Long-term neurological dysfunction associated with COVID-19: Lessons from influenza and inflammatory diseases?

As the COVID-19 pandemic persists, SARS-CoV-2 infection is increasingly associated with long-term neurological side effects including cognitive impairment, fatigue, depression, and anxiety, colloquially known as "long-COVID." While the full extent of long-COVID neuropathology across years or even decades is not yet known, we can perhaps take direction from long-standing research into other respiratory diseases, such as influenza, that can present with similar long-term neurological consequences. In this review, we highlight commonalities in the neurological impacts of influenza and COVID-19. We first focus on the common potential mechanisms underlying neurological sequelae of long-COVID and influenza, namely (1) viral neurotropism and (2) dysregulated peripheral inflammation. The latter, namely heightened peripheral inflammation leading to central nervous system dysfunction, is emerging as a shared mechanism in various peripheral inflammatory or inflammation-associated diseases and conditions. We then discuss historical and modern examples of influenza- and COVID-19-associated cognitive impairment, depression, anxiety, and fatigue, revealing key similarities in their neurological sequelae. Although we are learning that the effects of influenza and COVID differ somewhat in terms of their influence on the brain, as the impacts of long-COVID grow, such comparisons will likely prove valuable in guiding ongoing research into long-COVID, and perhaps foreshadow what could be in store for individuals with COVID-19 and their brain health.

Comparative sequence analysis elucidates the evolutionary patterns of Yersinia pestis in New Mexico over thirty-two years.

Background: Yersinia pestis, a Gram-negative bacterium, is the causative agent of plague. Y. pestis is a zoonotic pathogen that occasionally infects humans and became endemic in the western United States after spreading from California in 1899. Methods: To better understand evolutionary patterns in Y. pestis from the southwestern United States, we sequenced and analyzed 22 novel genomes from New Mexico. Analytical methods included, assembly, multiple sequences alignment, phylogenetic tree reconstruction, genotype-phenotype correlation, and selection pressure. Results: We identified four genes, including Yscp and locus tag YPO3944, which contained codons undergoing negative selection. We also observed 42 nucleotide sites displaying a statistically significant skew in the observed residue distribution based on the year of isolation. Overall, the three genes with the most statistically significant variations that associated with metadata for these isolates were sapA, fliC, and argD. Phylogenetic analyses point to a single introduction of Y. pestis into the United States with two subsequent, independent movements into New Mexico. Taken together, these analyses shed light on the evolutionary history of this pathogen in the southwestern US over a focused time range and confirm a single origin and introduction into North America.

Juvenile osteochondritis dissecans: a 5-year review of the natural history using clinical and MRI evaluation.

BACKGROUND: Although MRI prognostic features for juvenile osteochondritis dissecans (JOCD) have been determined, the natural history of JOCD on serial MRI has not been fully documented. OBJECTIVES: To document the natural history of JOCD on serial MRI and to correlate this with arthroscopy and clinical outcome over a 5-year follow-up. MATERIALS AND METHODS: Twenty-one knees in 19 patients (15 boys, 4 girls; age range 5-15 years) with JOCD underwent MRI and clinical follow-up over 5 years. Lesions were classified as stable or unstable on MRI and compared with clinical and arthroscopic data. RESULTS: On 5-year follow-up, 17 of 19 patients were asymptomatic and 2 of 19 had minimal pain. Fourteen arthroscopies were performed on 11/21 knees. One of twenty-one had fragment fixation. On initial MRI, eight knees had marked fragmentation, high signal at the fragment/bone interface and incomplete defects in the hyaline cartilage (MRI stage III-stable), but no tear. Of these, five had arthroscopy, all confirming intact cartilage. One of twenty-one knees was unstable (MRI stage IVb) with a detached osteochondral fragment, requiring surgery. CONCLUSIONS: Despite extensive subchondral bone changes on MRI, all cases with intact cartilage (95%) improved with conservative treatment. Early MRI allows prompt diagnosis and institution of conservative treatment. This results in healing and avoidance of surgery in most patients.