Severe consequences of COVID-19 infection among vaccinated kidney transplant recipients

Abstract

To the Editor: As the COVID-19 pandemic has reached its second year, the global worldwide vaccination effort is underway, placing the elderly and higher risk people in higher priority of receiving immunization. These high-risk people include, among others, kidney transplant recipients (KTR), who are known to be vulnerable to higher infection rate and mortality of COVID-19.1Pereira MR Mohan S Cohen DJ et al.COVID-19 in solid organ transplant recipients: initial report from the US epicenter.Am J Transplant. 2020; 20 (https://doi.org/10.1111/ajt.15941): 1800-1808Abstract Full Text Full Text PDF PubMed Scopus (545) Google Scholar A study by Rozen-Zvi et al 2Rozen-Zvi B, Yahav D, Agur T, et al. Antibody response to mRNA SARS-CoV-2 vaccine among kidney transplant recipients—Prospective cohort study [published online ahead of print]. Clin Microbiol Infect. 2021. https://doi.org/10.1016/j.cmi.2021.04.028Google Scholar has shown that over 60% of KTR do not develop appropriate levels of anti-SARS-CoV-2 antibodies, with similar findings seen in liver, heart, and lung transplant recipients,3Rabinowich L, Grupper A, Baruch R, et al. Low immunogenicity to SARS-CoV-2 vaccination among liver transplant recipients [published online ahead of print]. J Hepatol. 2021. https://doi.org/10.1016/j.jhep.2021.04.020Google Scholar, 4Itzhaki Ben Zadok O, Shaul AA, Ben-Avraham B, et al. Immunogenicity of the BNT162b2 mRNA Vaccine in heart transplanted patients—a prospective cohort study [published online ahead of print]. Eur J Heart Fail. 2021. https://doi.org/10.1002/ejhf.2198Google Scholar, 5Shostak Y, Shafran N, Heching M, et al. Early humoral response among lung transplant recipients vaccinated with BNT162b2 vaccine [published online ahead of print]. Lancet Respir Med. 2021. https://doi.org/10.1016/S2213-2600(21)00184-3Google Scholar but it is yet unknown whether these results translate to lower protective effect of the SARS-CoV-2 vaccines. Our KTR follow-up clinical includes 2350 recipients, the majority of whom have been vaccinated with at least one dose of the Pfizer-BioNTech SARS-CoV-2 vaccine (BNT162b2). We have identified 25 KTRs who received at least one vaccine dose and tested positive for SARS-CoV-2 using polymerase chain reaction, at least 14 days after the first dose. Data collection for these patients was approved by our institutional review board, and informed consent was waived. Patient characteristics are detailed in Table 1. Most were male (18/25); median time from transplantation was 4 years (range 0.4–20.8 years). None of the included KTRs had an event of organ rejection within the 12 months prior to vaccination. Eighteen (72%) KTRs who tested positive for SARS-CoV-2 received two vaccine doses prior to infection, 14 of them after over 14 days following the second vaccine dose (median 38, range 4–85 days). Ten KTRs who received two vaccine doses (10/18; 56%) required hospitalization, of whom nine with severe or critical COVID-19 (according to the disease severity classification defined by the World Health Organization), and four required invasive ventilation and later died in hospital. None required renal replacement therapy (RRT) during hospitalization. All hospitalized patients had their antimetabolite discontinued and steroid doses raised; three also had their tacrolimus dosage reduced. Of seven KTRs (28%) who tested positive following one vaccine dose, three (43%) were hospitalized, required mechanical ventilation, and died during hospitalization.TABLE 1Patient characteristicsNo. vaccine dosesGenderAgeTime from transplant (month)ComorbiditiesSource of COVID–19 infectionViremiaaBK virus viremia was defined as viral load of ≥10 000 copies/ml in the last 12 months. All patients were negative for CMV viremia in the 12 months prior to vaccination.BMI (kg/m2)Time from last vaccine dose to positive SARS-CoV–2 test (days)Maintenance therapyHospitalization statusCOVID–19 disease severitycAccording to the World Health Organization (WHO) scale World Health Organization (WHO) guidelines. COVID-19 Clinical management: living guidance (https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1).COVID–19 therapyOutcome1F5583UnknownNone22.57Tac, POutpatientNSNoneDischarged1F5838Family contactbContact with a COVID-19 PCR proven person.None19.114Tac, POutpatientNSNoneDischarged1M5558UnknownBK28.314E, PInpatientCriticalRem, dexaDied1M6048UnknownNone32.618Tac, MMF, POutpatientNSNoneDischarged1M515DM, IHDUnknownNone30.621Tac, MMF, PInpatientCriticalRem, dexa, convDied1M5749DMUnknownNone2422Tac, MMF, POutpatientNSNoneDischarged1F4264HTNUnknownNone22.424Tac, MMF, PInpatientCriticalDexa, convDied2M5123DM, HTN, IHDUnknownBK24.84Tac, MMF, PInpatientMildBamlanivimabDischarged2M3527HTNUnknownNone22.89Tac, MMF, PInpatientSevereNoneDischarged2M3413UnknownNone27.112Tac, MMF, POutpatientMildNoneDischarged2M3416HTMUnknownNone2612Tac, MMF, POutpatientMildNoneDischarged with elevated creatinine2M62246DM, HTNUnknownNone29.725S, MMF, PInpatientCriticalRem, dexa, convDied2M6425DM, IHD, HFUnknownNone3033Tac, MMF, PInpatientSevereRem, dexa, convDischarged2M497DM, HTN, IHD, HFFamily contactbContact with a COVID-19 PCR proven person.None24.635Tac, MMF, PInpatientSevereDexa, convDischarged2M6541DM, HTN, IHDPublic contactbContact with a COVID-19 PCR proven person.None30.436Tac, MMF, PInpatientCriticalRem, dexaDied2F26154Family contactbContact with a COVID-19 PCR proven person.None13.838Tac, MMF, POutpatientNSNoneDischarged2F40237Family contactbContact with a COVID-19 PCR proven person.None20.843Tac, POutpatientNSNoneDischarged2M779DM, HTN, IHDUnknownNone28.646Tac, MMF, PInpatientSevereDexaDischarged2M7859UnknownNone23.852Tac, MMF, POutpatientMildDexaDischarged2M7294IHDUnknownNone25.853Tac, PInpatientCriticalRem, dexa, convDied2M6823DM, HTN, IHD, HFPublic contactbContact with a COVID-19 PCR proven person.None27.553Tac, MMF, POutpatientNSNoneDischarged2M57121UnknownNone23.554Tac, MMF, POutpatientNSNoneDischarged2F6369UnknownNone30.473Tac, MMF, PInpatientSevereNSStill hospitalized2M26250UnknownNone24.885Tac, MMF, POutpatientNSNoneDischarged2F7045DM, HTN, IHD, HFUnknownNone37.1NSTac, MMF, PInpatientCriticalRem, convDiedAbbreviations: BMI, body mass index; Conv, convalescent plasma; Dexa, dexamethasone; DM, diabetes mellitus; E, everolimus; F, female; HF, heart failure; HTN, hypertension; IHD, ischemic heart disease; M, male; MMF, mycophenolic acid; NS, no specified; P-prednisone; Rem, remdesivir; S, sirolimus; Tac, tacrolimus.a BK virus viremia was defined as viral load of ≥10 000 copies/ml in the last 12 months. All patients were negative for CMV viremia in the 12 months prior to vaccination.b Contact with a COVID-19 PCR proven person.c According to the World Health Organization (WHO) scale World Health Organization (WHO) guidelines. COVID-19 Clinical management: living guidance (https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1). Open table in a new tab Abbreviations: BMI, body mass index; Conv, convalescent plasma; Dexa, dexamethasone; DM, diabetes mellitus; E, everolimus; F, female; HF, heart failure; HTN, hypertension; IHD, ischemic heart disease; M, male; MMF, mycophenolic acid; NS, no specified; P-prednisone; Rem, remdesivir; S, sirolimus; Tac, tacrolimus. In summary, our report describes 25 KTRs who had breakthrough COVID-19 infection after receiving one or two doses of mRNA-based SARS-CoV-2 vaccine. Overall, 12 patients were hospitalized with severe-critical disease; seven KTRs died in hospital, and four of them were fully vaccinated with two vaccine doses. Our findings, alongside other data showing lack of appropriate postvaccinated antibody development in KTRs2Rozen-Zvi B, Yahav D, Agur T, et al. Antibody response to mRNA SARS-CoV-2 vaccine among kidney transplant recipients—Prospective cohort study [published online ahead of print]. Clin Microbiol Infect. 2021. https://doi.org/10.1016/j.cmi.2021.04.028Google Scholar and higher morbidity and mortality from COVID-19 in this population,1Pereira MR Mohan S Cohen DJ et al.COVID-19 in solid organ transplant recipients: initial report from the US epicenter.Am J Transplant. 2020; 20 (https://doi.org/10.1111/ajt.15941): 1800-1808Abstract Full Text Full Text PDF PubMed Scopus (545) Google Scholar reinforce the necessity to continue monitoring of KTRs even after receiving vaccination. Moreover, these patients will likely require to continue with social distancing and wearing protective masks for prolonged periods, until the COVID-19 pandemic subsides. Meanwhile, we suggest vaccinating any possible household contacts. Furthermore, as our population received only a single type of vaccine, other studies are required to assess efficacy of other vaccines in this population, including those employing other technologies (e.g., viral vector). Additional booster doses should be considered, either universal or serology-based. The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.

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