EVA injection has been effective in preventing the onset of COVID-19, with a reduction rate of 71.5% [1]. Similar prophylactic efficacy was observed in our cohort. A systematic review and meta-analysis revealed that EVA was [2] 40.54%, 66.19%, 82.13%, and 92.39% effective in preventing COVID-19 breakthrough infection, hospital admission, intensive care admission, and COVID-specific mortality, respectively. In general, the prophylactic administration of passive antibodies is a tentative procedure for endemic viral infection because emerging resistance for monoclonal antibodies increases from viral spike protein mutation. After the pandemic COVID-19, the Food and Drug Administration approved three products of dual or single neutralizing antibodies for SARS-CoV-2, including bamlanivimab/etesevimab, casirivimab/imadevimab (Ronapreve®), sotrovimab (Xevudy®), and cilgavimab/tixagevimab (Evasheld®) [3]. EVA was the first intramuscularly injectable monoclonal antibody, especially for immunocompromised, mainly hematological malignancies. The Japanese MHWL recommended EVA as a prophylactic neutralizing antibody for the prophylaxis of SARS-CoV-2 infection. The first two monoclonal antibodies were treatable for mild to moderate COVID-19 illness with high risks for progressing to severe COVID-19, including elderly, immunodeficient, and having chronic diseases. In contrast, EVA was specially recommended, specifically for the specific immunocompromised, to treat COVID-19 infection or prevent infection. In the preventable use of EVA, the target population is hematological malignancies and solid/stem cell transplantation recipients, patients treated with lymphodepletion therapy with rituximab, and those with HIV.
All clinical data for EVA efficacy were obtained during the omicron-predominant era [2]. Clinical outcomes change depending on the endemic strain of SARS-CoV-2. Therefore, we estimate that the outbreak of mutant strains, such as XBB in Japan after April 2023, may have affected the study results. Our institutional policy recommended EVA administration in each department decision. At the least, our department protocol was systematic and covered all indicated patients. Our special research interest in this cohort was the total period to complete all the administration subjects to undergo EVA injection. We have almost administered EVA injection in 13 weeks, which we completed in 18 weeks. In Japan, the Japanese Society of Hematology released a statement for the use of EVA in August 2022. We started to inject EVA into our institute in November 2022. The preparation period was 3 months, which was spent negotiating and coordinating how to develop systematic injection in our institute. This preparation period should be shortened and minimized for rapid completion of the injection. Thus, all the total period from an initial government intention to a completion of injection were 6 months. For optimal prevention and control of COVID-19 epidemic wave, we need more rapid preparation of neutralizing antibody for vulnerables [4].
Passive monoclonal antibodies for COVID-19 prophylaxis were indicated among the high-risk, more vulnerable population such as those immunocompromised. EVA was approved only for immunocompromised patients undergoing cancer chemotherapy, including rituximab, hematopoietic stem cell transplantation, and CAR-T [5,6]. We experienced long-lasting COVID-19 reactivation [7], also known as long COVID [8]. In Japan, EVA administration has been limited only to prophylaxis among high-risk recipients and immunocompromised patients, including during lymphodepletion procedures. In reviewing the promising efficacy of EVA in patients with COVID-19 as a monoclonal antibody treatment [9], we feel a need to continuously harbor neutralizing antibodies “off-the-shelf,” which completely cover endemic SARS-CoV-2 strains. We recall a dismal sequence and clinical outcome among patients with hematological malignancies after COVID-19 complications. Engaging in treating patients in hematooncology aside from holding adequate neutralizing antibodies for COVID-19 strain in trend would be optimal, toward an era with COVID-19 [10].
The duration of viral protection is estimated to be at least six months [1]. In general, neutralizing antibodies for specific pathogens, such as endemic viruses, are required to treat within a period during which antibody-susceptive strains are spreading. The efficacy of adaptive antibodies lasts for several months. Circulating antibodies have up to 3 months of half-life in the monitoring study of injected neutralizing antibodies [11]. SARS-CoV-2 continuously changes to a new strain clone or new subtype, which should be resistant to available neutralizing antibodies. In such a situation, rapid prophylactic administration of neutralizing antibodies for all vulnerable individuals is most important. We required rapid completion of the overall EVA administration in our planned procedure because completing 95% of the administration took three months. Planning for mass vaccinations was considered necessary to promptly complete administration.
The limitations of our research are as follows. The EVA nontreated group, which was the comparison group, included a small number of cases, and bias may have existed based on patient reasons. Monitoring of the antibody acquisition rate and background of coronavirus vaccination have not been evaluated.
In conclusion, comparable prophylactic efficacy was confirmed by EVA administration in our study cohort, similar to the pivotal study [1]. No serious adverse events related to EVA administration were observed, and safety was fully acceptable. However, our study was conducted in a single center experience, and thus comprehensive management and systematic injection of prophylactic EVA yielded safer and more effective outcomes. Rapid preparation and protocol for prophylactic injection of EVA would have a preferable influence on clinical impact.
Table 1
Details of indicated diseases (1) Criteria from the Minister of Health and Labor Welfare (MHLW)
Patients with primary immunodeficiency who exhibit antibody production deficiency or combined immunodeficiency |
Patients who have received B-cell depletion therapy (such as rituximab) within 1 year |
Patients receiving Bruton’s tyrosine kinase inhibitors |
Chimeric antigen receptor T-cell recipient |
Recipients after hematopoietic stem cell transplantation who have chronic graft-versus-host disease or are taking immunosuppressive medications for another indication |
Patients with hematological malignancies receiving active treatment |
Lung transplant recipient |
Patients who have received a solid organ transplant (other than lung transplant) within 1 year |
Solid organ transplant recipients who have recently been treated with T-cell or B-cell-depleting agents for acute rejection |
Untreated HIV patients with CD4 T lymphocyte count of < 50 cells/µL |
(2) Criteria from the Japanese Society of Hematology
Patients who have received B-cell depletion therapy (such as rituximab) within 1 year |
| 1) Upon transition from inpatient to outpatient treatment after initial treatment induction |
| 2) During treatment or after completion of treatment within 1 year |
Hematopoietic stem cell transplantation recipients |
| 1) Before the preparation regimen for transplantation |
| 2) At stable conditions from engraftment to discharge |
| 3) The recipients taking immunosuppressants after transplantation |
Chimeric antigen receptor T cell (CAR-T) recipients |
| 1) After leukocyte apheresis |
| 2) At the stable condition from CAR-T therapy to discharge |
| 3) Persistent lymphodepletion after CAR-T therapy |