Immunogenicity and safety of SARS-CoV-2 mRNA vaccine in patients with nephrotic syndrome receiving immunosuppressive agents.

BACKGROUND: As there are no large-scale reports of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) mRNA vaccination in patients with nephrotic syndrome using immunosuppressive agents, we conducted the prospective study. METHODS: SARS-CoV-2 mRNA vaccines were administered to patients with nephrotic syndrome receiving immunosuppressive agents. The titers of SARS-CoV-2 spike protein receptor-binding domain antibodies were measured before and after vaccination. We evaluated factors associated with antibody titers after vaccination and analyzed adverse events. RESULTS: We enrolled 40 patients and evaluated vaccine immunogenicity in 35 of them. Seroconversion (> 0.8 U/mL) was achieved in all patients, and the median antibody titer was 598 U/mL (interquartile range, 89-1380 U/mL). Patients using mycophenolate mofetil (MMF) showed lower antibody titers than those who were not (median: 272 U/mL vs. 2660 U/mL, p = 0.0002), and serum immunoglobulin G (IgG) levels showed a weak linear relationship with antibody titers (R2 = 0.16). No breakthrough infections were noted. Three patients (7.5%) suffered from a relapse of nephrotic syndrome (2 and 3 days, respectively, after the first dose and 8 days after the second dose), two of whom had a history of relapse within 6 months before the vaccination. CONCLUSIONS: The SARS-CoV-2 mRNA vaccine was immunogenic in patients with nephrotic syndrome using immunosuppressive agents, although the use of MMF and low levels of serum IgG were associated with lower antibody titers after vaccination. Patients with high disease activity may experience a relapse of nephrotic syndrome after vaccination. A higher resolution version of the Graphical abstract is available as Supplementary information.

Immunogenicity and safety of SARS-CoV-2 vaccine with immunosuppressive agents.

BACKGROUND: We conducted a prospective study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccination in children and adolescents who were taking immunosuppressive agents. METHODS: Two doses of SARS-CoV-2 mRNA vaccine were administered to patients taking immunosuppressive agents. Titers of SARS-CoV-2 spike protein receptor-binding domain antibodies were measured before and after vaccination. Vaccine failure was defined as a postvaccination antibody titer of <0.8 U/mL. Seroconversion rates, factors associated with antibody titers after vaccination, clinical effectiveness against breakthrough infection, and adverse events were evaluated. RESULTS: A total of 42 patients (median age, 18.1 years) were enrolled. Immunogenicity was measured in 34 patients. The median SARS-CoV-2 spike antibody titer was 329 U/mL (interquartile range [IQR] 50-812 U/mL). Seroconversion (≥0.8 U/mL) was achieved in 29 patients (85%), whereas vaccine failure was diagnosed in five (15%). All patients with vaccine failure were recipients of solid organ transplants (SOTs) and were taking two immunosuppressants. The median antibody titer in SOT recipients (57 U/mL) was significantly lower than that in non-recipients (653 U/mL, P = 0.0002); that of patients taking two immunosuppressive agents (93 U/mL) was lower than that of patients taking one (506 U/mL, P = 0.003). Breakthrough infection occurred in three patients (7%). Adverse events were non-specific, and no flares of primary disease or acute rejection in SOT recipients occurred. CONCLUSIONS: SARS-CoV-2 mRNA vaccine was immunogenic in children and adolescents taking immunosuppressive agents, although SOT recipients and patients taking two immunosuppressive agents tended to show lower postvaccination antibody titers.

Immunogenicity and safety of SARS‐CoV‐2 vaccine with immunosuppressive agents

Background We conducted a prospective study of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) messenger RNA (mRNA) vaccination of children and adolescents who were taking immunosuppressive agents. Methods Two doses of SARS‐CoV‐2 mRNA vaccine were administered to patients taking immunosuppressive agents. Titers of SARS‐CoV‐2 spike protein receptor‐binding domain antibodies were measured before and after vaccination. Vaccine failure was defined as a postvaccination antibody titer of <0.8 U/mL. Seroconversion rates, factors associated with antibody titers after vaccination, clinical effectiveness against breakthrough infection, and adverse events were evaluated. Results A total of 42 patients (median age, 18.1 years) were enrolled. Immunogenicity was measured in 34. The median SARS‐CoV‐2 spike antibody titer was 329 U/mL (interquartile range [IQR] 50–812 U/mL). Seroconversion (≥0.8 U/mL) was achieved in 29 patients (85%), whereas vaccine failure was diagnosed in 5 (15%). All patients with vaccine failure were recipients of solid organ transplants (SOTs) and were taking two immunosuppressants. The median antibody titer in SOT recipients (57 U/mL) was significantly lower than that in nonrecipients (653 U/mL, p = 0.0002), and that of patients taking two immunosuppressive agents (93 U/mL) was lower than that of patients taking one (506 U/mL, p = 0.003). Breakthrough infection occurred in three patients (7%). Adverse events were nonspecific, and no flares of primary disease or acute rejection in SOT recipients occurred. Conclusions SARS‐CoV‐2 mRNA vaccine was immunogenic in children and adolescents taking immunosuppressive agents, although SOT recipients and patients taking two immunosuppressive agents tended to show lower postvaccination antibody titers.

Persistence of Robust Humoral Immune Response in Coronavirus Disease 2019 Convalescent Individuals Over 12 Months After Infection.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicits varying degrees of protective immunity conferred by neutralizing antibodies (nAbs). In this study, we report the persistence of nAb responses over 12 months after infection despite their decreasing trend noticed from 6 months. METHODS: The study included sera from 497 individuals who had been infected with SARS-CoV-2 between January and August 2020. Samples were collected at 6 and 12 months after onset. The titers of immunoglobulin (Ig)G to the viral nucleocapsid protein (NP) and receptor-binding domain (RBD) of the spike protein were measured by chemiluminescence enzyme immunoassay. The nAb titer was determined using lentivirus-based pseudovirus or authentic virus. RESULTS: Antibody titers of NP-IgG, RBD-IgG, and nAbs were higher in severe and moderate cases than in mild cases at 12 months after onset. Although the nAb levels were likely to confer adequate protection against wild-type viral infection, the neutralization activity to recently circulating variants in some of the mild cases (~30%) was undermined, implying the susceptibility to reinfection with the variants of concerns (VOCs). CONCLUSIONS: Coronavirus disease 2019 convalescent individuals have robust humoral immunity even at 12 months after infection albeit that the medical history and background of patients could affect the function and dynamics of antibody response to the VOCs.

New-onset pediatric nephrotic syndrome following Pfizer-BioNTech SARS-CoV-2 vaccination: a case report and literature review.

Various new vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been rapidly developed. The new onset and recurrence of nephrotic syndrome triggered by some vaccines have been documented and several adult cases of minimal change nephrotic syndrome newly developing after SARS-CoV-2 vaccination have been reported. However, no reports of pediatric cases have been published. Indications for SARS-CoV-2 vaccines have been expanded to those as young as 12 years old and vaccination of children has just started in Japan. We encountered a 15-year-old boy without underlying disease who newly developed nephrotic syndrome after SARS-CoV-2 vaccination with BNT162b2 (Pfizer-BioNTech). He developed eyelid edema 4 days after vaccination and peripheral edema of the lower extremities a further 4 days later. Twenty-one days after vaccination, 60 mg of oral daily prednisolone was started. He achieved complete remission in 12 days without complications such as hypertension or acute kidney injury. We clinicians should be aware of the possibility of nephrotic syndrome developing after SARS-CoV-2 vaccination, not only in adults, but also in children.

A case of multisystem inflammatory syndrome in children in a Japanese boy: with discussion of cytokine profile.

The new disease concept of multisystem inflammatory syndrome in children (MIS-C), which is a systemic inflammatory syndrome with multiple organ involvement after SARS-CoV2 infection, was established in 2020. MIS-C is common in Hispanic and black children in Europe and North America, with few reports in East Asians. A significant portion of patients with MIS-C develop Kawasaki disease (KD)-like symptoms. Therefore, differential diagnosis is challenging, especially in East Asia, where KD is most prevalent. No Japanese cases have been reported in the literatures so far. We report a case of MIS-C in Japan with KD-like symptoms. A 9-year-old Japanese boy, who was infected with SARS-CoV2 1 month previously along with his family, was admitted to our hospital owing to fever for 6 d and erythema mainly in the groyne and pubic area. He also had conjunctivitis, strawberry tongue and diarrhoea. His laboratory findings were as follows: WBC, 12,840/µL (lymphocytes, 4%); CRP, 22.6 mg/dL, pro-calcitonin, 1.8 ng/mL (normal, <0.50 ng/mL); NT pro-BNP, 7627 pg/mL (<125 pg/mL); and troponin T, 0.14 ng/mL (<0.01 ng/mL). His cardiac function was normal. We initially diagnosed him with KD. His fever rapidly resolved with intravenous immunoglobulin (IVIG) and there were no coronary artery lesions. Desquamation of the fingers was observed later. Finally, a history of SARS-COV2 infection, his age, atypical skin rash, elevation of markers of inflammation and heart failure and lymphopenia suggested the diagnosis of MIS-C rather than KD. Differentiation between KD and MIS-C is necessary even in Japan, especially in patients with atypical features of KD.