The Impact and Treatment of COVID-19 in Hemodialysis Patients

In December 2019, an outbreak of unknown viral pneumonia was reported among patients in Wuhan, Hubei Province, People's Republic of China. Over a short period, infection by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread worldwide. SARS-CoV-2 has been identified as an animal-derived coronavirus and is the same pathogen responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). On 11 March 2020, the World Health Organization (WHO) declared a pandemic status, and SARS-CoV-2 was linked to a severe acute respiratory condition. SARS-CoV-2 has been reported to be stable on environmental surfaces for approximately 3 days. Therefore, preventing infection among staff is crucial in medical institutions. Initial coronavirus disease 2019 (COVID-19) symptoms are similar to those of influenza, including fever, cough, malaise, and dyspnea. The median hospitalization time was 7 days. Diarrhea and taste and smell disorders may occur; however, they are not inevitable. Data from the COVID-19 Registry Japan (COVIREGI-JP), which is a Japanese registry of patients with COVID-19, showed that 60% of hospitalized patients did not require oxygen administration, whereas 30% required oxygen administration, 9% required ventilation or extracorporeal membrane oxygenation (ECMO), and 7.5% died. Therefore, predicting which patients will become critically ill is important for using limited medical resources. In severe cases, COVID-19 causes respiratory tract infection symptoms, such as acute respiratory distress syndrome and cytokine release syndrome (CRS)-like symptoms because of excessive inflammation. Endothelial cell damage and disruption of the immunomodulatory system lead to multiple organs failure. During the COVID-19 pandemic, the number of dialysis cases in the hospital was also reported to have increased greatly, partly due to the involvement of acute kidney injury. Therefore, in addition to antiviral drugs, various therapies have been investigated to suppress excess cytokines, such as steroids, neutralizing antibody therapy, and some blood purification therapies. However, patients undergoing dialysis are prone to severe disease, and their treatment options are limited because of renal dysfunction. This manuscript outlines the current impact of COVID-19 and its treatment in Japanese patients undergoing dialysis.

Multiple studies are summarized regarding COVID-19 in patients with end-stage renal disease (ESRD) and those on maintenance dialysis. Vaccine studies in hemodialysis and peritoneal dialysis populations reported similar efficacy of mRNA vaccination across modalities, with generally lower humoral responses than controls but high seroconversion rates and robust S-protein–reactive T-cell responses. Additional doses (third and fourth) increase antibody production in ESRD and kidney transplant populations. A Japanese analysis found that patients with breakthrough infection after vaccination had lower oxygen demand (OR 0.197, 95% CI 0.120–0.322; p < 0.001) and better prognosis than unvaccinated patients. Reports comparing home versus in-center dialysis suggested lower hospitalization and mortality with home modalities in some settings, though a Japanese registry analysis found no significant differences in overall survival or length of hospitalization between peritoneal dialysis and hemodialysis. Therapeutic literature indicates remdesivir use in dialysis patients is associated with better prognosis and shorter hospital stays in Japanese cohorts, with supportive retrospective data from the United States. Oral antivirals differ in renal considerations: molnupiravir requires no renal dose adjustment, while nirmatrelvir/ritonavir has significant drug–drug interactions and is not recommended in severe renal dysfunction or maintenance dialysis; data for ensitrelvir in renal dysfunction are lacking. Neutralizing monoclonal antibody activity is reduced against Omicron sublineages after BA.2 for sotrovimab, casirivimab-imdevimab, tixagevimab/cilgavimab, whereas bebtelovimab retains activity; small-molecule antivirals (remdesivir, molnupiravir, nirmatrelvir) remain effective against BA.2.12.1, BA.4, and BA.5. Japanese dialysis facilities implemented comprehensive infection control measures with very high uptake (>90%) during the pandemic.

This communication is a narrative review focusing on Japanese patients undergoing hemodialysis. It summarizes national surveillance and registry data from professional societies and governmental sources, and synthesizes published evidence on COVID-19 epidemiology, vaccine efficacy and safety, infection control practices, and therapeutic options (antivirals, immunomodulators, and neutralizing antibodies) relevant to patients on dialysis in Japan. No new primary data collection or interventional study was conducted.

- Infection burden and outcomes in Japanese dialysis patients: As of November 2022, 12,978 dialysis patients had confirmed COVID-19 (infection rate 3.8% of ~340,000 maintenance dialysis patients). There were 658 deaths (mortality rate 5.1%), markedly higher than in the general population (0.2%). Even after emergence of Omicron, mortality among dialysis patients remained higher than in the general population, including in those aged <60 years. - Vaccine effectiveness and immune response: Studies in hemodialysis and peritoneal dialysis patients showed similar mRNA vaccine effectiveness across modalities. Humoral responses were generally lower than in non-ESRD controls, but seroconversion rates and S-protein–reactive T-cell responses were high. Additional booster doses (third and fourth) increased antibody production in ESRD and transplant recipients. In Japan, breakthrough infections after vaccination were associated with reduced oxygen requirement (OR 0.197, 95% CI 0.120–0.322; p < 0.001) and better prognosis compared with unvaccinated patients. - Infection control and care delivery: Dialysis-center patients face higher exposure risk due to limited isolation capabilities. Infection prevention measures (health checks, universal masking around hemodialysis sessions, frequent disinfection) achieved >90% implementation during the pandemic. Policy evolved from routine hospitalization of all infected dialysis patients to selective outpatient management for mild/asymptomatic cases, supplemented by temporary medical facilities with dialysis capacity during surges (e.g., Tokyo in January 2022). - Antiviral therapies: Remdesivir is recommended within 7 days of onset for mild-to-moderate disease. In Japanese matched cohorts of hemodialysis patients (N=98 remdesivir vs N=294 no remdesivir), remdesivir was associated with better prognosis and shorter hospital stay. A U.S. retrospective cohort (N=486; 407 hemodialysis, 79 peritoneal dialysis) reported an estimated 30-day mortality hazard of 0.74 (95% CI 0.52–1.05) in remdesivir-treated versus untreated patients. Molnupiravir requires no renal dose adjustment and is feasible in outpatient dialysis settings, though capsule size may limit tolerability. Nirmatrelvir/ritonavir has significant CYP3A-mediated drug–drug interactions, requires dose adjustment in moderate renal impairment, and is not recommended for severe renal dysfunction or maintenance dialysis. Clinical trial data for ensitrelvir in renal dysfunction were not available. - Monoclonal antibodies and variants: Neutralizing activity of sotrovimab, casirivimab-imdevimab, and tixagevimab/cilgavimab is reduced against Omicron sublineages after BA.2, whereas bebtelovimab retains high activity against BA.2.12.1, BA.4, and BA.5. Small-molecule antivirals (remdesivir, molnupiravir, nirmatrelvir) remain effective against these subvariants.

Patients on maintenance hemodialysis are at elevated risk for SARS-CoV-2 exposure and severe outcomes, reflected by higher infection fatality compared with the general population, persisting even in the Omicron era. The reviewed data underscore the centrality of vaccination—including boosters—in mitigating severity, as evidenced by lower oxygen requirements and improved outcomes in breakthrough cases. Given renal constraints and drug–drug interactions, therapeutic strategies should prioritize agents with demonstrated safety and feasibility in dialysis (e.g., remdesivir, molnupiravir), while exercising caution with nirmatrelvir/ritonavir and recognizing the reduced efficacy of several monoclonal antibodies against newer variants. Robust infection control within dialysis facilities and adaptive healthcare delivery models (including outpatient management for mild cases and surge capacity with dialysis access) are critical to protect this high-risk population. Collectively, these findings support aggressive prevention (vaccination, infection control) and judicious use of effective antivirals tailored to renal status to reduce morbidity and mortality in dialysis patients.

This paper outlines the impact and treatment of COVID-19 on patients undergoing hemodialysis, which has not yet reached a global consensus. Therefore, it is important to continue to elucidate the pathogenesis of severe disease in patients with hemodialysis, leading to expanded vaccination and the establishment of more effective treatment strategies.

Findings are synthesized from heterogeneous observational studies and registries, limiting causal inference. Immune response studies vary in design and endpoints, and some therapeutic agents (e.g., ensitrelvir) lack clinical trial data in patients with renal dysfunction or on maintenance dialysis. Neutralizing monoclonal antibody efficacy is variant-dependent and diminished against several Omicron sublineages. Much of the data and policy context are specific to Japan, which may limit generalizability.