Psychometric analysis of the modified Covid-19 Yorkshire Rehabilitation Scale (C19-YRSm) in a prospective multicentre study (preprint)

BckgroundLong COVID is a novel multisystem clinical syndrome affecting millions of individuals worldwide. The modified COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm) is a condition-specific patient-reported outcome measure designed for assessment and monitoring of people with Long COVID (LC). ObjectivesTo evaluate the psychometric properties of the C19-YRSm in a prospective sample of people with Long COVID. Methods1314 patients attending UK specialist Long COVID clinics completed C19-YRSm and EQ-5D-5L longitudinally. Scale characteristics were derived for C19-YRSm subscales (Symptom Severity, SS; Functional Disability, FD; and Overall Health, OH) and internal consistency (Cronbachs alpha). Convergent validity was assessed using the FACIT-Fatigue scale. Known groups validity was assessed for the Other Symptoms (OS) subscale as tertiles, hospitalisation and intensive care admission. Responsiveness and test-retest reliability was evaluated for C19-YRSm subscales and EQ-5D-5L. The minimal important difference (MID) and minimal clinically important difference (MCID) were estimated. Confirmatory factor analysis was applied to determine the instruments two-factor structure. ResultsC19-YRSm demonstrated good scale characteristic properties. Item-total correlations were between 0.37 to 0.65 (for SS and FD), with good internal reliability (Cronbachs alphas >0.8). Item correlations between subscales ranged between 0.46 to 0.72. Convergent validity with FACIT was good (-0.46 to -0.62). The three subscales discriminated between different levels of symptom burden (p<0.001), and between patients admitted to hospital and intensive care. There was moderate responsiveness for the three subscales ranging from 0.22 (OH) to 0.50 (SS) and was greater than the EQ-5D-5L. Test-retest reliability was good for both SS 0.86 and FD 0.78. MID was 2 for SS, 2 for FD, and 1 for OH; MCID was 4 for both the SS and FD. The factor analysis supported the two-factor SS and FD structure. ConclusionsThe C19-YRSm is a condition-specific, reliable, valid, and responsive patient-reported outcome measure for Long COVID. Key messagesO_ST_ABSWhat is already known on this topicC_ST_ABSLong Covid or Post-COVID-19 syndrome is a multisystem, fluctuating condition. C19-YRSm is literatures first condition-specific patient reported outcome measure which needed validation in a large population sample. What this study addsC19-YRSm is a valid, reliable, responsive and easy to administer measure which is able to show clinically meaningful change in the status of the condition in people living with Long Covid. How this study might affect research, practice or policyC19-YRSm can be used in clinical and research settings to reliably capture the condition trajectory and the effect of interventions and also help inform clinical policy.

Pediatric Minimal Change Disease and AKI following the Pfizer-BioNTech COVID-19 Vaccine: causal or incidental correlation?

The global coronavirus 2019 (COVID-19) pandemic required vaccination even in children to reduce infection. We report on the development of acute kidney injury (AKI) and minimal change disease (MCD) nephrotic syndrome (NS), shortly after the first injection BNT162b2 COVID-19 vaccine (Pfizer-BioNTech). A 12-year-old previously healthy boy was referred to our hospital with complaints of peripheral edema and nephrotic range proteinuria. Nine days earlier he had received his first injection BNT162b2 COVID-19 vaccine (Pfizer-BioNTech). Seven days after injection, he developed leg edema, which rapidly progressed to anasarca with significant weight gain. On admission, serum creatinine was 1.3 mg/dL and 24-hour urinary protein excretion was 4 grams with fluid overload. As kidney function continued to decline over the next days, empirical steroid treatment and renal replacement therapy with ultrafiltration were started and kidney biopsy was performed. Seven days after steroid therapy, kidney function began to improve, gradually returning to normal. The association of MCD, nephrotic syndrome and AKI hasn't been previously described following the Pfizer-BioNTech COVID-19 vaccine in pediatric population, but this triad has been reported in adults. We need further similar case reports to establish the real incidence of this possible vaccine side effect.

Reactivation of minimal change disease after Pfizer vaccine against COVID-19.

This case follows a 54-year-old woman with a medical history of hypertension who experienced reactivation of minimal change disease (MCD) after receiving the Pfizer vaccine against COVID-19. She had her first episode of MCD 15 days after receiving the influenza vaccine in 2018. She remained in remission for over 3 years following treatment with steroids. She experienced foamy urine and leg edema after receiving the first dose of the Pfizer vaccine, but she did not consult medical professionals until she received the second dose. She wanted to be fully vaccinated because she worked in healthcare. Her initial diagnosis of MCD in 2018 was made following a kidney biopsy. The diagnosis of reactivation following COVID-19 vaccine was made with labs and presenting symptoms. At presentation, her urine protein was 9,977 mg/day. She was treated with prednisone 50 mg/day following her relapse with improvement in her urine protein to 85 mg/g within 4 weeks of starting treatment. She is currently undergoing treatment with prednisone with improvement in her presenting symptoms, which included foaming of urine and edema of legs. This case demonstrates the importance of vigilance in patients with a history of MCD when receiving the COVID-19 vaccine, particularly if they have a history of such reactions to other vaccines. Patients should discuss the benefits and risks of receiving the vaccine with their medical professionals and stay cognizant about the possibility of reactivation after receiving the COVID-19 vaccine.

Rates of idiopathic childhood nephrotic syndrome relapse are lower during the COVID-19 pandemic.

BACKGROUND: Infections are thought to be primarily responsible for triggering relapse in children with steroid-sensitive nephrotic syndrome (NS). The COVID-19 pandemic promoted physical distancing, facial mask wearing, and greater attention to infection-prevention measures resulting in decreased transmission of infections. We hypothesized there would also be a decreased rate of NS relapse during this period. METHODS: We conducted a single-center retrospective chart review of children with steroid-sensitive NS. Demographics, rate of relapses, and rate of hospitalizations were collected for a baseline pre-pandemic period (BPP) and for the social distancing period during the pandemic (SDP). RESULTS: One hundred twenty-two children with primary steroid-sensitive NS were identified and 109 were followed for the duration of the study period. The paired rate of relapse per subject per year was significantly lower during the SDP (0.6 relapses per subject per year ± 1 SD) compared to the BPP (1.0 relapses per subject per year ± 0.9 SD), P < 0.01. A subgroup of 32 subjects who were newly diagnosed with NS during the BPP similarly had significantly fewer relapses during the SDP (0.8 ± 1 SD) than during the BPP (1.4 ± 1 SD), P = 0.01. CONCLUSIONS: Our results support the hypothesis of lower rates of NS relapse and hospitalizations during social distancing for all subjects in our cohort and a subgroup of those newly diagnosed. Lower relapse rates were likely attributable to decreased transmission of infections and greater attention to infection prevention. A higher resolution version of the Graphical abstract is available as Supplementary information.

A de novo case of minimal change disease following the first dose of the Moderna mRNA-1273 SARS-CoV-2 vaccine without relapse after the second dose.

In recent times, new onset or relapse of nephrotic syndrome following the first dose of SARS-CoV-2 vaccines has been reported. Although the vaccination could trigger nephrotic syndrome, the question of whether the same vaccine should be administered as the second dose remains unanswered. A 25-year-old woman had taken the Moderna mRNA-1273 SARS-CoV-2 vaccine (mRNA-1273) and 26 days later, she noticed facial and peripheral edema. One week later she was referred and admitted to our hospital, wherein laboratory tests revealed that her serum creatinine level, serum albumin level, and urine protein-creatinine ratio were respectively 0.79 mg/dL, 2.5 g/dL, and 7.0 g/gCr. After a thorough inpatient examination including renal biopsy, she was diagnosed with minimal change disease (MCD) and treatment with steroids was initiated. She achieved complete remission the next day and did not experience a relapse upon receiving the second mRNA-1273 dose 56 days after the first, under treatment with 35 mg/day of oral prednisolone. This case report yields insight into determining whether patients who develop de novo MCD after the first mRNA-1273 dose should receive the second dose.

Nephrotic syndrome with minimal change disease after the Pfizer-BioNTech COVID-19 vaccine: two cases.

We present two cases of nephrotic syndrome with minimal change disease after the Pfizer-BioNTech COVID-19 vaccine. We discuss the initial presentation, investigation and management of these patients along with a discussion around the current evidence base for vaccine-induced nephrotic syndrome.

De Novo Minimal Change Disease following Vaccination with the Pfizer/BioNTech SARS-CoV-2 Vaccine in a Living Kidney Donor.

Coronavirus disease 2019 has developed as a pandemic. Immunization with the introduction of vaccines against COVID-19 seems be the only way to end this pandemic. We report on a case of a kidney donor, who developed minimal change disease (MCD) within 4 days post-vaccination with the SARS-CoV-2 BNT162b2 mRNA vaccine (Pfizer/BioNTech). She donated her kidney to her husband 4 years ago. After receiving the 1st vaccine dose, she presented with nephrotic syndrome, with complete remission 5 days later. She proceeded with the second dose of the BNT162b2 vaccine at the appointed time. Two days later, she presented with a relapse of full-blown nephrotic syndrome with preserved renal function. We performed an ultrasound-guided percutaneous kidney biopsy and the final diagnosis was consistent with minimal change disease. Oral prednisolone was promptly initiated at a dosage of 1 mg/kg daily and complete remission was achieved 10 days later. More data about this rare appearance of de novo glomerular diseases after SARS-CoV-2 vaccination are emerging and should be interpreted rigorously.

Minimal change disease following the Moderna COVID-19 vaccine: first case report.

BACKGROUND: There have been cases of minimal change disease (MCD) reported following previous vaccines. During the COVID-19 era, only 3 cases of new-onset MCD and a case of MCD relapse were reported following the Pfizer-BioNTech COVID-19 vaccine. We herein report the first case of MCD after receiving the Moderna COVID-19 vaccine. CASE PRESENTATION: A 43-year-old man presented to hospital 3 weeks after receiving the first dose of the Moderna vaccine, with both bilateral lower extremities and scrotal edema. He initially developed a sudden-onset bilateral lower extremities swelling on day 7 post-vaccine. He, then, developed dyspnea and scrotal swelling over a time span of 2 weeks. On physical examination, his blood pressure was 150/92 mmHg. There was a decreased air entry at lung bases, bilateral lower extremities and scrotal edema. Labs revealed hypoalbuminemia, hyperlipidemia and 15 g of proteinuria. His immunologic and serologic work up was negative. Renal biopsy showed concomitant MCD and IgA nephropathy. Patient was treated with oral steroids and had a good response; his edema resolved, serum albumin improved, and proteinuria decreased to 1 g within 2 weeks of treatment. CONCLUSIONS: To the best of our knowledge, MCD has not been previously reported after receiving the Moderna COVID-19 vaccine. It remains unclear whether the COVID-19 mRNA vaccines are associated with the development of MCD, or it coincided with the mass vaccination. Further studies are needed to determine the incidence of MCD post COVID-19 vaccines and the underlying pathophysiology of glomerular injury post vaccination.

COVID-19 and idiopathic nephrotic syndrome in children: systematic review of the literature and recommendations from a highly affected area.

BACKGROUND: Coronavirus Disease 2019 has spread from China as a global pandemic, Italy being one of the earliest affected countries. The infection displays a more complicated and often fatal course in adults with a history of kidney disease, while it does not seem to affect children in the same way. Pediatric patients with idiopathic nephrotic syndrome (INS), with or without chronic immunosuppressive therapy, are at greater risk of infections which may also trigger relapses. OBJECTIVES: We performed a systematic review of the literature to identify all articles on SARS-CoV-2 infections in children with INS in order to describe the severity of all SARS-CoV-2 infections reported in children with INS, to evaluate the risk of new onset and relapses associated with SARS-CoV-2 infection, and to draw recommendations on their management and vaccination. The search was conducted on the following databases: MEDLINE (via Pubmed), Google Scholar, and Web of Science. The search methodology used with the selected free text terms or MesH was ("nephrotic syndrome" OR "idiopathic nephrotic syndrome") and ("covid 19" OR "severe acute respiratory syndrome coronavirus 2" OR "2019-nCoV" OR "SARS-CoV-2"). RESULTS: The literature search provided 36 records. After screening for their relevance to the topic, 11 studies were selected. Two additional publications were identified through the reference list of all included articles and 13 articles were included in the review. A total of 43 cases of children with INS and SARS-CoV-2 infection have been reported; the course of the disease was mild for most patients with low need of respiratory support and no death in high income countries. In 5 patients, the infection was complicated by relapse, which anyway showed a good response to steroids. Two children had a new onset of INS during a SARS-CoV-2 infection. CONCLUSIONS: Children with INS, with or without immunosuppression, are not at higher risk of severe SARS-CoV-2 infection. Relapse is a possible complication, but steroid treatment is safe and effective. After summarizing the evidence, we have suggested recommendations for the management of children with INS during the pandemic and the vaccination campaign.

Tools of Systemic Change for Sustainable Future: Mindfulness and Degrowth in Post COVID World (preprint)

To address the issues of sustainability conundrum there is need to develop actionable decision matrix that harmonizes the roles and responsibilities of three actors, viz., community, state, and market. The COVID pandemic made the world realize that purely technical-economic solution has limits to the problem faced by human beings. In this backdrop we attempt to scan the foundational systemic change that needs to be addressed in social institutions to redesign the organization structure and functioning. The primary objective of this paper is to explore the core systemic challenges that we are facing. This exploration involves deep engagement with key stakeholders in the field of development, industry, administration, funding agency, innovator, educators’ etcetera. The purpose of this step is to find workable links between community, state, and market. We have done (continuing) more than 1850 hours of dialogue (in person, online mode) and engagement with 125 personnel from ninety-five institutions across ten domains, based in nine countries. The dialogue led us to identify that to address the future challenges we must address the issue of ‘mindfulness’ and ‘degrowth’ at individual and collective conscious level respectively in our society to reboot the social institutions.

New-onset Nephrotic Syndrome after Janssen COVID-19 Vaccination: a Case Report and Literature Review.

Various coronavirus disease 2019 (COVID-19) vaccines are being developed, which show practical preventive effects. Here, we report a 51-year-old healthy man with nephrotic syndrome secondary to minimal change disease (MCD) after Ad26.COV.2 (Janssen) vaccination. He had no comorbid disease and received Ad26.COV.2 on April 13, 2021. Seven days after vaccination, he developed edema and foamy urine. Edema rapidly aggravated with decreased urine volume. He was admitted to the hospital 28 days after vaccination, and his body weight increased by 21 kg after vaccination. His serum creatinine level was 1.54 mg/dL, and 24-h urinary protein excretion was 8.6 g/day. Kidney biopsy revealed no abnormality in the glomeruli and interstitium of the cortex and medulla under the light microscope. Electron microscopy revealed diffuse effacement of the podocyte foot processes, thus, he was diagnosed with MCD. High-dose steroid therapy was applied, and his kidney function improved three days after steroid therapy. Three weeks after steroid use, his serum creatinine decreased to 0.95 mg/dL, and spot urine protein-to-creatine decreased to 0.2 g/g. This case highlights the risk of new-onset nephrotic syndrome secondary to MCD after vectored COVID-19 vaccination. Although the pathogenesis is uncertain, clinicians need to be careful about adverse renal effects of COVID-19 vaccines.

Minimal Change Disease With Severe Acute Kidney Injury Following the Oxford-AstraZeneca COVID-19 Vaccine: A Case Report.

We report a case of minimal change disease (MCD) with severe acute kidney injury (AKI) following the first injection of the ChAdOx1 nCoV-19 (AZD1222) vaccine from Oxford-AstraZeneca against coronavirus disease 2019 (COVID-19). A 71-year-old man with a history of dyslipidemia and a baseline serum creatinine of 0.7mg/dL presented with nephrotic syndrome, AKI, and severe hypertension 13 days after receiving the Oxford-AstraZeneca vaccine. Refractory hyperkalemia and hypervolemia with oligoanuria prompted initiation of hemodialysis. His serum albumin was 2.6g/dL and his urinary protein-creatinine ratio was 2,321mg/mmol. Given a high suspicion for rapidly progressive glomerulonephritis, empirical glucocorticoid treatment was initiated (3 methylprednisolone pulses followed by high-dose prednisone). A kidney biopsy showed MCD and acute tubular injury. Kidney function and proteinuria subsequently improved, and hemodialysis was discontinued 38 days after the start of therapy. This case describes de novo MCD after the Oxford-AstraZeneca vaccine. It adds to the few published case reports of MCD after the Pfizer-BioNTech COVID-19 vaccine. Further reports and studies will be needed to elucidate whether MCD is truly associated with COVID-19 vaccination.