Incidence of new onset glomerulonephritis after SARS-CoV-2 mRNA vaccination is not increased.

Numerous cases of glomerulonephritis manifesting shortly after SARS-CoV-2 vaccination have been reported, but causality remains unproven. Here, we studied the association between mRNA-based SARS-CoV-2 vaccination and new-onset glomerulonephritis using a nationwide retrospective cohort and a case-cohort design. Data from all Swiss pathology institutes processing native kidney biopsies served to calculate incidence of IgA nephropathy, pauci-immune necrotizing glomerulonephritis, minimal change disease, and membranous nephropathy in the adult Swiss population. The observed incidence during the vaccination campaign (January to August 2021) was not different from the expected incidence calculated using a Bayesian model based on the years 2015 to 2019 (incidence rate ratio 0.86, 95% credible interval 0.73-1.02) and did not cross the upper boundary of the 95% credible interval for any month. Among 111 patients 18 years and older with newly diagnosed glomerulonephritis between January and August 2021, 38.7% had received at least one vaccine dose before biopsy, compared to 39.5% of the general Swiss population matched for age and calendar-time. The estimated risk ratio for the development of new-onset biopsy-proven glomerulonephritis was not significant at 0.97 (95% confidence interval 0.66-1.42) in vaccinated vs. unvaccinated individuals. Patients with glomerulonephritis manifesting within four weeks after vaccination did not differ clinically from those manifesting temporally unrelated to vaccination. Thus, vaccination against SARS-CoV-2 was not associated with new-onset glomerulonephritis in these two complementary studies with most temporal associations between SARS-CoV-2 vaccination and glomerulonephritis likely coincidental.

Renal Tubular Acidosis in Pregnant Critically Ill COVID-19 Patients: A Secondary Analysis of a Prospective Cohort.

BACKGROUND: Renal tubular acidosis (RTA) is an extremely rare cause of metabolic acidosis (10 in 100,000). RTA has been linked neither to pregnancy nor to severe coronavirus disease 2019 (COVID-19). The purpose of this study was to analyze the prevalence and clinical course of normal anion gap metabolic acidosis in critically ill pregnant COVID-19 patients and to compare them to an age-matched nonpregnant female patient cohort. METHODS: Secondary analysis was conducted on a prospective observational cohort of critically ill patients suffering from COVID-19 consecutively admitted to a tertiary intensive care unit (ICU) between February 2020 and April 2021. RESULTS: A total of 321 COVID-19 patients required admission to the ICU; 95 (30%) were female, and 18 (19%) were of childbearing age. Seven of eight (88%) pregnant women (all in the last trimester) required advanced respiratory support due to COVID-19. The estimated glomerular filtration rate was 135 (123-158) mL/min/m2 body surface area, and six pregnant women (86%) were diagnosed with a normal, respiratory compensated, anion gap metabolic acidosis (pHmin 7.3 (7.18-7.31), HCO3-min 14.8 (12.8-18.6) mmol/L, and paCO2 3.4 (3.3-4.5) kPa). Three (43%) acidotic pregnant women fulfilled diagnostic criteria for RTA. All women recovered spontaneously within less 7 days. CONCLUSIONS: Metabolic acidosis seems to be very common (85%) in pregnant critically ill COVID-19 patients, and the prevalence of RTA might be higher than normal. It remains to be demonstrated if this observation is an indirect epiphenomenon or due to a direct viral effect on the tubular epithelium.

Clinical spectrum of gross haematuria following SARS-CoV-2 vaccination with mRNA vaccines.

Background: Novel messenger RNA (mRNA)-based vaccines play an important role in current vaccination campaigns against SARS-CoV-2. They are highly efficacious and generally well tolerated. Vaccination in patients with immune-mediated kidney diseases is recommended. A number of cases with de novo or relapsing glomerulonephritis shortly after vaccine application have been reported, some of which presented with gross haematuria. Methods: We collected 10 cases of macrohaematuria following mRNA-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination at our tertiary care institution and referring centres. Additionally, we pooled all 25 published cases from the literature with ours to analyse their clinical characteristics. Results: Most macrohaematuria episodes (72.2%) began within 2 days after vaccination, the majority after the second dose. In some individuals, repeated episodes occurred after subsequent doses of the same vaccine. A total of 65.7% of patients never had macrohaematuria before. A total of 45.7% were known to suffer from immunoglobulin A nephropathy (IgAN); the rest had no prior renal diagnosis. IgAN was the most frequent new diagnosis, but anti-neutrophil cytoplasmic antibody-associated vasculitis and anti-glomerular basement membrane disease were also identified. Acute kidney injury (AKI) occurred in 28.6% of patients, with an increase in serum creatinine not meeting Kidney Disease: Improving Global Outcomes AKI criteria in 28.6%. Treatment ranged from conservative management, renin-angiotensin-aldosterone system inhibitors, steroids and cyclophosphamide to plasmapheresis. While renal outcomes were mainly favourable in isolated IgAN, they were poor in patients with additional or isolated small vessel vasculitis. Conclusion: Awareness of gross haematuria after SARS-CoV-2 vaccination is important. Close follow-up and additional work up, particularly in individuals without known underlying kidney disease or worsening renal function, is essential. For patients with vaccine-associated macrohaematuria, an alternative vaccine class might be considered for subsequent vaccinations.

Complement inhibition for the treatment of COVID-19 triggered thrombotic microangiopathy with cardiac failure: a case report.

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) has been increasingly recognized as a multisystem disease. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect literally any cell type that expresses its target receptor angiotensin-converting enzyme 2. However, COVID-19-associated organ dysfunction is not only mediated by direct viral effects but also by the interaction between the host's immune response, endotheliopathy, and microvascular coagulopathy. It has been proposed that the activation of the complement system plays a central role in the pathophysiology of severe COVID-19 and the associated endotheliopathy. CASE SUMMARY: A 76-year-old male patient with indeterminate cardiogenic shock in the setting of confirmed SARS-CoV-2 infection was admitted to our intensive care unit. Coronary angiography did not reveal a plausible explanation for his symptoms. The patient developed renal failure, neurological symptoms, severe thrombocytopenia, and a Coombs-negative haemolytic anaemia with schistocytes. All together the clinical picture was highly suggestive of a thrombotic microangiopathy (TMA) with microvascular cardiac involvement. Conventional therapeutic strategies including high-dose steroids and seven sessions of therapeutic plasma exchange were all unsuccessful. Interestingly, complement inhibition with Eculizumab as rescue approach led to a rapid clinical and laboratory improvement and the patients were discharged with normalized organ functions at Day 36. CONCLUSION: The aetiology of cardiogenic shock observed in this patient cannot simply be explained by his focal and chronic coronary findings. Although viral myocarditis was not formally excluded, both the clinical features of TMA and the rapid resolution of all clinical signs and symptoms after pharmacological complement inhibition suggest a SARS-CoV-2-driven microangiopathic origin of heart failure.