Multimorbidity and SARS-CoV-2-Related Outcomes: Analysis of a Cohort of Italian Patients.

BACKGROUND: Since the outbreak of the COVID-19 pandemic, identifying the main risk factors has been imperative to properly manage the public health challenges that the pandemic exposes, such as organizing effective vaccination campaigns. In addition to gender and age, multimorbidity seems to be 1 of the predisposing factors coming out of many studies investigating the possible causes of increased susceptibility to SARS-CoV-2 infection and adverse outcomes. However, only a few studies conducted have used large samples. OBJECTIVE: The objective is to evaluate the association between multimorbidity, the probability to be tested, susceptibility, and the severity of SARS-CoV-2 infection in the Piedmont population (Northern Italy, about 4 million inhabitants). For this purpose, we considered 5 main outcomes: access to the swab, positivity to SARS-CoV-2, hospitalization, intensive care unit (ICU) admission, and death within 30 days from the first positive swab. METHODS: Data were obtained from different Piedmont health administrative databases. Subjects aged from 45 to 74 years and infections diagnosed from February to May 2020 were considered. Multimorbidity was defined both with the Charlson Comorbidity Index (CCI) and by identifying patients with previous comorbidities, such as diabetes and oncological, cardiovascular, and respiratory diseases. Multivariable logistic regression models (adjusted for age and month of infection and stratified by gender) were performed for each outcome. Analyses were also conducted by separating 2 age groups (45-59 and 60-74 years). RESULTS: Of 1,918,549 subjects, 85,348 (4.4%) performed at least 1 swab, of whom 12,793 (14.9%) tested positive for SARS-CoV-2. Of these 12,793 subjects, 4644 (36.3%) were hospitalized, 1508 (11.8%) were admitted to the ICU, and 749 (5.9%) died within 30 days from the first positive swab. Individuals with a higher CCI had a higher probability of being swabbed but a lower probability of testing positive. We observed the same results when analyzing subjects with previous oncological and cardiovascular diseases. Moreover, especially in the youngest group, we identified a greater risk of being hospitalized and dying. Among comorbidities considered in the study, respiratory diseases seemed to be the most likely to increase the risk of having a positive swab and worse disease outcomes. CONCLUSIONS: Our study shows that patients with multimorbidity, although swabbed more frequently, are less likely to get infected with SARS-CoV-2, probably due to greater attention on protective methods. Moreover, a history of respiratory diseases is a risk factor for a worse prognosis of COVID-19. Nonetheless, whatever comorbidities affect the patients, a strong dose-response effect was observed between an increased CCI score and COVID-19 hospitalization, ICU admission, and death. These results are important in terms of public health because they help in identifying a group of subjects who are more prone to worse SARS-CoV-2 outcomes. This information is important for promoting targeted prevention and developing policies for the prioritization of public health interventions.

Improvements throughout the Three Waves of COVID-19 Pandemic: Results from 4 Million Inhabitants of North-West Italy.

At the very beginning of the European spread of SARS-CoV-2, Piedmont was one of the most affected regions in Italy, with a strong impact on healthcare organizations. In this study, we evaluated the characteristics and outcomes of the COVID-19 patients in an entire region during the first three pandemic waves, identifying similarities and differences in the SARS-CoV-2 epidemic's timeline. We collected the health-administrative data of all the Piedmont COVID-19 patients infected during the first three pandemic waves (1 March 2020-15 April 2020; 15 October 2020-15 December 2020; 1 March 2021-15 April 2021, respectively). We compared differences among the waves in subjects positive for SARS-CoV-2 and in patients admitted to ICU. Overall, 18.621 subjects tested positive during the first wave (405 patients/day), 144.350 (2366.4 patients/day) in the second, and 81.823 (1778.8 patients/day) in the third. In the second and third waves, we observed a reduction in median age, comorbidity burden, mortality in outpatients, inpatients, and patients admitted to ICU, in intubation, invasive ventilation and tracheostomy, and a parallel increase in the use of CPAP. Our study confirmed a trend towards younger and healthier patients over time but also showed an independent effect of the period on mortality and ICU admission. The appearance of new viral variants, the starting of vaccination, and organizational improvements in tracking, outpatients and inpatients management could have influenced these trends.

Characteristics of patients affecting the duration of positivity at SARS-CoV-2: a cohort analysis of the first wave of epidemic in Italy.

OBJECTIVES: to investigate the characteristics of patients affecting the duration of positivity test by RT-PCR in the population of Piedmont, a Region of North-West of Italy. DESIGN: observational cohort study. SETTING AND PARTICIPANTS: from the administrative database of the regional SARS-CoV-2 surveillance system, a cohort of all patients who tested positive by a RT-PCR assay to SARS-CoV-2 occurring from 22.02.2020 to 30.09.2020 in the Piedmont Region (N. 29,292) was obtained. The cohort has been linked to the hospital discharge database and to the vital statistics database. MAIN OUTCOMES MEASURES: outcome of the study was the risk of non negativization, estimated by fitting Generalizing Estimating Equation model (GEE), a longitudinal model which consider for each subject several records collected on fixed time intervals 15, 30, 45 or 60+ days from the first positive test. Negativization was defined as the condition in which two consecutive samples taken from the patient at least 24 hours apart were negative for the presence of SARS-CoV-2. RESULTS: the median duration of positive RT-PCR was 27 days. A higher median of days until positive persistence was observed in people over 80 (34 days, IQR 25-49), female (28 days, IQR 18-40), symptomatic patients (28 days, IQR 19-40), hospitalized people (32 days, IQR 21-44), patients with Charlson's index >0 (34 days, IQR 23-49), patients host of elderly nursing homes (37 days, IQR 25-51). In the GEE multivariable model, the variables associated to the non negativization at all times intervals were: older age (at 15th day: class 65+, OR 2.56, 95%CI 2.39-2.74), female gender (at 15th day: OR 1.12, 95%CI 1.06-1.18), and to be hospitalized for COVID-19 (at 15th day: OR 1.38, 95%CI 1.29-1.48). The presence of comorbidities and of symptoms were associate with the non negativization at 15th day (respectively, class 4+: OR 1.29, 95%CI 1.08-1.56 and symptoms: OR 1.20, 95%CI 1.13-1.27), but not at 45th day. CONCLUSIONS: older age, female gender, presence of comorbidities and severity of disease (proxy hospitalization for COVID-19) were risk factors for non negativization at all times intervals. The presence of symptoms was a risk factors for the non negativization after 2 weeks from the first diagnosis and not at 45th day. Using a longitudinal model for the analysis of the dataset, it is possible to compare the weight of the variables included in the model at different times and correct an overestimation of the attributable risk after the first considered time interval.

The broad spectrum of COVID-like patients initially negative at RT-PCR testing: a cohort study.

BACKGROUND: Patients that arrive in the emergency department (ED) with COVID-19-like syndromes testing negative at the first RT-PCR represent a clinical challenge because of the lack of evidence about their management available in the literature. Our first aim was to quantify the proportion of patients testing negative at the first RT-PCR performed in our Emergency Department (ED) that were confirmed as having COVID-19 at the end of hospitalization by clinical judgment or by any subsequent microbiological testing. Secondly, we wanted to identify which variables that were available in the first assessment (ED variables) would have been useful in predicting patients, who at the end of the hospital stay were confirmed as having COVID-19 (false-negative at the first RT-PCR). METHODS: We retrospectively collected data of 115 negative patients from2020, March 1st to 2020, May 15th. Three experts revised patients' charts collecting information on the whole hospital stay and defining patients as COVID-19 or NOT-COVID-19. We compared ED variables in the two groups by univariate analysis and logistic regression. RESULTS: We classified 66 patients as COVID-19 and identified the other 49 as having a differential diagnosis (NOT-COVID), with a concordance between the three experts of 0.77 (95% confidence interval (95%CI) 0.66- 0.73). Only 15% of patients tested positive to a subsequent RT-PCR test, accounting for 25% of the clinically suspected. Having fever (odds ratio (OR) 3.32, (95%CI 0.97-12.31), p = 0.06), showing a typical pattern at the first lung ultrasound (OR 6.09, (95%CI 0.87-54.65), p = 0.08) or computed tomography scan (OR 4.18, (95%CI 1.11-17.86), p = 0.04) were associated with a higher probability of having COVID-19. CONCLUSIONS: In patients admitted to ED with COVID-19 symptoms and negative RT-PCR a comprehensive clinical evaluation integrated with lung ultrasound and computed tomography could help to detect COVID-19 patients with a false negative RT-PCR result.

Urinary Concentrations of (+)-Catechin and (-)-Epicatechin as Biomarkers of Dietary Intake of Flavan-3-ols in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study.

This study examines the correlation of acute and habitual dietary intake of flavan-3-ol monomers, proanthocyanidins, theaflavins, and their main food sources with the urinary concentrations of (+)-catechin and (-)-epicatechin in the European Prospective Investigation into Cancer and Nutrition study (EPIC). Participants (N = 419, men and women) provided 24-h urine samples and completed a 24-h dietary recall (24-HDR) on the same day. Acute and habitual dietary data were collected using a standardized 24-HDR software and a validated dietary questionnaire, respectively. Intake of flavan-3-ols was estimated using the Phenol-Explorer database. Concentrations of (+)-catechin and (-)-epicatechin in 24-h urine were analyzed using tandem mass spectrometry after enzymatic deconjugation. Simple and partial Spearman's correlations showed that urinary concentrations of (+)-catechin, (-)-epicatechin and their sum were more strongly correlated with acute than with habitual intake of individual and total monomers (acute rpartial = 0.13-0.54, p < 0.05; and habitual rpartial = 0.14-0.28, p < 0.01), proanthocyanidins (acute rpartial = 0.24-0.49, p < 0.001; and habitual rpartial = 0.10-0.15, p < 0.05), theaflavins (acute rpartial = 0.22-0.31, p < 0.001; and habitual rpartial = 0.20-0.26, p < 0.01), and total flavan-3-ols (acute rpartial = 0.40-0.48, p < 0.001; and habitual rpartial = 0.23-0.33, p < 0.001). Similarly, urinary concentrations of flavan-3-ols were weakly correlated with both acute (rpartial = 0.12-0.30, p < 0.05) and habitual intake (rpartial = 0.10-0.27, p < 0.05) of apple and pear, stone fruits, berries, chocolate and chocolate products, cakes and pastries, tea, herbal tea, wine, red wine, and beer and cider. Moreover, all comparable correlations were stronger for urinary (-)-epicatechin than for (+)-catechin. In conclusion, our data support the use of urinary concentrations of (+)-catechin and (-)-epicatechin, especially as short-term nutritional biomarkers of dietary catechin, epicatechin and total flavan-3-ol monomers.

Clinical and epidemiological characteristics associated with pneumonia at disease onset in patients admitted for COVID-19 to the Emergency Department of a large Hospital in Piedmont (North-Western Italy).

OBJECTIVES: to explore clinical and epidemiological characteristics associated with an imaging feature of COVID-19 pneumonia at disease onset, in order to identify factors that may be evaluable by general practitioners at patient's home, and which may lead to identify a more severe disease, needing hospitalization. DESIGN: this is a retrospective/prospective observational hospital cohort. SETTING AND PARTICIPANTS: the study population includes all patients consecutively admitted to the emergency department of Città della salute e della scienza University Hospital from 01.03 to 31.05.2020 with a confirmed diagnosis of SARS-CoV-2 infection. MAIN OUTCOME MEASURES: patients were classified in two groups according to the findings of X-ray imaging, lung ultrasound and chest computer tomography, as pneumonia or not pneumonia patients. RESULTS: in multivariable analysis, factors most strongly associated with emergency department admission with pneumonia were age, oxygen saturation <90% (adj OR 4.16 ;95%CI 1.44-12.07), respiratory rate >24 breaths/min (adj OR 6.50; 95%CI 2.36-17.87), fever ≥38° (adj OR 3.05; 95%CI 1.53-6.08) and the presence of gastroenteric symptoms (vomiting and diarrhea). A delay (> 7 days) between the appearance of the initial lung symptoms (cough and dyspnea) and the admission to the emergency department was also related to a higher probability of receiving a positive imaging report (OR 4.99; 95%CI 2,02-12,34). CONCLUSIONS: in order to reorganize the management of COVID-19 patients in Italy, in view of the risk of a second wave of epidemic or of local outbreaks, it would be desirable to relocate the triage, and possibly the patient's care, from hospital to home. In this scenario it is important to identify all symptoms and signs associated with COVID-19 pneumonia that would facilitate the decision-making process of GPs leading to patients hospitalization.

Clinical characteristics and management of COVID-19 patients accessing the emergency department in a hospital in Northern Italy in March and April 2020.

BACKGROUND: the emergency due to SARS-CoV-2 pandemic struck the national and regional health system that needed an effort to reorganise and increase resources to cope with a sudden, uncertain, and previously unknown situation. This study was conducted in the immediate aftermath of this difficult period. OBJECTIVES: to describe clinical characteristics, short-term outcomes, and management of SARS-CoV-2 positive patients that accessed the emergency department (ED) of the San Luigi Gonzaga hospital of Orbassano (Turin district, Piedmont Region, Northern Italy) in March and April 2020. Furthermore, this study aimed at investigating if a difference in patients characteristics, clinical management, and outcomes was present during time. DESIGN: comparison of different periods in a clinical cohort. SETTING AND PARTICIPANTS: for each patient who accessed the ED and tested positive for SARS-CoV-2 swab, the ED medical record was collected and a descriptive analysis was performed on demographical characteristics, pre-existing comorbidities, parameters measured at triage, imaging exams results, lab tests results, separately for patients admitted at the ED in four different periods. MAIN OUTCOME MEASURES: discharge from ED, admission to hospital wards (low and high intensity of care), short term in-hospital mortality, hospital length of stay. The association between patients' characteristics and the main outcomes was measured using multivariable logistic models. RESULTS: age of patients increased significantly from March to April, together with female prevalence and associated comorbid conditions. A significant difference in symptoms at presentation was not observed nor it was in laboratory test results. Severity at triage and need of intensive care resources were higher in the first weeks, together with the typical clinical presentation with respiratory failure and imaging with signs of bilateral interstitial pneumonia. Accordingly, in-hospital mortality was higher in the first period. Nevertheless, nearly half of patients in the first period were discharged directly from ED showing mild COVID-19 cases. On the contrary, in April an increasing need of hospitalisation in low intensity of care beds was observed, whereas mild cases stopped to access the ED. CONCLUSIONS: the results of this study suggest that in few weeks of COVID-19 epidemic both management of the patients at the hospital level - and probably at territorial level resulting in a different population who accessed to the ED - and the clinical characteristics of the COVID-19 patients changed.

[Covid-19 and clinical-epidemiological research in Italy: proposal of a research agenda on priority topics by the Italian association of epidemiology]. / Covid-19 e ricerca clinico-epidemiologica in Italia: proposta di un'agenda di ricerca su temi prioritari da parte dell'Associazione italiana di epidemiologia.

BACKGROUND: the Covid-19 pandemic has provoked a huge of clinical and epidemiological research initiatives, especially in the most involved countries. However, this very large effort was characterized by several methodological weaknesses, both in the field of discovering effective treatments (with too many small and uncontrolled trials) and in the field of identifying preventable risks and prognostic factors (with too few large, representative and well-designed cohorts or case-control studies). OBJECTIVES: in response to the fragmented and uncoordinated research production on Covid-19, the   italian Association of Epidemiology (AIE) stimulated the formation of a working group (WG) with the aims of identifying the most important gaps in knowledge and to propose a structured research agenda of clinical and epidemiological studies considered at high priority on Covid-19, including recommendations on the preferable methodology. METHODS: the WG was composed by 25 subjects, mainly epidemiologists, statisticians, and other experts in specific fields, who have voluntarily agreed to the proposal. The agreement on a list of main research questions and on the structure of the specific documents to be produced were defined through few meetings and cycles of document exchanges. RESULTS: twelve main research questions on Covid-19 were identified, covering aetiology, prognosis, interventions, follow-up and impact on general and specific populations (children, pregnant women). For each of them, a two-page form was developed, structured in: background, main topics, methods (with recommendations on preferred study design and warnings for bias prevention) and an essential bibliography. CONCLUSIONS: this research agenda represents an initial contribution to direct clinical and epidemiological research efforts on high priority topics with a focus on methodological aspects. Further development and refinements of this agenda by Public Health Authorities are encouraged.