Neurological diagnoses in hospitalized COVID-19 patients during the B.1.1.529 surge.

OBJECTIVE: Emerging variants and sublineages of SARS-CoV-2 have differing disease severity, transmissibility, and immune evasion. The neurological conditions associated with the original strain of SARS-CoV-2 are well established. Our study assessed the neurological presentations specific to hospitalized patients during the B.1.1.529 (Omicron) variant surge in New York City. METHODS: A total of 178 cases with positive RT-PCR result within 6 weeks before admission, and subsequent development of select neurological conditions during the SARS-CoV-2 B.1.1.529 (Omicron) surge between December 1, 2021 and February 28, 2022, were included from 12,800 SARS-CoV-2-positive hospital admissions. Clinical data from acute hospitalizations were compared to findings of inpatient neurological cases with COVID-19 infections from the initial surge in NYC in the same hospital system. RESULTS: Compared to SARS-CoV-2 infections of the original strain, COVID-19 cases hospitalized during the Omicron surge (B.1.1.529) were associated with incidental and/or asymptomatic COVID-19 cases (96, 53.9%) and an increased incidence of pre-existing neurological and immunocompromising conditions. Encephalopathy, seizures, and stroke remained the most prevalent neurological conditions identified in hospitalized COVID-19 cases during the study period, reflecting a similar distribution of neurological presentations associated with the original strain. INTERPRETATION: In our cohort of 178 admitted SARS-CoV-2-positive patients with select neurological conditions during the Omicron B.1.1.529 surge, 54% of COVID-19 cases were considered incidental and/or asymptomatic, and the identified neurological conditions resembled those associated with the original SARS-CoV-2 strain. Further studies characterizing neurological presentation in Omicron sublineages and other variants are warranted in an ongoing COVID-19 pandemic.

Low nephron endowment increases susceptibility to renal stress and chronic kidney disease.

Preterm birth results in low nephron endowment and increased risk of acute kidney injury (AKI) and chronic kidney disease (CKD). To understand the pathogenesis of AKI and CKD in preterm humans, we generated potentially novel mouse models with a 30%-70% reduction in nephron number by inhibiting or deleting Ret tyrosine kinase in the developing ureteric bud. These mice developed glomerular and tubular hypertrophy, followed by the transition to CKD, recapitulating the renal pathological changes seen in humans born preterm. We injected neonatal mice with gentamicin, a ubiquitous nephrotoxic exposure in preterm infants, and detected more severe proximal tubular injury in mice with low nephron number compared with controls with normal nephron number. Mice with low nephron number had reduced proliferative repair with more rapid development of CKD. Furthermore, mice had more profound inflammation with highly elevated levels of MCP-1 and CXCL10, produced in part by damaged proximal tubules. Our study directly links low nephron endowment with postnatal renal hypertrophy, which in this model is maladaptive and results in CKD. Underdeveloped kidneys are more susceptible to gentamicin-induced AKI, suggesting that AKI in the setting of low nephron number is more severe and further increases the risk of CKD in this vulnerable population.