Factors Associated with SARS-CoV-2 Infection in Fully Vaccinated Nursing Home Residents and Workers.

Persons living or working in nursing homes faced a higher risk of SARS-CoV-2 infections during the pandemic, resulting in heightened morbidity and mortality among older adults despite robust vaccination efforts. This prospective study evaluated the humoral and cellular immunity in fully vaccinated residents and workers from two nursing homes in Madrid, Spain, from 2020 to 2021. Measurements of IgG levels were conducted in August 2020 (pre-vaccination) and June and September 2021 (post-vaccination), alongside assessments of neutralizing antibodies and cellular responses in September 2021 among the most vulnerable individuals. Follow-up extended until February 2022 to identify risk factors for SARS-CoV-2 infection or mortality, involving 267 residents (mean age 87.6 years, 81.3% women) and 302 workers (mean age 50.7 years, 82.1% women). Residents exhibited a significantly higher likelihood of experiencing COVID-19 before June 2021 compared with nursing staff (OR [95% CI], 7.2 [3.0 to 17.2], p < 0.01). Participants with a history of previous COVID-19 infection showed more significant increases in IgG levels in August 2020, June 2021 and September 2021, alongside an increased proportion of neutralizing antibodies in the most vulnerable individuals. However, IgG decay remained the same between June and September 2021 based on the previous COVID-19 status. During the Omicron variant wave, residents and staff showed a similar rate of SARS-CoV-2 infection. Notably, preceding clinical or immunological factors before receiving three vaccination doses did not demonstrate associations with COVID-19 infection or overall mortality in our participant cohort.

Membrane computing simulation of sexually transmitted bacterial infections in hotspots of individuals with various risk behaviors.

The epidemiology of sexually transmitted infections (STIs) is complex due to the coexistence of various pathogens, the variety of transmission modes derived from sexual orientations and behaviors at different ages and genders, and sexual contact hotspots resulting in network transmission. There is also a growing proportion of recreational drug users engaged in high-risk sexual activities, as well as pharmacological self-protection routines fostering non-condom practices. The frequency of asymptomatic patients makes it difficult to develop a comprehensive approach to STI epidemiology. Modeling approaches are required to deal with such complexity. Membrane computing is a natural computing methodology for the virtual reproduction of epidemics under the influence of deterministic and stochastic events with an unprecedented level of granularity. The application of the LOIMOS program to STI epidemiology illustrates the possibility of using it to shape appropriate interventions. Under the conditions of our basic landscape, including sexual hotspots of individuals with various risk behaviors, an increase in condom use reduces STIs in a larger proportion of heterosexuals than in same-gender sexual contacts and is much more efficient for reducing Neisseria gonorrhoeae than Chlamydia and lymphogranuloma venereum infections. Amelioration from diagnostic STI screening could be instrumental in reducing N. gonorrhoeae infections, particularly in men having sex with men (MSM), and Chlamydia trachomatis infections in the heterosexual population; however, screening was less effective in decreasing lymphogranuloma venereum infections in MSM. The influence of STI epidemiology of sexual contacts between different age groups (<35 and ≥35 years) and in bisexual populations was also submitted for simulation.IMPORTANCEThe epidemiology of sexually transmitted infections (STIs) is complex and significantly influences sexual and reproductive health worldwide. Gender, age, sexual orientation, sexual behavior (including recreational drug use and physical and pharmacological protection practices), the structure of sexual contact networks, and the limited application or efficiency of diagnostic screening procedures create variable landscapes in different countries. Modeling techniques are required to deal with such complexity. We propose the use of a simulation technology based on membrane computing, mimicking in silico STI epidemics under various local conditions with an unprecedented level of detail. This approach allows us to evaluate the relative weight of the various epidemic drivers in various populations at risk and the possible outcomes of interventions in particular epidemiological landscapes.

Rapid expansion of lymphogranuloma venereum infections with fast diversification and spread of Chlamydia trachomatis L genovariants.

IMPORTANCE: Numerous international organizations, including the World Health Organization, have been drawing attention to the global increase in sexually transmitted infections. Twenty years ago, lymphogranuloma venereum (LGV) was mainly considered a tropical disease; in recent decades, however, LGV has been increasingly present in high-income countries. This increase has been linked to men who have sex with men who participate in highly interconnected sexual networks, leading to a rapid spread of LGV. This study focuses on the spread of LGV, presenting the largest time series of LGV prevalence in Spain, which includes more than a thousand diagnosed cases in one large city. The number of LGV cases diagnosed was analyzed over time, and a selection of strains was subjected to molecular genotyping. The results indicate that the LGV epidemic is gradually evolving toward an increasingly complex diversification due to the selection of successful genovariants that have emerged by mutation and recombination events, suggesting that we are moving toward an unpredictable scenario.

Short- and Long-Term Humoral and Cellular Immune Responses to SARS-CoV-2 Vaccination in Patients with Multiple Sclerosis Treated with Disease-Modifying Therapies.

BACKGROUND: This study aimed to evaluate short- and long-term humoral and T-cell-specific immune responses to SARS-CoV-2 vaccines in patients with multiple sclerosis (MS) treated with different disease-modifying therapies (DMTs). METHODS: Single-center observational longitudinal study including 102 patients with MS who consecutively received vaccination against SARS-CoV-2. Serum samples were collected at baseline and after receiving the second dose of the vaccine. Specific Th1 responses following in vitro stimulation with spike and nucleocapsid peptides were analyzed by quantifying levels of IFN-γ. Serum IgG-type antibodies against the spike region of SARS-CoV-2 were studied by chemiluminescent microparticle immunoassay. RESULTS: Patients undergoing fingolimod and anti-CD20 therapies had a markedly lower humoral response than those treated with other DMTs and untreated patients. Robust antigen-specific T-cell responses were detected in all patients except those treated with fingolimod, who had lower IFN-γ levels than those treated with other DMTs (25.8 pg/mL vs. 868.7 pg/mL, p = 0.011). At mid-term follow-up, a decrease in vaccine-induced anti-SARS-CoV-2 IgG antibodies was observed in all subgroups of patients receiving DMTs, although most patients receiving induction DMTs or natalizumab and non-treated patients remained protected. Cellular immunity was maintained above protective levels in all DMT subgroups except the fingolimod subgroup. CONCLUSIONS: SARS-CoV-2 vaccines induce robust and long-lasting humoral and cell-mediated specific immune responses in most patients with MS.

Lost in Translation: Evaluation of Subcutaneous Interferon-ß Treatment for SARS-CoV-2 Infection in Real Life.

Despite in vitro activity of interferon-ß (IFN-ß) against SARS-CoV-2 infection, its clinical efficacy remains controversial. We evaluated the impact of IFN-ß treatment in a cohort of 3590 patients hospitalized with COVID-19 during March−April 2020. The primary endpoint was a composed variable of admission to intensive care unit (ICU)/death. Overall, 153 patients (4%) received IFN-ß. They were significantly more severely ill, with a worse clinical and analytical situation, explaining a higher ICU admission (30% vs. 17%; p < 0.01), and a shorter time to the composed variable. In a Cox regression analysis, older age, lymphopenia, renal failure, or increased neutrophil-to-lymphocyte ratio were associated with a greater hazard ratio (HR) of admission at ICU/death. Notably, the HR of IFN-ß for the outcome variable was no longer significant after adjustment (HR, 1.03; 95% CI, 0.82−1.30), and different sensitivity analysis (early IFN use, ICU admission) showed no changes in the estimates. A propensity score matching analysis showed no association of IFN-ß therapy and outcome. In conclusion, in this large cohort of hospitalized COVID-19 patients, IFN-ß was used mainly in patients with advanced disease, reflecting an important bias of selection. After adjusting by severity, IFN-ß was not associated with a higher rate of ICU admission or mortality.

Human Monkeypox in People With HIV: Transmission, Clinical Features, and Outcome.

We describe the first 25 persons with HIV diagnosed with human monkeypox virus (MPXV) in our hospital in an ongoing outbreak in Spain. Proctitis was the predominant finding in 52%, and MPXV DNA was detected in rectal swabs from 90%. Proctitis and demonstration of MPXV in rectal swabs support the sexual transmission of MPXV.

A Smartphone-Based Platform Assisted by Artificial Intelligence for Reading and Reporting Rapid Diagnostic Tests: Evaluation Study in SARS-CoV-2 Lateral Flow Immunoassays.

BACKGROUND: Rapid diagnostic tests (RDTs) are being widely used to manage COVID-19 pandemic. However, many results remain unreported or unconfirmed, altering a correct epidemiological surveillance. OBJECTIVE: Our aim was to evaluate an artificial intelligence-based smartphone app, connected to a cloud web platform, to automatically and objectively read RDT results and assess its impact on COVID-19 pandemic management. METHODS: Overall, 252 human sera were used to inoculate a total of 1165 RDTs for training and validation purposes. We then conducted two field studies to assess the performance on real-world scenarios by testing 172 antibody RDTs at two nursing homes and 96 antigen RDTs at one hospital emergency department. RESULTS: Field studies demonstrated high levels of sensitivity (100%) and specificity (94.4%, CI 92.8%-96.1%) for reading IgG band of COVID-19 antibody RDTs compared to visual readings from health workers. Sensitivity of detecting IgM test bands was 100%, and specificity was 95.8% (CI 94.3%-97.3%). All COVID-19 antigen RDTs were correctly read by the app. CONCLUSIONS: The proposed reading system is automatic, reducing variability and uncertainty associated with RDTs interpretation and can be used to read different RDT brands. The web platform serves as a real-time epidemiological tracking tool and facilitates reporting of positive RDTs to relevant health authorities.

The Negative Impact of COVID-19 in HCV, HIV, and HPV Surveillance Programs During the Different Pandemic Waves.

Background: The coronavirus disease 2019 (COVID-19) pandemic has been a worldwide stress test for health systems. 2 years have elapsed since the description of the first cases of pneumonia of unknown origin. This study quantifies the impact of COVID-19 in the screening program of chronic viral infections such as human papillomavirus (HPV), human immunodeficiency virus (HIV), and hepatitis C virus (HCV) along the six different pandemic waves in our population. Each wave had particular epidemiological, biological, or clinical patterns. Methods: We analyzed the number of samples for screening of these viruses from March 2020 to February 2022, the new infections detected in the pandemic period compared to the previous year, the time elapsed between diagnosis and linking to treatment and follow-up of patients, and the percentage of late HIV diagnosis. Moreover, we used the origin of the samples as a marker for quantifying the restoration of activity in primary care. Results: During the first pandemic year, the number of samples received was reduced by 26.7, 22.6, and 22.5% for molecular detection of HPV or serological HCV and HIV status respectively. The highest decrease was observed during the first wave with 70, 40, and 26.7% for HPV, HCV, and HIV. As expected, new diagnoses also decreased by 35.4, 58.2, and 40.5% for HPV, HCV, and HIV respectively during the first year of the pandemic. In the second year of the pandemic, the number of samples remained below pre-pandemic period levels for HCV (-3.6%) and HIV (-9.3%) but was slightly higher for HPV (8.0%). The new diagnoses in the second year of the pandemic were -16.1, -46.8, and -18.6% for HPV, HCV, and HIV respectively. Conclusions: Undoubtedly, an important number of new HPV, HCV, and HIV infections were lost during the COVID-19 pandemic, and surveillance programs were disrupted as a consequence of collapse of the health system. It is a priority to reinforce these surveillance programs as soon as possible in order to detect undiagnosed cases before the associated morbidity-mortality increases. New pandemic waves could increase the risk of reversing the achievements made over the last few decades.

Risk of SARS-CoV-2 Reinfections in a Prospective Inception Cohort Study: Impact of COVID-19 Vaccination.

The risk of reinfection could be related to the initial SARS-CoV-2 clinical presentation, but there are no data about the risk change after SARS-CoV-2 vaccination. We evaluated the rate of reinfection in an inception cohort study of 4943 health care workers (HCWs) according to symptoms and serologic results during March−May 2020. Incidence rates (IR) and IR ratios (IRR) before and after SARS-CoV-2 vaccination were determined by adjusting Poisson models. Overall, 1005 HCWs (20.3%) referred COVID-19 suggestive symptoms during the first surge of disease, and 33.5% and 55% presented a positive PCR or serology result, respectively. Meanwhile, 13% of asymptomatic HCWs had specific antibodies. During a follow up of 3422.2 person-years before vaccination, the rate of reinfection among seropositive individuals was 81% lower for those who were symptomatic compared with those who were asymptomatic (IRR of 0.19; 95% CI, 0.05−0.67; p = 0.003). During the 3100 person-years period after vaccination, an overall 74% decrease in the rate of infection was observed (IRR of 0.26; 95% CI, 0.21−0.32; p < 0.001), with a significant 83% and 70% decrease in seropositive and seronegative HCWs, respectively. In conclusion, the risk of SARS-CoV-2 reinfections is closely related to the clinical and serological presentation of COVID-19. COVID-19 vaccination further decreases the risk of reinfection more markedly among seropositive.

Pre-existing T cell immunity determines the frequency and magnitude of cellular immune response to two doses of mRNA vaccine against SARS-CoV-2.

Little is known about the factors associated with lack of T-cell response to mRNA vaccines against SARS-CoV-2. In a prospective cohort of 61 health care workers (HCWs), 21% and 16% after the first dose of mRNA BNT162b vaccine, and 12% and 7% after the second dose, showed lack of CD4+ and CD8+ T-cell response, respectively. Pre-existing T-cell immunity, due to past infection (46%) or cross-reactive cellular response (26%), was significantly associated with T-cell response in frequency (CD4+ T-cell, 100% vs 82% after two doses; p = 0.049) and in the magnitude of T-cell response during follow up. Furthermore, baseline CD4+ T-cell correlated positively with the titer of specific IgG-antibodies after first and second vaccine dose. Our data demonstrate that cross-reactive T-cells correlate with a better cellular response as well as an enhanced humoral response, and we confirm the close correlation of humoral and cellular response after mRNA vaccination.

Limited T cell response to SARS-CoV-2 mRNA vaccine among patients with cancer receiving different cancer treatments.

INTRODUCTION: Patients with cancer (PC) are at high risk of acquiring COVID-19 and can develop more serious complications. Deeper understanding of vaccines immunogenicity in this population is crucial for adequately planning vaccines programs. The ONCOVac study aimed to comprehensively assess the immunogenicity of mRNA-1273 vaccine in terms of humoral and cellular response. METHODS: We conducted a prospective, single-center study including patients with solid tumours treated with cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i), immunotherapy (IT) or chemotherapy (CT). Patients were enrolled previously to vaccination with mRNA-1273. We also involved health care workers (HCW) to serve as a control group. We took blood samples before first dose administration (BL), after first dose (1D), and after second dose (2D). The primary objective was to compare the rate and magnitude of T cell response after second dose whereas safety and humoral response were defined as secondary objectives. We also collected patient reported outcomes after both the first and second vaccine dose and a six-month follow-up period to diagnose incident COVID-19 cases was planned. RESULTS: The rate of specific anti-S serologic positivity (anti-S IgG cut-off point at 7,14 BAU/mL) was significantly higher in HCW compared to PC after 1D (100% versus 83.8%; p = 0.04), but similar after 2D (100% versus 95.8%; p = 0.5). This difference after 1D was driven by PC treated with CT (100% versus 64.5%; p = 0.001). Cellular response after 2D was significantly lower in PC than in HCW for both CD4+ (91.7% versus 59.7%; p = 0.001) and CD8+ (94.4% versus 55.6%; p < 0.001) T cells. We found a difference on pre-existing CD4+ T cell response in HCW comparing to PC (36% and 17%, p = 0.03); without difference in pre-existing CD8+ T cell response (31% and 23%, p = 0.5). After excluding patients with pre-existing T cell response, PC achieved even lower CD4+ (50.9% versus 95.5%, p < 0.001) and CD8+ (45.5% versus 95.5%, p < 0.001) T cell response compared with HCW. Regarding safety, PC reported notably more adverse events than HCW (96.6% versus 69.2%, p < 0.001). CONCLUSION: We demonstrated that PC showed a similar humoral response but a lower T cell response following two doses of mRNA-1273 vaccination. Further studies are needed to complement our results and determine the implication of low T cell response on clinical protection of PC against COVID-19.

Quantification of plasmid copy number as surrogate marker of virulence among different invasive and non-invasive genotypes of Chlamydia trachomatis.

The population dissemination of invasive genotypes of C. trachomatis and an increase of urogenital infections cases by non-invasive genotypes have been observed in many countries. In this epidemiological context, the descriptions of a high proportion of infections related to L-genotypes in asymptomatic patients, but also to infections caused by non-L genotypes in symptomatic patients have been unexpected finding. The plasmid copy number (PCN) has been proposed as a surrogate marker of virulence. We quantified the PCN in 233 samples and 179 samples carrying L-genotype and non-L genotypes respectively. A significant difference in the median of PCN was detected between symptomatic/asymptomatic patients (P < 0.001), independently of the genotype. Moreover, PCN could vary, in the same strain, among different anatomical sites suggesting that micro-environmental changes could affect virulence. These findings suggest that the quantification of PCN in clinical samples could improve the management of patients.

Specific high-resolution scheme to improve understanding of the spatio-temporal dispersion of lymphogranuloma venereum epidemic.

Introduction: Lymphogranuloma venereum (LGV) is already endemic in vulnerable populations in several European countries; however, molecular epidemiology data with improved accuracy are necessary to better understand LGV epidemic in these countries. Current strategies to study the molecular epidemiology of LGV cases involve schemes based on a few genetic fragments of Chlamydia trachomatis, which have demonstrated limited discriminatory power for LGV. Therefore, this study aimed to propose a new combination of molecular markers based on the most variable genes of L-genotype genomes to improve the characterization of the current LGV epidemic in Madrid, Spain. Methods: Four genes were selected according to their diversity index (CTLon_0054, CTLon_0087, CTLon_0243 and CTLon_0301) for use in combination with ompA. In silico and experimental studies were performed to compare the previously described multilocus sequence typing (MLST) schemes with our proposal. Moreover, the proposed scheme was applied (n = 68) to analyze the spatio-temporal spread of the LGV cases. Results: Our proposal demonstrated higher diversity allowing the identification of three main groups compared to the previously published MLST based on hypervariable genes wherein only a single sequence type was identified. The temporal analysis showed that the major cluster was progressively diversifying, revealing a very active transmission chain. Furthermore, an L2b genome identical to that of the origin of the epidemic was detected, suggesting reintroductions or a low screening rate in vulnerable populations. The spatial distribution suggests that the selection and spread of new variants occurs from the central district to the peripheral regions. Discussion: The scheme proposed in this study has proven to be useful for appropriate discrimination of LGV strains. This study, to our knowledge for the first time, demonstrates a spatio-temporal spread that increases our understanding and identifies areas with special susceptibility for maintenance of the endemic situation of LGV.

T-cell response after first dose of BNT162b2 SARS-CoV-2 vaccine among healthcare workers with previous infection or cross-reactive immunity.

OBJECTIVES: Antibody response to the first dose of BNT162b2 SARS-CoV-2 is greater in COVID-19-convalescent than in infection-naïve individuals. However, there are no data about T-cell response in individuals with pre-existing cellular immunity. METHODS: We evaluated T-cell responses in parallel with SARS-CoV-2 antibody level after first dose of BNT162b2 vaccine in 23 infection-naïve and 27 convalescent healthcare workers (HCWs) previously included in a study about humoral and T-cell immunity. RESULTS: Overall, the antibody response was lower in the infection-naïve group than in convalescent individuals (18 895 vs 662.7 AU mL-1, P < 0.001), and intermediate but significantly lower in convalescent HCWs with previous negative serology (25 174 vs 1793 AU mL-1; P = 0.015). Indeed, anti-spike IgG titres after the first dose correlated with baseline anti-nucleocapsid IgG titres (rho = 0.689; P < 0.001). Pre-existing T-cell immunity was observed in 78% of convalescent and 65% of the infection-naïve HCWs. T-cell response after the first dose of the vaccine was observed in nearly all the cases with pre-existing T-cell immunity, reaching 94% in convalescent HCWs and 93% in those with cross-reactive T cells. It was lower in the infection-naïve group (50%; P = 0.087) and in convalescent HCWs with negative serology (56%; P = 0.085). Notably, systemic reactogenicity after vaccination was mainly observed in those with pre-existing T-cell immunity (P = 0.051). CONCLUSION: Here, we report that the first dose of BTN162b2 elicits a similar S-specific T-cell response in cases of either past infection or cross-reactive T cells, but lower in the rest of infection-naïve individuals and in convalescent HCWs who have lost detectable specific antibodies during follow-up.