SARS-CoV-2 Spike- and Nucleoprotein-Specific Antibodies Induced After Vaccination or Infection Promote Classical Complement Activation.

Antibodies specific for the spike glycoprotein (S) and nucleocapsid (N) SARS-CoV-2 proteins are typically present during severe COVID-19, and induced to S after vaccination. The binding of viral antigens by antibody can initiate the classical complement pathway. Since complement could play pathological or protective roles at distinct times during SARS-CoV-2 infection we determined levels of antibody-dependent complement activation along the complement cascade. Here, we used an ELISA assay to assess complement protein binding (C1q) and the deposition of C4b, C3b, and C5b to S and N antigens in the presence of antibodies to SARS-CoV-2 from different test groups: non-infected, single and double vaccinees, non-hospitalised convalescent (NHC) COVID-19 patients and convalescent hospitalised (ITU-CONV) COVID-19 patients. C1q binding correlates strongly with antibody responses, especially IgG1 levels. However, detection of downstream complement components, C4b, C3b and C5b shows some variability associated with the subject group from whom the sera were obtained. In the ITU-CONV, detection of C3b-C5b to S was observed consistently, but this was not the case in the NHC group. This is in contrast to responses to N, where median levels of complement deposition did not differ between the NHC and ITU-CONV groups. Moreover, for S but not N, downstream complement components were only detected in sera with higher IgG1 levels. Therefore, the classical pathway is activated by antibodies to multiple SARS-CoV-2 antigens, but the downstream effects of this activation may differ depending the disease status of the subject and on the specific antigen targeted.

COVID-19 Associated Collapsing Variant of Focal Segmental Glomerulosclerosis: A Case Series of 7 Patients from a Single UK Centre

BACKGROUND AND AIMS Cases of collapsing glomerulopathy in association with COVID-19 infection have been reported worldwide, frequently referred to as COVAN (COVID-19 Associated Nephropathy). Affected patients are almost exclusively of Black ethnicity, likely associated with APOL-1 renal risk variants. There remains a paucity of data on patient outcomes, however, and it is unclear how the natural history of this disease may vary from HIV-associated nephropathy (HIVAN) and other non-viral causes of collapsing FSGS. Here, we present a case series of seven patients with presumed COVAN from a single tertiary UK renal centre;highlighting patient demography, biopsy findings, clinical management and short-term renal outcomes. METHOD We identified all adult patients presenting to our centre with nephrotic syndrome and a renal biopsy demonstrating collapsing glomerulopathy, in association with a positive COVID-19 PCR swab result. Detailed case note reviews were undertaken using electronic health records to extract data relevant to patient demography, co-morbidities, COVID -19 symptoms, renal biopsy findings, treatment and biochemical parameters, both at the time of presentation and during follow-up at 1, 3, 6 and 12 months respectively (where available). RESULTS In total, we identified seven patients with presumed COVAN. Three of the seven patients were male, median age was 60 years (range 25–80 years). Six of the seven patients were of Black ethnicity and one patient was of South Asian ethnicity (renal transplant recipient with donor ethnicity unknown). All seven patients had a background of hypertension, 5/7 had known chronic kidney disease (CKD), 5/7 had type 2 diabetes mellitus (T2DM) and 4/7 were obese (BMI > 30). In the vast majority of cases, associated COVID-19 symptoms were mild. All patients had profound nephrotic syndrome at the time of renal biopsy, with median urine ACR 1085 mg/mmol (range 682–1380 mg/mmol) and median serum albumin 15 g/L (range 8–20 g/L). Two of seven patients had mild AKI (stage 1) and 5/7 patients had severe AKI (stage 3), with 3 of these patients receiving acute haemodialysis therapy. Management of glomerulopathy was supportive in all cases, including diuresis and anticoagulation (two patients received a short course of oral dexamethasone for their COVID-19 symptoms). ACE inhibitors/angiotensin receptor blockers were re-introduced in two patients and newly commenced in two further patients during follow-up. At 6 months follow-up, one patient remained dialysis dependant and one patient had ongoing decline in renal function (renal transplant recipient);all other patients achieved at least partial remission, with > 50% reduction in urine ACR and some (but not complete) recovery in renal function (Fig. 1). There were no viral particles identified on direct examination of renal biopsy specimens, but 4/7 biopsies exhibited tubulo-reticular inclusions, suggesting an interferon-driven systemic inflammatory process. CONCLUSION In this case series of seven COVAN cases from a single tertiary UK centre, we noted that in keeping with reports from North America, Black ethnicity patients were disproportionately affected. Partial remission was achieved in most of our cases with supportive treatment only;however, ongoing monitoring of this cohort is required to better understand longer-term patient outcomes. Testing for APOL-1 gene mutations and molecular testing of biopsy samples for this cohort is also ongoing to facilitate better insights into pathophysiology and risk factors associated with this novel disease.

Review of Early Immune Response to SARS-CoV-2 Vaccination Among Patients With CKD.

The effects of the coronavirus disease-2019 (COVID-19) pandemic, particularly among those with chronic kidney disease (CKD), who commonly have defects in humoral and cellular immunity, and the efficacy of vaccinations against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are uncertain. To inform public health and clinical practice, we synthesized published studies and preprints evaluating surrogate measures of immunity after SARS-CoV-2 vaccination in patients with CKD, including those receiving dialysis or with a kidney transplant. We found 35 studies (28 published, 7 preprints), with sample sizes ranging from 23 to 1140 participants and follow-up ranging from 1 week to 1 month after vaccination. Seventeen of these studies enrolled a control group. In the 22 studies of patients receiving dialysis, the development of antibodies was observed in 18% to 53% after 1 dose and in 70% to 96% after 2 doses of mRNA vaccine. In the 14 studies of transplant recipients, 3% to 59% mounted detectable humoral or cellular responses after 2 doses of mRNA vaccine. After vaccination, there were a few reported cases of relapse or de novo glomerulonephritis, and acute transplant rejection, suggesting a need for ongoing surveillance. Studies are needed to better evaluate the effectiveness of SARS-CoV-2 vaccination in these populations. Rigorous surveillance is necessary for detection of long-term adverse effects in patients with autoimmune disease and transplant recipients. For transplant recipients and those with suboptimal immune responses, alternate vaccination platforms and strategies should be considered. As additional data arise, the NephJC COVID-19 page will continue to be updated (http://www.nephjc.com/news/covid-vaccine).

Acute kidney injury in patients admitted with COVID-19 in a south Birmingham trust

Demographic data, laboratory data and other clinical information were extracted from the electronic medical record system. After exclusion of anyone under the age of 16 years, patients on replacement therapy or with a working kidney transplant and anyone not requiring admission, the details of 2,325 patients were analysed. 55.2% of the patients were male, with 64.8% Caucasian, 14.7% Asian/Asian British and the rest either of mixed race, Black, Chinese or unknown. Coronavirus disease 19 infection does not result in acute kidney injury;an analysis of 116 hospitalised patients from Wuhan, China.