate combined with vitamin C for treating hospitalized COVID-19 patients: a retrospective, observational study	Jan/13/2022
CMV-associated T cell and NK cell terminal differentiation does not affect immunogenicity of ChAdOx1 vaccination	Nov/30/2021
SARS-CoV-2 infection associated with hepatitis in an infant with X-linked severe combined immunodeficiency	Feb/17/2022
Serology-based therapeutic strategy in SARS-CoV-2-infected patients	Oct/05/2021
Off-the-shelf CAR natural killer cells secreting IL-15 target spike in treating COVID-19	Nov/27/2020
Imiquimod - A toll like receptor 7 agonist - Is an ideal option for management of COVID 19.	Jun/23/2020
Distinct immune cell dynamics correlate with the immunogenicity and reactogenicity of SARS-CoV-2 mRNA vaccine.	Apr/22/2022
NK cell frequencies, function and correlates to vaccine outcome in BNT162b2 mRNA anti-SARS-CoV-2 vaccinated healthy and immunocompromised individuals	Feb/08/2022
GENERATING RESPONSES IMMUNE IN CELLULAR AND HUMORAL TREATMENT WITH EPITOPE SPIKE, EPITOPE ENVELOPE PROTEIN, AND EPITOPE MEMBRANE PROTEIN SARS-COV-2, HONEY, SAUSSUREA LAPPA, AND NIGELLA SATIVA	Apr/01/2022
Impact of chemotherapy and immunotherapy on the composition and function of immune cells in COVID-19 convalescent with gynecological tumors	Dec/04/2021
Innate Immune Responses of Vaccinees Determine Early Neutralizing Antibody Production After ChAdOx1nCoV-19 Vaccination	Jan/25/2022
An in-depth in silico and immunoinformatics approach for designing a potential multi-epitope construct for the effective development of vaccine to combat against SARS-CoV-2 encompassing variants of concern and interest.	Jul/30/2021
SARS-CoV-2 Immunization Orchestrates the Amplification of IFNgamma-Producing T Cell and NK Cell Persistence	Sep/30/2021
Early Use of Corticosteroid May Prolong SARS-CoV-2 Shedding in Non-Intensive Care Unit Patients with COVID-19 Pneumonia: A Multicenter, Single-Blind, Randomized Control Trial	Jan/22/2021
Serological SARS-CoV-2 antibody response, potential predictive markers and safety of BNT162b2 mRNA COVID-19 vaccine in haematological and oncological patients	Aug/03/2021
Induction of Innate Immune Response by TLR3 Agonist Protects Mice against SARS-CoV-2 Infection	Jan/19/2022
SARS-CoV-2 Nsp13 encodes for an HLA-E-stabilizing peptide that abrogates inhibition of NKG2A-expressing NK cells.	Feb/21/2022
A phase I/II dose-escalation multi-center study to evaluate the safety of infusion of natural killer cells or memory T cells as adoptive therapy in coronavirus pneumonia and/or lymphopenia: RELEASE study protocol.	Oct/02/2021
TRIM28 regulates SARS-CoV-2 cell entry by targeting ACE2	Jun/17/2021
Multifaceted Immunomodulatory Effects of the BTK Inhibitors Ibrutinib and Acalabrutinib on Different Immune Cell Subsets - Beyond B Lymphocytes.	Aug/13/2021
Natural killer cell-mediated ADCC in SARS-CoV-2-infected individuals and vaccine recipients	Apr/22/2022
SARS-CoV-2-specific immune response in COVID-19 convalescent individuals.	Jul/07/2021
Identifying SARS-CoV-2 'memory' NK cells from COVID-19 convalescent donors for adoptive cell therapy	Dec/02/2021
Exhausted NK cells and cytokine storms in COVID-19: Whether NK cell therapy could be a therapeutic choice.	Sep/08/2021
Successful Treatment of Persistent SARS-CoV-2 Infection in a B-Cell Depleted Patient with Activated Cytotoxic T and NK Cells: A Case Report	Feb/04/2021
Immunological Response Against SARS-COV-2 After BNT162b2 Vaccine Administration Is Impaired in Allogeneic but Not in Autologous Stem Cell Transplant Recipients	Sep/14/2021
Innate immunity in COVID-19 patients mediated by NKG2A receptors, and potential treatment using Monalizumab, Cholroquine, and antiviral agents	Apr/06/2020

Clinical trials

ID	Title	Status	Phase	Start date	Completion date
NCT04634370	Fase I Clinical Trial on NK Cells for COVID-19	Not yet recruiting	Phase 1	Jan/02/2021	Mar/30/2021
Alternative id - 20200210 Interventions - Biological: Natural Killer Cells infusion Study type - Interventional Study results - No Results Available Locations - Hospital de Clinicas de Porto Alegre, Porto Alegre, RS, Brazil Study designs - Allocation: N/A\|Intervention Model: Single Group Assignment\|Masking: None (Open Label)\|Primary Purpose: Treatment Enrollment - 24 Age - 18 Years and older (Adult, Older Adult) Outcome measures - Overall survival\|Changes on inflammatory C-reactive protein\|Hospital stay\|Oxygenation index (PaO2/FiO2)\|Improvement in Liao's score (2020)\|Radiological improvement
NCT04375176	Monocytes and NK Cells Activity in Covid-19 Patients	Recruiting		Apr/27/2020	Oct/31/2020
Alternative id - 67/2020 Interventions - Diagnostic Test: Study of immune-mediated mechanisms in patients tested positive for SARS-CoV-2 Study type - Observational Study results - No Results Available Locations - ATS Insubria, Varese, Italy Study designs - Observational Model: Case-Only\|Time Perspective: Prospective Enrollment - 150 Age - 18 Years and older (Adult, Older Adult) Outcome measures - Immune cells activity\|Protective factors and new therapeutic strategies
NCT04578210	Safety Infusion of NatuRal KillEr celLs or MEmory T Cells as Adoptive Therapy in COVID-19 pnEumonia or Lymphopenia	Recruiting	Phase 1\|Phase 2	Sep/04/2020	Mar/01/2021
Alternative id - RELEASE Interventions - Biological: T memory cells and NK cells Study type - Interventional Study results - No Results Available Locations - Hospital Universitario La Paz, Madrid, Spain Study designs - Allocation: Randomized\|Intervention Model: Parallel Assignment\|Masking: Triple (Participant, Care Provider, Investigator)\|Primary Purpose: Treatment Enrollment - 58 Age - up to 80 Years (Child, Adult, Older Adult) Outcome measures - Occurrence of DLTs in all patients during the study treatment, until 21 days after cell infusion and the MTD
NCT04797975	Off-the-shelf NK Cells (KDS-1000) as Immunotherapy for COVID-19	Withdrawn	Phase 1\|Phase 2	Dec/01/2020	Apr/01/2021
Alternative id - KNK-COV-001 Interventions - Biological: KDS-1000\|Other: Placebo Study type - Interventional Study results - No Results Available Locations - Study designs - Allocation: Randomized\|Intervention Model: Parallel Assignment\|Masking: Double (Participant, Investigator)\|Primary Purpose: Treatment Enrollment - 0 Age - 18 Years to 70 Years (Adult, Older Adult) Outcome measures - Determine the safety of KDS-1000 given at low and high doses compared to placebo by collecting the rate and severity of adverse events (AE)\|Determine the efficacy KDS-1000 given at low and high doses compared to placebo by COVID-19 specific questionnaire.\|Determine the efficacy KDS-1000 given at low and high doses compared to placebo by measurement of SARS-CoV-2 clearance.\|Determine the safety of KDS-1000 given at low and high doses compared to placebo by collecting the rate and severity of AE.
NCT04324996	A Phase I/II Study of Universal Off-the-shelf NKG2D-ACE2 CAR-NK Cells for Therapy of COVID-19	Recruiting	Phase 1\|Phase 2	Feb/21/2020	Aug/31/2022
Alternative id - ChongqingPublicHMC Interventions - Biological: NK cells,IL15-NK cells,NKG2D CAR-NK cells,ACE2 CAR-NK cells,NKG2D-ACE2 CAR-NK cells Study type - Interventional Study results - No Results Available Locations - Chongqing Public Health Medical Center, Chongqing, China Study designs - Allocation: Randomized\|Intervention Model: Parallel Assignment\|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)\|Primary Purpose: Treatment Enrollment - 90 Age - 18 Years and older (Adult, Older Adult) Outcome measures - Clinical response\|Side effects in the treatment group
NCT04280224	NK Cells Treatment for COVID-19	Recruiting	Phase 1	Feb/15/2020	Dec/31/2023
Alternative id - xinxiangM Interventions - Biological: NK Cells Study type - Interventional Study results - No Results Available Locations - The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China Study designs - Allocation: Randomized\|Intervention Model: Parallel Assignment\|Masking: None (Open Label)\|Primary Purpose: Treatment Enrollment - 30 Age - 18 Years to 65 Years (Adult, Older Adult) Outcome measures - Improvement of clinical symptoms including duration of fever\|Improvement of clinical symptoms including respiratory frequency\|Number of participants with treatment-related adverse events evaluated with CTCAE,version 4.0\|Time of virus nucleic acid test negative\|CD4+ and CD8+ T cell count\|Rate of mortality within 28-days\|Size of lesion area by thoracic imaging

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