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BACKGROUND: Delayed graft function is a manifestation of acute kidney injury unique to transplantation usually related to donor ischemia or recipient immunological causes. Ischemia also considered the most important trigger for innate immunity activation and production of non-HLA antibodies. While ischemia is inevitable after deceased donor transplantation, this complication is rare after living transplantation. Heterologous Immunity commonly used to describe the activation of T cells recognizing specific pathogen-related antigens as well unrelated antigens is common post-viral infection. In transplant-setting induction of heterologous immunity that cross-react with HLA-antigens and subsequent reactivation of memory T cells can lead to allograft rejection. METHODS: Here we describe a non-sensitized child with ESRD secondary to lupus nephritis and recent history of COVID-19 infection who experienced 17 days of anuria after first kidney living transplantation from her young HLA-haploidentical uncle donor. Graft histology showed acute cellular rejection, evidence of mild antibody-mediated rejection and vascular wall necrosis in some arterioles suggesting possibility of intraoperative graft ischemia. Both pre- and post-transplant sera showed very high level of several non-HLA antibodies. RESULTS: The patient was treated for cellular and antibody-mediated rejection while maintained on hemodialysis before her graft function started to improve on day seventeen post transplantation. CONCLUSION: The cellular rejection likely trigged by ischemia that activated T-cells-mediated immunity. The high level of non- HLA-antibodies further aggravated the damage and the rapid onset of rejection may be partly related to memory T-cell activation induced by heterologous immunity.
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It is well known that several viral infections are capable of triggering the formation of HLA antibodies; however, an association between SARS-CoV-2 and the development of anti-HLA antibodies is not yet confirmed. In this study, we compared the prevalence of HLA antibody before and after COVID-19 infection in a cohort of 3 groups included 58 healthy nonsensitized employees (HNEs), 130 kidney transplant recipients (KTRs), and 62 kidney transplant candidates. There were no significant changes observed in HLA class I antibodies in any of the groups, but evaluation of antibodies to HLA class II revealed a significant change in the KTR group (P = .0184) after acquiring COVID-19 infection and in the HNE group (P = .0043) when compared to the reported prevalence in a similar population. Although we observed the emergence of convalescent de novo donor-specific antibodies in 2 patients, we did not encounter any rejection episodes in the KTR group. Finally, the results of flow cytometry crossmatch in the HNE group were not consistent with the state of antibodies. In conclusion, COVID-19 infection has the potential to produce class II antibodies but with little effect on preexisting sensitization. These antibodies are likely to be transient and not necessarily causing positive crossmatch with the corresponding antigens at the proper mean fluorescent intensity and therefore should not affect access to transplantation. There is a need for further evaluation to ascertain the genuineness of these antibodies and their exact effect on transplant readiness and outcomes.
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Background: Assessing the humoral immune response to SARS-CoV-2 is crucial for inferring protective immunity from reinfection and for assessing vaccine efficacy. Data regarding the durability and sustainability of SARS-CoV-2 antibodies are conflicting. In this study, we aimed to determine the seroconversion rate of SARS-CoV-2 infection in a cohort of reverse-transcriptase polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infections and the antibody dynamics, durability, and the correlation of antibody titers with disease severity using the commercially available SARS-CoV-2 anti-spike (S1/S2) protein. Methods: A total of 342 subjects with PCR-confirmed COVID-19 were enrolled. A total of 395 samples were collected at different time points (0-204) after the onset of symptoms or from the day of positive PCR in asymptomatic patients. Demographics, clinical presentation and the date of PCR were collected. All samples were tested using the automated commercial chemiluminescent system (DiaSorin SARS-CoV-2 S1/S2 IgG) on the LIAISONXL® platform (LIAISON). Results: The seroconversion rate for samples collected 14 days after the onset of infection was much higher than that for samples collected before 14 days (79.4% vs. 39.4%). The rate of seroconversion in symptomatic participants (62.1%) was similar to that of asymptomatic participants (56.1%) (p = 0.496). The IgG titer distribution was also similar across both groups (p = 0.142), with a median IgG level of 27.86 AU/ml (3.8-85.5) and 15 AU/ml (3.8-58.85) in symptomatic and asymptomatic participants, respectively. However, IgG titers were significantly higher in ICU patients, with a median of 104 AU/ml (3.8-179) compared to 34 AU/ml (3.8-70) in the non-ICU participants (p < 0.0001). Furthermore, the median time to seroconversion occurred significantly faster in ICU patients than in non-ICU participants (19 versus 47 days) (P < 0.0001). IgG titers were also higher in subjects ≥50 years compared to those <50 years (p < 0.009), male compared to female (p < 0.054) and non-Saudi compared to Saudi (p < 0.003). Approximately 74% of all samples tested beyond 120 days were positive. Conclusion: Antibodies can persist in circulation for longer than 4 months after COVID-19 infection. The majority of patients with COVID-19 mounted humoral immune responses to SARS-CoV-2 infection that strongly correlated with disease severity, older age and male gender. However, the population of individuals who tested negative should be further evaluated.
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BACKGROUND: The seroprevalence of SARS-CoV-2 infection has been studied in immunocompetent children. However, data in the pediatric kidney transplant population (PKT) are lacking. METHODS: Using two commercial immunoassays that measured IgG antibodies against SARS-CoV-2 spike protein and IgG against the nucleocapsid (N) protein, we screened 72 PKT recipients who attended the outpatient clinic for routine blood work. The majority of patients with positive serology underwent an additional serology test at least once during subsequent clinical follow-up. Patients were confirmed to have SARS-CoV-2 infection if they had two positive tests. RESULTS: Eight patients out of the 72 screened (11.1%) had positive results for SARS-CoV-2 IgG antibodies in both serological tests. Of those who tested positive, 4 had positive SARS-CoV-2 PCR results before screening. All patients were asymptomatic or had a history of mild symptoms. All tested patients had persistently positive antibodies at a median follow-up time of 75 days (IQR, 44.5, 86.5 days). One patient had a positive PCR test at 75 days and a positive serology test at 120 days post infection. CONCLUSION: The seroprevalence of SARS-CoV-2 was relatively high (11.1%) in our population. Although all patients were asymptomatic or mildly symptomatic, they mounted a strong humoral immune response that persisted for a few months despite being on triple immunosuppressants. These findings have positive implications regarding vaccination efficacy in this group.
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OBJECTIVES: In this study, we aimed to study the clinical presentations, and viral clearance of SARS-COV-2 positive quarantined individuals. DESIGN: Cross-sectional study. SETTING: Governmental- designated facility in the eastern province, Saudi Arabia. PARTICIPANTS: 128 laboratory-confirmed COVID-19 quarantined individuals who had a history of travel abroad in the last 14 days before the quarantine or were in direct contact with laboratory-confirmed cases. The study was from March 18th-till April 16th. PRIMARY AND SECONDARY MEASURES: The clinical presentation, prevalence of asymptomatic carriers among SARS-COV-2 positive quarantined subjects, and the difference between virus clearance among symptomatic and asymptomatic individuals. RESULTS: Sixty-nine of the 128 residents (54%) were completely asymptomatic until the end of the study. The remaining 59 residents (46%) had only mild symptoms. The most common symptom was a sudden loss of smell and taste, accounting for 47.5%. The median time to virus clearance was significantly different between the two groups. Symptomatic residents cleared the virus at a median of 17 days (95% CI, 12.4-21.6) from the first positive PCR vs. 11days (95% CI, 8.7-13.3) in the asymptomatic group (P = 0.011). False-negative test results occurred in 18.8% of the total residents and false-positive results in 3%. CONCLUSION: The prevalence of asymptomatic carriers among quarantined travelers and those identified by contact tracing is high in our study. Therefore, testing, tracing, and isolating travelers and contacts of laboratory-confirmed cases, regardless of symptoms, were very effective measures for early disease identification and containment. Loss of taste and smell were the most common presentations in our mild symptomatic residents and should be used as a screening tool for COVID-19. The persistent positive PCR beyond 14 days observed in the mild symptomatic residents despite being symptoms free, warrant further studies to determine its implications on disease spread and control.