[Reduction of adverse outcome due to COVID-19 infection in a high-risk population: evaluation of an informative intervention through active call by General Practitioners]. / Riduzione degli outcome sfavorevoli dovuti all'infezione da COVID-19 su una popolazione ad alto rischio: valutazione di un intervento informativo mediante chiamata attiva da parte dei medici di medicina generale.

BACKGROUND: currently, individuals at risk of adverse outcomes for COVID-19 can access to vaccination and pharmacological interventions. But, during the first epidemic wave, there were no treatments or therapeutic strategies available to reduce adverse outcomes in patients at risk. OBJECTIVES: to assess the impact of an intervention at 15-month follow-up developed by the Agency for Health Protection of the Metropolitan Area of Milan (ATS Milan) based on telephone triage and consultation by the General Practitioners (GPs) for patient with high-risk for adverse outcomes. DESIGN: intervention on population. SETTING AND PARTICIPANTS: a total of 127,292 patients in the ATS aged ≥70 years and with comorbidities associated with an increased risk of dying from COVID-19 infection were identified. Using a specific information system, patients were assigned to their GPs for telephone triage and consultation. GPs inform them about the risks of the disease, non-pharmacological prevention measures, and precautions in contacts with family members and other persons. No specific clinical intervention was carried out, only an information/training intervention was performed. MAIN OUTCOME MEASURES: by the end of May 2020, 48.613 patients had been contacted and 78.679 had not been contacted. Hazard Ratios (HRs) of infection hospitalisation and death at 3 and 15 months were estimated using Cox regression models adjusted by confounder. RESULTS: no differences in gender, age class distribution, prevalence of specific diseases, and Charlson Index were found between the two groups (treated such as called patients and not called). Called patients had a higher propensity for influenza and antipneumococcal vaccination and have more comorbidities and greater access to pharmacological therapies. Non-called patients have a greater risk for COVID-19 infection: HR was 3.88 (95%CI 3.48-4.33) at 3 months and 1.28 (95%CI 1.23-1.33) at 15 months; for COVID-19 hospitalization HR was 2.66 (95%CI 2.39-2,95) at 3 months and 1.31 (95%CI 1.25-1.37) at 15 months; for overall mortality HR was 2,52 (95%CI 2.35-2:72) at 3 months and 1.23 (95%CI 1.19-1.27) at 15 months. CONCLUSIONS: the results of this study show a reduction in hospitalization and deaths and support, in case of pandemic events, the implementation of new care strategies based on adapted stratification systems in order to protect the population's health. This study presents some limits: it is not randomized; a selection bias is present (called patients were those most in contact with the GPs); the intervention is indication-based (on march 2020, the actual benefit of protection and distancing for high-risk groups was unclear), and the adjustment is not able to fully control for confounding. However, this study points out the importance to develop information systems and improve methods to best protect the health of the population in setting of territorial epidemiology.

Boosters and time from the last anti-COVID-19 vaccine dose: lead public health choices by real-time epidemiological assessment.

BACKGROUND: the levels of anti-SARS-CoV-2 antibodies after the second vaccine dose decline in the following months; the administration of an additional vaccine dose (booster) is able to restore the immune system in the short period significantly reducing the risk of a severe disease. In the winter of 2021, a new particularly infectious variant caused the urgent need to increase the coverage of the booster dose. OBJECTIVES: to present, using real data, an evaluation of the efficacy of the booster dose in reducing the severe disease of SARS-CoV-2 infection in terms of hospital admissions, intensive care and death from all causes. DESIGN: descriptive study of vaccine adherence; associative study of the factors linked with adherence of vaccination and COVID-19 symptoms; associative study of vaccine effectiveness against hospital admission and mortality. SETTING AND PARTICIPANTS: population-based study in the Milan and Lodi provinces (Lombardy Region, Northern Italy) with subjects aged >=19 years alive at 01.10.2021, not residing in a nursery home, followed up to 31.12.2021. MAIN OUTCOME MEASURES: COVID-19 symptoms, hospitalization for COVID-19, intensive care hospitalization, and all-cause mortality in the period 01.10.2021-31.12.2021. RESULTS: the cohort included 2,936,193 patients at 01.10.2021: at the end of the follow-up period (31.12.2021), 378,616 (12.9%) had no vaccine, 128,879 (4.3%) had only 1 dose, 412,227 (14.0%) had a 2nd dose given since less than 4 months, 725. 806 (25%) had a 2nd dose given since 4-7 months, 74,152 (2.5%) had a 2nd dose given since 7+ months, 62,614 (2.1%) had a 2nd dose and have had the disease, and 1,153,899 (39.3%) received the booster. In the study period (01.10.2021-31.12.2021), characterized by a very high prevalence of the omicron variant, 121,620 cases (antigenic/molecular buffer positive), 3,661 hospitalizations for COVID-19, 162 ICU hospitalizations, and 7,508 deaths from all causes were identified. Compared to unvaccinated people, subjects who had the booster dose had half the risk of being symptomatic, in particular for asthenia, muscle pain, and dyspnoea which are the most commons COVID-19 symptoms. In comparison with the subjects who had the booster dose, the unvaccinated had a 10-fold risk of hospitalization for COVID-19, a 9-fold risk of intensive care, and a 3-fold risk of dying. CONCLUSIONS: this work highlights the vaccination efficacy in reducing serious adverse events for those who undergo the booster and the need to implement specific engagement policies to bring to a booster those who had taken the second dose since the longest time.

Evaluation of the anti-COVID-19 vaccination campaign in the Metropolitan Area of Milan (Lombardy Region, Northern Italy).

OBJECTIVES: to present an evaluation of the campaign for vaccination against COVID-19 in the territory covered by the Agency for Health Protection of the Metropolitan Area of Milan from 01.01.2021 to 30.09.2021. DESIGN: descriptive study of vaccine adherence; predictive study of the factors associated with vaccine adherence, efficacy of vaccination in terms of hospitalization and mortality, and factors that increase the risk of hospital admission following full vaccination. SETTING AND PARTICIPANTS: population-based study with subjects aged >18 years eligible for vaccination (N. 2,981,997). An information system obtained by integrating various administrative healthcare sources made it possible to analyse socioeconomic characteristics, COVID-19 related hospitalizations, and general mortality in subjects eligible for vaccination. MAIN OUTCOME MEASURES: full vaccination (2 doses); COVID-19-related hospitalizations, COVID-19-related hospitalizations occurring more than 15 days after the second dose, general mortality. RESULTS: in the first nine months of the vaccination campaign, 74.7% of the subjects (N. 2,228,915) was fully vaccinated, whereas 15.6% (N. 465,829) did not even receive one dose. Women have a lower probability of getting vaccinated than men; the 50-59 years and 70+ years age groups emerge as the most problematic to reach, while the younger one (<40) is the most adherent. A social gradient emerged, with residents of more disadvantaged areas progressively less incline to get vaccinated than those living in more affluent areas. Adherence is greater in Italian citizenship and is likely to increase with an increase in the number of chronic conditions. Hospitalizations amounted to 1.22% (N. 5,672) in the unvaccinated population compared to 0.05% (N. 1,013) in the vaccinated population; general mortality was 4.51% (N. 15,198) in the unvaccinated population against 0.32% (N. 8.733) in the vaccinated population. Sociodemographic factors and the presence of previous health conditions are important predictors of hospitalization outcomes even within the fully vaccinated population. Specifically, the highest hazard ratios are found in subjects with heart failure (HR 2.15; 95%CI 1.83-2.53), in immunocompromised patients (HR 2.02; 95%CI 1.52-2.69), and in transplant recipients (HR 1.92; 95%CI 1.10-3.33). CONCLUSIONS: vaccination campaign adherence is affected by the sociodemographic characteristics of the population and is a determining factor in preventing hospitalizations for COVID-19 and death. The persistent higher risk of hospitalization in chronic subjects following the second dose emphasizes the need to direct booster doses to the more vulnerable. Information systems proved to be effective monitoring tools in the absence of specific trials.

Strategy to identify priority groups for COVID-19 vaccination: A population based cohort study.

BACKGROUND: Evidence from COVID-19 outbreak shows that individuals with specific chronic diseases are at higher risk of severe prognosis after infection. Public health authorities are developing vaccination programmes with priorities that minimize the risk of mortality and severe events in individuals and communities. We propose an evidence-based strategy that targets the frailest subjects whose timely vaccination is likely to minimize future deaths and preserve the resilience of the health service by preventing infections. METHODS: The cohort includes 146,087 cases with COVID-19 diagnosed in 2020 in Milan (3.49 million inhabitants). Individual level data on 42 chronic diseases and vital status updated as of January 21, 2021, were available in administrative data. Analyses were performed in three sub-cohorts of age (16-64, 65-79 and 80+ years) and comorbidities affecting mortality were selected by means of LASSO cross-validated conditional logistic regression. Simplified models based on previous results identified high-risk categories worth targeting with highest priority. Results adjusted by age and gender, were reported in terms of odds ratios and 95%CI. RESULTS: The final models include as predictors of mortality (7,667 deaths, 5.2%) 10, 12, and 5 chronic diseases, respectively. The older age categories shared, as risk factors, chronic renal failure, chronic heart failure, cerebrovascular disease, Parkinson disease and psychiatric diseases. In the younger age category, predictors included neoplasm, organ transplantation and psychiatric conditions. Results were consistent with those obtained on mortality at 60 days from diagnosis (6,968 deaths). CONCLUSION: This approach defines a two-level stratification for priorities in the vaccination that can easily be applied by health authorities, eventually adapted to local results in terms of number and types of comorbidities, and rapidly updated with current data. After the early phase of vaccination, data on effectiveness and safety will give the opportunity to revise prioritization and discuss the future approach in the remaining population.

Trend of pneumonia diagnosis in emergency departments as a COVID-19 surveillance system: a time series study.

OBJECTIVE: In Italy, the first diagnosis of COVID-19 was confirmed on 20 February 2020 in the Lombardy region. Given the rapid spread of the infection in the population, it was suggested that in Europe, and specifically in Italy, the virus had already been present in the last months of 2019. In this paper, we aim to evaluate the hypothesis on the early presence of the virus in Italy by analysing data on trends of access to emergency departments (EDs) of subjects with a diagnosis of pneumonia during the 2015-2020 period. DESIGN: Time series cohort study. SETTING: We collected data on visits due to pneumonia between 1 October 2015 and 31 May 2020 in all EDs of the Agency for Health Protection of Milan (ATS of Milan). Trend in the winter of 2019-2020 was compared with those in the previous 4 years in order to identify unexpected signals potentially associated with the occurrence of the pandemic. Aggregated data were analysed using a Poisson regression model adjusted for seasonality and influenza outbreaks. PRIMARY OUTCOME MEASURES : Daily pneumonia-related visits in EDs. RESULTS : In the studied period, we observed 105 651 pneumonia-related ED visits. Compared with the expected, a lower occurrence was observed in January 2020, while an excess of pneumonia visits started in the province of Lodi on 21 February 2020, and almost 10 days later was observed in the remaining territory of the ATS of Milan. Overall, the peak in excess was found on 17 March 2020 (369 excess visits compared with previous years, 95% CI 353 to 383) and ended in May 2020, the administrative end of the Italian lockdown. CONCLUSIONS : An early warning system based on routinely collected administrative data could be a feasible and low-cost strategy to monitor the actual situation of the virus spread both at local and national levels.

Assessment of the Overall Mortality during the COVID-19 Outbreak in the Provinces of Milan and Lodi (Lombardy Region, Northern Italy).

OBJECTIVES: to describe the overall mortality increase in the provinces of Milan and Lodi - area covered by the Agency for Health Protection of Milan - during the COVID-19 epidemic in the first four months of 2020, compare it with the same time period in the years 2016-2019, and evaluate to what extent the mortality can be directly attributed to the outbreak. DESIGN: cohort study. SETTING AND PARTICIPANTS: using a new information system developed during the pandemic, we gathered data on the number of daily deaths in the population residing in the provinces of Milan and Lodi by Local Health Unit (ASST) and age groups. To describe the case fatality of COVID-19, we performed a record linkage with a database specially constructed during the epidemic to identify deaths that occurred in confirmed cases. MAIN OUTCOME MEASURES: mortality and excess mortality were analysed by comparing the number of observed deaths in the first 4 months of 2020 with the average deaths of the years 2016-2019 in the same calendar period and with expected deaths, estimated using a Poisson model. Furthermore, a measure of relative risk was calculated as observed/expected ratio with a 95% confidence interval. RESULTS: the increase in mortality for all causes occurring in the study population in the first 4 months of 2020 was 48.8%, 30.8% for ages between 60 and 69, 43.9% for ages between 70 and 79, and 56.7% for subjects above 80 years of age. Focusing on the epidemic period, from 1 March to 30 April, the excess is quantifiable as more than 2-fold and mainly concerns the population over 60 years of age. The excess mortality was observed in all local health units (ASSTs). The highest increments were in the province of Lodi and the North-East of Milan (ASST Nord). In the ASSTs of Lodi and Melegnano-Martesana the mortality excess was detectable from March 15th, while for the other ASSTs the increase began in the first week of April. CONCLUSIONS: evaluation of overall mortality in the provinces of Milan and Lodi during the first wave of the Covid-19 epidemic showed a significant excess compared to the first 4 months of the years 2016-2019, mainly in the population over 60 years of age. However, this excess cannot be completely attributed directly to COVID-19 itself. This phenomenon was more intense in the Lodi ASST, with daily deaths up to 5 times higher than expected.

Describing the epidemic trends of COVID-19 in the area covered by Agency for Health Protection of the Metropolitan Area of Milan.

OBJECTIVES: to describe the epidemic trends of COVID-19 over time and by area in the territory covered by Milan's Agency for Health Protection (ATS-MI) from February to May 2020. DESIGN: descriptive study of COVID-19 cases. SETTING AND PARTICIPANTS: a new information system was developed to record COVID-19 cases with positive nasopharyngeal swab. Patients resident in the area covered by ATS-MI with symptom onset between February and May 2020 were selected. Different epidemic periods were considered based on the timeline of the various regional and national containment measures. MAIN OUTCOME MEASURES: case fatality ratios, incidence rates, and reproduction number by epidemic period and sub-area of ATS-MI. RESULTS: a total of 27,017 swab-positive COVID-19 cases were included. Mean age was 65 years and males were 45%. Incidence in the ATS-MI area was 776 per 100,000 population. The number of deaths was 4,660, the crude case fatality ratio was 17.3%, higher in males (21.2%) than in females (14.0%). The estimated reproduction number registered its peak (3.0) in the early stages of the epidemic and subsequently decreased. Territorial differences were observed in the epidemic spread, with a higher incidence in the Lodi area. CONCLUSIONS: estimated incidence and case fatality ratios were higher than national estimates for Italy. Each ATS-MI area had different epidemic spread patterns.