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Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in solid organ transplant (SOT) recipients is associated with poorer antibody response (AbR) compared with non-SOT recipients. However, its impact on the risk of breakthrough infection (BI) has yet to be assessed., Methods: Single-center prospective longitudinal cohort study enrolling adult SOT recipients who received SARS-CoV-2 vaccination during a 1-year period (February 2021 - January 2022), end of follow-up April 2022. Patients were tested for AbR at multiple time points. The primary end-point was BI (laboratory-confirmed SARS-CoV-2 infection ≥14 days after the second dose). Immunization (positive AbR) was considered an intermediate state between vaccination and BI. Probabilities of being in vaccination, immunization, and BI states were obtained for each type of graft and vaccination sequence using multistate survival analysis. Then, multivariable logistic regression was performed to analyze the risk of BI related to AbR levels., Results: 614 SOT (275 kidney, 163 liver, 137 heart, 39 lung) recipients were included. Most patients (84.7%) received 3 vaccine doses. The first 2 consisted of BNT162b2 and mRNA-1273 in 73.5% and 26.5% of cases, respectively. For the third dose, mRNA-1273 was administered in 59.8% of patients. Overall, 75.4% of patients reached immunization and 18.4% developed BI. Heart transplant recipients showed the lowest probability of immunization (0.418) and the highest of BI (0.323); all mRNA-1273 vaccine sequences showed the highest probability of immunization (0.732) and the lowest of BI (0.098). Risk of BI was higher for non-high-level AbR, younger age, and shorter time from transplant., Conclusions: SOT patients with non-high-level AbR and shorter time from transplantation and heart recipients are at highest risk of BI., Competing Interests: Potential conflicts of interest. G. C. reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Alexion, Novartis, and Hansa. C. G. reports receipt of a research grant for performing serological tests. M. G. reports participation in advisory boards on Nirmatrelvir/Ritonavir (Pfizer). L. S. reports support for attending meetings and/or travel from European Society of Clinical Microbiology and Infectious Diseases (ESCMID). P. V. reports consulting fees from bioMérieux, Mundipharma, AstraZeneca, Tillots Pharma, Gilead, Shionogi, Sobi, Advanzpharma, MSD, Angelini, and Pfizer. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: Extracellular vesicles (EVs) and particles (EPs) represent reliable biomarkers for disease detection. Their role in the inflammatory microenvironment of severe COVID-19 patients is not well determined. Here, we characterized the immunophenotype, the lipidomic cargo and the functional activity of circulating EPs from severe COVID-19 patients (Co-19-EPs) and healthy controls (HC-EPs) correlating the data with the clinical parameters including the partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) and the sequential organ failure assessment (SOFA) score., Methods: Peripheral blood (PB) was collected from COVID-19 patients (n=10) and HC (n=10). EPs were purified from platelet-poor plasma by size exclusion chromatography (SEC) and ultrafiltration. Plasma cytokines and EPs were characterized by multiplex bead-based assay. Quantitative lipidomic profiling of EPs was performed by liquid chromatography/mass spectrometry combined with quadrupole time-of-flight (LC/MS Q-TOF). Innate lymphoid cells (ILC) were characterized by flow cytometry after co-cultures with HC-EPs or Co-19-EPs., Results: We observed that EPs from severe COVID-19 patients: 1) display an altered surface signature as assessed by multiplex protein analysis; 2) are characterized by distinct lipidomic profiling; 3) show correlations between lipidomic profiling and disease aggressiveness scores; 4) fail to dampen type 2 innate lymphoid cells (ILC2) cytokine secretion. As a consequence, ILC2 from severe COVID-19 patients show a more activated phenotype due to the presence of Co-19-EPs., Discussion: In summary, these data highlight that abnormal circulating EPs promote ILC2-driven inflammatory signals in severe COVID-19 patients and support further exploration to unravel the role of EPs (and EVs) in COVID-19 pathogenesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Forte, Pellegrino, Trabanelli, Tonetti, Ricci, Cenerenti, Comai, Tazzari, Lazzarotto, Buratta, Urbanelli, Narimanfar, Alabed, Mecucci, La Manna, Emiliani, Jandus, Ranieri, Cavo, Catani and Palandri.)

BACKGROUND Rhabdomyolysis is a syndrome characterized by muscle necrosis and the subsequent release of intracellular muscle constituents into the bloodstream. Although the specific cause is frequently evident from the history or from the immediate events, such as a trauma, extraordinary physical exertion, or a recent infection, sometimes there are hidden risk factors that have to be identified. For instance, individuals with sickle cell trait (SCT) have been reported to be at increased risk for rare conditions, including rhabdomyolysis. Moreover, there have been a few case reports of SARS-CoV-2 infection-related rhabdomyolysis. CASE REPORT We present a case of a patient affected by unknown SCT and admitted with SARS-CoV-2 pneumonia, who suffered non-traumatic non-exertional rhabdomyolysis leading to acute kidney injury (AKI), requiring acute hemodialysis (HD). The patients underwent 13 dialysis session, of which 12 were carried out using an HFR-Supra H dialyzer. He underwent kidney biopsy, where rhabdomyolysis injury was ascertained. No viral traces were found on kidney biopsy samples. The muscle biopsy showed the presence of an "open nucleolus" in the muscle cell, which was consistent with virus-infected cells. After 40 days in the hospital, his serum creatinine was 1.62 mg/dL and CPK and Myoglobin were 188 U/L and 168 ng/mL, respectively; therefore, the patient was discharged. CONCLUSIONS SARS-CoV-2 infection resulted in severe rhabdomyolysis with AKI requiring acute HD. Since SARS-CoV-2 infection can trigger sickle-related complications like rhabdomyolysis, the presence of SCT needs to be ascertained in African patients.

Background: The acute and long-term effects of severe acute respiratory syndrome coronavirus 2 infection in individuals with GN are still unclear. To address this relevant issue, we created the International Registry of COVID-19 infection in GN., Methods: We collected serial information on kidney-related and -unrelated outcomes from 125 GN patients (63 hospitalized and 62 outpatients) and 83 non-GN hospitalized patients with coronavirus disease 2019 (COVID-19) and a median follow-up period of 6.4 (interquartile range 2.3-9.6) months after diagnosis. We used logistic regression for the analyses of clinical outcomes and linear mixed models for the longitudinal analyses of eGFR. All multiple regression models were adjusted for age, sex, ethnicity, and renin-angiotensin-aldosterone system inhibitor use., Results: After adjustment for pre-COVID-19 eGFR and other confounders, mortality and AKI did not differ between GN patients and controls (adjusted odds ratio for AKI=1.28; 95% confidence interval [CI], 0.46 to 3.60; P =0.64). The main predictor of AKI was pre-COVID-19 eGFR (adjusted odds ratio per 1 SD unit decrease in eGFR=3.04; 95% CI, 1.76 to 5.28; P <0.001). GN patients developing AKI were less likely to recover pre-COVID-19 eGFR compared with controls (adjusted 6-month post-COVID-19 eGFR=0.41; 95% CI, 0.25 to 0.56; times pre-COVID-19 eGFR). Shorter duration of GN diagnosis, higher pre-COVID-19 proteinuria, and diagnosis of focal segmental glomerulosclerosis or minimal change disease were associated with a lower post-COVID-19 eGFR., Conclusions: Pre-COVID-19 eGFR is the main risk factor for AKI regardless of GN diagnosis. However, GN patients are at higher risk of impaired eGFR recovery after COVID-19-associated AKI. These patients (especially those with high baseline proteinuria or a diagnosis of focal segmental glomerulosclerosis or minimal change disease) should be closely monitored not only during the acute phases of COVID-19 but also after its resolution., Competing Interests: O. Bestard reports patents and inventions with Oxford Immunotec and is associate editor of Transplant International and Frontiers in Immunology. A. Bruchfeld reports consultancy agreements with AstraZeneca, Chemocentryx, Fresenius, and Merck; a research grant from AstraZeneca; honoraria from Bayer, Chemocentryx, Fresenius, Merck, and Vifor; and is a member of the ERA-EDTA scientific advisory board 2018–2024, chair of the ERA-EDTA Immunonephrology Working Group, and vice-chair of the Swedish Renal Fund. G. Comai reports honoraria from Alexion, Astellas, and Novartis. P. Cravedi reports honoraria as an advisor for Chinook Therapeutics and is associate editor for the Journal of Nephrology and the American Journal of Transplantation. G. Fernandez Juarez reports research funding from Instituto Salud Calos III and honoraria from Alexion and GSK. E. Fiaccadori is on the editorial board of the Journal of Nephrology and Blood Purification and is a member of the Italian Society of Nephrology and the European Society of Parenteral and Enteral Nutrition. O. Flossmann reports consultancy agreements with Vifor Pharma has other interests/relationships with the British Medical Association, European Vasculitis Society, Renal Association (UK), Royal College of Physicians London, and UK Ireland Vasculitis Society. C. García-Carro reports consultancy agreements with Astellas, AstraZeneca, Boehringer Ingelheim Lilly, Esteve, Novartis and Baxter, Novo Nordisk, and Otsuka; honoraria from Astellas, AstraZeneca, Boehringer Ingelheim Lilly, Esteve, Novartis and Baxter, Novo Nordisk, and Otsuka; and is a scientific advisor for or member of AstraZeneca, Boehringer Ingelheim Lilly, Mundipharma, and Novo Nordisk. M. Griffith reports honoraria from Retrophin’s advisory board. A. J. Hamilton is on the editorial board of the Journal of Kidney Care and is a member of the SONG-Kids Life Participation Expert Working Group. T. Leach reports honoraria from Janssen for conference attendance in 2012 and is a scientific advisor to the National Institute for Health and Care Excellence. L. Lightstone reports consultancy agreements with Achillion, Alexion, AstraZeneca, Aurinia, BMS, GSK, Kezar, Novartis, Pfizer, and Roche; honoraria from Alexion, AstraZeneca, BMS, GSK, and Pfizer; is a scientific advisor or member of EU Exec Lupus Nephritis Trials Network; is on the advisory board of Nature Reviews Nephrology; participates in a speakers’ bureau for Alexion and GSK; is a trustee of Kidney Research UK 2018–2022; is an executive member of the International Society of Nephrology 2021–2023; is deputy chair of Western Regional Board of the International Society of Nephrology; and is a clinical expert representing the Renal Association response to NICE on STA for belimumab in lupus 2020–2021. U. Maggiore reports consultancy agreements with Biotest, Chiesi, GSK, Hansa, Novartis, Sandoz, and Takeda. J. Manrique is a scientific advisor for or member of AstraZeneca, Boehringer, and Viphor Pharma. E. Morales reports consultancy agreements with Alexion, Celgene, Viphor Fresenius, and Vifor Pharma. J.A. Niño-Cruz reports research funding from Pfizer Scientific Institute and participates in a speakers’ bureau for Takeda and Roche. A. Ortiz reports consultancy agreements with Retrophin and Sanofi Genzyme; research funding from AstraZeneca, Mundipharma, and Sanofi Genzyme; honoraria from Advicciene, Alexion, Amgen, Amicus, Astellas, AstraZeneca, Bayer, Chiesi, Fresenius Medical Care, Idorsia, Kyowa Kirin, Menarini, Otsuka, Sanofi Genzyme, and Vifor Fresenius Medical Care Renal Pharma; is a member of the Spanish Society of Nephrology; is editor-in-chief of the Clinical Kidney Journal; is on the editorial boards of the Journal of Nephrology, Journal of the American Society of Nephrology, and Peritoneal Dialysis International; is a member of SOMANE and ERA Councils; is on the board of directors for IIS-Fundacion Jimenez Diaz UAM; is on the scientific advisory board of the Dutch Kidney Foundation; honoraria listed above are for speaker engagements: Advicciene, Alexion, Astellas, AstraZeneca, Amicus, Amgen, Bayer, Chiesi, Fresenius Medical Care, Idorsia, Kyowa Kirin, Menarini, Otsuka, Sanofi Genzyme, and Vifor Fresenius Medical Care Renal Pharma. S. Sinha reports consultancy agreements with Sanifit; research funding from Amgen, AstraZeneca, and Ethicon; and honoraria from AstraZeneca, Bayer, Napp Pharmaceuticals, Novartis, and Sanofi Genzyme. M.F. Slon-Roblero reports consultancy agreements with Baxter, Fresenius, and Nipro; and honoraria from Baxter, Fresenius, and Nipro. M.J. Soler reports consultancy agreements with AstraZeneca, Bayer, Boehringer, Esteve, Jansen, Mundipharma, Novo Nordisk, Travere, and ICU; research funding from Abbvie and Boehringer; honoraria from AstraZeneca, Boehringer, Esteve, FMC, Jansen, ICU Medical, Mundipharma, Novo Nordisk, Otsuka, and Travere; patents and inventions: U691ES00; is a scientific advisor for or member of BMC Nephrology and Clinical Kidney Journal; is a former member of ERA-EDTA Council; participates in a speakers’ bureau for AstraZeneca, Bayer, Boehringer, Esteve, FMC, Jansen, Mundipharma, Novo Nordisk, and Vifor; is a member of the Sociedad Española de Nefrología and Sociedad Catalana de Nefrologia; and is elected editor-in-chief of the Clinical Kidney Journal. All remaining authors have nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)

Coronavirus disease 2019 (COVID-19) may be associated with worse outcome in solid organ transplant (SOT) recipients. We performed a prospective cohort study of hospitalized patients with confirmed diagnosis of COVID-19, from March 15 to April 30, 2020, at two tertiary hospitals in Emilia-Romagna Region. SOT recipients were compared with non-SOT patients. Primary endpoint was all-cause 30-day mortality. Relationship between SOT status and mortality was investigated by univariable and multivariable Cox regression analysis. Patients were assessed from COVID-19 diagnosis to death or 30-day whichever occurred first. Study cohort consisted of 885 patients, of them 24 SOT recipients (n = 22, kidney, n = 2 liver). SOT recipients were younger, had lower BMI, but higher Charlson Index. At admission they presented less frequently with fever and respiratory failure. No difference in 30-day mortality between the two groups (19% vs 22.1%) was found; however, there was a trend toward higher rate of respiratory failure (50% vs 33.1%, P = .07) in SOT recipients. Superinfections were more represented in SOT recipients, (50% vs 15.5%, P < .001). At multivariate analysis adjusted for main covariates, there was no association between SOT and 30-day mortality HR 1.15 (95% CI 0.39-3.35) P = .79. Our data suggest that mortality among COVID-19 SOT recipients is similar to general population., (© 2020 Wiley Periodicals LLC.)

The effects of SARS-CoV-2 infection on individuals with immune-mediated glomerulonephritis, who are often undergoing immunosuppressive treatments, are unknown. Therefore, we created the International Registry of COVID infection in glomerulonephritis (IRoc-GN) and identified 40 patients with glomerulonephritis and COVID-19 followed in centers in North America and Europe. Detailed information on glomerulonephritis diagnosis, kidney parameters, and baseline immunosuppression prior to infection were recorded, as well as clinical presentation, laboratory values, treatment, complications, and outcomes of COVID-19. This cohort was compared to 80 COVID-positive control cases from the general population without glomerulonephritis matched for the time of infection. The majority (70%) of the patients with glomerulonephritis and all the controls were hospitalized. Patients with glomerulonephritis had significantly higher mortality (15% vs. 5%, respectively) and acute kidney injury (39% vs. 14%) than controls, while the need for kidney replacement therapy was not statistically different between the two groups. Receiving immunosuppression or renin-angiotensin-aldosterone system inhibitors at presentation did not increase the risk of death or acute kidney injury in the glomerulonephritis cohort. In the cohort with glomerulonephritis, lower serum albumin at presentation and shorter duration of glomerular disease were associated with greater risk of acute kidney injury and need for kidney replacement therapy. No differences in outcomes occurred between patients with primary glomerulonephritis versus glomerulonephritis associated with a systemic autoimmune disease (lupus or vasculitis). Thus, due to the higher mortality and risk of acute kidney injury than in the general population without glomerulonephritis, patients with glomerulonephritis and COVID-19 should be carefully monitored, especially when they present with low serum albumin levels., (Copyright © 2020 International Society of Nephrology. All rights reserved.)

Although most patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) experience respiratory manifestations, multi-organ dysfunction is frequent. Almost 20% of hospitalized patients with SARS-CoV-2 infection develop acute kidney injury (AKI). The pathophysiology of AKI is a result of both the direct and indirect effects of SARS-CoV-2 infection, including systemic inflammatory responses, the activation of the renin-angiotensin-aldosterone system (RAAS), and endothelial and coagulative dysfunction. Underlying SARS-CoV-2 infection-associated AKI, an immunological hyper-response with an unbalanced innate and adaptative response defined as a "cytokine storm" has emerged. Numerous agents have been tested in an effort to mitigate the cytokine storm, and a range of extracorporeal cytokine removal techniques have been proposed as potential therapeutic options. In the present review, we summarize the main pathogenetic mechanisms underlying COVID-19-related AKI in order to provide an appropriate individual therapeutic strategy to improve clinical outcomes and limit the progression of early disease. [ABSTRACT FROM AUTHOR]

Previous studies assessing the antibody response (AbR) to mRNA COVID-19 vaccines in solid organ transplant (SOT) recipients are limited by short follow-up, hampering the analysis of AbR kinetics. We present the ORCHESTRA SOT recipients cohort assessed for AbR at first dose (t0), second dose (t1), and within 3 ± 1 month (t2) after the first dose. We analyzed 1062 SOT patients (kidney, 63.7%; liver, 17.4%; heart, 16.7%; and lung, 2.5%) and 5045 health care workers (HCWs). The AbR rates in the SOTs and HCWs were 52.3% and 99.4%. The antibody levels were significantly higher in the HCWs than in the SOTs (p < 0.001). The kinetics showed an increase (p < 0.001) in antibody levels up to 76 days and a non-significant decrease after 118 days in the SOT recipients versus a decrease up to 76 days (p = 0.02) and a less pronounced decrease between 76 and 118 days (p = 0.04) in the HCWs. Upon multivariable analysis, liver transplant, ≥3 years from SOT, mRNA-1273, azathioprine, and longer time from t0 were associated with a positive AbR at t2. Older age, other comorbidities, mycophenolate, steroids, and impaired graft function were associated with lower AbR probability. Our results may be useful to optimize strategies of immune monitoring after COVID-19 vaccination and indications regarding timing for booster dosages calibrated on SOT patients' characteristics. [ABSTRACT FROM AUTHOR]