BREAKING! COVID-19 News: French Researchers Warn That Post-COVID Children And Teenagers Are At Risk Of Developing Kidney Disease!
: Medical researchers and pediatric specialists from over 28 hospitals medical colleges and research institutions in France are warning that Post COVID children and teenagers are at a high risk of developing kidney disease after a recent study that was conducted by the team revealed disturbing data.
The study team led by medical scientists from the Department of Pediatric Nephrology, MARHEA Reference Center, INSERM U1163, Imagine Institute, Paris Cité University, Necker-Enfants Malades Hospital,Paris – France, observed a striking increase in the incidence of acute tubulointerstitial nephritis (aTIN) without or with uveitis (TINUs) among children who had earlier contracted COVID-19.
These occurrences prompted the study team to examine whether SARS-CoV-2 might be the underlying trigger.
The researchers conducted a French nationwide retrospective cohort study. They included all consecutive children diagnosed with aTIN or TINUs of undetermined cause between April-2020 and March-2021. SARS-CoV-2 antibody responses were tested by a luciferase immunoprecipitation system and compared to age-matched controls. Immunohistochemistry, immunofluorescence and molecular microbiology analyses were performed on kidney biopsies.
The study found forty-eight children were with a median age at diagnosis of 14.7 years (9.4-17.6). aTIN and TINUs incidence rates increased 3-fold and 12-fold, respectively, compared to pre-pandemic years.
All the pediatric patients had impaired kidney function with a median eGFR of 31.9 ml/min/1.73m2 at diagnosis. Kidney biopsies showed lesions of acute tubulointerstitial nephritis and 25% of patients had fibrosis. No patient had concomitant acute COVID-19.
It was found that 16 children tested had high anti-N IgG titers and one had anti-S IgGs. Next-generation sequencing failed to detect any infectious agents in kidney biopsies. However, SARS-CoV-2 RNA was detected by PCR in two kidney samples supporting a potential direct link between SARS-CoV-2 and aTIN/TINUs. The study findings a novel form of post-acute COVID-19 syndrome in children, unique in its exclusive kidney and eye involvement, and its distinctive anti-SARS-CoV-2 N+/S- serological profile.
Interestingly, the study findings support a causal association linking SARS-CoV-2 infection to this newly-reported burst of renal/eye inflammation.
The study findings were published on a preprint server and are currently being peer reviewed.
The study findings also correlate with warnings from the U.S. CDC that many American children and teenagers are also facing kidney issues in Long COVID besides diabetes, clots and heart issues!
In our previous
coverages, we had already warned that SARS-CoV-2 infections leads to acute kidney injury (AKI) and also kidney damage and failure in many Long COVID individuals.
Worryingly, according to one meta-analysis study in 2020, the incidence of acute kidney injury or AKI in COVID-19 was 8.9%.
Even worse, more recent studies are showing the that the actual figures could be as high as between 31 to 46% of all individuals who have been exposed to the SARS-CoV-2 virus!
Acute kidney injury or AKI occurs frequently in COVID-19 patients infected by the coronavirus SARS-CoV-2 and infection of kidney cells by this virus has been frequently reported.
This new French study however is the first to date showing an increased incidence of pediatric aTIN and TINUs superimposed to the first wave of the COVID-19 pandemic.
The association of acute tubulointerstitial nephritis (aTIN) and COVID-19 has been suggested in few past studies and case reports.
The French researchers inferred from their study findings that aTIN/TINUs could be considered as a novel form of post-COVID-19 disease in children.
Importantly, epidemiological data, positive SARS-CoV-2 serologies and ELISpot in all tested patients (16/16 and 5/5, respectively), and in situ detection of SARS-CoV-2 in two kidney biopsies, strongly support a causal link.
COVID-19 was asymptomatic in 44/48 (90%) children at the acute phase, as reported in most post-COVID-19 MIS-C series.
It was found that these patients had a unique N+/S- serological profile, which differs from those observed in adults with COVID-19 and children with MIS-C who develop both anti-S and anti-N IgGs.
In the same light, children with mild COVID-19 predominantly generate anti-S IgGs.
It was noted that the presence of anti-SARS-CoV-2 IgGs in all tested children in the present series further exemplifies the post-infectious nature of COVID-19-related aTIN/TINUs.
Moreover, the lack of detection of SARS-CoV-2 mRNA in most kidney samples further supports a resolved infection.
The clinical and histological features in the present series were similar to those of pre-pandemic TINUs, and affected mostly adolescents.
Hence, this suggests that SARS-CoV-2- induced aTIN/TINUs cases share common pathogenic pathways with other forms.
The French study team therefore propose that SARS-CoV-2 could prime autoinflammation through molecular mimicry, as reported in other post-COVID-19 long-term symptoms (Long COVID-19).
The SARS-CoV-2 virus uses the receptors angiotensin-converting enzyme II (ACE2) and transmembrane protease serine 2 (TMPRSS2) for cell entry and protein S priming, respectively. Importantly, these two proteins are expressed in renal tubules and in eye components.
Thus, the study team hypothesizes that both tissues were infected during the acute phase, triggering an overly potent and long-lasting detrimental immune response, despite subsequent clearance of the virus.
Importantly, the presence of a predominant lympho-histiocytic infiltrate and the absence of immunoglobulin deposits are in favor of a cell-mediated mechanism.
The relatively large cohort of this rare disease provides additional insights into the pathophysiology of TINUs and suggests that SARS-CoV-2 should be considered among the infectious agents responsible for pediatric aTIN/TINUs.
The study limitations are mainly the recruitment through biopsy-based registry, potentially subject to selection bias, the retrospective design precluding fresh sampling for functional immunological testing, including T-cell response to IFN, and the absence of available serological samples from pre-pandemic aTIN/TINUs patients. However, the three contemporaneous children with ibuprofen-related aTIN/TINUs had a negative SARS-CoV-2 LIPS serology.
The study findings should raise awareness that post-COVID-19 aTIN/TINUs may be responsible for chronic renal damage in adolescents that may compromise kidney function in adulthood.
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