Autoantibodies in COVID-19, a possible role in the pathogenesis of the disease.

OBJECTIVES: In this study, we investigated whether SARS-CoV-2 stimulates autoantibody production. METHODS: The study included 91 patients hospitalized due to COVID 19, with no previous history of immunological diseases. Immunofluorescence assays were performed to detect antinuclear antibodies (ANAs) and antineutrophil cytoplasmic antibodies (ANCAs), along with tests for specific autoantibodies. RESULTS: The median age (57% male) was 74 years (range 38-95 years). Autoantibodies were positive in 67 (74%), ANA in 65 (71%), and ANCA in 11 (12%) patients. Female gender (p = 0.01), age (p = 0.005), and Charlson comorbidity index (p = 0.004) were significant predictors for the development of ANA/ANCA antibodies (p = 0.004). Nuclear mitotic apparatus (NuMA)-like, positivity was the strongest predictor of acute kidney injury (AKI), together with noninvasive ventilation and eGFR (χ2 = 49.01, P < 0.001). CONCLUSION: Positive autoantibodies in a large proportion of patients suggest a role of autoimmunity in the pathophysiology of acute COVID-19 disease. NuMA was the strongest predictor of AKI.

Collapsing Focal Segmental Glomerulosclerosis After Kidney Transplantation: Is It a Consequence of Viral Infections?

BACKGROUND: The aim of this case study was to explore the possible link between viral infections and collapsing focal segmental glomerulosclerosis (cFSGS) in patients who underwent kidney transplantation. METHODS: This case study included 3 case reports of patients who underwent kidney transplantation. The case reports were presented clinically and pathohistologically with cFsGS as a possible consequence of viral infections. RESULTS: The first patient developed cFSGS after polymerase chain reaction for SARS-CoV2 was positive twice. He gradually developed terminal stage chronic kidney disease. The second patient developed cFSGS with high range proteinuria after cytomegalovirus infection, which has been treated with 3 lines of antiviral medicaments. The third patient developed cFSGS as a possible consequence of hepatitis B virus infection. CONCLUSIONS: This case study highlighted the importance of viral etiology in the pathway of cFSGS. Pathogenic links between viral infections and concomitant glomerulopathies are challenging, especially in immunocompromised transplanted patients.

Kidney Transplantation in Patients With the History of SARS-CoV-2 Infection.

BACKGROUND: The aim of this study is to present the experience and results of kidney transplantation in patients with the history of SARS-CoV-2 infection. METHODS: We retrospectively analyzed waitlisted patients who had a history of SARS-CoV-2 infection and offered a kidney transplant between March 2020 and December 2021. RESULTS: Of the 97 waitlisted potential kidney transplant recipients who were offered a kidney, 13 (13.4%) had a history of SARS-CoV-2 infection. All patients were tested negative for SARS-CoV-2 at the time of the kidney offer. Successful transplantation was performed in 9 patients (5 male; average age was 40.8 years), with the average time between SARS-CoV-2 infection and transplantation of 8 months. Four of 13 patients with a history of SARS-CoV-2 infection were finally not transplanted, with 2 patients not eligible for transplantation due to significant post-COVID findings in routine pretransplant chest CT scans, and 2 patients were not transplanted because of poor donor organ quality. CONCLUSIONS: Kidney transplantation after SARS-CoV-2 infection is possible in a setting of full recovery from acute infection, negative PCR test, and no pneumonic infiltrates on chest CT scan. A growing number of waitlisted patients with a history of SARS-CoV-2 infection imposes the need for decision-making tools and guidelines for risk/benefit assessment in these patients.

Hospitalization and death after recovery from acute COVID-19 among renal transplant recipients.

INTRODUCTION: Data on post-COVID-19 in renal transplant recipients (RTR) is scarce. We investigated the rate of hospitalizations, reasons for hospital admission, and mortality rate among RTR who survived acute COVID-19. METHODS: A multi-center retrospective observational cohort study measured hospital admission and death to 180 days after acute SARS-CoV-2 infection in 308 adult patients. RESULTS: The median age was 57 years, 64.9% were male. All patients had at least one comorbidity, and 26.3% had diabetes. Data on post-COVID-19 course was available for 267 patients, and 49 of them (15.9%) required hospital treatment after recovery from the acute infection. The most common indications included pneumonia (24.5%) and renal allograft dysfunction (22.4%), 7 (14.3%) had sepsis and 5 (10.2%) had thrombotic events. A median duration of the hospital stay was 12 days. Six patients (2.2%) died due to multiorgan failure, respiratory insufficiency or urosepsis. The strongest predictor for hospitalization after acute COVID-19 was hospitalization for acute SARS-CoV-2 infection, while better allograft function decreased the probability of hospitalization. CONCLUSION: Delayed consequences of acute COVID-19 are highly prevalent and the health care systems should be prepared to respond to the needs of RTR suffering from post-COVID-19 complications.

Histopathologic findings on indication renal allograft biopsies after recovery from acute COVID-19.

Current knowledge on histopathological changes occurring after COVID-19 in transplanted kidneys is limited. Herein, we present renal allograft pathology findings in patients recovered from COVID-19. Six patients underwent indication biopsy, and one required allograft nephrectomy after acute COVID-19. Demographic data, clinical characteristics, and laboratory findings were recorded. The histopathological analysis included light microscopy, immunostaining, and electron microscopy. Five patients were hospitalized for acute COVID-19, and all were diagnosed with imaging-confirmed pneumonia, one requiring mechanical ventilation, and two requiring dialysis. Two patients had mild form. Histopathologic examination of renal allograft specimens revealed collapsing, perihilar, tip-lesion and secondary FSGS in one patient each. One patient had borderline acute cellular rejection, and two had chronic antibody-mediated rejection. Histopathologic changes of glomerular tufts were accompanied by acute tubular injury in four patients. None of our patients had signs of viral inclusions in kidney cells. One patient died and one remained dialysis-dependent after the good initial response to treatment. Patients with collapsing and perihilar FSGS had further progression of their chronic allograft nephropathy still without need for dialysis. In conclusion, diverse kidney pathology may be found in SARS-CoV-2-infected renal transplant patients. It seems that viral infection may affect the immune system with triggering of glomerular diseases, while the acute tubular injury is of multifactorial etiology. Direct viral effect is less likely.

COVID-19 pandemic and worldwide organ transplantation: a population-based study.

BACKGROUND: Preliminary data suggest that COVID-19 has reduced access to solid organ transplantation. However, the global consequences of the COVID-19 pandemic on transplantation rates and the effect on waitlisted patients have not been reported. We aimed to assess the effect of the COVID-19 pandemic on transplantation and investigate if the pandemic was associated with heterogeneous adaptation in terms of organ transplantation, with ensuing consequences for waitlisted patients. METHODS: In this population-based, observational, before-and-after study, we collected and validated nationwide cohorts of consecutive kidney, liver, lung, and heart transplants from 22 countries. Data were collected from Jan 1 to Dec 31, 2020, along with data from the same period in 2019. The analysis was done from the onset of the 100th cumulative COVID-19 case through to Dec 31, 2020. We assessed the effect of the pandemic on the worldwide organ transplantation rate and the disparity in transplant numbers within each country. We estimated the number of waitlisted patient life-years lost due to the negative effects of the pandemic. The study is registered with ClinicalTrials.gov, NCT04416256. FINDINGS: Transplant activity in all countries studied showed an overall decrease during the pandemic. Kidney transplantation was the most affected, followed by lung, liver, and heart. We identified three organ transplant rate patterns, as follows: countries with a sharp decrease in transplantation rate with a low COVID-19-related death rate; countries with a moderate decrease in transplantation rate with a moderate COVID-19-related death rate; and countries with a slight decrease in transplantation rate despite a high COVID-19-related death rate. Temporal trends revealed a marked worldwide reduction in transplant activity during the first 3 months of the pandemic, with losses stabilising after June, 2020, but decreasing again from October to December, 2020. The overall reduction in transplants during the observation time period translated to 48 239 waitlisted patient life-years lost. INTERPRETATION: We quantified the impact of the COVID-19 pandemic on worldwide organ transplantation activity and revealed heterogeneous adaptation in terms of organ transplantation, both at national levels and within countries, with detrimental consequences for waitlisted patients. Understanding how different countries and health-care systems responded to COVID-19-related challenges could facilitate improved pandemic preparedness, notably, how to safely maintain transplant programmes, both with immediate and non-immediate life-saving potential, to prevent loss of patient life-years. FUNDING: French national research agency (INSERM) ATIP Avenir and Fondation Bettencourt Schueller.

Follow-up of renal transplant recipients after acute COVID-19-A prospective cohort single-center study.

INTRODUCTION: Although most patients recover within several weeks after acute COVID-19, some of them develop long-lasting clinical symptoms. Renal transplant recipients have an increased mortality risk from COVID-19. We aimed to describe complications occurring after COVID-19 in this group of patients. METHODS: A prospective single-center cohort study was conducted at University Hospital Centre Zagreb. Patients with two negative reverse transcriptase-polymerase chain reaction (RT-PCR) tests for SARS-CoV-2 after COVID-19 were eligible for further follow-up at our outpatient clinic. They underwent detailed clinical and laboratory assessments. The primary outcome was the development of complications after COVID-19. RESULTS: Only 11.53% of renal transplant recipients who survived acute COVID-19 were symptomless and free from new-onset laboratory abnormalities during the median follow-up of 64 days (range: 50-76 days). Three patients died from sepsis after discharge from the hospital. In 47 patients (45.2%), clinical complications were present, while 74 patients (71.2%) had one or more laboratory abnormalities. The most common clinical complications included shortness of breath (19.2%), tiredness (11.5%), peripheral neuropathy (7.7%), self-reported cognitive impairments (5.7%), and dry cough (7.7%). Most common laboratory abnormalities included shortened activated partial thromboplastin time (50%), elevated D-dimers (36.5%), elevated fibrinogen (30.16%), and hypogammaglobulinemia (24%). Positive RT-PCR for cytomegalovirus (8.7%), Epstein-Barr virus (26%), or BK virus (16.3%). Multivariate analysis identified the history of diabetes mellitus and eGFR CKD-EPI as predictors for the development of post-COVID clinical complications. Six months after acute COVID-19, elevated D-dimers persisted with normalization of other laboratory parameters. Twenty-nine patients were hospitalized, mostly with several concomitant problems. However, initially reported clinical problems gradually improved in the majority of patients. CONCLUSION: Post-COVID-19 clinical and laboratory complications are frequent in the renal transplant population, in some of them associated with significant morbidity. All patients recovered from acute COVID-19 should undergo long-term monitoring for evaluation and treatment of complications.

Can hyperimmune anti-CMV globulin substitute for convalescent plasma for treatment of COVID-19?

Information on treatment of COVID-19 infection in renal transplant recipients is scarce, especially in symptomatic patients and patients with recent major clinical events. This group of patients suffers from different opportunistic infections which may coexist with COVID-19. Currently available expert opinions suggest reduction of immunosuppression therapy for renal transplant recipients with symptomatic COVID-19 infection with either antiviral drugs, hydroxychloroquine and/or azithromycin. Inspired by our experience in treatment of CMV pneumonia and literature data on the potential benefit of convalescent plasma for treatment of different viral diseases we suggest use of the hyperimmune anti-CMV gamma globulins in addition to other available therapies. Besides the immunosuppression reduction which is supposed to be beneficial, immunoglobulins with their immunomodulatory effects and possible antiviral role, may increase a possibility for favorable outcome.