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The SARS-CoV-2 Omicron variant emerged in South Africa in November 2021, and has later been identified worldwide, raising serious concerns. A real-time RT-PCR assay was designed for the rapid screening of the Omicron variant, targeting characteristic mutations of the spike gene. The assay was used to test 737 sewage samples collected throughout Italy (19/21 Regions) between 11 November and 25 December 2021, with the aim of assessing the spread of the Omicron variant in the country. Positive samples were also tested with a real-time RT-PCR developed by the European Commission, Joint Research Centre (JRC), and through nested RT-PCR followed by Sanger sequencing. Overall, 115 samples tested positive for Omicron SARS-CoV-2 variant. The first occurrence was detected on 7 December, in Veneto, North Italy. Later on, the variant spread extremely fast in three weeks, with prevalence of positive wastewater samples rising from 1.0% (1/104 samples) in the week 5-11 December, to 17.5% (25/143 samples) in the week 12-18, to 65.9% (89/135 samples) in the week 19-25, in line with the increase in cases of infection with the Omicron variant observed during December in Italy. Similarly, the number of Regions/Autonomous Provinces in which the variant was detected increased from one in the first week, to 11 in the second, and to 17 in the last one. The presence of the Omicron variant was confirmed by the JRC real-time RT-PCR in 79.1% (91/115) of the positive samples, and by Sanger sequencing in 66% (64/97) of PCR amplicons. In conclusion, we designed an RT-qPCR assay capable to detect the Omicron variant, which can be successfully used for the purpose of wastewater-based epidemiology. We also described the history of the introduction and diffusion of the Omicron variant in the Italian population and territory, confirming the effectiveness of sewage monitoring as a powerful surveillance tool.

ImportanceData on the association of COVID-19 vaccination with intensive care unit (ICU) admission and outcomes of patients with SARS-CoV-2–related pneumonia are scarce.ObjectiveTo evaluate whether COVID-19 vaccination is associated with preventing ICU admission for COVID-19 pneumonia and to compare baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU.Design, Setting, and ParticipantsThis retrospective cohort study on regional data sets reports: (1) daily number of administered vaccines and (2) data of all consecutive patients admitted to an ICU in Lombardy, Italy, from August 1 to December 15, 2021 (Delta variant predominant). Vaccinated patients received either mRNA vaccines (BNT162b2 or mRNA-1273) or adenoviral vector vaccines (ChAdOx1-S or Ad26.COV2). Incident rate ratios (IRRs) were computed from August 1, 2021, to January 31, 2022; ICU and baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU were analyzed from August 1 to December 15, 2021.ExposuresCOVID-19 vaccination status (no vaccination, mRNA vaccine, adenoviral vector vaccine).Main Outcomes and MeasuresThe incidence IRR of ICU admission was evaluated, comparing vaccinated people with unvaccinated, adjusted for age and sex. The baseline characteristics at ICU admission of vaccinated and unvaccinated patients were investigated. The association between vaccination status at ICU admission and mortality at ICU and hospital discharge were also studied, adjusting for possible confounders.ResultsAmong the 10 107 674 inhabitants of Lombardy, Italy, at the time of this study, the median [IQR] age was 48 [28-64] years and 5 154 914 (51.0%) were female. Of the 7 863 417 individuals who were vaccinated (median [IQR] age: 53 [33-68] years; 4 010 343 [51.4%] female), 6 251 417 (79.5%) received an mRNA vaccine, 550 439 (7.0%) received an adenoviral vector vaccine, and 1 061 561 (13.5%) received a mix of vaccines and 4 497 875 (57.2%) were boosted. Compared with unvaccinated people, IRR of individuals who received an mRNA vaccine within 120 days from the last dose was 0.03 (95% CI, 0.03-0.04; P P P P P o2) and fraction of inspiratory oxygen (FiO2) at ICU admission (median [IQR]: 138 [100-180] vs 120 [90-158] mm Hg; P = .007). Factors associated with ICU and hospital mortality were higher age, premorbid heart disease, lower Pao2/FiO2 at ICU admission, and female sex (this factor only for ICU mortality). ICU and hospital mortality were similar between vaccinated and unvaccinated patients.Conclusions and RelevanceIn this cohort study, mRNA and adenoviral vector vaccines were associated with significantly lower risk of ICU admission for COVID-19 pneumonia. ICU and hospital mortality were not associated with vaccinated status. These findings suggest a substantial reduction of the risk of developing COVID-19–related severe acute respiratory failure requiring ICU admission among vaccinated people.

Influenza is one of the most common respiratory viral infections worldwide. Numerous vaccines are used to prevent influenza. Their selection should be informed by the best available evidence. We aimed to estimate the comparative efficacy and safety of seasonal influenza vaccines in children, adults and the elderly.We conducted a systematic review and network meta-analysis (NMA). We searched the Cochrane Library Central Register of Controlled Trials, MEDLINE and EMBASE databases, and websites of regulatory agencies, through December 15th, 2020. We included placebo- or no vaccination-controlled, and head-to-head randomized clinical trials (RCTs). Pairs of reviewers independently screened the studies, abstracted the data, and appraised the risk of bias in accordance to the Cochrane Handbook for Systematic Reviews of Interventions. The primary outcome was laboratory-confirmed influenza. We also synthesized data for hospitalization, mortality, influenza-like illness (ILI), pneumonia or lower respiratory-tract disease, systemic and local adverse events (AEs). We estimated summary risk ratios (RR) using pairwise and NMA with random effects. This study is registered with PROSPERO, number CRD42018091895.We identified 13,439 citations. A total of 231 RCTs were included after screening: 11 studies did not provide useful data for the analysis; 220 RCTs [100,677 children ( 18 years) and 329,127 adults (18-60 years) and elderly (≥ 61 years)] were included in the NMA. In adults and the elderly, all vaccines, except the trivalent inactivated intradermal vaccine (3-IIV ID), were more effective than placebo in reducing the risk of laboratory-confirmed influenza, with a RR between 0.33 (95% credible interval [CrI] 0.21-0.55) for trivalent inactivated high-dose (3-IIV HD) and 0.56 (95% CrI 0.41-0.74) for trivalent live-attenuated vaccine (3-LAIV). In adults and the elderly, compared with trivalent inactivated vaccine (3-IIV), no significant differences were found for any, except 3-LAIV, which was less efficacious [RR 1.41 (95% CrI 1.04-1.88)]. In children, compared with placebo, RR ranged between 0.13 (95% CrI 0.03-0.51) for trivalent inactivated vaccine adjuvanted with MF59/AS03 and 0.55 (95% CrI 0.36-0.83) for trivalent inactivated vaccine. Compared with 3-IIV, 3-LAIV and trivalent inactivated adjuvanted with MF59/AS03 were more efficacious [RR 0.52 (95% CrI 0.32-0.82) and RR 0.23 (95% CrI 0.06-0.87)] in reducing laboratory-confirmed influenza. With regard to safety, higher systemic AEs rates after vaccination with 3-IIV, 3-IIV HD, 3-IIV ID, 3-IIV MF59/AS03-adj, quadrivalent inactivated (4-IIV), quadrivalent adjuvanted (4-IIV MF59/AS03-adj), quadrivalent recombinant (4-RIV), 3-LAIV or quadrivalent live attenuated (4-LAIV) vaccines were noted in adults and the elderly [RR 1.5 (95% CrI 1.18-1.89) to 1.15 (95% CrI 1.06-1.23)] compared with placebo. In children, the systemic AEs rate after vaccination was not significantly higher than placebo.All vaccines cumulatively achieved major reductions in the incidence of laboratory-confirmed influenza in children, adults, and the elderly. While the live-attenuated was more efficacious than the inactivated vaccine in children, many vaccine types can be used in adults and the elderly.The directorate general of welfare, Lombardy region.

SARS-CoV-2 was declared a pandemic by the WHO on March 11th, 2020. Public protective measures were enforced in every country to limit the diffusion of SARS-CoV-2. Its transmission, mainly by droplets, has been measured by the effective reproduction number (Rt) that counts the number of secondary cases caused in a population by an average infectious individual at time t. Current strategies to calculate Rt reflect the number of secondary cases after several days, due to a delay from symptoms onset to reporting. We propose a complementary Rt estimation using supervised machine learning techniques to predict short term variations with more timely results.Our primary goal was to predict Rt of the current day in the twelve provinces of Lombardy with the highest possible accuracy, and with no influence of the local testing strategies. We gathered data about mobility, weather, and pollution from different public sources as a proxy of human behavior and public health measures. We built four supervised machine learning algorithms with different strategies: the outcome variable was the daily median Rt values per province obtained from officially adopted algorithms.Data from 243 days for every province were presented to our four models (from February 15th, 2020, to October 14th, 2020). Two models using differential calculation of Rt instead of the raw values showed the highest mean coefficient of determination (0.93 for both) and residuals reported the lowest mean error (-0.03 and 0.01) and standard deviation (0.13 for both) as well. The one with access to the value of Rt of the day before heavily relied on that feature for prediction, while the other one had more distributed weights.The model that had not access to the Rt value of the previous day and used Rt differential value as outcome (FDRt) was considered the most robust according to the metrics. Its forecasts were able to predict the trend that Rt values would have developed over different weeks, but it was not particularly accurate in predicting the precise value of Rt. A correlation among mobility, atmospheric, features, pollution and Rt values is plausible, but further testing should be performed.

During the spring of 2020, the coronavirus disease 2019 (COVID-19) epidemic caused an unprecedented demand for intensive-care resources in the Lombardy region of Italy. Using data on 43,538 hospitalized patients admitted between February 21 and July 12, 2020, we evaluated variations in intensive care unit (ICU) admissions and mortality over the course of 3 periods: the early phase of the pandemic (February 21–March 13), the period of highest pressure on the health-care system (March 14–April 25, when numbers of COVID-19 patients exceeded prepandemic ICU bed capacity), and the declining phase (April 26–July 12). Compared with the early phase, patients aged 70 years or more were less often admitted to an ICU during the period of highest pressure on the health-care system (odds ratio (OR) = 0.47, 95% confidence interval (CI): 0.41, 0.54), with longer ICU delays (incidence rate ratio = 1.82, 95% CI: 1.52, 2.18) and lower chances of dying in the ICU (OR = 0.47, 95% CI: 0.34, 0.64). Patients under 56 years of age had more limited changes in the probability of (OR = 0.65, 95% CI: 0.56, 0.76) and delay to (incidence rate ratio = 1.16, 95% CI: 0.95, 1.42) ICU admission and increased mortality (OR = 1.43, 95% CI: 1.00, 2.07). In the declining phase, all quantities decreased for all age groups. These patterns may suggest that limited health-care resources during the peak phase of the epidemic in Lombardy forced a shift in ICU admission criteria to prioritize patients with higher chances of survival.

Background The aim of this study is to quantify the hospital burden of COVID-19 during the first wave and how it changed over calendar time; to interpret the results in light of the emergency measures introduced to manage the strain on secondary healthcare. Methods This is a cohort study of hospitalised confirmed cases of COVID-19 admitted from February–June 2020 and followed up till 17th July 2020, analysed using a mixture multi-state model. All hospital patients with confirmed COVID-19 disease in Regione Lombardia were involved, admitted from February–June 2020, with non-missing hospital of admission and non-missing admission date. Results The cohort consists of 40,550 patients hospitalised during the first wave. These patients had a median age of 69 (interquartile range 56–80) and were more likely to be men (60%) than women (40%). The hospital-fatality risk, averaged over all pathways through hospital, was 27.5% (95% CI 27.1–28.0%); and steadily decreased from 34.6% (32.5–36.6%) in February to 7.6% (6.3–10.6%) in June. Among surviving patients, median length of stay in hospital was 11.8 (11.6–12.3) days, compared to 8.1 (7.8–8.5) days in non-survivors. Averaged over final outcomes, median length of stay in hospital decreased from 21.4 (20.5–22.8) days in February to 5.2 (4.7–5.8) days in June. Conclusions The hospital burden, in terms of both risks of poor outcomes and lengths of stay in hospital, has been demonstrated to have decreased over the months of the first wave, perhaps reflecting improved treatment and management of COVID-19 cases, as well as reduced burden as the first wave waned. The quantified burden allows for planning of hospital beds needed for current and future waves of SARS-CoV-2 i.

Nursing home residents were the most vulnerable population to be affected by Coronavirus disease 2019 (COVID-19) in Italy. The Italian vaccination strategy decided to indicate them as the target population in the first phase of the massive vaccination campaign. We carried out an analysis on an outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection which occurred in a nursing home in northern Italy (Cremona) after the administration of the complete vaccination cycle affecting most of the guests of the structure.Data relating to the outbreak were obtained through the Regional Surveillance System for Infectious Diseases of Lombardia Region.During the outbreak, among the 61 guests, 56 were vaccinated. Thirty four were found positive for COVID-19: 22 were asymptomatic, 12 were symptomatic and 4 died. The observed difference in the number of deaths between vaccinated and non-vaccinated subjects was significant. During the outbreak 104 healthcare workers (HCWs) were employed in the nursing home, only 66 were vaccinated. Eight HCWs were found COVID-19 positive, 4 of them were vaccinated and of female gender.Similarly to data reported in literature for described outbreaks, we observed that the vaccine is able to protect from the symptomatic form and a valid antibody response protect from a symptomatic disease. The low number of HCWs found positive indicates a correct use of individual protective devices.

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p

In September 2018 in Brescia province, northern Italy, an outbreak of Legionnaires' disease (LD) caused by Legionella pneumophila serogroup 2 (Lp2) occurred. The 33 cases (two fatal) resided in seven municipalities along the Chiese river. All cases were negative by urinary antigen test (UAT) and most were diagnosed by real-time PCR and serology. In only three cases, respiratory sample cultures were positive, and Lp2 was identified and typed as sequence type (ST)1455. In another three cases, nested sequence-based typing was directly applied to respiratory samples, which provided allelic profiles highly similar to ST1455. An environmental investigation was undertaken immediately and water samples were collected from private homes, municipal water systems, cooling towers and the river. Overall, 533 environmental water samples were analysed and 34 were positive for Lp. Of these, only three samples, all collected from the Chiese river, were Lp2 ST1455. If and how the river water could have been aerosolised causing the LD cases remains unexplained. This outbreak, the first to our knowledge caused by Lp2, highlights the limits of UAT for LD diagnosis, underlining the importance of adopting multiple tests to ensure that serogroups other than serogroup 1, as well as other Legionella species, are identified.

BackgroundThe ability to identify the positive subjects is crucial for public health practice to reduce transmission and supporting contact tracing and isolation. The reliability of the criteria of the test-based criteria as the required condition for the reintroduction of the asymptomatic and positive patients of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the community was evaluated assessing the time span from positive to negative for RNA detection by Real Time – Polymerase Chain Reaction (RT-PCR). Methods. We used information concerning negative conversion time and the respective times. Cumulative probabilities of negative conversion time during the follow-up were evaluated by Crude Cumulative Incidences (CCIs). Non-parametric estimates of CCIs and respective 95% C.I.s were obtained.Results. We report the results for 52,186 individuals. 33486 subjects resulted negative or potentially negative with a CCI of 75.2% at 70 days from the first swab (95% CI: 74.8% to 75.7%). 11,000 subjects deceased before 14/05/2020 without diagnosis of negative status (CCI 21.9%; 95% CI: 21.5% to 22.3%), at 56 days from the first swab (maximum observed time to death).Conclusions. SARS-CoV-2 positivity is a condition that frequently lasts more than 30 days. More solid studies are required to determinate the significance of a prolonged state of positivity and the consequences on the policies of dismission of quarantine and isolation.

Wastewater-based viral surveillance is a promising approach to monitor the circulation of SARS-CoV-2 in the general population. The aim of this study was to develop an analytical method to detect SARS-CoV-2 RNA in urban wastewater, to be implemented in the framework of a surveillance network in the Lombardy region (Northern Italy). This area was the first hotspot of COVID-19 in Europe. Composite 24h samples were collected weekly in eight cities from end-March to mid-June 2020 (first peak of the epidemic). The method developed and optimized, involved virus concentration, using PEG centrifugation, and one-step real-time RT-PCR for analysis. SARS-CoV-2 RNA was identified in 65 (61%) out of 107 samples, and the viral concentrations (up to 2.1 E +05 copies/L) were highest in March-April. By mid-June, wastewater samples tested negative in all the cities. Viral loads were used for inter-city comparison and Brembate, Ranica and Lodi had the highest. The pattern of decrease of SARS-CoV-2 in wastewater was closely comparable to the decline of active COVID-19 cases in the population, reflecting the effect of lock-down. Wastewater surveillance of SARS-CoV-2 can integrate ongoing virological surveillance of COVID-19, providing information from both symptomatic and asymptomatic individuals, and monitoring the effect of health interventions.

We evaluated the performance of the exponentially weighted moving average (EWMA) model for comparing two families of predictors (i.e., structured and unstructured data from visits to the emergency department (ED)) for the early detection of SARS-CoV-2 epidemic waves. The study included data from 1,282,100 ED visits between 1 January 2011 and 9 December 2021 to a local health unit in Lombardy, Italy. A regression model with an autoregressive integrated moving average (ARIMA) error term was fitted. EWMA residual charts were then plotted to detect outliers in the frequency of the daily ED visits made due to the presence of a respiratory syndrome (based on coded diagnoses) or respiratory symptoms (based on free text data). Alarm signals were compared with the number of confirmed SARS-CoV-2 infections. Overall, 150,300 ED visits were encoded as relating to respiratory syndromes and 87,696 to respiratory symptoms. Four strong alarm signals were detected in March and November 2020 and 2021, coinciding with the onset of the pandemic waves. Alarm signals generated for the respiratory symptoms preceded the occurrence of the first and last pandemic waves. We concluded that the EWMA model is a promising tool for predicting pandemic wave onset.

Key Points Question What is the association of age with the likelihood of developing respiratory symptoms or fever greater than or equal to 37.5 °C and the association of age with the likelihood of progressing to critical disease after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection? Findings In this cohort study, 5484 quarantined case contacts were monitored daily for symptoms for at least 2 weeks and were tested for infection via real-time reverse transcriptase–polymerase chain reaction or serological screening more than 1 month after identification. Only 26.1% of infected individuals younger than 60 years developed respiratory symptoms or fever greater than or equal to 37.5 °C, but 6.6% of infected participants aged 60 years or older developed critical disease. Meaning The low proportion of children and young adults who developed symptoms highlights the possible challenges in readily identifying SARS-CoV-2 infections., This cohort study examines the association of age with the likelihood of experiencing symptoms and progressing to critical illness after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Italy., Importance Solid estimates of the risk of developing symptoms and of progressing to critical disease in individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are key to interpreting coronavirus disease 2019 (COVID-19) dynamics, identifying the settings and the segments of the population where transmission is more likely to remain undetected, and defining effective control strategies. Objective To estimate the association of age with the likelihood of developing symptoms and the association of age with the likelihood of progressing to critical illness after SARS-CoV-2 infection. Design, Setting, and Participants This cohort study analyzed quarantined case contacts, identified between February 20 and April 16, 2020, in the Lombardy region of Italy. Contacts were monitored daily for symptoms and tested for SARS-CoV-2 infection, by either real-time reverse transcriptase–polymerase chain reaction using nasopharyngeal swabs or retrospectively via IgG serological assays. Close contacts of individuals with laboratory-confirmed COVID-19 were selected as those belonging to clusters (ie, groups of contacts associated with an index case) where all individuals were followed up for symptoms and tested for SARS-CoV-2 infection. Data were analyzed from February to June 2020. Exposure Close contact with individuals with confirmed COVID-19 cases as identified by contact tracing operations. Main Outcomes and Measures Age-specific estimates of the risk of developing respiratory symptoms or fever greater than or equal to 37.5 °C and of experiencing critical disease (defined as requiring intensive care or resulting in death) in SARS-CoV-2–infected case contacts. Results In total, 5484 case contacts (median [interquartile range] age, 50 [30-61] years; 3086 female contacts [56.3%]) were analyzed, 2824 of whom (51.5%) tested positive for SARS-CoV-2 (median [interquartile range] age, 53 [34-64] years; 1604 female contacts [56.8%]). The proportion of infected persons who developed symptoms ranged from 18.1% (95% CI, 13.9%-22.9%) among participants younger than 20 years to 64.6% (95% CI, 56.6%-72.0%) for those aged 80 years or older. Most infected contacts (1948 of 2824 individuals [69.0%]) did not develop respiratory symptoms or fever greater than or equal to 37.5 °C. Only 26.1% (95% CI, 24.1%-28.2%) of infected individuals younger than 60 years developed respiratory symptoms or fever greater than or equal to 37.5 °C; among infected participants older than 60 years, 6.6% (95% CI, 5.1%-8.3%) developed critical disease. Female patients were 52.7% (95% CI, 24.4%-70.7%) less likely than male patients to develop critical disease after SARS-CoV-2 infection. Conclusions and Relevance In this Italian cohort study of close contacts of patients with confirmed SARS-CoV-2 infection, more than one-half of individuals tested positive for the virus. However, most infected individuals did not develop respiratory symptoms or fever. The low proportion of children and young adults who developed symptoms highlights the possible challenges in readily identifying SARS-CoV-2 infections.

* Abbreviation: COVID-19 — : coronavirus disease 2019 In Italy, 15.8% of the residents are children

Additional file 1.

Objective: Women treated for Cervical Intraepithelial Neoplasia (CIN) grade 2 or 3 are at increased risk of CIN and cervical cancer. Human Papillomavirus (HPV) vaccination is effective in preventing CIN in women who are not infected by HPV. Some studies suggested that vaccination may reduce the risk of CIN2 or 3 in women treated for CIN. A working group including all Italian scientific societies involved in tackling cervical cancer developed a recommendation on vaccination against HPV for women treated for CIN2 or CIN3. Data sources, methodsofstudyselection: The group conducted a systematic review of the literature published from January 2006 to May 2019. Evidence on safety outcomes was retrieved by a recent Cochrane Review on vaccination in the general population. To develop the final recommendation, evidences were appraised and integrated by a Panel of Experts using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence to Decision framework. Tabulation, integrationandresults: Six eligible studies were included. Four were RCTs and two were cohort studies, with different timing of vaccination. An additional study, published in October 2019, was taken into consideration after external review. A reduction of 70% CIN2+ in the treatment group was estimated; the vaccine was considered safe. Conclusion: The working group recommends the use of HPV vaccination in women treated for CIN2 or 3. The strong recommendation is based on large estimated desirable effects and trivial anticipated undesirable effects (moderate certainty of evidence), negligible costs and savings (no studies included), and a positive judgment in terms of feasibility, acceptability, and impact on equity.

Background: Understanding the risk factors associated with hospital burden of COVID-19 is crucial for healthcare planning for any future waves of infection. Methods: An observational cohort study is performed, using data on all RT-PCR confirmed cases of COVID-19 in Regione Lombardia, Italy, during the first wave of infection from February-June 2020. A multi-state modelling approach is used to simultaneously estimate risks of progression through hospital to final outcomes of either death or discharge, by pathway (via critical care or not) and the times to final events (lengths of stay). Logistic and time-to-event regressions are used to quantify the association of patient and population characteristics with the risks of hospital outcomes and lengths of stay respectively. Findings: Risks of severe outcomes such as ICU admission and mortality have decreased with month of admission and increased with age. Care home residents aged 65+ are at increased risk of hospital mortality and decreased risk of ICU admission. Being a healthcare worker appears to have a protective effect on mortality risk and length of stay. Lengths of stay decrease with month of admission for survivors, but do not appear to vary with month for non-survivors. Interpretation: Improvements in clinical knowledge, treatment, patient and hospital management and public health surveillance, together with the waning of the first wave after the first lockdown, are hypothesised to have contributed to the reduced risks and lengths of stay over time. Funding: This work has been funded by the Medical Research Council (De Angelis, Jackson, Presanis: Unit programme number MC UU 00002/11; Kunzmann: Unit programme number MC_UU_00002/10); and the UKRI-MRC COVID-19 Rapid Call (Presanis, De Angelis, grant no MC_PC_19074). Declaration of Interests: None to declare.

BackgroundDuring the spring of 2020, the SARS-CoV-2 epidemic has caused significant resource strain in hospitals of Lombardy, Italy, with the demand for intensive care beds for COVID-19 patients exceeding the overall pre-crisis capacity. In this study, we evaluate the effect of healthcare strain on ICU admission and survival.MethodsWe used data on 43,538 patients admitted to a hospital in the region between February 20 and July 12, 2020, of which 3,993 (9.2%) were admitted to an ICU. We applied logistic regression to model the probability of being admitted to an ICU and the probability of survival among ICU patients. Negative binomial regressions were used to model the time between hospital and ICU admission and the length of stay in ICU.ResultsDuring the period of highest hospital strain (March 16 – April 22), individuals older than 70 years had a significantly lower probability of being admitted to an ICU and significantly longer times between hospital and ICU admission, indicating elective admission due to constrained resources. Healthcare strain did not have a clear effect on mortality, with the overall proportion of deaths declining from 52.1% (95%CI 49.8-54.5) for ICU patients admitted to the hospital before March 16, to 43.4% (95%CI 41.5-45.6) between March 16 and April 22, to 27.6% (95%CI 20.0-35.2) after April 22.ConclusionsThese data demonstrate and quantify the adoption of elective admission to ICUs during the peak phase of the SARS-CoV-2 epidemic in Lombardy. However, we show that for patients admitted to ICUs, clinical outcomes progressively improved despite the saturation of healthcare resources.

Objectives. To assess the time span from positive to negative SARS-CoV-2 RNA detection by RT-PCR, and to evaluate the reliability of the test-based criteria as the required condition for the reintroduction of the asymptomatic SARS-CoV-2 positive patient in the community. Methods. We used information concerning negativization and the respective times. Cumulative probabilities of negativization during the follow-up were evaluated by Crude Cumulative Incidences (CCIs). Non-parametric estimates of CCIs and respective 95% C.I.s were obtained.Results. We report only the results for 52,186 individuals. 33486 subjects resulted negative or potentially negative with a CCI of 75.2% at 70 days from the first swab (95% CI: 74.8% to 75.7%). 11,000 subjects deceased before 14/05/2020 without diagnosis of negative status (CCI 21.9%; 95% CI: 21.5% to 22.3%), at 56 days from the first swab (maximum observed time to death).Conclusions. SARS-CoV-2 positivity is a condition that frequently lasts more than 30 days. Since the determination of isolation based only on a status of positivity could be excessive, more solid studies are required to determinate the significance of a prolonged state of positivity and the consequences on the policies of dismission of quarantine and isolation.

The clinical presentation of symptomatic SARS-CoV-2 not only includes viral pneumonia, but also milder illness overlapping with influenza-like illness (ILI), allowing a potential tracking of the infection in the framework of the national influenza surveillance system (SS). By comparing the data recorded by the influenza SS in 2019-20 season to those collected for the previous years, we want to evaluate whether the implementation of ILI SS could succeed in early detection and monitoring of Covid-19 diffusion. We analyzed the data recorded by the influenza SS and we compared the distribution of ILI incidence rate by week for 2017-18, 2018-19 and 2019-20 season in order to understand whether the SS detected any abnormality coinciding with Covid-19 outbreak. The distribution of ILI cases in the three seasons presented a similar pattern up to the 9th week; after then, a reduction in the ILI incidence rate was observed in the 2017-18 and the 2018-19 season while an increase was detected for 2019-20. During 2019-20 season, three major characteristics stand out: i) at the beginning of Covid-19 epidemic (7th-9th week) 9,17/1000 cases were reported; ii) during the recognition of the COVID-19 outbreak (9th-10th week) 6,36/1000 cases; iii) during the spread of Covid-19 (10th-11th week) an unexpected increase to 7,72/1000 cases. Additionally, their geographical distribution was concentrated in the areas known to be most affected by the epidemic. The influenza SS enabled us to detect the introduction and distribution of COVID-19. Implementation of the system should be prioritized in order to early identify new waves of Covid-19 but also any future novel respiratory pathogen. In order to empower the SS, it would be advisable to increase the population coverage about 2% which is the actual standard. Key messages The influenza surveillance system detected the first wave of Covid-19 in Lombardy Region, Italy. The influenza surveillance system should be implemented in order to bring a benefit both to the current situation and in sight of future public health challenges.

Issue COVID-19 pandemic began in Italy on February 20th, 2020. Since the beginning of the emergency Healthcare Workers' (HCWs) involvement was prominent, mainly due to direct assistance to COVID-19 patients. Therefore, we implemented a prevention policy for HCW screening through serological and RT-PCR testing. Description of the problem HCW screening for SARS-CoV-2 infection is essential for prevention and control of the pandemic. Lombardy's Healthcare authorities settled a screening process for HCWs divided into three steps: 1) body temperature assessment at the beginning and the end of work shift, if fever > 37.5 °C was present the HCW was sent back home and a nasopharyngeal swab was performed; 2) progressive recruitment for serological testing; 3) on those positive to IgG a nasopharyngeal swab was performed and tested for viral RNA by RT-PCR. Results Among 79185 HCW tested, 9589 (12%) were positive on serological IgG testing. Of the 9589 positive a nasopharyngeal swab was performed on 6884. Of these 358 (5%) tested positive and the remaining 6526 (95%) negative to RT-PCR. We calculated a Positive Predictive Value of 5.2%. The rate of positive serological tests for each Healthcare facility varied between 0% and 78%. Five percent of all facilities, belonging to Brescia, Bergamo and Cremona area, reported a positivity rate higher than 40% in HCWs. A second cluster (18% of all facilities), involving the same geographical area, reported a rate between 20% and 40%, whereas the remaining facilities (76%) of the region a rate Lessons Serological IgG testing can be, if followed by immediate nasopharyngeal swab testing, a valid screening intervention on asymptomatic HCWs especially in a high infection prevalence setting. Key messages Serological IgG testing can be, if followed by immediate nasopharyngeal swab testing, a valid screening intervention on asymptomatic HCWs. Infection prevention in HCW may benefit from a screening campaign especially in high prevalence settings.

We analysed 5,484 close contacts of coronavirus disease (COVID-19) cases in Italy, all tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infection fatality ratio was 0.43% (95% confidence interval (CI): 0.21–0.79) for individuals younger than 70 years and 10.5% (95% CI: 8.0–13.6) for older individuals. Risk of death after infection was 62% lower (95% CI: 31–80) in clusters identified after 16 March 2020 and 1.8-fold higher for males (95% CI: 1.03–3.16).

In July 2018, a large outbreak of Legionnaires’ disease (LD) caused by Legionella pneumophila serogroup 1 (Lp1) occurred in Bresso, Italy. Fifty-two cases were diagnosed, including five deaths. We performed an epidemiological investigation and prepared a map of the places cases visited during the incubation period. All sites identified as potential sources were investigated and sampled. Association between heavy rainfall and LD cases was evaluated in a case-crossover study. We also performed a case–control study and an aerosol dispersion investigation model. Lp1 was isolated from 22 of 598 analysed water samples; four clinical isolates were typed using monoclonal antibodies and sequence-based typing. Four Lp1 human strains were ST23, of which two were Philadelphia and two were France-Allentown subgroup. Lp1 ST23 France-Allentown was isolated only from a public fountain. In the case-crossover study, extreme precipitation 5–6 days before symptom onset was associated with increased LD risk. The aerosol dispersion model showed that the fountain matched the case distribution best. The case–control study demonstrated a significant eightfold increase in risk for cases residing near the public fountain. The three studies and the matching of clinical and environmental Lp1 strains identified the fountain as the source responsible for the epidemic.

In July 2018, a large outbreak of Legionnaires’ disease (LD) caused by Legionella pneumophila serogroup 1 (Lp1) occurred in Bresso, Italy. Fifty-two cases were diagnosed, including five deaths. We performed an epidemiological investigation and prepared a map of the places cases visited during the incubation period. All sites identified as potential sources were investigated and sampled. Association between heavy rainfall and LD cases was evaluated in a case-crossover study. We also performed a case–control study and an aerosol dispersion investigation model. Lp1 was isolated from 22 of 598 analysed water samples; four clinical isolates were typed using monoclonal antibodies and sequence-based typing. Four Lp1 human strains were ST23, of which two were Philadelphia and two were France-Allentown subgroup. Lp1 ST23 France-Allentown was isolated only from a public fountain. In the case-crossover study, extreme precipitation 5–6 days before symptom onset was associated with increased LD risk. The aerosol dispersion model showed that the fountain matched the case distribution best. The case–control study demonstrated a significant eightfold increase in risk for cases residing near the public fountain. The three studies and the matching of clinical and environmental Lp1 strains identified the fountain as the source responsible for the epidemic.

BackgroundCOVID-19 case fatality rate in hospitalized patients varies across countries and studies, but reliable estimates specific for age, sex, and comorbidities are needed to design trials for COVID-19 interventions. Aim of this study is to provide population-based survival curves of hospitalized COVID-19 patients.MethodsA cohort study was conducted in Lombardy, Veneto, and Reggio Emilia using COVID-19 registries linked to hospital discharge databases containing patient clinical histories. All patients with positive SARS-CoV-2 RT-PCR test on oral/nasopharyngeal swabs hospitalized from 21st February to 21st April 2020 were identified. Kaplan Meier survival estimates were calculated at 14 and 30 days for death in any setting, stratifying by age, sex and Charlson Index.FindingsOverall, 42,926 hospitalized COVID-19 patients were identified. Patients’ median age was 69 years (IQR: 57-79), 62·6% were males, 69·4% had a Charlson Index of 0. In total, 11,205 (26·1%) patients died over a median follow-up of 24 days (IQR: 10-35). Survival curves showed that 22·0% of patients died within 14 days and 27·6% within 30 days of hospitalization. Survival was higher in younger patients and in females. Younger patients with comorbidities had a lower survival than older ones with comorbidities.InterpretationOver 27% of hospitalized COVID-19 patients died within one month in three areas of Northern Italy that were heavily affected by SARS-CoV-2 infection. Such a high fatality rate suggests that trials should focus on survival and have follow-up of at least one month.FundingThe study did not receive any external funding.Research in contextEvidence before this studyTwo recent systematic reviews with meta-analyses report case fatality rates of three to four percent in COVID-19 patients. Most studies on hospitalized cohorts report only slightly higher figures. These figures do not correspond to those derived from routinely collected clinical data in most European countries, reporting a 10% case fatality rate which has been increasing over time since the epidemic started.Robust and precise survival estimates of hospitalized COVID-19 patients which take into account prognostic factors such as age, sex and burden of comorbidities are needed to design appropriate phase II and phase III clinical studies of drugs targeting COVID-19.Added value of this studyIn this study we present the first survival estimates by age, sex and Charlson index for a large population-based cohort of Italian hospitalized COVID-19 patients.Implications of all the available evidenceOver 27% of COVID-19 patients died within one month from hospital admission. Such a high fatality rate suggests that studies should prioritize mortality as primary outcome. Furthermore, we found that the fatality rate reaches a plateau 30 days after hospitalization, suggesting that studies should have at least one month of follow up to observe deaths; shorter follow-up could lead to overestimation of treatment benefits.

This study evaluates the association between SARS-CoV-2 load in urban wastewater and surveillance indicators of infection prevalence and severity in Milan, Italy.

Wastewater-based viral surveillance was proposed as a promising approach to monitor the circulation of SARS-CoV-2 in the general population. The aim of this study was to develop an analytical method to detect SARS-CoV-2 RNA in urban wastewater, and apply it to follow the trends of epidemic in the framework of a surveillance network in the Lombardy region (Northern Italy). This area was the first hotspot of COVID-19 in Europe and was severely affected. Composite 24 h samples were collected weekly in eight cities from end-March to mid-June 2020 (first peak of the pandemic). The method developed and optimized, involved virus concentration using PEG centrifugation, and one-step real-time RT-PCR for analysis. SARS-CoV-2 RNA was identified in 65 (61%) out of 107 samples, and the viral concentrations (up to 2.1 E + 05 copies/L) were highest in March-April. By mid-June, wastewater samples tested negative in all the cities corresponding to the very low number of cases recorded in the same period. Viral loads were calculated considering the wastewater daily flow rate and the population served by each wastewater treatment plant, and were used for inter- city comparison. The highest viral loads were found in Brembate, Ranica and Lodi corresponding to the hotspots of the first peak of pandemic. The pattern of decrease of SARS-CoV-2 in wastewater was closely comparable to the decline of active COVID-19 cases in the population, reflecting the effect of lock-down. This study tested wastewater surveillance of SARS-CoV-2 to follow the pandemic trends in one of most affected areas worldwide, demonstrating that it can integrate ongoing virological surveillance of COVID-19, providing information from both symptomatic and asymptomatic individuals, and monitoring the effect of health interventions., Graphical abstract Unlabelled Image

Sustained coronavirus disease (COVID-19) transmission is ongoing in Italy, with 7,375 reported cases and 366 deaths by 8 March 2020. We provide a model-based evaluation of patient records from Lombardy, predicting the impact of an uncontrolled epidemic on the healthcare system. It has the potential to cause more than 250,039 (95% credible interval (CrI): 147,717–459,890) cases within 3 weeks, including 37,194 (95% CrI: 22,250–67,632) patients requiring intensive care. Aggressive containment strategies are required.

This cross-sectional study investigates seroprevalence and odds of SARS-CoV-2 infection among health care workers in different professional categories and operational units in Italy., Key Points Question What are the seroprevalence and the relative odds of SARS-CoV-2 infection among health care workers (HCWs) employed in different professional categories and operational units? Findings In this cross-sectional study of 82 961 serological tests of Italian HCWs, 12.2% of participants were positive for IgG antibodies against SARS-CoV-2. Higher odds of infection were found among nurses, health assistants, and workers enrolled in emergency departments or in treatment of patients with subacute disease. Meaning These findings suggest that equipment and training of personnel less accustomed to managing infectious disease but directly exposed to patients who may be infected with SARS-CoV-2 should be prioritized to decrease infection risks in health care settings., Importance Identifying health care settings and professionals at increased risk of SARS-CoV-2 infection is crucial to defining appropriate strategies, resource allocation, and protocols to protect health care workers (HCWs) and patients. Moreover, such information is crucial to decrease the risk that HCWs and health care facilities become amplifiers for SARS-CoV-2 transmission in the community. Objective To assess the association of different health care professional categories and operational units, including in-hospital wards, outpatient facilities, and territorial care departments, with seroprevalence and odds of SARS-CoV-2 infection. Design, Setting, and Participants This cross-sectional study was conducted using IgG serological tests collected from April 1 through May 26, 2020, in the Lombardy region in Italy. Voluntary serological screening was offered to all clinical and nonclinical staff providing any health care services or support to health care services in the region. Data were analyzed from June 2020 through April 2021. Exposures Employment in the health care sector. Main Outcomes and Measures Seroprevalence of positive IgG antibody tests for SARS-CoV-2 was collected, and odds ratios of experiencing infection were calculated. Results A total of 140 782 professionals employed in the health sector were invited to participate in IgG serological screening, among whom 82 961 individuals (59.0% response rate) were tested for SARS-CoV-2 antibodies, with median (interquartile range [IQR]; range) age, 50 (40-56; 19-83) years and 59 839 (72.1%) women. Among these individuals, 10 115 HCWs (12.2%; 95% CI, 12.0%-12.4%) had positive results (median [IQR; range] age, 50 [39-55; 20-80] years; 7298 [72.2%] women). Statistically significantly higher odds of infection were found among health assistants (adjusted odds ratio [aOR], 1.48; 95% CI, 1.33-1.65) and nurses (aOR, 1.28; 95% CI, 1.17-1.41) compared with administrative staff and among workers employed in internal medicine (aOR, 2.24; 95% CI, 1.87-2.68), palliative care (aOR, 1.84; 95% CI, 1.38-2.44), rehabilitation (aOR, 1.59; 95% CI, 1.33-1.91), and emergency departments (aOR, 1.56; 95% CI, 1.29-1.89) compared with those working as telephone operators. Statistically significantly lower odds of infection were found among individuals working in forensic medicine (aOR, 0.40; 95% CI, 0.19-0.88), histology and anatomical pathology (aOR, 0.71; 95% CI, 0.52-0.97), and medical device sterilization (aOR, 0.54; 95% CI, 0.35-0.84) compared with those working as telephone operators. The odds of infection for physicians and laboratory personnel were not statistically significantly different from those found among administrative staff. The odds of infection for workers employed in intensive care units and infectious disease wards were not statistically significantly different from those of telephone operators. Conclusions and Relevance These findings suggest that professionals partially accustomed to managing infectious diseases had higher odds of SARS-CoV-2 infection. The findings further suggest that adequate organization of clinical wards and personnel, appropriate personal protective equipment supply, and training of all workers directly and repeatedly exposed to patients with clinical or subclinical COVID-19 should be prioritized to decrease the risk of infection in health care settings.

Objective: Cervical cancer prevention shows a variability across Italian Regions unjustified by available evidence, increasing the health, economic and organizational burden. Evidence-based recommendations on topics not covered by international guidelines are needed to tackle existing inequalities. This article describes the rationale, methods, and process for development of the Multisociety Italian Guidelines for cervical cancer prevention. Methods: The Italian legislative framework requires guidelines to be consistent with methodological standards set by the National System for Guidelines (SNLG) of the National Institute of Health. Results: The nine scientific societies involved in cervical cancer prevention participated to the project, including clinicians, policy makers, methodologists, and researchers. Patients were involved as full voting panel members. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach was adopted to assess the certainty of evidence collected by systematic reviews. The GRADE Evidenceto- Decision framework (EtD) was used to structure the appraisal of evidence and to formulate final recommendations. The EtD and a conflict-of-interests management policy were adopted to minimize the influence of competing interests. Discussion: Full transparency guided the reporting of each step of the process, to support the implementation of recommendations in each context and the future updating process. Considerations for subgroups, monitoring and evaluation of the implementation of recommendations and research priorities were also provided. A two-step review process by external experts and SNLG reviewers, prior to online publication, ensured the methodological robustness underlying final recommendations. Finally, to increase publication timeliness, guidelines are organised in chapters that group sets of related recommendations to be published independently.

This study aimed at assessing the frequency and the distribution of influenza virus types/subtypes in 172 laboratory-confirmed influenza-positive patients admitted to intensive care units (ICUs) during the 2017&ndash, 2018 season in the Lombardy region (Northern Italy), and to investigate the presence of molecular pathogenicity markers. A total of 102/172 (59.3%) patients had influenza A infections (83 A/H1N1pdm09, 2 H3N2 and 17 were untyped), while the remaining 70/172 (40.7%) patients had influenza B infections. The 222G/N mutation in the hemagglutinin gene was identified in 33.3% (3/9) of A/H1N1pdm09 strains detected in the lower respiratory tract (LRT) samples and was also associated with more severe infections, whereas no peculiar mutations were observed for influenza B strains. A single-point evolution was observed in site 222 of A/H1N1pdm09 viruses, which might advantage viral evolution by favouring virus binding and replication in the lungs. Data from 17 paired upper respiratory tract (URT) and LRT samples showed that viral load in LRT samples was mostly higher than that detected in URT samples. Of note, influenza viruses were undetectable in 35% of paired URT samples. In conclusion, LRT samples appear to provide more accurate clinical information than URT samples, thus ensuring correct diagnosis and appropriate treatment of patients with severe respiratory infections requiring ICU admission.

Background Colorectal cancer screening may reduce disease-related mortality by early-stage detection of cancers. Aims To study the effect of a single immunochemical faecal occult blood test (i-FOBt) screening round on reduction in colorectal cancer-related-mortality among average risk subjects. Methods Comparison of 5-year mortality rates in 3 cohorts from a Northern Italian province: (1) colorectal cancers detected at the 1st biennial round of a mass-screening programme targeting 50–69 years old subjects, (2) non-screening cancers symptomatically diagnosed during the same time period, and (3) cancers detected in the pre-screening biennium. Multivariate analyses were performed with the Cox regression model including tumour node metastasis (TNM) stage at diagnosis, anatomical distribution of cancers, age at diagnosis, gender and patient group. Kaplan–Meyer survival estimates and log-rank test for equality of survivor functions were calculated. Results Stage distribution significantly differed between screening and non-screening colorectal cancers: 73% of screen-detected colorectal cancers were stages I and II versus 43% and 40% of non-screening and pre-screening colorectal cancers. Cumulative 5-year mortality rate was significantly lower in screening compared to non-screening or pre-screening colorectal cancers patients (19% versus 37% and 41%, p Conclusions Colorectal cancers were detected at earlier stages in i-FOBT-positive subjects in comparison with non-screening patients; colorectal cancers found at screening had a significantly improved 5-year survival.

A large measles outbreak has been ongoing in Milan and surrounding areas. From 1 March to 30 June 2017, 203 measles cases were laboratory-confirmed (108 sporadic cases and 95 related to 47 clusters). Phylogenetic analysis revealed the co-circulation of two different genotypes, D8 and B3. Both genotypes caused nosocomial clusters in two hospitals. The rapid analysis of epidemiological and phylogenetic data allowed effective surveillance and tracking of transmission pathways.

Increased participation in cancer screening programs is undoubtedly a primary objective in Public Health. The Green and Kreuter model, structured in an Access program, was presented to the Regional Coordinators for cancer screening during specific training events. This survey was carried out to verify their appreciation of the model and whether those who participated in the project intended to use the program.

Cross-sector, life-course, and setting approaches are identified in the 2015-2018 Regional Prevention Plan (PRP) of Lombardy Region (Northern Italy) as valuable strategies to ensure the efficacy and sustainable prevention of the non-communicable disease (NCDs). The involvement of non-health sectors in health promotion activities represents a suitable strategy to affect on social, economic, and political determinants and to change environmental factors that could cause NCDs. A dialogue among communities, urban planning, and prevention know-how is a prerequisite to develop a system of policies suitable to promote healthy lifestyle in general and, specifically, active lifestyles. The 2015-2018 Lombardy PRP pursues its aims of health promotion and behavioural risk factors for NCDs prevention through programmes that implement their own setting networks (Health Promoting Schools - SPS; Workplace Health Promotion - WHP) and develop new networks. Sedentary lifestyle prevention and active lifestyle promotion are performed through the approach promoted by the Healthy Cities Programme (WHO), encouraging two main processes: 1. creating integrated capacity-building among health and social prevention services, academic research, and local stakeholders on different urban planning and design issues; 2. promoting community empowerment through active citizens participation. Through this process, Lombardy Region aims to orient its services developing evidence-based programmes and enhancing advocacy and mediating capacity skills in order to create a profitable partnership with non-health sectors. This paper reports the main impact data: 26,000 children that reach school by foot thanks to walking buses, 57% of 145 companies joining WHP are involved in promoting physical activity, 18,891 citizens who attend local walking groups.

Background The use of e-learning, defined as any educational intervention mediated electronically via the Internet, has steadily increased among health professionals worldwide. Several studies have attempted to measure the effects of e-learning in medical practice, which has often been associated with large positive effects when compared to no intervention and with small positive effects when compared with traditional learning (without access to e-learning). However, results are not conclusive. Objectives To assess the effects of e-learning programmes versus traditional learning in licensed health professionals for improving patient outcomes or health professionals' behaviours, skills and knowledge. Search methods We searched CENTRAL, MEDLINE, Embase, five other databases and three trial registers up to July 2016, without any restrictions based on language or status of publication. We examined the reference lists of the included studies and other relevant reviews. If necessary, we contacted the study authors to collect additional information on studies. Selection criteria Randomised trials assessing the effectiveness of e-learning versus traditional learning for health professionals. We excluded non-randomised trials and trials involving undergraduate health professionals. Data collection and analysis Two authors independently selected studies, extracted data and assessed risk of bias. We graded the certainty of evidence for each outcome using the GRADE approach and standardised the outcome effects using relative risks (risk ratio (RR) or odds ratio (OR)) or standardised mean difference (SMD) when possible. Main results We included 16 randomised trials involving 5679 licensed health professionals (4759 mixed health professionals, 587 nurses, 300 doctors and 33 childcare health consultants).When compared with traditional learning at 12-month follow-up, low-certainty evidence suggests that e-learning may make little or no difference for the following patient outcomes: the proportion of patients with low-density lipoprotein (LDL) cholesterol of less than 100 mg/dL (adjusted difference 4.0%, 95% confidence interval (CI) -0.3 to 7.9, N = 6399 patients, 1 study) and the proportion with glycated haemoglobin level of less than 8% (adjusted difference 4.6%, 95% CI -1.5 to 9.8, 3114 patients, 1 study). At 3- to 12-month follow-up, low-certainty evidence indicates that e-learning may make little or no difference on the following behaviours in health professionals: screening for dyslipidaemia (OR 0.90, 95% CI 0.77 to 1.06, 6027 patients, 2 studies) and treatment for dyslipidaemia (OR 1.15, 95% CI 0.89 to 1.48, 5491 patients, 2 studies). It is uncertain whether e-learning improves or reduces health professionals' skills (2912 health professionals; 6 studies; very low-certainty evidence), and it may make little or no difference in health professionals' knowledge (3236 participants; 11 studies; low-certainty evidence).Due to the paucity of studies and data, we were unable to explore differences in effects across different subgroups. Owing to poor reporting, we were unable to collect sufficient information to complete a meaningful 'Risk of bias' assessment for most of the quality criteria. We evaluated the risk of bias as unclear for most studies, but we classified the largest trial as being at low risk of bias. Missing data represented a potential source of bias in several studies. Authors' conclusions When compared to traditional learning, e-learning may make little or no difference in patient outcomes or health professionals' behaviours, skills or knowledge. Even if e-learning could be more successful than traditional learning in particular medical education settings, general claims of it as inherently more effective than traditional learning may be misleading.

We evaluated SARS-CoV-2 RNA and neutralising antibodies in blood donors (BD) residing in the Lodi Red Zone, Italy. Of 390 BDs recruited after 20 February 2020 − when the first COVID-19 case in Lombardy was identified, 91 (23%) aged 19–70 years were antibody positive. Viral RNA was detected in an additional 17 (4.3%) BDs, yielding ca 28% (108/390) with evidence of virus exposure. Five stored samples collected as early as 12 February were seropositive.