External validation of unsupervised COVID-19 clinical phenotypes and their prognostic impact.

BACKGROUND: Hospitalized patients with coronavirus disease 2019 (COVID-19) can be classified into different clinical phenotypes based on their demographic, clinical, radiology, and laboratory features. We aimed to validate in an external cohort of hospitalized COVID-19 patients the prognostic value of a previously described phenotyping system (FEN-COVID-19) and to assess the reproducibility of phenotypes development as a secondary analysis. METHODS: Patients were classified in phenotypes A, B or C according to the severity of oxygenation impairment, inflammatory response, hemodynamic and laboratory tests according to the FEN-COVID-19 method. RESULTS: Overall, 992 patients were included in the study, and 181 (18%), 757 (76%) and 54 (6%) of them were assigned to the FEN-COVID-19 phenotypes A, B, and C, respectively. An association with mortality was observed for phenotype C vs. A (hazard ratio [HR] 3.10, 95% confidence interval [CI] 1.81-5.30, p < 0.001) and for phenotype C vs. B (HR 2.20, 95% CI 1.50-3.23, p < 0.001). A non-statistically significant trend towards higher mortality was also observed for phenotype B vs. A (HR 1.41; 95% CI 0.92-2.15, p = 0.115). By means of cluster analysis, three different phenotypes were also identified in our cohort, with an overall similar gradient in terms of prognostic impact to that observed when patients were assigned to FEN-COVID-19 phenotypes. CONCLUSIONS: The prognostic impact of FEN-COVID-19 phenotypes was confirmed in our external cohort, although with less difference in mortality between phenotypes A and B than in the original study.

Hospitalized patients with COVID-19 can be classified into different clinical phenotypes based on their demographic, clinical, radiology, and laboratory featuresIn this study, we externally confirmed the prognostic impact of clinical phenotypes previously identified by Gutierrez-Gutierrez and colleagues in a Spanish cohort of hospitalized patients with COVID-19, and the usefulness of their simplified probabilistic model for phenotypes assignmentThis could indirectly support the validity of both phenotype's development and their extrapolation to other hospitals and countries for management decisions during other possible future viral pandemics.

The future for COVID-19 vaccines: public health assessment and perspectives based on scientific evidence

SUMMARY The development and use of messenger RNA-based (mRNA) vaccines against the SARS-CoV-2 spike protein have proven to be highly effective against symptomatic COVID-19, especially for severe forms. Since the declaration of a public health emergency in early 2020, however, the SARS-CoV-2 virus has continuously evolved, giving rise to several variants that have caused and continue to cause concern in the scientific community. Currently, viruses circulating worldwide belong to the Omicron lineage, with several identified sub-variants. In response to virus mutation, mRNA vaccines have been adapted into bivalent vaccines containing two mRNAs: one encoding the original Wuhan SARS-CoV-2 spike protein and one encoding the BA.1 or BA.4–5 spike protein of the Omicron sub-variant. This strategy is based on the hypothesis that the immune system's response improves when variants are included in the vaccine, leading to an increase in the magnitude and diversity of both the humoral and cellular immune response. The evidence gathered to date confirms the use of bivalent vaccines as the optimal strategy. In the light of current knowledge, and in the awareness of the impossibility of making precise predictions on the evolution of the COVID-19 pandemic, as a group of experts we propose some considerations for the progressive evolution of vaccination against SARS-CoV-2 from pandemic to endemic vaccination.

Epidemiology and molecular characteristics of respiratory syncytial virus (RSV) among italian community-dwelling adults, 2021/22 season.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infections worldwide. While historically RSV research has been focused on children, data on RSV infection in adults are limited. The goal of this study was to establish the prevalence of RSV in community-dwelling Italian adults and analyze its genetic variability during the 2021/22 winter season. METHODS: In this cross-sectional study, a random sample of naso-/oropharyngeal specimens from symptomatic adults seeking for SARS-CoV-2 molecular testing between December 2021 and March 2022 were tested for RSV and other respiratory pathogens by means of reverse-transcription polymerase chain reaction. RSV-positive samples were further molecularly characterized by sequence analysis. RESULTS: Of 1,213 samples tested, 1.6% (95% CI: 0.9-2.4%) were positive for RSV and subgroups A (44.4%) and B (55.6%) were identified in similar proportions. The epidemic peak occurred in December 2021, when the RSV prevalence was as high as 4.6% (95% CI: 2.2-8.3%). The prevalence of RSV detection was similar (p = 0.64) to that of influenza virus (1.9%). All RSV A and B strains belonged to the ON1 and BA genotypes, respectively. Most (72.2%) RSV-positive samples were also positive for other pathogens being SARS-CoV-2, Streptococcus pneumoniae and rhinovirus the most frequent. RSV load was significantly higher among mono-detections than co-detections. CONCLUSION: During the 2021/22 winter season, characterized by the predominant circulation of SARS-CoV-2 and some non-pharmaceutical containment measures still in place, a substantial proportion of Italian adults tested positive for genetically diversified strains of both RSV subtypes. In view of the upcoming registration of vaccines, establishment of the National RSV surveillance system is urgently needed.

Assessment of 2021/22 influenza epidemic scenarios in Italy during SARS-CoV-2 outbreak.

Global mitigation strategies to tackle the threat posed by SARS-CoV-2 have produced a significant decrease of the severity of 2020/21 seasonal influenza, which might result in a reduced population natural immunity for the upcoming 2021/22 influenza season. To predict the spread of influenza virus in Italy and the impact of prevention and control measures, we present an age-structured Susceptible-Exposed-Infectious-Removed (SEIR) model including the role of social mixing patterns and the impact of age-stratified vaccination strategies and Non-Pharmaceutical Interventions (NPIs) such as school closures, partial lockdown, as well as the adoption of personal protective equipment and the practice of hand hygiene. We find that vaccination campaigns with standard coverage would produce a remarkable mitigation of the spread of the disease in moderate influenza seasons, making the adoption of NPIs unnecessary. However, in case of severe seasonal epidemics, a standard vaccination coverage would not be sufficiently effective in fighting the epidemic, thus implying that a combination with the adoption of NPIs is necessary to contain the disease. Alternatively, our results show that the enhancement of the vaccination coverage would reduce the need to adopt NPIs, thus limiting the economic and social impacts that NPIs might produce. Our results highlight the need to respond to the influenza epidemic by strengthening the vaccination coverage.

The future for COVID-19 vaccines: public health assessment and perspectives based on scientific evidence.

The development and use of messenger RNA-based (mRNA) vaccines against the SARS-CoV-2 spike protein have proven to be highly effective against symptomatic COVID-19, especially for severe forms. Since the declaration of a public health emergency in early 2020, however, the SARS-CoV-2 virus has continuously evolved, giving rise to several variants that have caused and continue to cause concern in the scientific community. Currently, viruses circulating worldwide belong to the Omicron lineage, with several identified sub-variants. In response to virus mutation, mRNA vaccines have been adapted into bivalent vaccines containing two mRNAs: one encoding the original Wuhan SARS-CoV-2 spike protein and one encoding the BA.1 or BA.4-5 spike protein of the Omicron sub-variant. This strategy is based on the hypothesis that the immune system's response improves when variants are included in the vaccine, leading to an increase in the magnitude and diversity of both the humoral and cellular immune response. The evidence gathered to date confirms the use of bivalent vaccines as the optimal strategy. In the light of current knowledge, and in the awareness of the impossibility of making precise predictions on the evolution of the COVID-19 pandemic, as a group of experts we propose some considerations for the progressive evolution of vaccination against SARS-CoV-2 from pandemic to endemic vaccination.

Rapid differential diagnosis of SARS-CoV-2, influenza A/B and respiratory syncytial viruses: Validation of a novel RT-PCR assay.

BACKGROUND: Influenza and respiratory syncytial (RSV) viruses are expected to co-circulate with SARS-CoV-2 in the upcoming seasons and clinical differential diagnosis between them is difficult. Laboratory-based RT-PCR is a gold standard diagnostic method for influenza, RSV and SARS-CoV-2. The objective of this study was to estimate the diagnostic performance of a novel point-of-care RT-PCR assay STANDARD M10 Flu/RSV/SARS-CoV-2 (SD Biosensor) in a large number of clinical specimens with diversified (co)-infection patterns and viral loads. METHODS: This was a retrospective study, in which all samples were tested in both STANDARD M10 Flu/RSV/SARS-CoV-2 index and Allplex SARS-CoV-2/Respiratory Panel 1 (Seegene) reference kits. Samples with discordant results were further processed in a third resolver test (Resp-4-Plex, Abbott). RESULTS: A total of 1,019 naso-/oropharyngeal samples (50.3% positive for at least one virus) were processed in both STANDARD M10 Flu/RSV/SARS-CoV-2 and Allplex assays and the overall between-assay agreement was as high as 94.6%. Positive percent agreement of the STANDARD M10 Flu/RSV/SARS-CoV-2 was 100%, 96.6%, 97.3% and 99.4% for influenza A, B, RSV and SARS-CoV-2, respectively. The corresponding negative percent agreement was 99.7%. 100%, 100% and 98.4%, respectively. The expected positive and negative predictive values for all viruses were constantly above 96% in a reasonable range of disease prevalence. CONCLUSIONS: STANDARD M10 Flu/RSV/SARS-CoV-2 is a reliable RT-PCR assay able to detect influenza A, influenza B, RSV and SARS-CoV-2 in one hour or less, fostering a rapid differential diagnosis of common respiratory viruses.

Surveillance of Severe Acute Respiratory Infection and Influenza Vaccine Effectiveness among Hospitalized Italian Adults, 2021/22 Season.

Following an extremely low incidence of influenza during the first waves of the ongoing COVID-19 pandemic, the 2021/22 Northern Hemisphere winter season saw a resurgence of influenza virus circulation. The aim of this study was to describe epidemiology of severe acute respiratory infections (SARIs) among Italian adults and estimate the 2021/22 season influenza vaccine effectiveness. For this purpose, a test-negative case-control study was conducted in a geographically representative sample of Italian hospitals. Of 753 SARI patients analyzed, 2.5% (N = 19) tested positive for influenza, most of which belonged to the A(H3N2) subtype. Phylogenetic analysis showed that these belonged to the subclade 3C.2a1b.2a.2, which was antigenically different from the 2021/22 A(H3N2) vaccine component. Most (89.5%) cases were registered among non-vaccinated individuals, suggesting a protective effect of influenza vaccination. Due to a limited number of cases, vaccine effectiveness estimated through the Firth's penalized logistic regression was highly imprecise, being 83.4% (95% CI: 25.8-97.4%) and 83.1% (95% CI: 22.2-97.3%) against any influenza type A and A(H3N2), respectively. Exclusion of SARS-CoV-2-positive controls from the model did not significantly change the base-case estimates. Within the study limitations, influenza vaccination appeared to be effective against laboratory-confirmed SARI.

Monitoring influenza vaccination coverage among healthcare workers during the COVID-19 pandemic: a three-year survey in a large university hospital in North-Western Italy.

Introduction: Healthcare workers (HCWs) are one of the highest priority groups recommended for seasonal influenza vaccination (SIV). Greater awareness of the importance of influenza vaccination was observed among HCWs after the start of the COVID-19 pandemic. The aim of this study was to analyze SIV coverage rates in the 2019-2020, 2020-2021 and 2021-2022 seasons among HCWs employed at the IRCCS Ospedale Policlinico San Martino in Genoa, in order to observe how coverage has changed since the COVID-19 pandemic began. Methods: A retrospective, single-center study was conducted among HCWs working at the IRCCS Ospedale Policlinico San Martino in Genoa. The vaccinated population was stratified by gender, age, qualification and area of activity, and the characteristics of vaccinated HCWs were analyzed. Results: While SIV coverage was below the recommended target in all seasons, a sharp increase was observed in 2020/2021 (12.8%; 40.9% and 23% in 2019/2020, 2020/2021 and 2021/2022, respectively). The mean and median age of vaccinees also increased during the 2020/2021 vaccination campaign (46.7 and 49 years, respectively) in comparison with the 2019/2020 season (43.5 and 45, respectively). In the 2019/2020 and 2021/2022 seasons, a higher proportion of vaccinees were physicians. Vaccinated females outnumbered males, but the coverage rate resulted greater in males than females in all three seasons. While a higher proportion of vaccinated subjects worked in medical areas, the most evident increase over the three years was seen among subjects working in the services area. Conclusions: This survey highlights the importance of studying the determinants that influence vaccination adherence and how the COVID-19 pandemic has affected SIV coverage.

Evaluation of humoral and cellular response to four vaccines against COVID-19 in different age groups: A longitudinal study.

To date there has been limited head-to-head evaluation of immune responses to different types of COVID-19 vaccines. A real-world population-based longitudinal study was designed with the aim to define the magnitude and duration of immunity induced by each of four different COVID-19 vaccines available in Italy at the time of this study. Overall, 2497 individuals were enrolled at time of their first vaccination (T0). Vaccine-specific antibody responses induced over time by Comirnaty, Spikevax, Vaxzevria, Janssen Ad26.COV2.S and heterologous vaccination were compared up to six months after immunization. On a subset of Comirnaty vaccinees, serology data were correlated with the ability to neutralize a reference SARS-CoV-2 B strain, as well as Delta AY.4 and Omicron BA.1. The frequency of SARS-CoV-2-specific CD4+ T cells, CD8+ T cells, and memory B cells induced by the four different vaccines was assessed six months after the immunization. We found that mRNA vaccines are stronger inducer of anti-Spike IgG and B-memory cell responses. Humoral immune responses are lower in frail elderly subjects. Neutralization of the Delta AY.4 and Omicron BA.1 variants is severely impaired, especially in older individuals. Most vaccinees display a vaccine-specific T-cell memory six months after the vaccination. By describing the immunological response during the first phase of COVID-19 vaccination campaign in different cohorts and considering several aspects of the immunological response, this study allowed to collect key information that could facilitate the implementation of effective prevention and control measures against SARS-CoV-2.

Who Is at Higher Risk of SARS-CoV-2 Reinfection? Results from a Northern Region of Italy.

The SARS-CoV-2 pandemic continues to spread worldwide, generating a high impact on healthcare systems. The aim of the study was to examine the epidemiological burden of SARS-CoV-2 reinfections and to identify potential related risk factors. A retrospective observational study was conducted in Liguria Region, combining data from National Vaccines Registry and Regional Chronic Condition Data Warehouse. In the study period (September 2021 to May 2022), 335,117 cases of SARS-CoV-2 infection were recorded in Liguria, of which 15,715 were reinfected once. During the Omicron phase (which predominated from 3 January 2022), the risk of reinfection was 4.89 times higher (p < 0.001) than during the Delta phase. Unvaccinated and vaccinated individuals with at least one dose for more than 120 days were at increased risk of reinfection compared with vaccinated individuals with at least one dose for ≤120 days, respectively (odds ratio (OR) of 1.26, p < 0.001; OR of 1.18, p < 0.001). Healthcare workers were more than twice as likely to be reinfected than non-healthcare workers (OR of 2.38, p < 0.001). Lower ORs were seen among people aged 60 to 79 years. Two doses or more of vaccination were found to be protective against the risk of reinfection rather than a single dose (mRNA vaccines: OR of 0.06, p < 0.0001, and OR of 0.1, p < 0.0001; vector vaccines: OR of 0.05, p < 0.0001). Patients with chronic renal failure, cardiovascular disease, bronchopneumopathy, neuropathy and autoimmune diseases were at increased risk of reinfection (OR of 1.38, p = 0.0003; OR of 1.09, p < 0.0296; OR of 1.14, p = 0.0056; OR of 1.78, p < 0.0001; OR of 1.18, p = 0.0205). Estimating the epidemiological burden of SARS-CoV-2 reinfections and the role played by risk factors in reinfections is relevant for identifying risk-based preventive strategies in a pandemic context characterized by a high circulation of the virus and a high rate of pathogen mutations.

Seroprevalence of infection-induced SARS-CoV-2 antibodies among health care users of Northern Italy: results from two serosurveys (October-November 2019 and September-October 2021).

OBJECTIVES: The objective was to estimate the seroprevalence of SARS-CoV-2 in autumn 2019 (before case zero was identified in Italy) and 2021 among residual sera samples from health care users in the Piedmont region of northwestern Italy. METHODS: Two serosurveys were conducted. Using a semiquantitative method, samples were tested for the presence of immunoglobulin G (IgG) antibodies against the S1 domain of the spike protein. Samples with positive test results from the 2019 survey were independently retested using a multiplex panel to detect IgG antibodies against the receptor binding domain, S1 and S2 domains, and nucleocapsid. Samples with positive test results from the 2021 survey underwent repeat testing with enzyme-linked immunosorbent assay to detect anti-nucleocapsid IgG antibodies. Prevalence rates according to gender and age groups, together with their respective 95% confidence intervals (CIs), were calculated. RESULTS: Overall, the proportion of samples with positive test results was 2/353 in 2019 and 22/363 in 2021, with an estimated seroprevalence of 0.27% (95% CI 0-1.86) and 6.21% (95% CI 3.9-9.31) in 2019 and 2021 respectively. CONCLUSION: Results of this study support the hypothesis that the virus was circulating in Italy as early as autumn 2019. The role of these early cases in broader transmission dynamics remains to be determined.

Adverse Reactions after the Third Dose of the BNT162b2 mRNA COVID-19 Vaccine among Medical School Residents in a Regional Reference University Hospital in Italy.

The recent emergence of new variants of concern (VOCs) of SARS-CoV-2 and the uncertain duration of protection provided by the primary immunization cycle have highlighted the need for COVID-19 booster vaccinations. However, only a few studies have assessed the safety and reactogenicity profile of mRNA booster doses. Therefore, we conducted an online survey with the aim of assessing the adverse reaction profile in the 7 days following a third dose of the BNT162b2 vaccine in a population of resident physicians who had already been investigated after the primary vaccination. Among the 512 resident physicians (female = 53.2%, mean age = 29.8 years) invited to participate in the survey, 222 completed the survey (56.5% female, mean age of 29.9 years), with an average time from second to third dose of 8.6 months. The most common adverse reactions were local pain (88.3%), fatigue (58.1%), muscle/joint pain (44.1%), and headache (38.3%), all subsiding in 48-72 h. While the local reaction rate was similar to that following the first two doses, the systemic reactions were considerably less common and milder compared to the second vaccination. Nonetheless, over one third (36.1%) of participants reported interference with their normal activities. These results complement our previous findings and could aid occupational and public health professionals in the counselling of vaccinees.

Seroprevalence of infection-induced SARS-CoV-2 antibodies among healthcare users of Northern Italy – results from two serosurveys (October-November 2019 – September-October 2021)

Objective To estimate the seroprevalence of SARS-CoV-2 in autumn 2019 (before case zero was identified in Italy) and 2021 among residual sera samples of healthcare users of Piedmont, Northwestern Italy. Methods Two serosurveys were conducted. Samples were tested for the detection of IgG antibodies against the S1 domain of the spike protein, using a semi-quantitative method. Positive samples from the 2019 survey were independently re-tested using a multiplex panel for the detection of IgG antibodies against the receptor-binding domain, S1 and S2, and nucleocapsid (N). Positive samples from the 2021 survey underwent repeat testing with ELISA for the detection of IgG anti-N antibodies. Prevalence rates according to gender and age groups, together with their respective 95% CIs, were calculated. Results Overall, the proportion of positive samples was 2/353 in 2019 and 22/363 in 2021, with an estimated seroprevalence of 0.27% (95% CI 0 – 1.86) and 6.21% (95% CI 3.9 – 9.31), in 2019 and 2021 respectively. Conclusion Results of this study support the hypothesis that the virus was circulating in Italy as early as autumn 2019. The role of these early cases in broader transmission dynamics remains to be determined.

Herpes Simplex Virus 1 (HSV-1) Reactivation in Critically Ill COVID-19 Patients: A Brief Narrative Review.

Systemic or pulmonary reactivations of herpes simplex virus 1 (HSV-1) have been reported in critically ill patients with COVID-19, posing a dilemma for clinicians in terms of their diagnostic and clinical relevance. Prevalence of HSV-1 reactivation may be as high as > 40% in this population, but with large heterogeneity across studies, likely reflecting the different samples and/or cut-offs for defining reactivation. There is frequently agreement on the clinical significance of HSV-1 reactivation in the presence of severe manifestations clearly attributable to the virus. However, the clinical implications of HSV-1 reactivations in the absence of manifest signs and symptoms remain controversial. Our review aims at providing immunological background and at reviewing clinical findings on HSV-1 reactivations in critically ill patients with COVID-19.

COVID-19: opinions and behavior of Italian general population during the first epidemic phase.

BACKGROUND AND AIM: On January 9, 2020, the World Health Organization (WHO) declared that Chinese health authorities had identified a new coronavirus strain never before isolated in humans, the 2019-nCoV later redefined SARS-CoV-2, that still today represent a public health problem. The present survey started on 10 February 2020 with the aim of a) assessing the risk perception in healthcare workers and young students, following the evolution of attitudes, perception and knowledge over time, b) provide useful information to the general population during survey. RESULTS: A study sample consisting of 4116 Italian individuals of both sexes was enrolled. High levels of risk perception, low perception of self-efficacy and low levels of knowledge scores (24.55 ± 5.76 SD) were obtained indicating the need for continuous population monitoring as well as further communication strategies carried out at institution levels. CONCLUSION: The results of the present study could help public health authorities in carrying out informative campaigns for general population and could be an important tool in evaluating public knowledge and misperceptions during the management of the COVID-19. (www.actabiomedica.it).

High Diagnostic Accuracy of a Novel Lateral Flow Assay for the Point-of-Care Detection of SARS-CoV-2.

Highly accurate lateral flow immunochromatographic tests (LFTs) are an important public health tool to tackle the ongoing COVID-19 pandemic. The aim of this study was to assess the comparative diagnostic performance of the novel ND COVID-19 LFT under real-world conditions. A total of 400 nasopharyngeal swab specimens with a wide range of viral loads were tested in both reverse-transcription polymerase chain reaction and ND LFT. The overall sensitivity and specificity were 85% (95% CI: 76.7-90.7%) and 100% (95% CI: 98.7-100%), respectively. There was a clear association between the false-negative rate and sample viral load: the sensitivity parameters for specimens with cycle threshold values of <25 (>3.95 × 106 copies/mL) and ≥30 (≤1.29 × 105 copies/mL) were 100% and 50%, respectively. The performance was maximized in testing samples with viral loads ≥1.29 × 105 copies/mL. These findings suggest that the ND LFT is sufficiently accurate and useful for mass population screening programs, especially in high-prevalence and resource-constrained settings or during periods when the epidemic curve is rising. Other public health implications were also discussed.

Efficacy of the Sentinox Spray in Reducing Viral Load in Mild COVID-19 and Its Virucidal Activity against Other Respiratory Viruses: Results of a Randomized Controlled Trial and an In Vitro Study.

Sentinox (STX) is an acid-oxidizing solution containing hypochlorous acid in spray whose virucidal activity against SARS-CoV-2 has been demonstrated. In this paper, results of a randomized controlled trial (RCT) on the efficacy of STX in reducing viral load in mild COVID-19 patients (NCT04909996) and a complementary in vitro study on its activity against different respiratory viruses are reported. In the RCT, 57 patients were randomized (1:1:1) to receive STX three (STX-3) or five (STX-5) times/day plus standard therapy or standard therapy only (controls). Compared with controls, the log10 load reduction in groups STX-3 and STX-5 was 1.02 (p = 0.14) and 0.18 (p = 0.80), respectively. These results were likely driven by outliers with extreme baseline viral loads. When considering subjects with baseline cycle threshold values of 20-30, STX-3 showed a significant (p = 0.016) 2.01 log10 reduction. The proportion of subjects that turned negative by the end of treatment (day 5) was significantly higher in the STX-3 group than in controls, suggesting a shorter virus clearance time. STX was safe and well-tolerated. In the in vitro study, ≥99.9% reduction in titers against common respiratory viruses was observed. STX is a safe device with large virucidal spectrum and may reduce viral loads in mild COVID-19 patients.

Comparative Diagnostic Accuracy of the STANDARD M10 Assay for the Molecular Diagnosis of SARS-CoV-2 in the Point-of-Care and Critical Care Settings.

Accurate and rapid molecular diagnosis of COVID-19 is a crucial step to tackle the ongoing pandemic. The primary objective of this study was to estimate the real-world performance of the novel RT-PCR STANDARD M10 SARS-CoV-2 assay in a large number of nasopharyngeal (NP) specimens eluted in universal transport medium. The secondary objective was to evaluate the compatibility of this kit in testing NP samples eluted in an inactivated transport medium (essential for point-of-care testing) and lower respiratory tract (LRT) specimens, which are commonly collected in critical care. A total of 591 samples were analyzed. Compared with the standard extraction-based RT-PCR Allplex 2019-nCoV (time-to-result of 270 min), the sensitivities of the STANDARD M10 were 100% (95% CI: 98.1-100%), 95.5% (95% CI: 91.7-97.6%), and 99.5% (95% CI: 97.2-99.9%) for ≥1 gene, the ORF1ab gene, and the E gene, respectively, while the specificity was 100% (95% CI: 98.7-100%). The diagnostic accuracy was 100% in testing both NP samples eluted in an inactivated transport medium and LRT specimens. STANDARD M10 reliably detects SARS-CoV-2 in 60 min, may be used as a POC tool, and is suitable for testing LRT specimens in the critical care setting.

COVID-19 and Seasonal Influenza Vaccination: Cross-Protection, Co-Administration, Combination Vaccines, and Hesitancy.

SARS-CoV-2 and influenza are the main respiratory viruses for which effective vaccines are currently available. Strategies in which COVID-19 and influenza vaccines are administered simultaneously or combined into a single preparation are advantageous and may increase vaccination uptake. Here, we comprehensively review the available evidence on COVID-19/influenza vaccine co-administration and combination vaccine candidates from the standpoints of safety, immunogenicity, efficacy, policy and public acceptance. While several observational studies have shown that the trained immunity induced by influenza vaccines can protect against some COVID-19-related endpoints, it is not yet understood whether co-administration or combination vaccines can exert additive effects on relevant outcomes. In randomized controlled trials, co-administration has proved safe, with a reactogenicity profile similar to that of either vaccine administered alone. From the immunogenicity standpoint, the immune response towards four influenza strains and the SARS-CoV-2 spike protein in co-administration groups is generally non-inferior to that seen in groups receiving either vaccine alone. Several public health authorities have advocated co-administration. Different combination vaccine candidates are in (pre)-clinical development. The hesitancy towards vaccine co-administration or combination vaccines is a multifaceted phenomenon and may be higher than the acceptance of either vaccine administered separately. Public health implications are discussed.

Weight of risk factors for mortality and short-term mortality displacement during the COVID-19 pandemic.

Background: We conducted a population-based cohort study to estimate mortality before, during and after the COVID-19 peak and to compare mortality in 2020 with rates reported in previous years, with a view to helping decision makers to apply containment measures for high-risk groups. Methods: All deaths were collected between 2015 and 2020 from municipal registry database. In 2020, weeks 1-26 were stratified in three periods: before, during and after the COVID mortality peak. The Poisson Generalized Linear regression Model showed the "harvesting effect". Three logistic regressions for 8 dependent variables (age and comorbidities) and a t-test of differences described all-cause mortality risk factors in 2019 and 2020 and differences between COVID and non-COVID patients. Results: A total of 47,876 deaths were collected. All-cause deaths increased by 38.5% during the COVID peak and decreased by 18% during the post-peak period in comparison with the average registered during the control period (2015-19), with significant mortality displacement in 2020. Except for chronic renal injuries in subjects aged 45-64 years, diabetes and chronic cardiovascular diseases in those aged 65-84 years, and neuropathies in those aged > 84 years, the weight of comorbidities in deaths was similar or lower in COVID subjects than in non-COVID subjects. Discussions: Surprisingly, the weight of comorbidities in death, compared to weight in non-COVID subjects allows you to highlight some surprising results such as COPD, IBD and Cancer. The excess mortality that we observed in the entire period were modest in comparison with initial estimates during the peak, owing to the mild influenza season and the harvesting effect starting from the second half of May.