Clinical Microbiology and Infection

IntroductionEarly reports showed that Omicron (BA.1) SARS-CoV-2 could be less severe. However, the magnitude of risk reduction of hospitalization and mortality of Omicron (BA.1) infections compared with Delta (B.1.617.2) is not yet clear. This study compares the risk of severe disease among patients infected with the Omicron (BA.1) variant with patients infected with Delta (B.1.617.2) variant in Portugal. MethodsWe conducted a cohort study in individuals diagnosed with SARS-CoV-2 infection between 1st and 29th December 2021. Cases were individuals with a positive PCR test notified to the national surveillance system. SARS-CoV-2 variants were classified first by whole genomic sequencing (WGS) and, if this information was unavailable, by detecting the S gene target failure. We considered a hospitalization for all the patients admitted within the 14 days after the SARS-CoV-2 infection; after that period, they were censored. The comparison of the risk of hospitalization between Omicron (BA.1) and Delta (B.1.617.2) VOC was estimated using a Cox proportional hazards model. The mean length of stay was compared using linear regression, and the risk of death between Omicron and Delta patients was estimated with a penalized logistic regression. All models were adjusted for sex, age, previous infection, and vaccination status. ResultsWe included 15 978 participants aged 16 or more years old, 9 397 infected by Delta (B.1.617.2) and 6 581 infected with Omicron (BA.1). Within the Delta (B.1.617.2) group, 148 (1.6%) were hospitalized, and 16 (0.2%) were with the Omicron (BA.1). A total of 26 deaths were reported, all in participants with Delta (B.1.617.2) infection. Adjusted HR for hospitalization for the Omicron (BA.1) variant compared with Delta (B.1.617.2) was 0.25 (95%CI 0.15 to 0.43). The length of stay in hospital for Omicron (BA.1) patients was significantly shorter than for Delta (confounding-adjusted difference -4.0 days (95%CI -7.2 to -0.8). The odds of death were 0.14 (95% CI 0.0011 to 1.12), representing a reduction in the risk of death of 86% when infected with Omicron (BA.1) compared with Delta (B.1.617.2). ConclusionOmicron (BA.1) was associated with a 75% risk reduction of hospitalization compared with Delta (B.1.617.2) and reduced length of hospital stay.

BackgroundCandida parapsilosis is a frequent cause of candidemia worldwide. Its incidence is associated with the use of medical implants, such as central venous catheters or parenteral nutrition. This species has reduced susceptibility to echinocandins and is susceptible to polyenes and azoles. Multiple outbreaks caused by fluconazole non-susceptible strains have been reported recently. A similar trend has been observed among the C. parapsilosis isolates received in the last two years at the Spanish Mycology Reference Laboratory. MethodsYeast were identified by molecular biology and antifungal susceptibility testing was performed using EUCAST protocol. ERG11 gene was sequenced to identify resistance mechanisms, and typification was carried out by microsatellite analysis. ResultsWe examined the susceptibility profile of the C. parapsilosis isolates available at our Reference Laboratory since 2000 (around 1,300 strains). During the last two years, the number of isolates with acquired resistance to fluconazole and voriconazole has increased in at least eight different Spanish hospitals. Typification of the isolates revealed that some prevalent clones had spread through several hospitals of the same geographical region. One of these clones was found in hospitals from the region of Catalonia, another in hospitals from Madrid and Burgos, and two other different genotypes from Santander. ConclusionsOur data suggests that the epidemiological situation caused by the COVID-19 pandemic might have induced a selection of fluconazole-resistant C. parapsilosis isolates that were already present at the hospitals. Further measures must be taken to avoid the establishment of clinical outbreaks that could threaten the life of infected patients.

BackgroundAlthough a number of antiviral agents have been evaluated for coronaviruses there are no approved drugs available. To provide an overview of the landscape of therapeutic research for COVID-19, we conducted a review of registered clinical trials. MethodsA review of currently registered clinical trials was performed on registries, including the Chinese (chictr.org.cn) and US (clinicaltrials.gov) databases to identify relevant studies up to March, 7th 2020. The search was conducted using the search terms "2019-nCoV", "COVID-19", "SARS-CoV-2", "Hcov-19", "new coronavirus", "novel coronavirus". We included interventional clinical trials focusing on patients with COVID-19 and assessing antiviral drugs or agents. FindingsOut of the 353 studies identified, 115 clinical trials were selected for data extraction. Phase IV trials were the most commonly reported study type (n=27, 23%). However, 62 trials (54%) did not describe the phase of the study. Eighty percent (n=92) of the trials were randomized with parallel assignment and the median number of planned inclusions was 63 (IQR, 36-120). Open-label studies were the most frequent (46%) followed by double-blind (13%) and single blind studies (10%). The most frequently assessed therapies were: stem cells therapy (n=23 trials), lopinavir/ritonavir (n=15), chloroquine (n=11), umifenovir (n=9), hydroxychloroquine (n=7), plasma treatment (n=7), favipiravir (n=7), methylprednisolone (n=5), and remdesivir (n=5). Remdesivir was tested in 5 trials with a median of 400 (IQR, 394-453) planned inclusions per trial, while stem cells therapy was tested in 23 trials, but had a median of 40 (IQR, 23-60) planned inclusions per trial. Lopinavir/ritonavir was associated with the highest total number of planned inclusions (2606) followed by remdesivir (2155). Only 52% of the clinical trials reported the treatment dose (n=60) and only 34% (n=39) the duration. The primary outcome was clinical in 76 studies (66%), virological in 27 (23%); radiological in 9 (8%) or immunological in three studies (3%). InterpretationNumerous clinical trials have been registered since the beginning of the COVID-19 outbreak, however, a number of information regarding drugs or trial design were lacking. FundingNone

BackgroundIn France, cervical cancer screening for females aged 30 to 65 primarily targets high-risk human papillomavirus (HPV) infections using DNA tests ( HR HPV test). AimThe primary goal was to map the prevalence of cervical infections caused by HPV16 and/or 18, or by any of 12 other carcinogenic genotypes (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68). The secondary goal was to compare prevalence estimates obtained from tests conducted after spontaneous medical visits ( opportunistic screening) or as part of the national screening programme ( organised screening). MethodsThe analytic sample contained 362,963 results of HR HPV tests collected, between 2020 and 2023, in metropolitan France. A full hierarchical Bayesian model was used to compute spatially resolved prevalence maps at the postcode level. ResultsAmong samples from organised and opportunistic screening, 2.9% and 3.8% were positive for HPV16 and/or 18, respectively. For other genotypes, these percentages were 6.9% and 9.4%, respectively. During the last week of the study period, among females aged 30, opportunistic screening was associated with a greater HPV infection prevalence for HPV16 and/or 18 (other genotypes) in 97.2 [72.9,100.0]% (99.9 [99.3,100.0]%) of postcodes. The probability of this percentage being lower among females aged 66 was below 95% for both genotype groups. After correcting for this effect, a pronounced northwest/southeast gradient in HR HPV infection prevalence was found across France, for both genotype groups, with some hotspots located at the border with Spain and Italy and Switzerland. ConclusionOpportunistic screening is associated with systematic inflation in HR HPV infection prevalence.

IntroductionWe assessed the incidence of redetection with the same human papillomavirus (HPV) genotype, predictors of first HPV detections and redetections, and prevalence of cytological lesions during HPV redetections. MethodsThe Ludwig-McGill cohort study followed women aged 18-60 years from Sao Paulo, Brazil in 1993-1997 for up to 10 years. Women provided cervical samples for cytology testing and HPV DNA testing at each visit. A redetection was defined as a recurring genotype-specific HPV positive result after one or more intervening negative visits. Predictors of genotype-specific redetection were assessed using adjusted hazard ratios (aHR) with Cox regression modeling. Results2184 women contributed 2368 incident HPV genotype-specific first detections and 308 genotype-specific redetections over a median follow-up of 6.5 years. The cumulative incidence of redetection with the same genotype was 7% at 1 year and 15% at 5 years after the loss of positivity of the first detection. Neither age (aHR 0.90, 95%CI 0.54-1.47 for [&ge;]45y vs. <25y) nor new sexual partner acquisition (aHR 0.98, 95%CI 0.70-1.35) were statistically associated with genotype-specific redetection. High-grade squamous intraepithelial lesion prevalence was similar during first HPV detections (2.9%) and redetection (3.2%). ConclusionsOur findings suggest many HPV redetections were likely reactivations of latent recurring infections.

Universal masking the health care setting and in the community to contain the spread of SARS-CoV-2 has been recently recommended by the WHO, but supporting data are rare. The City of Jena was the first community in Germany to issue an order on mandatory public masking. Here, we report the development of the number of novel infections in our hospital and in the city of Jena after implementation of universal masking in our hospital and the city.

We report a 19-fold increase in 2024 of qPCR diagnoses of Chlamydia pneumoniae infections in Marseille, Southern France, with 37 cases versus 10 between 2018-2023. These mostly affected children, and young adults. We obtained four C. pneumoniae genomes, all of serotype ST16, suggesting an epidemic circulation in our geographical area.

The authors have withdrawn this manuscript because analytic strategies for this project have changed. Therefore, the authors do not wish this work to be cited as reference for the project.

BackgroundCOVID-19 pneumonia is associated with significant mortality and has no approved antiviral therapy. Interferon beta1 has shown in vitro studies a potent inhibition of SARS-CoV and MERS-CoV. In an in vitro study, SARS-CoV-2 had more sensitivity to IFN-I pretreatment that SARS-CoV. A combination of IFN beta1b administered subcutaneously with other antiviral treatments has been recommended in several guidelines. However, clinical trial results for the treatment of COVID-19 are pending. We aimed to assess the efficiency of IFN beta1b in COVID19 comparing the in-hospital mortality between patients who received IFN beta1b and patients did not receive. MethodsIn this retrospective cohort study, we included hospitalized adults with COVID-19 between February 23th and April 4th, 2020, at the Central Defense Hospital (Madrid, Spain). Subcutaneous interferon beta-1b was recommended in moderate-severe pneumonia. The primary endpoint was in-hospital mortality. Univariate and multivariate analysis was performed to identify variables associated with in-hospital mortality. FindingsWe analyzed 256 patients (106 patients in interferon group and 150 patients in control group). At admission, patients who did not receive interferon beta1b presented a greater number of comorbidities. The overall mortality rate was 24.6% (63/256). Twenty-two patients (20.8%) in the interferon group died and 41 (27.3%) in the control group (p=0.229). In the multivariate analysis, the predictors of in-hospital mortality were age, severity of clinical picture at admission and hydroxychloroquine treatment. InterpretationIn hospitalized patients with COVID-19, interferon beta1b treatment was not associated to decrease in-hospital mortality. Further assessment of the earlier administration of this drug in randomized trials is recommended. Fundingnone. RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSWe searched Pubmed on April 27th, 2020, for articles evaluating the efficacy of interferon beta in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), using the terms: "interferon beta and (COVID-19 or SARS-CoV-2)". We only found 5 articles. Of them, there was only one original article in English, which was a descriptive study of a case series with solid organ transplant from Spain. Added value of this studyThis is the first article that reports the efficacy of interferon beta1b in the treatment of patients with COVID-19. We compared the in-hospital mortality between patients who received interferon beta1b and patients who did not. Patients in both groups received other drugs with a potential antiviral and immunomodulatory effect. There was no significant difference in in-hospital mortality between both groups. Implications of all the available evidenceIn our retrospective cohort, treatment with interferon beta1b had not impact on in-hospital survival, however it would be of clinical interest to evaluate the effect of early administration of this drug in the control of SARS-CoV-2 infection in larger randomized clinical trials.

ObjectiveTo evaluate the performance of two available rapid immunological tests for identification of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) antibodies and their subsequent application to a regional screening of health care workers (HCW) in Tuscany (Italy). Designmeasures of accuracy and HCW serological surveillance Setting6 major health facilities in Tuscany, Italy. Participants17,098 HCW of the Tuscany Region. Measures of accuracy were estimated to assess sensitivity in 176 hospitalized Covid-19 clinical subjects at least 14 days after a diagnostic PCR-positive assay result. Specificity was assessed in 295 sera biobanked in the pre-Covid-19 era in winter or summer 2013-14 Main outcome measuresSensitivity and specificity, and 95% confidence intervals, were measured using two serological tests, named T-1 and T-2. Positive and Negative predictive values were estimated at different levels of prevalence. HCW of the health centers were tested using the serological tests, with a follow-up nasopharyngeal PCR-test swab in positive tested cases. ResultsSensitivity was estimated as 99% (95%CI: 95%-100%) and 97% (95% CI: 90%-100%), whereas specificity was the 95% and 92%, for Test T-1 and T-2 respectively. In the historical samples IgM cross-reactions were detected in sera collected during the winter period, probably linked to other human coronaviruses. Out of the 17,098 tested, 3.1% have shown the presence of SARS-CoV-2 IgG antibodies, among them 6.8% were positive at PCR follow-up test on nasopharyngeal swabs. ConclusionBased on the low prevalence estimate observed in this survey, the use of serological test as a stand-alone test is not justified to assess the individual immunity status. Serological tests showed good performance and might be useful in an integrated surveillance, for identification of infected subjects and their contacts as required by the policy of contact tracing, with the aim to reduce the risk of dissemination, especially in health service facilities.

Background and ObjectivesTest-to-stay concepts apply serial testing of children in daycare after exposure to SARS-CoV-2 without use of quarantine. This study aims to assess safety of a test-to-stay screening in daycare facilities. Methods714 daycare facilities and approximately 50,000 children [&le;]6 years in Cologne, Germany participated in a SARS-CoV-2 Pool-PCR screening from March 2021 to April 2022. The screening initially comprised post-exposure quarantine and was adapted to a test-to-stay approach during its course. To assess safety of the test-to-stay approach, we explored potential changes in frequencies of infections among children following the adaptation to the test-to-stay approach by applying regression discontinuity in time (RDiT) analyses. To this end, PCR-test data were linked with routinely collected data on reported infections in children and analyzed using ordinary least squares regressions. Results219,885 Pool-PCRs and 352,305 Single-PCRs were performed. 6,440 (2.93%) Pool-PCRs tested positive, and 17,208 infections in children were reported. We estimated that during a period of 30 weeks, the test-to-stay concept avoided between 7 and 20 days of quarantine per eligible daycare child. RDiT revealed a 26% reduction (Exp. Coef: 0.74, CI:0.52;1.06) in infection frequency among children and indicated no significant increase attributable to the test-to-stay approach. This result was not sensitive to adjustments for 7-day incidence, season, SARS-CoV-2 variant, and socioeconomic status. ConclusionOur analyses provide evidence that suggest safety of the test-to-stay approach compared to traditional quarantine measures. This approach offers a promising option to avoid use of quarantine after exposure to respiratory pathogens in daycare settings.

ObjectiveAntimicrobial resistance (AMR) is an urgent global health threat, resulting in more than 5 million deaths globally in 2019. Timely and complete antimicrobial agent (AMA) clinical trial results reporting is essential to evaluate the safety and efficacy of investigational therapies. The Food and Drug Administration Amendments Act (FDAAA) of 2007 mandated results reporting for applicable clinical trials to ClinicalTrials.gov. After nearly ten years of underreporting, the HHS issued the Final Rule, requiring a designated responsible party to submit results to ClinicalTrials.gov and clarifying applicable clinical trial (ACT) criteria. ACTs and probable ACTs (pACTs) are interventional studies regulated by the FDA with at least one site based in the United States. However, pACTs were initiated prior to January 2017, when the Final Rule came into effect. This study investigates the compliance and timeliness of results reporting of ACTs and probable ACTs (pACTs) for AMAs. DesignWe extracted data from ClinicalTrials.gov for trials involving AMAs with primary completion dates between May 1, 2013, and May 1, 2023. We analyzed the time from primary completion to results reporting and estimated the hazard ratio to compare timeliness between ACTs and pACTs. Additionally, we assessed delays in reporting across different study types and funding sources. ResultsOur search resulted in 2629 NCT records. After exclusion of ineligible trials, we included 2525 trials. We found 1769 pACTs (70.1%; 95% CI, 69.3%-72.9%) and 756 ACTs (29.9%; 95% CI, 28.2%-31.8%). Among the 2525 eligible trials, 2249 trials (89.1%; 95% CI, 87.8%-90.2%) were reported on ClinicalTrials.gov or in journal publications. Overall, 81.3% (95% CI, 79.7%-82.3%) of trials were reported late or missing (75.0% of ACTs vs 83.6% of pACTs). ACTs were more likely to report results earlier than pACTs, with a hazard ratio of 1.4 (95% CI, 1.3-1.5). ConclusionsACTs demonstrated greater reporting compliance and shorter delays in the reporting of overdue results. While this analysis provides initial insights, limitations related to timeline and sample scope suggest that broader investigations are needed to fully evaluate the impact of the Final Rule.

ObjectivesWe aimed to determine risk factors for the development of long coronavirus disease (COVID) in healthcare workers (HCWs). MethodsWe conducted a case-control study among HCWs who had confirmed COVID-19 infection working in a Brazilian healthcare system between March 1, 2020 and July 15, 2022. Cases were defined as those having long COVID per the Centers for Disease Control and Prevention definition. Controls were defined as HCWs who had documented COVID-19 infection but did not develop long COVID. Multiple logistic regression was used to assess the association between exposure variables and long COVID during 180 days of follow-up. ResultsOf 7,051 HCWs diagnosed with COVID-19 infection, 1,933 (27.4%) who developed long COVID were compared to 5,118 (72.6%) who did not. The majority of those with long COVID (51.8%) had 3 or more symptoms. Factors associated with development of long COVID were female sex (OR 1.21 [CI95 1.05-1.39]), age (OR 1.01 [CI95 1.00-1.02]), and two or more COVID-19 infections (1.27 [CI95 1.07-1.50]). Those infected with the Delta variant (OR 0.30 [CI95 0.17-0.50]) or the Omicron variant (OR 0.49 [CI95 0.30-0.78]), and those receiving four COVID-19 vaccine doses prior to infection (OR 0.05 [CI95 0.01-0.19]) were significantly less likely to develop long COVID. ConclusionsLong COVID can be prevalent among HCWs. We found that acquiring more than one COVID-19 infection was a major risk factor for long COVID, while maintenance of immunity via vaccination was highly protective.

IntroductionThis is a single-centre prospective cohort study to validate the Spanish Society of Infectious Diseases and Microbiology (SEIMC) score for predicting 28-days mortality in vaccinated patients with SARS-CoV-2 pneumonia. MethodsWe included 127 adult patients with confirmed SARS-CoV-2 infection by polymerase chain reaction (PCR) admitted to the hospital ward. Among them, 92 were unvaccinated, 17 one-dose vaccinated and 18 two-doses. The SEIMC score was calculated at admission, and we analysed its correlation with 28-days mortality. ResultsWe found significant differences between the number of vaccinations according to the SEIMC score classification. The SEIMC score and 28-days mortality were significantly correlated in the whole cohort (p=0.001), in unvaccinated patients (p=0.001) and in those with some vaccine doses (p=0.003) or two-doses (p = 0.005), but not in one-dose vaccinated patients (p=0.235). ConclusionThe SEIMC score remains a useful scale for predicting 28-day mortality in vaccinated patients.

ObjectivesAn IFN-2b and IFN-{gamma} combination has demonstrated favorable pharmacodynamics for genes underlying antiviral activity which might be involved in the defense of a host from a SARS-CoV-2 infection. Considering this synergy, we conducted a randomized controlled clinical trial for efficacy and safety evaluation of subcutaneous IFN - 2b and IFN-{gamma} administration in patients positive for SARS-CoV-2. MethodsWe enrolled 19-82 years-old inpatients at the Military Central Hospital Luis Diaz Soto, Havana, Cuba. They were hospitalized after confirmed diagnosis for SARS-CoV-2 RNA by real-time reverse transcription polymerase chain reaction. Patients were randomly assigned in a 1:1 ratio to receive either, subcutaneous treatment with a co-lyophilized combination of 3.0 MIU IFN-2b and 0.5 MIU IFN-{gamma} (HeberFERON, CIGB, Havana, Cuba), twice a week for two weeks, or thrice a week intramuscular injection of 3.0 MIU IFN-2b (Heberon(R) Alpha R, CIGB, Havana, Cuba). Additionally, all patients received lopinavir-ritonavir (200/50 mg every 12 h) and chloroquine (250 mg every 12 h, i.e.standard of care). The primary endpoints were, from the start of treatment, the time to elimination of viral RNA and the time to progression to severe COVID-19. The protocol was approved by the Ethics Committee on Clinical Investigation from the Hospital and the Center for the State Control of Medicines, Equipment and Medical Devices in Cuba. Informed consent was obtained from each participant (INSTITUTION PROTOCOL IG/IAG/CV/2001). ResultsA total of 79 patients with laboratory-confirmed SARS-CoV-2 infection, including symptomatic or asymptomatic conditions, fulfilled the inclusion criteria and underwent randomization. Thirty-three subjects were assigned to the HeberFERON group, and 33 to the Heberon Alpha R group. Sixty-three patients were analyzed for viral elimination, of these 78.6% in the HeberFERON group eliminated the virus after 4 days of treatment versus 40.6% of patients in the Heberon Alpha R groups (p=0.004). Time to reach the elimination of SARS-CoV-2, as measured by RT-PCR was 3.0 and 5.0 days for the HeberFERON and Heberon Alpha R groups, respectively. A significant improvement in the reduction of time for virus elimination was attributable to HeberFERON (p=0.0027, Log-rank test) with a Hazard Ratio of 3.2 and 95% CI of 1.529 to 6.948, as compared to the Heberon Alpha R treated group. Worsening of respiratory symptoms was detected in two (6.6%) and one (3.3%) patients in HeberFERON and IFN-2b groups, respectively. However, none of the subjects transited to severe COVID-19 during the study or during the following clinical evaluation (21 more days). RT-PCR on day 14 after the start of the treatment was negative to SARS-CoV-2 in 100% and 91% of patients of the combination of IFNs and IFN-2b, respectively. Elimination in HeberFERON treated patients was related to a significant increase in lymphocytes counts and also a significant reduction in CRP as early as 7 days after commencing the therapeutic schedule. All the patients in both cohorts recovered and had their laboratory parameters return to normal values by day 14 after treatment initiation. Adverse events were identified in 31.5% of patients, 28.5% in the control group, and 34.4% in the HeberFERON group, with the most frequent adverse event being headaches (17.4%). ConclusionsIn a cohort of 63 hospitalized patients between 19 to 82 years-old with positive SARS-CoV-2, HeberFERON significantly eliminated the virus on day 4 of treatment when compared to treatment with IFN-2b alone. However, Heberon Alpha R alone also showed efficacy for the treatment of the viral infection. Both treatments were safe and positively impacted on the resolution of the symptoms. None of the patients developed severe COVID-19.

BackgroundNumerous interventions for coronavirus disease 2019 (COVID-19) have been investigated by randomized controlled trials (RCTs). This systematic review and Bayesian network meta-analysis (NMA) aim to provide a comprehensive evaluation of efficacy of available treatments for COVID-19. MethodsWe searched for candidate COVID-19 studies in WHO COVID-19 Global Research Database, PubMed, PubMed Central, LitCovid, Proquest Central and Ovid up to December 19, 2020. RCTs for suspected or confirmed COVID-19 patients were included, regardless of publication status or demographic characteristics. Bayesian NMA with fixed effects was conducted to estimate the effect sizes using posterior means and 95% equal-tailed credible intervals (CrIs), while that with random effects was carried out as well for sensitivity analysis. Bayesian hierarchical models were used to estimate effect sizes of treatments grouped by their drug classifications. ResultsWe identified 96 eligible RCTs with a total of 51187 patients. Compared with the standard of care (SOC), this NMA showed that dexamethasone led to lower risk of mortality with an odds ratio (OR) of 0.85 (95% CrI [0.76, 0.95]; moderate certainty) and lower risk of mechanical ventilation (MV) with an OR of 0.68 (95% CrI [0.56, 0.83]; low certainty). For hospital discharge, remdesivir (OR 1.37, 95% CrI [1.15, 1.64]; moderate certainty), dexamethasone (OR 1.20, 95% CrI [1.08, 1.34]; low certainty), interferon beta (OR 2.15, 95% CrI [1.26, 3.74]; moderate certainty), tocilizumab (OR 1.40, 95% CrI [1.05, 1.89]; moderate certainty) and baricitinib plus remdesivir (OR 1.75, 95% CrI [1.28, 2.39]; moderate certainty) could all increase the discharge rate respectively. Recombinant human granulocyte colony-stimulating factor indicated lower risk of MV (OR 0.20, 95% CrI [0.10, 0.40]; moderate certainty); and patients receiving convalescent plasma resulted in better viral clearance (OR 2.28, 95% CrI [1.57, 3.34]; low certainty). About two-thirds of the studies included in this NMA were rated as high risk of bias, and the certainty of evidence was either low or very low for most of the comparisons. ConclusionThe Bayesian NMA identified superiority of several COVID-19 treatments over SOC in terms of mortality, requirement of MV, hospital discharge and viral clearance. These results provide a comprehensive comparison of current COVID-19 treatments and shed new light on further research and discovery of potential COVID-19 treatments.

BackgroundOn January 31st the first case of COVID-19 was detected in Spain, an imported case from Germany in Canary Islands, and thereafter on February 25th the first case was detected in Madrid. The first case of COVID-19 was confirmed at the Hospital Universitario 12 de Octubre on March 1st, a large public hospital with 1200 beds, covering an area over 400000 inhabitants in southern Madrid. During March 2020 highly active circulation of SARS-CoV-2 was experienced in Madrid with 24090 cases officially reported by March 29th. MethodsSince the beginning of the epidemics the Occupational Health and Safety Service (OHSS) organized the consulting and testing of the hospital personnel with confirmed exposure and also those presenting symptoms suggestive of viral respiratory infection. For molecular diagnosis of SARS-CoV-2 infection both nasopharyngeal and oropharyngeal swabs were obtained from suspected cases and processed at the Microbiology Laboratory by automatized specific PCR methods that was operative from February 25th as part of the preparedness. ResultsFrom a total of 6800 employees of the hospital, 2085 (30,6 %) were tested during the period 1-29 March 2020, some of them repeatedly (2286 total samples). The first HCW infected was confirmed on March 9th. A total of 791 HCW and personnel were confirmed to be infected by March 29th, representing 38% of those tested and 11,6 % of all the hospital workers. The proportion of infected individuals was estimated among the different groups of occupational exposure and the evolution of the cases during the expansive epidemic wave was compared between HCW and those patients attending at the Emergency Department (ER) during the same period and adjusted by the same age range. There were no statistically significant differences in the proportion of SARS- CoV-2 positive PCR detection between HCW from high risk areas involved in close contact with COVID-19 patients in comparison with clerical, administrative or laboratory personnel without direct contact with patients. The curves of evolution of accumulated cases between patients and HCW during March 2020 showed an almost parallel shape. DiscussionThe recommendation from our OHSS did not include testing of asymptomatic cases but was highly proactive in testing even patients with minor symptoms therefore, a high proportion of HCW and non-sanitary personnel was tested in March 2020 during the rapid period of expansion of the epidemics in Madrid, accounting for a total of 30,6 % of the hospital employees. Most of the COVID-19 cases among the hospital HCW and personnel were mild and managed at home under self-isolation measures, however 23 (3%) required hospitalization mostly due to severe bilateral interstitial pneumonia, two of those cases required mechanical ventilation at the ICU. No fatalities occurred during the study period. Although there were some cases of highly probable transmission from COVID-19 patients to HCWs, mainly at the first phase of the epidemics, there were no significant differences on the infection rates of HCW and hospital personnel that can be related to working in areas of high exposure risk. Furthermore, the evolution of cases during the same time period (March 2020) between patients attending the ER and hospital staff suggests that both groups were driven by the same dynamics. This experience is similar to the communicated from Wuhan verified by the WHO Joint Mission and also from recent experiences at hospital in the Netherlands, where most of the infections of HCW were related to household or community contacts. SignificanceSince the collective of hospital HCW are exhaustively screened in specific centers, their rate of infection for SARS-CoV-2 could be an indicator of the epidemic dynamics in the community. There appears to be a close connection between HCW infection and the driving forces of transmission in the community. Although we cannot exclude an additional risk factor of infection by SARS-CoV-2 due to the fact of the hospital environment, the similar proportions of positive cases among all the areas of the hospital and the evolutive wave of infection, as compared with the community, are clear arguments against a major factor of occupational risk. Exhaustive testing, such as the one carried out in our institution, covering over one third of all the workers, could be used as a reference of the population infected in the community. Since a significant proportion of COVID-19 cases can be asymptomatic and not all the hospital employees were actually tested, it is highly likely that this 11,6 % is a minimum estimation of the impact of SARS-CoV-2 circulation in Madrid during the first 4 weeks of the epidemics. This is in high and clear contrast with the official figures circulating at national and international levels. This has important implications to more precisely estimate the actual number of cases in the community and to develop public health policies for containment, treatment and recovery.

A new SARS-CoV-2 clade (GV) characterized by S substitution A222V, first reported from Spain in March, is rapidly spreading across Europe. To establish the A222V variant involvement in the infection rise in Italy, all GISAID sequences from Italy and those from our Laboratory (Lazio) in the period June-October were analysed. A222V, first recognized in August, represents 11.2% of sequences in this period, reaching 100% of autochthonous sequences in October, supporting increased GV circulation in Italy.

Since the COVID-19 outbreak began, a large number of studies have been conducted in a short period. However, it is unclear whether countries involved in this crisis have made adequate efforts and allocated resources to cutting-edge SARS-CoV-2 research. We analyzed the dynamics of and professional fields represented by papers about this novel coronavirus published before June 15, 2020. High-infection countries produced more scientific output than low-infection countries, and high-income and upper-middle-income countries were the main contributors. However, the research areas overlapped substantially, indicating a waste of resources. Our findings also suggest that international cooperation among countries is still relatively lacking, and all countries should make better use of their strengths to face the epidemic jointly.

BackgroundEstimated vaccine efficacy (VE) at 15 years for a single dose of quadrivalent human papillomavirus (HPV) vaccine in adolescent girls in India exceeded 90% against persistent infection (PI) from HPV 6/11/16/18, similar to VE for two or three doses [1]. Binding and neutralizing antibodies were evaluated as correlates of risk. MethodsHPV-specific antibody titers were measured by ELISA and pseudovirion-based neutralization assay on 25 PI cases of HPV 6, 11, 16, 18 and/or 31 and on 126 matched controls. HPV 31 was included, given cross-protection, to provide sufficient cases for analysis; limited numbers prevented assessment of correlates to each type. Age-adjusted logistic regression models assessed antibody biomarkers as correlates. ResultsHPV 18 binding antibody titers inversely correlated with PI: OR=0.62, 95%CI=(0.39, 0.99), p=0.045 per 10-fold titer increase. Our analysis identified no other correlate. ConclusionHigher HPV 18 titers were associated with a lower risk of PI with HPV 6/11/16/18/31. The clinical trial is registered with ISRCTN, ISRCTN98283094, and ClinicalTrials.gov, NCT00923702.