[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.

Algorithm for Individual Prediction of COVID-19-Related Hospitalization Based on Symptoms: Development and Implementation Study.

BACKGROUND: The COVID-19 pandemic has placed a huge strain on the health care system globally. The metropolitan area of Milan, Italy, was one of the regions most impacted by the COVID-19 pandemic worldwide. Risk prediction models developed by combining administrative databases and basic clinical data are needed to stratify individual patient risk for public health purposes. OBJECTIVE: This study aims to develop a stratification tool aimed at improving COVID-19 patient management and health care organization. METHODS: A predictive algorithm was developed and applied to 36,834 patients with COVID-19 in Italy between March 8 and the October 9, 2020, in order to foresee their risk of hospitalization. Exposures considered were age, sex, comorbidities, and symptoms associated with COVID-19 (eg, vomiting, cough, fever, diarrhea, myalgia, asthenia, headache, anosmia, ageusia, and dyspnea). The outcome was hospitalizations and emergency department admissions for COVID-19. Discrimination and calibration of the model were also assessed. RESULTS: The predictive model showed a good fit for predicting COVID-19 hospitalization (C-index 0.79) and a good overall prediction accuracy (Brier score 0.14). The model was well calibrated (intercept -0.0028, slope 0.9970). Based on these results, 118,804 patients diagnosed with COVID-19 from October 25 to December 11, 2020, were stratified into low, medium, and high risk for COVID-19 severity. Among the overall study population, 67,030 (56.42%) were classified as low-risk patients; 43,886 (36.94%), as medium-risk patients; and 7888 (6.64%), as high-risk patients. In all, 89.37% (106,179/118,804) of the overall study population was being assisted at home, 9% (10,695/118,804) was hospitalized, and 1.62% (1930/118,804) died. Among those assisted at home, most people (63,983/106,179, 60.26%) were classified as low risk, whereas only 3.63% (3858/106,179) were classified at high risk. According to ordinal logistic regression, the odds ratio (OR) of being hospitalized or dead was 5.0 (95% CI 4.6-5.4) among high-risk patients and 2.7 (95% CI 2.6-2.9) among medium-risk patients, as compared to low-risk patients. CONCLUSIONS: A simple monitoring system, based on primary care data sets linked to COVID-19 testing results, hospital admissions data, and death records may assist in the proper planning and allocation of patients and resources during the ongoing COVID-19 pandemic.

Strategy to reduce adverse health outcomes in subjects highly vulnerable to COVID-19: results from a population-based study in Northern Italy.

OBJECTIVES: This study describes a new strategy to reduce the impact of COVID-19 on the elderly and other clinically vulnerable subjects, where general practitioners (GPs) play an active role in managing high-risk patients, reducing adverse health outcomes. DESIGN: Retrospective cohort study. SETTING: Population-based study including subjects resident in the province of Milan and Lodi. PARTICIPANTS: 127 735 residents older than 70 years, with specific chronic conditions. INTERVENTIONS: We developed a predictive algorithm for overall mortality risk based on demographic and clinical characteristics. All residents older than 70 years were classified as being at low or high risk of death from COVID-19 infection according to the algorithm. The high-risk group was assigned to their GPs for telephone triage and consultation. The high-risk cohort was divided into two groups based on GP intervention: patients who were not contacted and patients who were contacted by their GPs. OUTCOME MEASURES: Overall mortality, COVID-19 morbidity and hospitalisation. RESULTS: Patients with increased risk of death from COVID-19 were 127 735; 495 669 patients were not at high risk and were not included in the intervention. Out of the high-risk subjects, 79 110 were included but not contacted by their GPs, while 48 625 high-risk subjects were included and contacted. Overall mortality, morbidity and hospitalisation was higher in high-risk patients compared with low-risk populations. High-risk patients contacted by their GPs had a 50% risk reduction in COVID-19 mortality, and a 70% risk reduction in morbidity and hospitalisation for COVID-19 compared with non-contacted patients. CONCLUSIONS: The study showed that, during the COVID-19 outbreak, involvement of GPs and changes in care management of high-risk groups produced a significant reduction in all adverse health outcomes.

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.