Table 4.
Potential therapeutic candidates for immunomodulation in COVID-19 infection
| Therapeutic candidates | Types of vaccines or drugs | Haematological malignancies | Description (advantage, disadvantage, function, or target) | Ref |
|---|---|---|---|---|
| BNT162b2 | mRNA vaccine | Lymphoma patients | BNT162b2 vaccine induces a significant humoral response in a significant proportion of patients with B-cell non-Hodgkin's lymphoma (B-NHL) regardless of gender or age. However, patients receiving active treatment with anti-CD20 antibodies experience impaired humoral responses. In fact, it is impossible to achieve a humoral response in the first 9 months after anti-CD20 therapy. However, response rates gradually improved after this period and continued to increase over time. | [221] |
| mRNA-1273 (Moderna) | Nanoparticle–encapsulated mRNA vaccine | Lymphoma patients | Vaccination with mRNA-1273 or Ad26.CoV2.S prime vaccination, as well as the mRNA-1273 booster compared to BNT162b2, resulted in higher levels of antiviral antibodies in patients with HM, (haematological malignancies), unlike the similar efficacy observed in healthy individuals. These differences in immunogenicity could be attributed to variations in spike mRNA quantity, coding sequence, lipid composition of vaccines, and dosing schedules. | [222, 223] |
| Recombinant subunit zoster vaccine* | Recombinant subunit | B-NHL |
• Prevention of HZ in adults over 50 years of age • Provide immunity in a significant proportion of immunocompromised adult patients over 18 years of age, while maintaining an acceptable safety profile |
[224–226] |
| Johnson & Johnson* | Adenovirus based vaccine | N.A |
• A single vaccination was up to 66% successful in preventing moderate to severe COVID-19, while completely preventing hospitalization and death from COVID-19 • There were no reports of severe hypersensitivity or adverse reactions to vaccination |
[227, 228] |
| Dexamethasone* | Small-molecule inhibitor | CLL | • A glucocorticoid drug | [229] |
| Baracitinib/tofacinib* | Small-molecule inhibitor | Pyoderma gangrenosum | • JAK–inhibitor | [230] |
| TKI* | Small-molecule inhibitor | CLL | • Tyrosine kinase | [231] |
| Hydroxyurea therapy* | Small-molecule inhibitor | SCA and CML |
• Increases fetal hemoglobin and reduces the number of attacks • Inhibiting the enzyme ribonucleotide reductase by scavenging tyrosyl free radicals decreases the production of deoxyribonucleotides as these radicals play a role in reducing NDPs |
[232] |
| Remdesivir* | Small-molecule inhibitor | CLL, Lymphoma |
• It is a nucleoside-like compound that inhibits the RdRp of coronaviruses • Dynamics of temperature, C-reactive protein, and lymphocyte count indicate SARS-CoV-2 reinfection |
[233] |
| Ibrutinib* | Small-molecule inhibitor | N.A |
• XLA • MCL • CLL |
[234] |
| Ruxolitinib* (Jakafi, Incyte) | Small-molecule inhibitor | N.A | • Myelofibrosis | [235] |
| Venetoclax* | Small-molecule inhibitor | SLL, CLL and AML | • Bcl-2 inhibitor | [236] |
| RTX* | Anti-CD20 Monoclonal antibody | Non-Hodgkin's B-cell lymphoma and rheumatoid arthritis |
• This results in the removal of CD20 from the cells, allowing them to persist and resist clearance • Used to treat haematological and autoimmune diseases by depleting CD20-expressing B-cells |
[237] |
| Casirivimab/Imdevimab* | Monoclonal antibody | Leukemias, myelodysplastic syndromes, myeloproliferative neoplasms, lymphomas, and MM | • A mixture of two MABs neutralizing human IgG1 against SARS-CoV-2 spike protein | [238, 239] |
| Tocilizumab, sarilumab* | Human monoclonal antibody | HLH | • Anti-IL-6 | [240] |
| Temelimab* | IgG4 monoclonal antibody | N.A |
• Increased intensity of HERV-W envelope protein expression in leukocytes of COVID-19 patients • HERV-W is a potential biomarker in severe cases of COVID-19 • Temelimab targets the HERV-W** protein and can be investigated as an option to reduce the severity of COVID-19 in patients with blood malignancies |
[241, 242] |
| Isatuximab/daratumumab* | Anti-CD38 antibody | MM, CLL, AML, etc | • Allosteric kinetic inhibitors of CD38 | [243] |
| hATG* | An infusion of horse or rabbit-derived antibodies against human T cells and their precursors | Severe acquired aplastic anemia and AML | • The use of hATG in AML patients receiving intensive ventilation had no significant adverse effect on clinical outcomes | [244] |
| HCT and cell therapy* | N.A | Many inherited or acquired disorders of the hematopoietic system such as ALL | • High safety and low toxicity data from patients treated with allogeneic HCT after receiving CAR-T therapy | [245] |
| Convalescent plasma therapy* | N.A | ALL | • Shorter hospital stay and lower mortality | [246] |
| IG* | Mediated by the Fe portion of IgG and by the spectrum of variable (V) regions contained in the immune globulin preparations | Malignant lymphoma and MM idiopathic thrombocytopenic purpura, Kawasaki disease, Guillain-Barré syndrome, dermatomyositis |
• Immunomodulatory properties • Involved in association with T cell surface molecules critical for immune regulation, such as αβ TCR, CD5, CD4, invariant components of MHC class I molecules, and T- and B-cell adhesion molecules • Increased platelet count |
[247] |
| AZD1222* | Replication-deficient simian adenovirus expressing SARS-CoV-2 spike protein | WM, CLL, and NHL |
• Neutralization of antibodies and antigen-specific T cells against SARS-CoV-2 spike protein • After the first vaccine dose, WM/CLL/NHL patients had lower neutralizing Ab titers than controls |
[248, 249] |
| Anakinra* | Recombinant human IL-1 receptor antagonis | HLH | • Anti-IL1 | [250] |
Abbreviations: ALL Acute lymphoid leukemia, AML Acute myeloid leukemia, B-NHL B-cell non-Hodgkin lymphoma, CAR Chimeric antigen receptor, CLL Chronic lymphocytic leukemia, CML Chronic myeloid leukemia, DVM Donor versus malignancy, DVR Donor versus recipient, HCT Hematopoietic cell transplantation, HSCT Hematopoietic stem cell transplantation, HLH Hemophagocytic lymphohistiocytosis, HZ herpes zoster, Hatg Horse anti-thymocyte globulin, IG Immune globulin, IgG Immunoglobulin gamma, IL Interleukin, MCL Mantle cell lymphoma, NHL Non-Hodgkin lymphoma, NDPs Nucleoside diphosphates, RVD Recipient versus donor, RTX Rituximab, RdRp RNA-dependent RNA polymerase, SCA Sickle cell anemia, SLL Small lymphocytic lymphoma, WM Waldenstrom Macroglobulinemia, XLA X-linked agammaglobulinemia
*Hypotheses about the use of vaccines and other treatments, as well as the possibility of finding new treatment methods in people with blood diseases exposed to this virus, have been proposed with further studies
**It is important to mention that with the progress in treatments, HERVs can be part of side effects related to treatment and drug resistance mechanisms. For example, aberrant transcription of MDR-1 by ERV1 LTR MER57 found in lymphoma cells is a clear example. As a result, to reduce the transcription of harmful genes, several inhibitors of DNA methyltransferase (DNMT) and histone deacetylase (HDAC) are used in the treatment of malignancies