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Anelloviruses are ubiquitous in humans and represent a major component of the human virome. Its best-known representative is Torque teno virus (i.e., the Alphatorquevirus genus), which is considered a potential immunity biomarker. Recent metagenomic investigations revealed not only the extraordinary genomic diversity of anellovirus sequences, but also that co-detection of genera, genotypes, or species seems to be the rule in humans. SCANellome was developed to represent a user-friendly tool to analyze the primate (both human and non-human) anellovirus composition at the genus, species, and genotype level from metagenomics data based on an up-to-date database. This SCANellome update includes >900 additional reference sequences from GenBank. Using a clustering at 90% identity, the FASTA database was updated and generated 134 new representative sequences. Based on ORF1, the analysis of these new sequences indicates the presence of 206 potential new species, including four nonhuman primates, and adds four new non-human primate species which will be the subject of a proposal to the International Committee on Taxonomy of Viruses (ICTV). In addition, SCANellome V2 provides now the user with an interactive up-to-date phylogenetic analysis (of ORF1) to show the distribution among the 12 human and nonhuman primate genera of these new potential species. Finally, the Anelloviridae taxonomy was updated to rename species names in binomial format as required by the ICTV. [ABSTRACT FROM AUTHOR]

During the SARS-CoV-2 pandemic, the Dr. Risch medical group employed the multiplex TaqPathTM COVID-19 CE-IVD RT-PCR Kit for large-scale routine diagnostic testing in Switzerland and the principality of Liechtenstein. The TaqPath Kit is a widely used multiplex assay targeting three genes (i.e., ORF1AB, N, S). With emergence of the B.1.1.7 (Alpha) variant, a diagnostic flaw became apparent as the amplification of the S-gene target was absent in these samples due to a deletion (ΔH69/V70) in the Alpha variant genome. This S-gene target failure (SGTF) was the earliest indication of a new variant emerging and was also observed in subsequent variants such as Omicron BA.1 and BA4/BA.5. The Delta variant and Omicron BA.2 did not present with SGTF. From September 2020 to November 2022, we investigated the applicability of the SGTF as a surrogate marker for emerging variants such as B.1.1.7, B.1.617.2 (Delta), and Omicron BA.1, BA.2, and BA.4/BA.5 in samples with cycle threshold (Ct) values < 30. Next to true SGTF-positive and SGTF-negative samples, there were also samples presenting with delayed-type S-gene amplification (higher Ct value for S-gene than ORF1ab gene). Among these, a difference of 3.8 Ct values between the S- and ORF1ab genes was found to best distinguish between "true" SGTF and the cycle threshold variability of the assay. Samples above the cutoff were subsequently termed partial SGTF (pSGTF). Variant confirmation was performed by whole-genome sequencing (Oxford Nanopore Technology, Oxford, UK) or mutation-specific PCR (TIB MOLBIOL). In total, 17,724 (7.4%) samples among 240,896 positives were variant-confirmed, resulting in an overall sensitivity and specificity of 93.2% [92.7%, 93.7%] and 99.3% [99.2%, 99.5%], respectively. Sensitivity was increased to 98.2% [97.9% to 98.4%] and specificity lowered to 98.9% [98.6% to 99.1%] when samples with pSGTF were included. Furthermore, weekly logistic growth rates (α) and sigmoid's midpoint (t0) were calculated based on SGTF data and did not significantly differ from calculations based on comprehensive data from GISAID. The SGTF therefore allowed for a valid real-time estimate for the introduction of all dominant variants in Switzerland and Liechtenstein. [ABSTRACT FROM AUTHOR]

With nearly half of the world's population being at risk of infection, dengue virus represents a major global health issue. The use of dengue antigen rapid diagnostic tests (Ag-RDTs) represents an alternative to PCR methods for the diagnosis of acute infections since they display excellent sensitivities and specificities and can be performed outside the laboratory. The high genetic diversity of the dengue virus genome represents a challenge for vaccine development, and the progressive expansion of this virus into previously nonendemic regions justifies the implementation of a genomic surveillance program. In this proof-of-concept study, we show the feasibility of sequencing dengue virus genomes directly from positive Ag-RDT (Standard Q Dengue Duo Test assay, n = 7) cassettes stored up to 31 days at room temperature after testing. For 5 of the 7 samples, a high number of reads were obtained allowing phylogenetic analyses to be carried out to determine not only the serotypes (dengue 1, 2, 3 and 4 were detected) but also the genotypes. Furthermore, in one sample, our unbiased metagenomic next-generation sequencing approach made it possible to detect epizootic hemorrhagic disease virus sequences, an arthropod-transmitted virus in ruminants. To conclude, as such an approach requires no cold storage or freezing of samples, dengue Ag-RDTs represent a very pragmatic and robust alternative for the genomic surveillance of dengue virus. [ABSTRACT FROM AUTHOR]

Influenza virus is one of the main causes of respiratory infections worldwide. Despite the availability of seasonal vaccines and antivirals, influenza virus infections cause an important health and economic burden. Therefore, the need to identify alternative antiviral strategies persists. In this study, we identified non-steroidal estrogens as potent inhibitors of influenza virus due to their interaction with the hemagglutinin protein, preventing viral entry. This activity is maintained in vitro, ex vivo, and in vivo. Therefore, we found a new domain to target on the hemagglutinin and a class of compounds that could be further optimized for influenza treatment. [ABSTRACT FROM AUTHOR]

Anelloviruses are extremely prevalent in the human population and are considered to be commensal parts of the human virome. The best-known member in humans is the Torque teno virus. Recent metagenomic next-generation sequencing investigations have helped reveal the considerable number of species and genotypes from the same genus that can be co-detected within a single individual and that this diversity increases as a function of age during the first months/years of life. As a result, to date, the bioinformatics analysis of this genetic diversity remains complex and constraining for researchers. Here, we present SCANellome, a user-friendly tool to investigate the anellome composition at the genus, species, and genotype levels of samples from metagenomics data generated by the Illumina and Nanopore platforms. SCANellome is based on an in-house up-to-date database that includes all human and non-human primate anellovirus reference sequences available on GenBank and meets the latest classification criteria established by the International Committee on Taxonomy of Viruses. [ABSTRACT FROM AUTHOR]

Metagenomics revealed novel and routinely overlooked viruses, representing sources of unrecognized infections after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aim to describe DNA and RNA virus prevalence and kinetics in allo-HSCT recipients' plasma for one year post HSCT. We included 109 adult patients with first allo-HSCT from 1 March 2017 to 31 January 2019 in this observational cohort study. Seventeen DNA and three RNA viral species were screened with qualitative and/or quantitative r(RT)-PCR assays using plasma samples collected at 0, 1, 3, 6, and 12 months post HSCT. TTV infected 97% of patients, followed by HPgV-1 (prevalence: 26–36%). TTV (median 3.29 × 105 copies/mL) and HPgV-1 (median 1.18 × 106 copies/mL) viral loads peaked at month 3. At least one Polyomaviridae virus (BKPyV, JCPyV, MCPyV, HPyV6/7) was detected in >10% of patients. HPyV6 and HPyV7 prevalence reached 27% and 12% at month 3; CMV prevalence reached 27%. HSV, VZV, EBV, HHV-7, HAdV and B19V prevalence remained <5%. HPyV9, TSPyV, HBoV, EV and HPg-V2 were never detected. At month 3, 72% of patients had co-infections. TTV and HPgV-1 infections were highly prevalent. BKPyV, MCPyV and HPyV6/7 were frequently detected relative to classical culprits. Further investigation is needed into associations between these viral infections and immune reconstitution or clinical outcomes. [ABSTRACT FROM AUTHOR]

Torque teno virus (TTV) is considered to be an ubiquitous member of the commensal human blood virome commonly reported in mixed genotype co-infections. This study investigates the genomic diversity of TTV in blood samples from 816 febrile Tanzanian children. Metagenomic next-generation sequencing was used to screen for TTV in individual blood samples from a cohort of 816 febrile Tanzanian paediatric outpatients. For positive samples, the number of TTV species and genotypes present were evaluated. We investigate the linear relationship between individual TTV diversity and the patient age by linear regression. TTV was detected in 97.2% of sera. ORF1 analysis revealed the presence of 149 genotypes from 38 species, suggesting the presence of 13 new species. These genotypes were mostly present as co-infections with a median of 11 genotypes/subject (range: 1–71). In terms of species, we found a median of nine species/subject (range: 1–29). We further show a significant association between the diversity of co-detected TTV and the age of the subjects (p value < 0.0001). This study shows that significant TTV genomic diversity is acquired by the age of five and that this diversity tends to increase with age, which indicates a repetitive TTV acquisition during the first months/years of life. [ABSTRACT FROM AUTHOR]

Human rhinoviruses (HRVs) and enteroviruses (HEVs) belong to the Enterovirus genus and are the most frequent cause of infection worldwide, but data on their molecular epidemiology in Africa are scarce. To understand HRV and HEV molecular epidemiology in this setting, we enrolled febrile pediatric patients participating in a large prospective cohort assessing the causes of fever in Tanzanian children. Naso/oropharyngeal swabs were systematically collected and tested by real-time RT-PCR for HRV and HEV. Viruses from positive samples were sequenced and phylogenetic analyses were then applied to highlight the HRV and HEV types as well as recombinant or divergent strains. Thirty-eight percent (378/1005) of the enrolled children harboured an HRV or HEV infection. Although some types were predominant, many distinct types were co-circulating, including a vaccinal poliovirus, HEV-A71 and HEV-D68. Three HRV-A recombinants were identified: HRV-A36/HRV-A67, HRV-A12/HRV-A67 and HRV-A96/HRV-A61. Four divergent HRV strains were also identified: one HRV-B strain and three HRV-C strains. This is the first prospective study focused on HRV and HEV molecular epidemiology in sub-Saharan Africa. This systematic and thorough large screening with careful clinical data management confirms the wide genomic diversity of these viruses, brings new insights about their evolution and provides data about associated symptoms. [ABSTRACT FROM AUTHOR]

Background: Long COVID has become a burden on healthcare systems worldwide. Research into the etiology and risk factors has been impeded by observing all diverse manifestations as part of a single entity. We aimed to determine patterns of symptoms in convalescing COVID-19 patients. Methods: Symptomatic patients were recruited from four countries. Data were collected regarding demographics, comorbidities, acute disease and persistent symptoms. Factor analysis was performed to elucidate symptom patterns. Associations of the patterns with patients' characteristics, features of acute disease and effect on daily life were sought. Results: We included 1027 symptomatic post-COVID individuals in the analysis. The majority of participants were graded as having a non-severe acute COVID-19 (N = 763, 74.3%). We identified six patterns of symptoms: cognitive, pain-syndrome, pulmonary, cardiac, anosmia-dysgeusia and headache. The cognitive pattern was the major symptoms pattern, explaining 26.2% of the variance; the other patterns each explained 6.5–9.5% of the variance. The cognitive pattern was higher in patients who were outpatients during the acute disease. The pain-syndrome pattern was associated with acute disease severity, higher in women and increased with age. The pulmonary pattern was associated with prior lung disease and severe acute disease. Only two of the patterns (cognitive and cardiac) were associated with failure to return to pre-COVID occupational and physical activity status. Conclusion: Long COVID diverse symptoms can be grouped into six unique patterns. Using these patterns in future research may improve our understanding of pathophysiology and risk factors of persistent COVID, provide homogenous terminology for clinical research, and direct therapeutic interventions. [ABSTRACT FROM AUTHOR]

Respiratory viral infections (RVIs) in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients can be of concern due to the patients' depressed immune status, but few data are available about the significance of a pre-transplant positive testing. In this retrospective observational study, we analyzed a cohort of patients that were transplanted between 1 January 2010 and 31 October 2019 in the Geneva University Hospitals with at least one RVI before or after transplantation. At least one RVI was detected in 319/533 (63.5%) transplanted patients. Rhinoviruses were most frequently identified (37%), followed by human coronaviruses (17.1%), parainfluenza viruses (13.9%), and influenza viruses (9.9%). First infection in the post-transplant period occurred at a mean time of 334 days (SD 338). Specific analysis of a subgroup of 65 patients with pre-transplant RVIs was performed. Among them, 39 (59%) patients had symptoms and 14 (21.2%) had a lower respiratory tract infection. Four patients (6.1%) (three rhinovirus and one influenza) needed an intensive care unit admission, of which, three (4.5%) (two rhinovirus and one influenza) were intubated. The patient with influenza infection diagnosed the day of the transplantation died within the first 30 days of the infection. Two patients with rhinovirus infection died within 3 months of unrelated causes. Our data show that rhinovirus infections are predominant in allo-HSCT patients, including among pre-transplant infections; however, mortality due to pre-transplant RVI is low and was only clearly identified in one patient with influenza infection. RVI within the month preceding allo-HSCT is not associated with direct morbidity or mortality in this cohort. [ABSTRACT FROM AUTHOR]

The burden of COVID-19 has disproportionately impacted the elderly, who are at increased risk of severe disease, hospitalization, and death. This cross-sectional study aimed to assess the association between SARS-CoV-2 seroprevalence among nursing home staff, and cumulative incidence rates of COVID-19 cases, hospitalizations, and deaths among residents. Staff seroprevalence was estimated within the SEROCoV-WORK+ study between May and September 2020 across 29 nursing homes in Geneva, Switzerland. Data on nursing home residents were obtained from the canton of Geneva for the period between March and August 2020. Associations were assessed using Spearman's correlation coefficient and quasi-Poisson regression models. Overall, seroprevalence among staff ranged between 0 and 31.4%, with a median of 8.3%. A positive association was found between staff seroprevalence and resident cumulative incidence of COVID-19 cases (correlation coefficient R = 0.72, 95%CI 0.45–0.87; incidence rate ratio [IRR] = 1.10, 95%CI 1.07–1.17), hospitalizations (R = 0.59, 95%CI 0.25–0.80; IRR = 1.09, 95%CI 1.05–1.13), and deaths (R = 0.71, 95%CI 0.44–0.86; IRR = 1.12, 95%CI 1.07–1.18). Our results suggest that SARS-CoV-2 transmission between staff and residents may contribute to the spread of the virus within nursing homes. Awareness among nursing home professionals of their likely role in the spread of SARS-CoV-2 has the potential to increase vaccination coverage and prevent unnecessary deaths due to COVID-19. [ABSTRACT FROM AUTHOR]

Concomitant respiratory viral infections may influence clinical outcomes of acute decompensated heart failure (ADHF) but this association is based on indirect observation. The aim of this study was to evaluate the prevalence and impact of laboratory-confirmed influenza or respiratory syncytial virus (RSV) infection on outcomes in patients hospitalised for ADHF. Prospective cohort of patients hospitalised for ADHF with systematic influenza and RSV screening using real-time PCR on nasopharyngeal swabs. The primary outcome was all-cause mortality or readmission at 90 days. Among 803 patients with ADHF, 196 (24.5%) patients had concomitant flu-like symptoms of influenza. PCR was positive in 45 patients (27 for influenza, 19 for RSV). At 90 days, PCR positive patients had lower rates of all-cause mortality or readmission as compared to patients without flu-like symptoms (HR 0.40, 95% CI 0.18–0.91, p = 0.03), and non-significantly less all-cause mortality (HR 0.30, 95% CI 0.04–2.20, p = 0.24), or HF-related death or readmission (HR 0.36, 95% CI 0.13–0.99, p = 0.05). The prevalence of influenza or RSV infection in patients admitted for ADHF was low and associated with less all-cause mortality and readmission. Concomitant viral infection with ADHF may not in itself be a predictor of poor outcomes. (ClinicalTrials.gov NCT02444416). [ABSTRACT FROM AUTHOR]

Background: Oncological patients have a higher risk of prolonged SARS-CoV-2 shedding, which, in turn, can lead to evolutionary mutations and emergence of novel viral variants. The aim of this study was to analyze biological samples of a cohort of oncological patients by deep sequencing to detect any significant viral mutations. Methods: High-throughput sequencing was performed on selected samples from a SARS-CoV-2-positive oncological patient cohort. Analysis of variants and minority variants was performed using a validated bioinformatics pipeline. Results: Among 54 oncological patients, we analyzed 12 samples of 6 patients, either serial nasopharyngeal swab samples or samples from the upper and lower respiratory tracts, by high-throughput sequencing. We identified amino acid changes D614G and P4715L as well as mutations at nucleotide positions 241 and 3037 in all samples. There were no other significant mutations, but we observed intra-host evolution in some minority variants, mainly in the ORF1ab gene. There was no significant mutation identified in the spike region and no minority variants common to several hosts. Conclusions: There was no major and rapid evolution of viral strains in this oncological patient cohort, but there was minority variant evolution, reflecting a dynamic pattern of quasi-species replication. [ABSTRACT FROM AUTHOR]

Extended community testing constitutes one of the main strategic pillars in controlling the COVID-19 pandemic. Reverse transcription PCR (RT-PCR) targeting the SARS-CoV-2 genome on nasopharyngeal swab samples is currently the reference test. While displaying excellent analytical sensitivity and specificity, this test is costly, often requires a substantial turnaround time, and, more importantly, is subject to reagent and other material shortages. To complement this technology, rapid antigen tests have been developed and made available worldwide, allowing cheap, quick, and decentralized SARS-CoV-2 testing. The main drawback of these tests is the reduced sensitivity when RT-PCR is the gold standard. In this study, we evaluate Visby an innovative, portable, easy-to-use RT-PCR point-of-care (POC) diagnostic device. Our retrospective analysis shows that overall, compared to the Cobas 6800 RT-qPCR assay (Roche), this RT-PCR POC technology detects SARS-CoV-2 RNA with 95% sensitivity (95%CI = 86.3–99%) and 100% specificity (95% CI = 80.5–100%). For samples with cycle-threshold values below 31, we observed 100% sensitivity (95% CI = 66.4–100%). While showing an analytical sensitivity slightly below that of a standard RT-qPCR system, the evaluated Visby RT-PCR POC device may prove to be an interesting diagnostic alternative in the COVID-19 pandemic, potentially combining the practical advantages of rapid antigen tests and the robust analytical performances of nucleic acid detection systems. [ABSTRACT FROM AUTHOR]

Purpose: To assess the diagnostic performances of five automated anti-SARS-CoV-2 immunoassays, Epitope (N), Diasorin (S1/S2), Euroimmun (S1), Roche N (N), and Roche S (S-RBD), and to provide a testing strategy based on pre-test probability. Methods: We assessed the receiver operating characteristic (ROC) areas under the curve (AUC) values, along with the sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs), of each assay using a validation sample set of 172 COVID-19 sera and 185 negative controls against a validated S1-immunofluorescence as a reference method. The three assays displaying the highest AUCs were selected for further serodetection of 2033 sera of a large population-based cohort. Results: In the validation analysis (pre-test probability: 48.1%), Roche N, Roche S and Euroimmun showed the highest discriminant accuracy (AUCs: 0.99, 0.98, and 0.98) with PPVs and NPVs above 96% and 94%, respectively. In the population-based cohort (pre-test probability: 6.2%) these three assays displayed AUCs above 0.97 and PPVs and NPVs above 90.5% and 99.4%, respectively. A sequential strategy using an anti-S assay as screening test and an anti-N as confirmatory assays resulted in a 96.7% PPV and 99.5% NPV, respectively. Conclusions: Euroimmun and both Roche assays performed equally well in high pre-test probability settings. At a lower prevalence, sequentially combining anti-S and anti-N assays resulted in the optimal trade-off between diagnostic performances and operational considerations. [ABSTRACT FROM AUTHOR]

Respiratory viral infections constitute a global public health concern. Among prevalent respiratory viruses, two pneumoviruses can be life-threatening in high-risk populations. In young children, they constitute the first cause of hospitalization due to severe lower respiratory tract diseases. A better understanding of their pathogenesis is still needed as there are no approved efficient anti-viral nor vaccine against pneumoviruses. We studied Respiratory Syncytial virus (RSV) and human Metapneumovirus (HMPV) in single and dual infections in three-dimensional cultures, a highly relevant model to study viral respiratory infections of the airway epithelium. Our investigation showed that HMPV is less pathogenic than RSV in this model. Compared to RSV, HMPV replicated less efficiently, induced a lower immune response, did not block cilia beating, and was more sensitive to IFNs. In dual infections, RSV-infected epithelia were less permissive to HMPV. By neutralizing IFNs in co-infection assays, we partially prevented HMPV inhibition by RSV and significantly increased the number of co-infected cells in the tissue. This suggests that interference in dual infection would be at least partly mediated by the host immune response. In summary, this work provides new insight regarding virus-host and virus-virus interactions of pneumoviruses in the airway epithelium. This could be helpful for the proper handling of at-risk patients. [ABSTRACT FROM AUTHOR]

The huge genetic diversity of circulating viruses is a challenge for diagnostic assays for emerging or rare viral diseases. High-throughput technology offers a new opportunity to explore the global virome of patients without preconception about the culpable pathogens. It requires a solid reference dataset to be accurate. Virosaurus has been designed to offer a non-biased, automatized and annotated database for clinical metagenomics studies and diagnosis. Raw viral sequences have been extracted from GenBank, and cleaned up to remove potentially erroneous sequences. Complete sequences have been identified for all genera infecting vertebrates, plants and other eukaryotes (insect, fungus, etc.). To facilitate the analysis of clinically relevant viruses, we have annotated all sequences with official and common virus names, acronym, genotypes, and genomic features (linear, circular, DNA, RNA, etc.). Sequences have been clustered to remove redundancy at 90% or 98% identity. The analysis of clustering results reveals the state of the virus genetic landscape knowledge. Because herpes and poxviruses were under-represented in complete genomes considering their potential diversity in nature, we used genes instead of complete genomes for those in Virosaurus. [ABSTRACT FROM AUTHOR]

Background: Comparative data of SARS-CoV-2 IgM/IgG serology rapid diagnostic tests (RDTs) is scarce. We thus performed a head-to-head comparison of three RDTs. Methods: In this unmatched case-control study, blood samples from 41 RT-PCR-confirmed COVID-19 cases and 50 negative controls were studied. The diagnostic accuracy of three commercially available COVID-19 RDTs: NTBIO (RDT-A), Orient-Gene (RDT-B), and MEDsan (RDT-C), against both a recombinant spike-expressing immunofluorescence assay (rIFA) and Euroimmun IgG ELISA, was assessed. RDT results concordant with the reference methods, and between whole blood and plasma, were established by the Kendall coefficient. Results: COVID-19 cases' median time from RT-PCR to serology was 22 days (interquartile range (IQR) 13–31 days). Whole-blood IgG detection with RDT-A, -B, and -C showed 0.93, 0.83, and 0.98 concordance with rIFA. Against rIFA, RDT-A sensitivity (SN) was 92% (95% CI: 78–98) and specificity (SP) 100% (95% CI: 91–100), RDT-B showed 87% SN (95% CI: 72–95) and 98% SP (95% CI: 88–100), and RDT-C 100% SN (95% CI: 88–100) and 98% SP (95% CI: 88–100). Against ELISA, SN and SP were above 90% for all three RDTs. Conclusions: RDT-A and RDT-C displayed IgG detection SN and SP above 90% in whole blood. These RDTs could be considered in the absence of routine diagnostic serology facilities. [ABSTRACT FROM AUTHOR]

Shotgun metagenomics using next generation sequencing (NGS) is a promising technique to analyze both DNA and RNA microbial material from patient samples. Mostly used in a research setting, it is now increasingly being used in the clinical realm as well, notably to support diagnosis of viral infections, thereby calling for quality control and the implementation of ring trials (RT) to benchmark pipelines and ensure comparable results. The Swiss NGS clinical virology community therefore decided to conduct a RT in 2018, in order to benchmark current metagenomic workflows used at Swiss clinical virology laboratories, and thereby contribute to the definition of common best practices. The RT consisted of two parts (increments), in order to disentangle the variability arising from the experimental compared to the bioinformatics parts of the laboratory pipeline. In addition, the RT was also designed to assess the impact of databases compared to bioinformatics algorithms on the final results, by asking participants to perform the bioinformatics analysis with a common database, in addition to using their own in-house database. Five laboratories participated in the RT (seven pipelines were tested). We observed that the algorithms had a stronger impact on the overall performance than the choice of the reference database. Our results also suggest that differences in sample preparation can lead to significant differences in the performance, and that laboratories should aim for at least 5–10 Mio reads per sample and use depth of coverage in addition to other interpretation metrics such as the percent of coverage. Performance was generally lower when increasing the number of viruses per sample. The lessons learned from this pilot study will be useful for the development of larger-scale RTs to serve as regular quality control tests for laboratories performing NGS analyses of viruses in a clinical setting. [ABSTRACT FROM AUTHOR]

Meningitis, encephalitis, and myelitis are various forms of acute central nervous system (CNS) inflammation, which can coexist and lead to serious sequelae. Known aetiologies include infections and immune-mediated processes. Despite advances in clinical microbiology over the past decades, the cause of acute CNS inflammation remains unknown in approximately 50% of cases. High-throughput sequencing was performed to search for viral sequences in cerebrospinal fluid (CSF) samples collected from 26 patients considered to have acute CNS inflammation of unknown origin, and 10 patients with defined causes of CNS diseases. In order to better grasp the clinical significance of viral sequence data obtained in CSF, 30 patients without CNS disease who had a lumbar puncture performed during elective spinal anaesthesia were also analysed. One case of human astrovirus (HAstV)-MLB2-related meningitis and disseminated infection was identified. No other viral sequences that can easily be linked to CNS inflammation were detected. Viral sequences obtained in all patient groups are discussed. While some of them reflect harmless viral infections, others result from reagent or sample contamination, as well as index hopping. Altogether, this study highlights the potential of high-throughput sequencing in identifying previously unknown viral neuropathogens, as well as the interpretation issues related to its application in clinical microbiology. [ABSTRACT FROM AUTHOR]

The burden of COVID-19 has disproportionately impacted the elderly, who are at increased risk of severe disease, hospitalization, and death. This cross-sectional study aimed to assess the association between SARS-CoV-2 seroprevalence among nursing home staff, and cumulative incidence rates of COVID-19 cases, hospitalizations, and deaths among residents. Staff seroprevalence was estimated within the SEROCoV-WORK+ study between May and September 2020 across 29 nursing homes in Geneva, Switzerland. Data on nursing home residents were obtained from the canton of Geneva for the period between March and August 2020. Associations were assessed using Spearman's correlation coefficient and quasi-Poisson regression models. Overall, seroprevalence among staff ranged between 0 and 31.4%, with a median of 8.3%. A positive association was found between staff seroprevalence and resident cumulative incidence of COVID-19 cases (correlation coefficient R = 0.72, 95%CI 0.45-0.87; incidence rate ratio [IRR] = 1.10, 95%CI 1.07-1.17), hospitalizations (R = 0.59, 95%CI 0.25-0.80; IRR = 1.09, 95%CI 1.05-1.13), and deaths (R = 0.71, 95%CI 0.44-0.86; IRR = 1.12, 95%CI 1.07-1.18). Our results suggest that SARS-CoV-2 transmission between staff and residents may contribute to the spread of the virus within nursing homes. Awareness among nursing home professionals of their likely role in the spread of SARS-CoV-2 has the potential to increase vaccination coverage and prevent unnecessary deaths due to COVID-19.