Comparison of the Risk of Hospitalization and Severe Disease Among Co-circulating Severe Acute Respiratory Syndrome Coronavirus 2 Variants.

BACKGROUND: We compare the risk of coronavirus disease 2019 (COVID-19) outcomes among co-circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants between January 2021 and May 2022 in Navarra, Spain. METHODS: We compared the frequency of hospitalization and severe disease (intensive care unit admission or death) due to COVID-19 among the co-circulating variants. Variants analyzed were nonvariants of concern (non-VOCs), Alpha, Delta, Omicron BA.1, and Omicron BA.2. Logistic regression models were used to estimate adjusted odds ratio (aOR). RESULTS: The Alpha variant had a higher risk of hospitalization (aOR, 1.86 [95 confidence interval {CI}, 1.282.71]) and severe disease (aOR, 2.40 [95 CI, 1.314.40]) than non-VOCs. The Delta variant did not show a significantly different risk of hospitalization (aOR, 0.73 [95 CI, .401.30]) and severe disease (aOR, 3.04 [95 CI, .5716.22]) compared to the Alpha variant. The Omicron BA.1 significantly reduced both risks relative to the Delta variant (aORs, 0.28 [95 CI, .16.47] and 0.23 [95 CI, .12.46], respectively). The Omicron BA.2 reduced the risk of hospitalization compared to BA.1 (aOR, 0.52 [95 CI, .29.95]). CONCLUSIONS: The Alpha and Delta variants showed an increased risk of hospitalization and severe disease, which decreased considerably with the Omicron BA.1 and BA.2. Surveillance of variants can lead to important differences in severity.

Effectiveness of influenza vaccination in preventing influenza in primary care, Navarre, Spain, 2021/22.

Compared with individuals unvaccinated in the current and three previous influenza seasons, in 2021/22, influenza vaccine effectiveness at primary care level was 37% (95% CI: 16 to 52) for current season vaccination, regardless of previous doses, and 35% (95% CI: -3 to 45) for only previous seasons vaccination. Against influenza A(H3N2), estimates were 39% (95% CI: 16 to 55) and 24% (95% CI: -8 to 47) suggesting moderate effectiveness of current season vaccination and possible remaining effect of prior vaccinations.

Multicenter clinical evaluation of a novel transcription-mediated amplification assay for SARS-CoV-2 molecular testing.

INTRODUCTION: The onset and spread of COVID-19 pandemic has forced clinical laboratories to rapidly expand testing capacity for SARS-CoV-2. This study evaluates the clinical performance of the TMA Procleix SARS-CoV-2 assay in comparison to the RT-PCR assay AllplexTM SARS-CoV-2 for the qualitative detection of SARS-CoV-2 RNA. METHODS: Between November 2020 and February 2021, 610 upper-respiratory specimens received for routine SARS-CoV-2 molecular testing were prospectively collected and selected at the Hospital Universitari Vall d'Hebron and the Hospital Universitari Bellvitge in Barcelona, Spain. All samples were processed in parallel with the TMA and the RT-PCR assays, and results were compared. Discrepancies were retested by an additional RT-PCR method and the clinical history of these patients was reviewed. RESULTS: Overall, the level of concordance between both assays was 92.0% (κ, 0.772). Most discordant results (36/38, 94.7%) corresponded to samples testing positive with the TMA assay and negative with the RT-PCR method. Of these discrepant cases, most (28/36, 77.8%) were finally classified as confirmed or probable SARS-CoV-2 cases according to the discrepant analysis. CONCLUSION: In conclusion, the TMA Procleix SARS-CoV-2 assay performed well for the qualitative detection of SARS-CoV-2 RNA in a multisite clinical setting. This novel TMA assay demonstrated a greater sensitivity in comparison to RT-PCR methods for the molecular detection of SARS-CoV-2. This higher sensitivity but also the qualitative feature of this detection of SARS-CoV-2 should be considered when making testing algorithm decisions.

Evaluation of the Fully Automated Chemiluminescence Analyzer Liaison XL for the Performance of the QuantiFERON-TB Gold Plus Assay in an Area with a Low Incidence of Tuberculosis.

Diagnosis of latent tuberculosis infection (LTBI) is considered key in the control of tuberculosis. Interferon gamma (IFN-γ) release assays, such as the QuantiFERON-TB Gold Plus test (QFT-Plus), are now widely implemented for the in vitro diagnosis of LTBI. To date, the detection and quantification of IFN-γ has been mostly performed with semiautomated enzyme-linked immunosorbent assays (ELISAs), but several limitations currently exist. The study aims to evaluate the chemiluminescence immunoassay (CLIA) analyzer Liaison XL compared to ELISA for the performance of the QFT-Plus test. Between February and April 2020, 333 heparin blood samples from 323 adult patients were collected at a tertiary teaching hospital in Barcelona, Spain. Overall, the CLIA analyzer Liaison XL performed well for the detection of IFN-γ compared to the ELISA method, demonstrating substantial agreement (κ, 0.872) and great correlation between assays (r, >0.950). CLIA produced significantly higher values of IFN-γ IU per milliliter than the ELISA (P = 0.004 for the TB1 tube and P = 0.010 for the TB2 tube). Many discrepant cases (8/15, 53.3%) corresponded to indeterminate results with ELISA (NIL-corrected mitogen value of <0.5 IU/ml), which, when analyzed with the CLIA analyzer Liaison XL, reverted to interpretable results. In conclusion, this analysis suggests that CLIA presents a greater sensitivity for the identification of LTBI, especially among immunocompromised patients. Furthermore, the analytical variability reported between both ELISA and CLIA methods, especially around the standardized 0.35-IU/ml positivity threshold, suggests the need to refine the interpretative algorithm.

Emergence of SARS-CoV-2 Variant B.1.575.2, Containing the E484K Mutation in the Spike Protein, in Pamplona, Spain, May to June 2021.

With the emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the acquisition of novel mutations in existing lineages, the need to implement methods capable of monitoring viral dynamics arises. We report the emergence and spread of a new SARS-CoV-2 variant within the B.1.575 lineage, containing the E484K mutation in the spike protein (named B.1.575.2), in a region in northern Spain in May and June 2021. SARS-CoV-2-positive samples with cycle threshold values of ≤30 were selected to screen for presumptive variants using the TaqPath coronavirus disease 2019 (COVID-19) reverse transcription (RT)-PCR kit and the TaqMan SARS-CoV-2 mutation panel. Confirmation of variants was performed by whole-genome sequencing. Of the 200 samples belonging to the B.1.575 lineage, 194 (97%) corresponded to the B.1.575.2 sublineage, which was related to the presence of the E484K mutation. Of 197 cases registered in the Global Initiative on Sharing Avian Influenza Data (GISAID) EpiCoV database as lineage B.1.575.2, 194 (99.5%) were identified in Pamplona, Spain. This report emphasizes the importance of complementing surveillance of SARS-CoV-2 with sequencing for the rapid control of emerging viral variants.

Product-specific COVID-19 vaccine effectiveness against secondary infection in close contacts, Navarre, Spain, April to August 2021.

COVID-19 vaccine effectiveness by product (two doses Comirnaty, Spikevax or Vaxzevria and one of Janssen), against infection ranged from 50% (95% CI: 42 to 57) for Janssen to 86% (70 to 93) for Vaxzevria-Comirnaty combination; among ≥ 60 year-olds, from 17% (-26 to 45) for Janssen to 68% (48 to 80) for Spikevax; and against hospitalisation from 74% (43 to 88) for Janssen to > 90% for other products. Two doses of vaccine were highly effective against hospitalisation, but suboptimal for infection control.

Single-Locus-Sequence-Based Typing of the mgpB Gene Reveals Transmission Dynamics in Mycoplasma genitalium.

Sexually transmitted infections (STIs) by Mycoplasma genitalium are a major problem worldwide, especially given their marked and rapid propensity for developing antimicrobial resistance. Since very few treatment options exist, clinicians face an important challenge in the management of the infection. In this scenario, little is known regarding the transmission dynamics of M. genitalium and the epidemiology of antimicrobial resistance. This mgpB-based molecular typing study, conducted among 54 asymptomatically infected individuals prospectively recruited from an STI screening service, reveals two distinct epidemiological clusters that significantly correlate with sexual conduct in heterosexuals and men who have sex with men (MSM), respectively. This well-defined structuration suggests the presence of two independent sexual networks with little connectivity between them. On the other hand, the study demonstrates the multiclonal feature of the emergence of antibiotic resistance in M. genitalium to both macrolides and fluoroquinolones. The high prevalence of macrolide resistance in M. genitalium among MSM, influenced by dense network connectivity and strong antibiotic selective pressure, may correspond to allodemics affecting other STIs such as gonorrhea, syphilis and enteric pathogens. Collaterally, the structural and functional impact of mutations in the mgpB gene, encoding the major adhesin P140 (MgpB), may require further investigation.

Prevalence of Mycoplasma genitalium and macrolide resistance among asymptomatic people visiting a point of care service for rapid STI screening: a cross-sectional study.

OBJECTIVES: Although rapid screening and treatment programmes have been recently implemented to tackle STIs, testing Mycoplasma genitalium (MG) among asymptomatic populations is not currently recommended due to the lack of scientific evidence and the emergence of antibiotic resistance. The main objective of this study was to estimate the prevalence of MG and macrolide resistance among asymptomatic people visiting a point of care service for rapid STI screening and to identify risk factors associated with the acquisition of this infection. METHODS: Between October 2017 and January 2018, a total of 890 asymptomatic individuals attending to the STI screening service Drassanes Exprés in Barcelona, Spain, were tested for MG and macrolide resistance using the molecular ResistancePlus MG assay (SpeeDx, Australia). Asymptomatically infected individuals were invited to attend the STI Unit for resistance-guided antimicrobial therapy. RESULTS: Overall, the prevalence of MG was 7.4% (66/890; 95% CI 5.8% to 9.3%), being higher among men who have sex with men (MSM) (46/489) compared with heterosexual men and women (20/401; p=0.012). Macrolide resistance was found in 32/46 (69.6%; 95% CI 54.2% to 82.3%) MSM, while only 2/20 (10.0%; 95% CI 1.2% to 31.7%) infections among heterosexuals presented macrolide resistance-mediated mutations (p<0.001). MSM behaviour, receptive anal intercourse, HIV positive status, syphilis history and high-risk sexual activity (more than five sexual partners in the last 3 months) were significantly associated with MG infection. Furthermore, the resistance-guided therapy approach was implemented in 36/66 (54.6%) individuals. CONCLUSIONS: The research provides further data regarding the prevalence of MG and macrolide resistance among asymptomatic individuals. It also identifies higher risk subpopulations which might be targets for MG screening. Nevertheless, there is insufficient data to justify MG testing among asymptomatic individuals and current STI guidelines should be followed until evidence shows the cost and effectiveness of screening.

Multicenter Clinical Evaluation of a Novel Multiplex Real-Time PCR (qPCR) Assay for Detection of Fluoroquinolone Resistance in Mycoplasma genitalium.

Mycoplasma genitalium causes a common sexually transmitted infection with a marked propensity to develop antimicrobial resistance. As few treatment options exist, this poses significant challenges to clinicians. Recent diagnostic advances have resulted in tests that report the simultaneous detection of M. genitalium and any resistance to macrolides, the first-line treatment. This allows for therapy to be tailored to the individual, thereby optimizing treatment outcomes. However, resistance to fluoroquinolones, the second-line treatment, is increasing in M. genitalium In this study, we describe a new assay, MG+parC (beta), which simultaneously reports the detection of M. genitalium and five parC mutations that have been associated with resistance to fluoroquinolones. These mutations affect the amino acid sequence of ParC at residues S83R (A247C), S83I (G248T), D87N (G259A), D87Y (G259T), and D87H (G259C). The study tested the MG+parC (beta) assay with 202 M. genitalium-positive clinical samples from Australia (n = 141) and Spain (n = 61). Compared to Sanger sequencing, the assay performed with a kappa value of 0.985 (95% confidence interval [CI], 0.955 to 1.000), with a mutation detection sensitivity of 97.6% (95% CI, 87.4 to 99.9), and specificity of 100.0% (95% CI, 97.7 to 100.0). Fluoroquinolone resistance-associated mutations in parC targeted by the assay were more prevalent among the Australian cohort (23.4% [95% CI,16.3 to 31.8]) compared to the Spanish population (8.8% [95% CI, 2.9% to 19.3%]) (P = 0.019). The MG+parC (beta) kit is a simple and reliable method for simultaneous detection of M. genitalium and fluoroquinolone resistance-associated mutations in clinical settings. This novel diagnostic tool may extend the utility of the second line of antimicrobial therapies in M. genitalium infection.

Novel tp0548 Sequence-Type of Treponema pallidum Identified in Barcelona, Spain.

A novel tp0548 sequence-type of Treponema pallidum has been identified in a genital ulcer sample collected from a patient diagnosed with primary syphilis at the Hospital Universitari Vall d'Hebron in Barcelona. Following the nomenclature used in the Enhanced Centers for Disease Control and Prevention Typing methodology, letter "z" has been assigned to the new sequence type.

Mycoplasma genitalium Macrolide and Fluoroquinolone Resistance: Prevalence and Risk Factors Among a 2013-2014 Cohort of Patients in Barcelona, Spain.

BACKGROUND: Macrolide and fluoroquinolone resistance is alarmingly emerging in M. genitalium worldwide. This article provides the first estimates of the current prevalence of macrolide and fluoroquinolone resistance-mediating mutations in Barcelona, Spain, and identifies risk factors associated with the acquisition of these resistances. METHODS: The study was conducted retrospectively with specimens submitted between February 2013 and March 2014 to the microbiology department of the Vall d'Hebron Hospital, Barcelona, where M. genitalium was detected using nucleic acid amplification methods. DNA sequencing of 23S ribosomal RNA gene and parC was performed in the Statens Serum Institut, Copenhagen, to detect genotypic macrolide and fluoroquinolone resistance markers, respectively. RESULTS: Macrolide resistance-mediating mutations were detected in 35% (95% confidence interval, 24%-47%) of the M. genitalium-positive episodes, whereas 8% (95% confidence interval, 3%-17%) carried fluoroquinolone resistance mutations. Of them, three cases harbored multidrug resistance to both classes of antibiotics. Men who had sex with men (P = 0.002) and treatment with azithromycin within the previous 12 months (P = 0.006) were strongly associated with macrolide resistance. CONCLUSION: The widespread appearance of resistances, also in Spain, makes imperative the implementation of combined diagnostic-resistance detection assays for M. genitalium to facilitate the optimization of antibiotic treatment in the management of nongonococcal urethritis and potentially reduce the transmission of resistances.

Prevalence of Respiratory Viral Infections in Deceased Persons during the COVID-19 Pandemic Season 2021-2022: A Population-Based Observational Study.

Although the omicron variant of SARS-CoV-2 circulated intensely during the 2021-2022 season, many patients with severe acute respiratory disease tested negative for COVID-19. The aim of this study was to assess the presence of different respiratory viruses in deceased persons. The proportion of deceased persons with respiratory viral infections in the 2021-2022 season in Navarre, Spain, was estimated considering all deaths caused by confirmed COVID-19 according to the epidemiological surveillance and the results of multiplex PCR tests for respiratory viruses performed in a sample of deceased persons with a cause of death other than COVID-19. Of 3578 deaths, 324 (9.1%) were initially reported as caused by pre-mortem confirmed COVID-19. A sample of 242 persons who died by causes other than COVID-19 were tested post-mortem; 64 (26.4%) of them were positive for any respiratory virus: 11.2% for SARS-CoV-2, 5.8% for rhinovirus, 3.7% for human coronavirus, 2.5% for metapneumovirus, 1.7% for respiratory syncytial virus, 1.7% for parainfluenza, 1.2% for influenza, and less than 1% each for adenovirus and bocavirus. Combining both approaches, we estimated that 34.4% of all deceased persons during the study period had a respiratory viral infection and 19.2% had SARS-CoV-2. Only 33.3% (9/27) of SARS-CoV-2 and 5.0% (2/40) of other viruses detected post-mortem had previously been confirmed pre-mortem. In a period with very intense circulation of SARS-CoV-2 during the pandemic, other respiratory viruses were also frequently present in deceased persons. Some SARS-CoV-2 infections and most other viral infections were not diagnosed pre-mortem. Several respiratory viruses may contribute to excess mortality in winter.

Hospitalisations and Deaths Averted by COVID-19 Vaccination in Navarre, Spain, 2021-2022.

In 2021-2022, most of the Spanish population received COVID-19 vaccines and a high proportion of them had SARS-CoV-2 infection. We estimated the rate of hospitalisations and deaths that were averted by risk reduction among vaccinated COVID-19 cases. Hospitalisations and deaths were analysed among COVID-19 cases confirmed in 2021 and 2022 in Navarre, Spain. To calculate the number of prevented outcomes by sex, age, comorbidities, and semester, the difference in the risk of each outcome between unvaccinated and vaccinated cases was multiplied by the number of vaccinated cases. COVID-19 vaccination coverage with any dose reached 88%, 86% with full vaccination, and 56% with a booster dose. The cumulative rates per 1000 inhabitants were 382 COVID-19 confirmed cases, 6.70 hospitalisations, and 1.15 deaths from COVID-19. The estimated rates of prevented events by vaccination were 16.33 hospitalisations and 3.39 deaths per 1000 inhabitants, which was 70.9% and 74.7% of expected events without vaccination, respectively. People aged 80 years and older or with major chronic conditions accounted for the majority of hospitalizations and deaths prevented by COVID-19 vaccination. One hospitalisation and death due to COVID-19 were averted for every 53 and 258 people vaccinated, respectively. The high COVID-19 vaccine effect in reducing the risk of severe outcomes and the high vaccination coverage in risk populations prevented three out of four hospitalisations and deaths due to COVID-19 during a period of intense circulation of SARS-CoV-2.