Children with COVID-19-related acute tubulointerstitial nephritis and uveitis

A recent study described a unique type of post-acute coronavirus disease 2019 (COVID-19) syndrome in kids on the medRxiv* preprint server.

The authors of the study have previously documented an increase in the prevalence of acute tubulointerstitial nephritis (aTIN) and tubulointerstitial nephritis and uveitis (TINU) syndrome in pediatric populations during the first year of the COVID-19 pandemic. Systemic illnesses, medications, and infections are some of the known causes of aTIN. Rare syndrome known as TINU may be brought on by an immune process that is less well understood. Investigation into the relationship between severe acute respiratory syndrome coronavirus 2 and aTIN/TINU is warranted given its increased prevalence (SARS-CoV-2).

The study’s results
Researchers in the current study looked into the possibility that SARS-CoV-2 is to blame for the rise in pediatric aTIN/TINU cases. From April 2020 to March 2021, 48 children in France received an idiopathic aTIN or TINU diagnosis, compared to 8–10 aTIN cases in 2018–19 and 46 cases of TINU syndrome from 2000–18.

Four of the children showed COVID-19 symptoms in the weeks before their diagnosis, but all of the children tested negative for SARS-CoV-2 at that time. Only one child tested positive for antibodies against the viral spike, whereas antibodies against the SARS-CoV-2 nucleocapsid were negative in all other test subjects. The group carried out a luciferase immunoprecipitation assay for SARS-CoV-2 serology in hindsight.

16 children with a TIN/TINU diagnosis had serum samples available, and all of the samples tested positive for anti-nucleocapsid immunoglobulin G. (IgG). In contrast, the presence of anti-spike IgG antibodies was only detected in one sample. SARS-CoV-2 antibodies were not seen in three controls with ibuprofen-induced aTIN.

Two of the 16 samples used in the SARS-CoV-2 pseudovirus neutralization experiment had neutralizing action, which is consistent with the absence of anti-spike antibodies. The researchers next contrasted the serologic profiles and antibody titers of patients with age-matched controls who had been diagnosed with mild COVID-19 or pediatric multisystem inflammatory disease (MIS-C).

Anti-spike and anti-nucleocapsid antibodies were primarily positive in MIS-C participants (N+S+), with significantly higher antibody levels than in other subjects. Compared to aTIN/TINU participants, mild COVID-19 subjects had higher anti-spike antibody levels but lower anti-nucleocapsid antibody levels. The TINU syndrome’s phenotype did not significantly differ between pandemic cases (2020–21) and earlier cases (2000-18).

Inflammatory signs, fever, polyuria, and abrupt weight loss characterized the typical clinical presentation. All patients had reduced estimated glomerular filtration rates at diagnosis, but these rates rose at the one-year checkup. Kidney biopsies were performed on 39 individuals. Acute interstitial nephritis with mononuclear cell infiltration and multiple tubulitis lesions without immunoglobulin deposits were visible under light microscopy.

After a week-long search, a missing radioactive capsule was discovered in Western Australia on a roadside.

Except for fewer eosinophils and greater fibrosis in the pandemic cohort, the team discovered no discernible morphological differences between the pre-pandemic and pandemic cohorts. No specific pathogen was found during the metagenomic next-generation sequencing of 11 kidney samples. Low SARS-CoV-2 messenger ribonucleic acid (mRNA) loads were detected by reverse transcription polymerase chain reaction (RT-PCR) in two of these samples.

According to the researchers, a post-COVID-19 syndrome in pediatric populations may take on a new shape as a result of aTIN/TINU. SARS-CoV-2 findings in two kidney biopsies and epidemiologic, serologic, and ELISpot information point to a causal relationship. Notably, patients had a unique N+S- serologic profile, which is different from that seen in infants with MIS-C and adults with COVID-19. They had antibodies against nucleocapsid but not spike.

What Can We Learn About Infectious Diseases from COVID-19?

Antibodies against SARS-CoV-2 support the idea that COVID-19-associated aTIN/TINU is a post-infection. The absence of SARS-CoV-2 mRNA in the majority of kidney specimens shows that the infection was successfully treated. It’s interesting to note that after April 2021, the incidence of aTIN/TINU in children decreased, maybe as a result of the COVID-19 vaccine, herd immunity, or other viral variations. These findings all point to a causal relationship between SARS-CoV-2 infection and newly appearing renal/ocular inflammation.

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