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Persistent ill health after acute COVID-19—referred to as long COVID, the post-acute COVID-19 syndrome, or the post-COVID-19 condition—has emerged as a major concern. We undertook an international consensus exercise to identify research priorities with the aim of understanding the long-term effects of acute COVID-19, with a focus on people with pre-existing airways disease and the occurrence of new-onset airways disease and associated symptoms. 202 international experts were invited to submit a minimum of three research ideas. After a two-phase internal review process, a final list of 98 research topics was scored by 48 experts. Patients with pre-existing or post-COVID-19 airways disease contributed to the exercise by weighting selected criteria. The highest-ranked research idea focused on investigation of the relationship between prognostic scores at hospital admission and morbidity at 3 months and 12 months after hospital discharge in patients with and without pre-existing airways disease. High priority was also assigned to comparisons of the prevalence and severity of post-COVID-19 fatigue, sarcopenia, anxiety, depression, and risk of future cardiovascular complications in patients with and without pre-existing airways disease. Our approach has enabled development of a set of priorities that could inform future research studies and funding decisions. This prioritisation process could also be adapted to other, non-respiratory aspects of long COVID.

Background: Viral respiratory infections represent a significant burden of illness with high morbidity and mortality, which has been further magnified in recent years by the emergence of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Viruses including SARS-CoV-2, Influenza A Virus (Flu-A), and Respiratory Syncytial Virus (RSV) utilize the nasopharynx for viral entry, replication and infection. The nasopharynx epithelial cell mucous membrane harbors a diverse community of bacteria, called the nasal microbiota (NM). Flu-A can modulate changes in the NM community and lead to pathobiont enrichment. Therefore, here we aim to investigate the NM of individuals with SARS-CoV-2, Flu-A and RSV infection, and identify correlates between the NM community and viral load (VL) and SARS-CoV-2 variants of concern (VOC). Methods: Nasopharyngeal (NP) swabs were collected and tested for SARS-CoV-2, Flu-A, and RSV by validated real-time PCR (RT-PCR) assays. RNA extraction was performed using a Maxwell automatic nucleic acid extractor followed by 16S rRNA Illumina Next Generation Sequencing (NGS) library sample preparation for NGS on a MiSeq Sequencer. QIIME II, Microbiome Analyst and PRISM 9.0.0 were used for data analysis. Results: NP swabs from 118 SARS-CoV-2, 40 Flu-A, 26 RSV positive and 45 negative controls (NC) were included. An increase in alpha and beta bacterial diversity (p<0.001) was observed in the NM of SARS-CoV-2 patients and an enrichment in Streptococcus and Staphylococcus species and depletion of Bifidobacterium and Moraxella species compared to NC’s (p<0.001). Compared to Flu-A and RSV patients, SARS-CoV-2 positives showed enrichment in Streptococcus, and depletion in Haemophilus species (p<0.002). 73/118 SARS-CoV-2 specimens were further sequenced to identify VOC lineage and stratified by VL. No significance in bacterial richness, diversity, or abundance correlated to VL. Only a significant difference in beta diversity was observed between the alpha/delta and omicron cohorts (p<0.001). Conclusions: This study demonstrates that the NM community is different in individuals with respiratory illness and distinct between SARS-CoV-2, Flu-A and RSV infected individuals. This study also demonstrated that NM beta diversity was different between individuals with different SARS-CoV-2 lineages, suggesting virus-NM interplay that may be important in explaining differences in transmission potentials and pathogenesis between SARS-CoV-2 VOCs.

The incessant changes in all areas of economy, science, politics and society, with a greater acceleration in recent years, are affecting also the transport regulation, one of the most stable of all the branches of law, having in mind that one of its areas, the Maritime Law, has maintained almost unchanged over the centuries many of the institutes and figures that most characterize it, such as general average, salvage, limitation of the liability of the shipowner, the charterparty, the bill of lading, the role of the master and the crew. In a world in which phenomena such as the Covid-19 pandemic, Brexit and the ever-increasing use of new technologies, despite being profoundly different from each other, have had and certainly do have a prominent role, operators in any sector find themselves having to face, often from one moment to the next, and therefore unexpectedly and in no time, a multiplicity of problems that are largely completely new, in order to avoid, or at least mitigate, the consequences of total or partial paralysis of their activities. Given the circumstances, legislators, national and international regulatory bodies and jurists are called upon to urgently reconsider and/or integrate the disciplines currently in force, both from the public and private aspects, taking into account the critical issues that are gradually emerging. Clearly, in a globalized context like the one we live in, characterized by a strong interconnection of activities and sectors with each other and where the interaction of multiple factors is inevitable, the panorama is of such complexity that, at the time being, no one is yet able to predict what future developments may be in detail, in the full awareness, however, that the playground is in constant becoming. The choice of the regulatory approach to be followed from time to time is far from easy, especially in the knowledge that on the one hand the evolution of legislation, geopolitics, technology and the behavior of operators on the relevant market are closely interconnected, and that on the other hand a not well shaped regulation could become an obstacle to the development of trade and, more generally, of global economy. New phenomena always give rise to unprecedented problems and, if it is not possible to give a full solution to them by means of the rules already in force, the legislators, making use of various forms of regulatory instruments, in terms both of quality and of extension of territorial effectiveness, should implement an evolution of the regulations, introducing new norms or modifying existing ones, also in light of the interests of the different stakeholders, often conflicting and variously declined, and of the practices that in some cases have been established and have remained constant and unchanged for a very long time. The multiplicity and multiformity of the problems that arise must not discourage, but rather act as a further stimulus: in such a tumultuous contingent situation, it is essential to maintain a certain order and an adequate methodological rigor in dealing with the individual problems, putting them into focus one by one, in order to then slowly expand the view and obtain an overall picture. In this perspective, the selected essays collected in this volume examine, in their dual scientific-academic and practical soul, both issues that arise as a result of the new phenomena mentioned above, and more “classic” topics of the matter, but analyzing them having regard to their most recent developments.

Long-term care homes play an essential role within health and social care. Successful measures to support older people at home for longer have led to increased prevalence of disability, frailty and cognitive impairment in those who live in care homes over the last two decades. The need for care home places is projected to increase for the next two decades. Modern care homes provide care for people who are predominantly over 80, have multiple long-term conditions, take multiple medicines, are physically dependent and live with cognitive impairment. Residents do better when services recognise the contributions of staff and care home providers rather than treating residents as individual patients living in a communal setting. There is a strong case given residents' frailty, multimorbidity and disability, that care should be structured around Comprehensive Geriatric Assessment (CGA). Care should be designed to allow opportunities for multiprofessional teams to come together for CGA, particularly if healthcare professionals are based outside care homes. Good data about care homes and residents are central to efforts to deliver high quality care-in some countries, these data are collected but not collated. Collating such data is a priority. Care home staff are under-recognised and underpaid-parity of pay and opportunity with NHS staff is the bare minimum to ensure that the best are recruited and retained in the sector. During the COVID-19 pandemic, residents and relatives have frequently been left out of decisions about policies that affect them, and better consultation is needed to deliver high quality care.

A global cross-discipline effort is ongoing to characterize the evolution of SARS-CoV-2 virus and generate reliable epidemiological models of its diffusion. To this end, phylogenomic approaches leverage accumulating genomic mutations as barcodes to track the evolutionary history of the virus and can benefit from the surge of sequences deposited in public databases. Yet, such methods typically rely on consensus sequences representing the dominant virus lineage, whereas a complex sublineage architecture is often observed within single hosts. Furthermore, most approaches do not account for variants accumulation processes and might produce inaccurate results in condition of limited sampling, as witnessed in most countries currently affected by the epidemics. We here introduce a new framework for the characterization of viral (sub)lineage evolution and transmission of SARS-CoV-2, which considers both clonal and intra-host minor variants and exploits the achievements of cancer evolution research to account for mutation accumulation and uncertainty in the data. The application of our approach to 18 SARS-CoV-2 samples for which raw sequencing data are available reveals a high-resolution phylogenomic model, which confirms and improves recent findings on viral types and highlights the existence of patterns of co-occurrence of minor variants, uncovering likely infection paths among hosts harboring the same viral lineage. Our findings confirm a significant increase of genomic diversity of SARS-CoV-2 in time, which is reflected in minor variants, and show that standard methods may struggle when handling datasets with important sampling limitations. Importantly, our framework allows to pinpoint minor variants that might be positively selected across distinct lineages and regions of the viral genome under purifying selection, thus driving the design of treatments and vaccines. In particular, minor variant g.29039A>U, detected in multiple viral lineages and validated on an independent dataset, shows that SARS-CoV-2 can lose its main Nucleocapsid immunogenic epitopes, raising concerns about the effectiveness of vaccines targeting the C-terminus of this protein. To conclude, we advocate the use of our framework in combination with data-driven epidemiological models, to deliver a high-precision platform for pathogen detection, surveillance and analysis.