The influence of meteorological factors on COVID-19 spread in Italy during the first and second wave.

The relation between meteorological factors and COVID-19 spread remains uncertain, particularly with regard to the role of temperature, relative humidity and solar ultraviolet (UV) radiation. To assess this relation, we investigated disease spread within Italy during 2020. The pandemic had a large and early impact in Italy, and during 2020 the effects of vaccination and viral variants had not yet complicated the dynamics. We used non-linear, spline-based Poisson regression of modeled temperature, UV and relative humidity, adjusting for mobility patterns and additional confounders, to estimate daily rates of COVID-19 new cases, hospital and intensive care unit admissions, and deaths during the two waves of the pandemic in Italy during 2020. We found little association between relative humidity and COVID-19 endpoints in both waves, whereas UV radiation above 40 kJ/m2 showed a weak inverse association with hospital and ICU admissions in the first wave, and a stronger relation with all COVID-19 endpoints in the second wave. Temperature above 283 K (10 °C/50 °F) showed a strong non-linear negative relation with COVID-19 endpoints, with inconsistent relations below this cutpoint in the two waves. Given the biological plausibility of a relation between temperature and COVID-19, these data add support to the proposition that temperature above 283 K, and possibly high levels of solar UV radiation, reduced COVID-19 spread.

[Integrated Surveillance in Italy: outputs and related activities]. / La sorveglianza integrata COVID-19 in Italia: output e attività correlate.

OBJECTIVES: to describe the integrated surveillance system of COVID-19 in Italy, to illustrate the outputs used to return epidemiological information on the spread of the epidemic to the competent public health bodies and to the Italian population, and to describe how the surveillance data contributes to the ongoing weekly regional monitoring and risk assessment system. METHODS: the COVID-19 integrated surveillance system is the result of a close and continuous collaboration between the Italian National Institute of Health (ISS), the Italian Ministry of Health, and the regional and local health authorities. Through a web platform, it collects individual data of laboratory confirmed cases of SARS-CoV-2 infection and gathers information on their residence, laboratory diagnosis, hospitalisation, clinical status, risk factors, and outcome. Results, for different levels of aggregation and risk categories, are published daily and weekly on the ISS website, and made available to national and regional public health authorities; these results contribute one of the information sources of the regional monitoring and risk assessment system. RESULTS: the COVID-19 integrated surveillance system monitors the space-time distribution of cases and their characteristics. Indicators used in the weekly regional monitoring and risk assessment system include process indicators on completeness and results indicators on weekly trends of newly diagnosed cases per Region. CONCLUSIONS: the outputs of the integrated surveillance system for COVID-19 provide timely information to health authorities and to the general population on the evolution of the epidemic in Italy. They also contribute to the continuous re-assessment of risk related to transmission and impact of the epidemic thus contributing to the management of COVID-19 in Italy.

The value of public-private collaborative real-world evidence platforms to monitor vaccine performance post authorization: DRIVE - a European initiative.

INTRODUCTION: Fighting pandemics requires an established infrastructure for pandemic preparedness, with existing, sustainable platforms ready to be activated. This includes platforms for disease surveillance, virus circulation, and vaccine performance monitoring based on Real-World data, to complement clinical trial evidence. AREAS COVERED: Because of its complexity, this can best be done by combining efforts between public and private sectors, developing a multi-stakeholder approach. Public-Private-Partnerships increasingly play a critical role in combating infectious diseases but are still looked at with hesitancy. The Development of Robust and Innovative Vaccine Effectiveness (DRIVE) project, which established a platform for measuring brand-specific influenza vaccine effectiveness in Europe, exemplifies how to build a collaborative platform with transparent governance, state-of-the-art methodology, and a large network of participating sites. Lessons learned from DRIVE have been cardinal to set up COVIDRIVE, a platform for brand-specific COVID-19 vaccine effectiveness monitoring. EXPERT OPINION: The DRIVE partners propose that a debate on the benefits of Public-Private-Partnership-generated real-world evidence for vaccine effectiveness monitoring should be pursued to clarify roles and responsibilities, set up expectations, and decide the future environment for vaccine monitoring in Europe. In parallel, the driving factors behind PPP hesitancy should be studied.

COVID-19 treatments approved in the European Union and clinical recommendations for the management of non-hospitalized and hospitalized patients.

BACKGROUND: The COVID-19 pandemic caused by SARS-CoV-2 continues to have a serious impact on public health worldwide. Most patients develop mild to moderate symptoms and recover without requiring special treatment, but up to 15% develop severe (dyspnea, hypoxia, lung involvement) or critical symptoms (respiratory failure, septic shock, thromboembolism, multiorgan dysfunction). Although vaccination is having a substantial impact on case numbers, hospitalizations and deaths, there remains a need for new effective treatments against COVID-19. METHODS: This short review aims at reporting on current therapeutics against SARS-CoV-2 focussing on new drugs authorized in the European Union, describing the treatment strategies and the clinical recommendations for the management of hospitalized and non-hospitalized COVID-19 patients based on the available guidelines for clinical practice. RESULTS: New effective drugs, like antiviral medications and monoclonal antibodies, have been developed as therapy against severe and life-threatening disease courses. Specifically, the European Medicines Agency has authorized two antiviral medicines (nirmatrelvir/ritonavir, remdesivir), supporting also early use of molnupiravir before marketing authorization, and four monoclonal antibodies (regdanvimab, casirivimab/imdevimab, sotrovimab, tixagevimab/cilgavimab). In addition, three drugs (anakinra, tocilizumab, baricitinib) previously authorized for the treatment of rheumatoid arthritis are also available to treat COVID-19. CONCLUSIONS: Recommendations and guidelines for clinical practice should be regularly updated as further evidence becomes available in favour or against specific interventions, to inform all stakeholders involved in the health care of COVID-19 patients both in the community and in the hospital setting, aiming at improving the quality of care and therefore the patient outcome.KEY MESSAGESCOVID-19 has been recognized as a multisystem disorder affecting many body systems; this wide spectrum of clinical patterns made difficult an appropriate choice of treatments able to counteract severe symptoms of the disease and alleviate the burden on the healthcare system.New effective drugs, like antiviral medications and monoclonal antibodies, have been developed and approved by the European Medicines Agency as therapy against severe and life-threatening disease courses.Recommendations and guidelines should be regularly updated as further evidence becomes available in favour or against specific interventions aiming at improving the quality of care and therefore the patient outcome.

Substantial impact of mobility restrictions on reducing COVID-19 incidence in Italy in 2020.

BACKGROUND: Italy was the first country after China to be severely affected by the COVID-19 pandemic, in early 2020. The country responded swiftly to the outbreak with a nationwide two-step lockdown, the first one light and the second one tight. By analyzing 2020 national mobile phone movements, we assessed how lockdown compliance influenced its efficacy. METHODS: We measured individual mobility during the first epidemic wave with mobile phone movements tracked through carrier networks, and related this mobility to daily new SARS-CoV-2 infections, hospital admissions, intensive care admissions and deaths attributed to COVID-19, taking into account reason for travel (work-related or not) and the means of transport. RESULTS: The tight lockdown resulted in an 82% reduction in mobility for the entire country and was effective in swiftly curbing the outbreak as indicated by a shorter time-to-peak of all health outcomes, particularly for provinces with the highest mobility reductions and the most intense COVID-19 spread. Reduction of work-related mobility was accompanied by a nearly linear benefit in outbreak containment; work-unrelated movements had a similar effect only for restrictions exceeding 50%. Reduction in mobility by car and by airplane was nearly linearly associated with a decrease in most COVID-19 health outcomes, while for train travel reductions exceeding 55% had no additional beneficial effects. The absence of viral variants and vaccine availability during the study period eliminated confounding from these two sources. CONCLUSIONS: Adherence to the COVID-19 tight lockdown during the first wave in Italy was high and effective in curtailing the outbreak. Any work-related mobility reduction was effective, but only high reductions in work-unrelated mobility restrictions were effective. For train travel, there was a threshold above which no further benefit occurred. These findings could be particular to the spread of SARS-CoV-2, but might also apply to other communicable infections with comparable transmission dynamics.

Epidemiological characteristics of COVID-19 cases in non-Italian nationals notified to the Italian surveillance system.

BACKGROUND: International literature suggests that disadvantaged groups are at higher risk of morbidity and mortality from SARS-CoV-2 infection due to poorer living/working conditions and barriers to healthcare access. Yet, to date, there is no evidence of this disproportionate impact on non-national individuals, including economic migrants, short-term travellers and refugees. METHODS: We analyzed data from the Italian surveillance system of all COVID-19 laboratory-confirmed cases tested positive from the beginning of the outbreak (20th of February) to the 19th of July 2020. We used multilevel negative-binomial regression models to compare the case fatality and the rate of admission to hospital and intensive care unit (ICU) between Italian and non-Italian nationals. The analysis was adjusted for differences in demographic characteristics, pre-existing comorbidities, and period of diagnosis. RESULTS: We analyzed 213 180 COVID-19 cases, including 15 974 (7.5%) non-Italian nationals. We found that, compared to Italian cases, non-Italian cases were diagnosed at a later date and were more likely to be hospitalized {[adjusted rate ratio (ARR)=1.39, 95% confidence interval (CI): 1.33-1.44]} and admitted to ICU (ARR=1.19, 95% CI: 1.07-1.32), with differences being more pronounced in those coming from countries with lower human development index (HDI). We also observed an increased risk of death in non-Italian cases from low-HDI countries (ARR=1.32, 95% CI: 1.01-1.75). CONCLUSIONS: A delayed diagnosis in non-Italian cases could explain their worse outcomes compared to Italian cases. Ensuring early access to diagnosis and treatment to non-Italians could facilitate the control of SARS-CoV-2 transmission and improve health outcomes in all people living in Italy, regardless of nationality.

HLA and AB0 Polymorphisms May Influence SARS-CoV-2 Infection and COVID-19 Severity.

BACKGROUND: SARS-CoV-2 infection is heterogeneous in clinical presentation and disease evolution. To investigate whether immune response to the virus can be influenced by genetic factors, we compared HLA and AB0 frequencies in organ transplant recipients and waitlisted patients according to presence or absence of SARS-CoV-2 infection. METHODS: A retrospective analysis was performed on an Italian cohort composed by transplanted and waitlisted patients in a January 2002 to March 2020 time frame. Data from this cohort were merged with the Italian registry of COVID+ subjects, evaluating infection status of transplanted and waitlisted patients. A total of 56 304 cases were studied with the aim of comparing HLA and AB0 frequencies according to the presence (n = 265, COVID+) or absence (n = 56 039, COVID-) of SARS-CoV-2 infection. RESULTS: The cumulative incidence rate of COVID-19 was 0.112% in the Italian population and 0.462% in waitlisted/transplanted patients (OR = 4.2; 95% CI, 3.7-4.7; P < 0.0001). HLA-DRB1*08 was more frequent in COVID+ (9.7% and 5.2%: OR = 1.9, 95% CI, 1.2-3.1; P = 0.003; Pc = 0.036). In COVID+ patients, HLA-DRB1*08 was correlated to mortality (6.9% in living versus 17.5% in deceased: OR = 2.9, 95% CI, 1.15-7.21; P = 0.023). Peptide binding prediction analyses showed that these DRB1*08 alleles were unable to bind any of the viral peptides with high affinity. Finally, blood group A was more frequent in COVID+ (45.5%) than COVID- patients (39.0%; OR = 1.3; 95% CI, 1.02-1.66; P = 0.03). CONCLUSIONS: Although preliminary, these results suggest that HLA antigens may influence SARS-CoV-2 infection and clinical evolution of COVID-19 and confirm that blood group A individuals are at greater risk of infection, providing clues on the spread of the disease and indications about infection prognosis and vaccination strategies.

Epidemiological characteristics of COVID-19 cases and estimates of the reproductive numbers 1 month into the epidemic, Italy, 28 January to 31 March 2020.

BackgroundOn 20 February 2020, a locally acquired coronavirus disease (COVID-19) case was detected in Lombardy, Italy. This was the first signal of ongoing transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the country. The number of cases in Italy increased rapidly and the country became the first in Europe to experience a SARS-CoV-2 outbreak.AimOur aim was to describe the epidemiology and transmission dynamics of the first COVID-19 cases in Italy amid ongoing control measures.MethodsWe analysed all RT-PCR-confirmed COVID-19 cases reported to the national integrated surveillance system until 31 March 2020. We provide a descriptive epidemiological summary and estimate the basic and net reproductive numbers by region.ResultsOf the 98,716 cases of COVID-19 analysed, 9,512 were healthcare workers. Of the 10,943 reported COVID-19-associated deaths (crude case fatality ratio: 11.1%) 49.5% occurred in cases older than 80 years. Male sex and age were independent risk factors for COVID-19 death. Estimates of R0 varied between 2.50 (95% confidence interval (CI): 2.18-2.83) in Tuscany and 3.00 (95% CI: 2.68-3.33) in Lazio. The net reproduction number Rt in northern regions started decreasing immediately after the first detection.ConclusionThe COVID-19 outbreak in Italy showed a clustering onset similar to the one in Wuhan, China. R0 at 2.96 in Lombardy combined with delayed detection explains the high case load and rapid geographical spread. Overall, Rt in Italian regions showed early signs of decrease, with large diversity in incidence, supporting the importance of combined non-pharmacological control measures.

Impact of a Nationwide Lockdown on SARS-CoV-2 Transmissibility, Italy.

On March 11, 2020, Italy imposed a national lockdown to curtail the spread of severe acute respiratory syndrome coronavirus 2. We estimate that, 14 days after lockdown, the net reproduction number had dropped below 1 and remained stable at ¼0.76 (95% CI 0.67-0.85) in all regions for >3 of the following weeks.

COVID-19 Disease Severity Risk Factors for Pediatric Patients in Italy.

OBJECTIVES: To describe the epidemiological and clinical characteristics of coronavirus disease (COVID-19) pediatric patients aged <18 years in Italy. METHODS: Data from the national case-based surveillance system of confirmed COVID-19 infections until May 8, 2020, were analyzed. Demographic and clinical characteristics of subjects were summarized by age groups (0-1, 2-6, 7-12, 13-18 years), and risk factors for disease severity were evaluated by using a multilevel (clustered by region) multivariable logistic regression model. Furthermore, a comparison among children, adults, and elderly was performed. RESULTS: Pediatric patients (3836) accounted for 1.8% of total infections (216 305); the median age was 11 years, 51.4% were male, 13.3% were hospitalized, and 5.4% presented underlying medical conditions. The disease was mild in 32.4% of cases and severe in 4.3%, particularly in children ≤6 years old (10.8%); among 511 hospitalized patients, 3.5% were admitted in ICU, and 4 deaths occurred. Lower risk of disease severity was associated with increasing age and calendar time, whereas a higher risk was associated with preexisting underlying medical conditions (odds ratio = 2.80, 95% confidence interval = 1.74-4.48). Hospitalization rate, admission in ICU, disease severity, and days from symptoms onset to recovery significantly increased with age among children, adults and elderly. CONCLUSIONS: Data suggest that pediatric cases of COVID-19 are less severe than adults; however, age ≤1 year and the presence of underlying conditions represent severity risk factors. A better understanding of the infection in children may give important insights into disease pathogenesis, health care practices, and public health policies.