Linking pathogenic and likely pathogenic gene variants to long-COVID symptoms.

OBJECTIVE: Long-COVID is a clinical syndrome characterized by the presence of symptoms related to SARS-CoV-2 infection that persist for at least four weeks after recovery from COVID-19. Genetics have been proposed to play an important role in long-COVID syndrome onset. This study aimed to identify genetic pathogenetic and likely pathogenetic causative variants of Mendelian genetic diseases in patients with Long-COVID syndrome. Additionally, we aimed to establish an association between these genetic variants and the clinical symptoms manifested during long-COVID syndrome. PATIENTS AND METHODS: 95 patients affected by long-COVID syndrome were analyzed with a Next-Generation Sequencing (NGS) panel comprising 494 genes. The analyzed genes and the symptoms of the patients collected with an ad-hoc questionnaire were divided into four groups (cardiological, respiratory, immunological, and neurological). Finally, a statistical analysis comprising descriptive statistics, classification based on reported symptoms, and comparative analysis against a control group of healthy individuals was conducted. RESULTS: 12 patients resulted positive for genetic testing with an autosomal dominance (8) or autosomal recessive (4) inheritance, showing a higher prevalence of cardiovascular genetic diseases (9) in the analyzed cohort compared to the normal population. Moreover, the onset of the long-COVID syndrome and its cardiovascular manifestations was compliant with the onset reported in the literature for the identified genetic diseases, suggesting that COVID-19 could manifest late-onset genetic diseases associated with their appearance. Apart from the 12 positive patients, 57 were healthy carriers of genetic diseases. Analyzing the whole cohort, a statistical correlation between prevalent symptomatology and the gene class was established, suggesting an association between the genetic susceptibility of an individual and the possibility of developing specific long-COVID syndrome symptoms, especially cardiovascular symptoms. Furthermore, 17 genetic variants were identified in CFTR. Finally, we identified genetic variants in IFNAR2 and POLG, supporting their respective involvement in inflammation and mitochondria mechanisms, correlated with long-COVID syndrome according to literature data. CONCLUSIONS: This study proposed COVID-19 to act as a manifest of underlying late-onset genetic diseases Mendelian associated with carrier status. Moreover, according to our results, mutations in cardiological genes are more present in patients who show cardiological symptoms during the syndrome. This underscores the necessity for cardiological investigation and genetic screening in long-COVID patients to address existing or potential clinical implications.

The long search for a serotype independent pneumococcal vaccine.

Introduction: Serotype replacement - a consequence of polysaccharide vaccine use - will continue to drive the inclusion of new serotypes on conjugate vaccines, increasing production complexity and costs, and making an already expensive vaccine less accessible to developing countries, where prevalence is higher and resources available for health systems, scarcer. Serotype-independent formulations are a promising option, but so far they have not been successful in reducing colonization/transmission.Areas covered: Protein-based and whole-cell vaccine candidates studied in the past 30 years. Challenges for serotype-independent vaccine development and alternative approaches.Expert opinion: Clinical trials performed so far demonstrated the importance to establish more reliable animal models and better correlates of protection. Defining appropriate endpoints for clinical trials of serotype-independent vaccine candidates has been a challenge. Inhibition of colonization has been evaluated, but concern on the extent of bacterial elimination is still a matter of debate. Challenges on establishing representative sites for clinical trials, sample sizes and appropriate age groups are discussed. On a whole, although many challenges will have to be overcome, establishing protein-based antigens as serotype-independent vaccines is still the best alternative against the huge burden of pneumococcal diseases in the world.

The long search for a serotype independent pneumococcal vaccine

Introduction: Serotype replacement – a consequence of polysaccharide vaccine use – will continue to drive the inclusion of new serotypes on conjugate vaccines, increasing production complexity and costs, and making an already expensive vaccine less accessible to developing countries, where prevalence is higher and resources available for health systems, scarcer. Serotype-independent formulations are a promising option, but so far they have not been successful in reducing colonization/transmission.Areas covered: Protein-based and whole-cell vaccine candidates studied in the past 30 years. Challenges for serotype-independent vaccine development and alternative approaches.Expert opinion: Clinical trials performed so far demonstrated the importance to establish more reliable animal models and better correlates of protection. Defining appropriate endpoints for clinical trials of serotype-independent vaccine candidates has been a challenge. Inhibition of colonization has been evaluated, but concern on the extent of bacterial elimination is still a matter of debate. Challenges on establishing representative sites for clinical trials, sample sizes and appropriate age groups are discussed. On a whole, although many challenges will have to be overcome, establishing protein-based antigens as serotype-independent vaccines is still the best alternative against the huge burden of pneumococcal diseases in the world

The long search for a serotype independent pneumococcal vaccine

Introduction: Serotype replacement – a consequence of polysaccharide vaccine use – will continue to drive the inclusion of new serotypes on conjugate vaccines, increasing production complexity and costs, and making an already expensive vaccine less accessible to developing countries, where prevalence is higher and resources available for health systems, scarcer. Serotype-independent formulations are a promising option, but so far they have not been successful in reducing colonization/transmission.Areas covered: Protein-based and whole-cell vaccine candidates studied in the past 30 years. Challenges for serotype-independent vaccine development and alternative approaches.Expert opinion: Clinical trials performed so far demonstrated the importance to establish more reliable animal models and better correlates of protection. Defining appropriate endpoints for clinical trials of serotype-independent vaccine candidates has been a challenge. Inhibition of colonization has been evaluated, but concern on the extent of bacterial elimination is still a matter of debate. Challenges on establishing representative sites for clinical trials, sample sizes and appropriate age groups are discussed. On a whole, although many challenges will have to be overcome, establishing protein-based antigens as serotype-independent vaccines is still the best alternative against the huge burden of pneumococcal diseases in the world