Viruses

Post-acute sequelae of SARS-CoV-2 infection (PASC) frequently includes persistent fatigue and cognitive dysfunction, but the relationship between these symptoms remains poorly defined. In this prospective observational study at the Henry Ford St. John Long COVID Clinic (LCC) from July 2023 to March 2025, we assessed fatigue severity using the Fatigue Assessment Scale (FAS) and examined its relationship with depression and cognitive symptoms. New patients completed demographic and clinical questionnaires, Patient Health Questionnaire (PHQ)-9, and Montreal Cognitive Assessment (MoCA) at their first LCC visit. Among 41 patients, 35 (85.4%) met the inclusion criteria for fatigue (FAS ≥ 22), with 18 (51.5%) experiencing severe fatigue (FAS > 34). Severe fatigue was significantly associated with shortness of breath, chest pain, and depression. Patients experiencing severe fatigue had significantly higher median PHQ-9 scores (12.5) compared to those with mild to moderate fatigue (5.0, p < 0.001). However, there were no significant differences in MoCA scores between these groups. Our study suggests a strong relationship between fatigue and depression in patients with PASC, emphasizing the importance of integrated physical and psychological healthcare. Moreover, since cognitive performance does not vary with fatigue levels, all PASC patients with cognitive dysfunction should receive routine cognitive screenings, regardless of the severity of their fatigue.

Monkeypox virus (MPXV), which previously caused mainly zoonotic infections, is currently the causative agent of the mpox outbreak that began in 2022. Since the mpox outbreak is characterized by sustained human-to-human transmission, the evolutionary trajectory of MPXV is an important scientific issue. The prevailing hypothesis suggests that the modern orthopoxviruses originated from cowpox-like ancestors with larger genomes that infected a wide range of hosts. Subsequent evolution included the reduction of the genome and the accumulation of substitutions in key proteins. Molecular dating of MPXV evolution revealed 5–6-fold acceleration in the evolutionary rate that was observed in subclade IIb after 2018, reaching 1.8 × 10⁻⁵ substitutions/site/year, likely due to virus’ adaptation to humans. The origin of MPXV from its precursor was primarily driven by the accumulation of non-synonymous substitutions in the key host range genes, including those associated with the protein inhibiting host protein synthesis (OPG173) and host immune evasion (OPG027). The subsequent divergence of MPXV into clades I and II largely depended on mutations in the gene encoding the Bcl-2-like protein. Finally, the division of clade II into subclades IIa and IIb was facilitated by further non-synonymous substitutions in the soluble interferon alpha/beta receptor and hemagglutinin genes.

Highly pathogenic avian influenza A virus (HPAIV) H5N1, clade 2.3.4.4b, has emerged as a significant zoonotic threat. H5N1 is widely circulating in wild birds, and an increasing number of spillover events have been observed in a wide range of mammalian species. These cases are primarily reported in countries on the European and American continents. This review describes the likely transmission routes, lesions, and clinical manifestations of HPAIV H5N1 clade 2.3.4.4b in naturally infected mammals, with a focus on the involvement of the central nervous system (CNS). In the analysis, pathological findings were categorized by organ system and host species, which were further divided into terrestrial mammals, marine mammals, and dairy cattle. The most frequently reported clinical manifestations were neurological and respiratory signs in marine mammals and neurological signs and lethargy in terrestrial mammals. Macroscopic and histological lesions were commonly found in the CNS and lungs of terrestrial and marine mammals, while dairy cattle showed mainly gastrointestinal and mammary gland involvement. Immunohistochemistry and reverse transcriptase real-time PCR analyses confirmed high viral loads in brain tissues, indicating a neurological tropism of H5N1 clade 2.3.4.4b. Routes of CNS invasion remain uncertain, though both hematogenous and olfactory nerve pathways are discussed. Recent evidence suggests mammal-to-mammal and vertical transmission, raising concerns for the zoonotic and pandemic potential of this virus. In conclusion, the findings emphasize an urgent need for enhanced surveillance to effectively disclose changes in viral pathogenicity and transmissibility among mammalian hosts.