Clinical characteristics and outcomes of vaccinated patients hospitalised with SARS-CoV-2 breakthrough infection: Multi-IPV, a multicentre study in Northern Italy.

BACKGROUND: Despite the well-known efficacy of anti-COVID-19 vaccines in preventing morbidity and mortality, several vaccinated individuals are diagnosed with SARS-CoV-2 breakthrough infection, which might require hospitalisation. This multicentre, observational, and retrospective study aimed to investigate the clinical characteristics and outcomes of vaccinated vs. non-vaccinated patients, both hospitalised with SARS-CoV-2 infection in 3 major hospitals in Northern Italy. METHODS: Data collection was retrospective, and paper and electronic medical records of adult patients with a diagnosed SARS-CoV-2 infection were pseudo-anonymised and analysed. Vaccinated and non-vaccinated individuals were manually paired, using a predetermined matching criterion (similar age, gender, and date of hospitalisation). Demographic, clinical, treatment, and outcome data were compared between groups differing by vaccination status using Pearson's Chi-square and Mann-Whitney tests. Moreover, multiple logistic regression analyses were performed to assess the impact of vaccination status on ICU admission or intra-hospital mortality. RESULTS: Data from 360 patients were collected. Vaccinated patients presented with a higher prevalence of relevant comorbidities, like kidney replacement therapy or haematological malignancy, despite a milder clinical presentation at the first evaluation. Non-vaccinated patients required intensive care more often than their vaccinated counterparts (8.8% vs. 1.7%, p = 0.002). Contrariwise, no difference in intra-hospital mortality was observed between the two groups (19% vs. 20%, p = 0.853). These results were confirmed by multivariable logistic regressions, which showed that vaccination was significantly associated with decreased risk of ICU admission (aOR=0.172, 95%CI: 0.039-0.542, p = 0.007), but not of intra-hospital mortality (aOR=0.996, 95%CI: 0.582-1.703, p = 0.987). CONCLUSIONS: This study provides real-world data on vaccinated patients hospitalised with COVID-19 in Northern Italy. Our results suggest that COVID-19 vaccination has a protective role in individuals with higher risk profiles, especially regarding the need for ICU admission. These findings contribute to our understanding of SARS-CoV-2 infection outcomes among vaccinated individuals and emphasise the importance of vaccination in preventing severe disease, particularly in those countries with lower first-booster uptake rates.

EuCARE-hospitalised study protocol: a cohort study of patients hospitalised with COVID-19 in the EuCARE project.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), can lead to hospitalisation, particularly in elderly, immunocompromised, and non-vaccinated or partially vaccinated individuals. Although vaccination provides protection, the duration of this protection wanes over time. Additional doses can restore immunity, but the influence of viral variants, specific sequences, and vaccine-induced immune responses on disease severity remains unclear. Moreover, the efficacy of therapeutic interventions during hospitalisation requires further investigation. The study aims to analyse the clinical course of COVID-19 in hospitalised patients, taking into account SARS-CoV-2 variants, viral sequences, and the impact of different vaccines. The primary outcome is all-cause in-hospital mortality, while secondary outcomes include admission to intensive care unit and length of stay, duration of hospitalisation, and the level of respiratory support required. METHODS: This ongoing multicentre study observes hospitalised adult patients with confirmed SARS-CoV-2 infection, utilising a combination of retrospective and prospective data collection. It aims to gather clinical and laboratory variables from around 35,000 patients, with potential for a larger sample size. Data analysis will involve biostatistical and machine-learning techniques. Selected patients will provide biological material. The study started on October 14, 2021 and is scheduled to end on October 13, 2026. DISCUSSION: The analysis of a large sample of retrospective and prospective data about the acute phase of SARS CoV-2 infection in hospitalised patients, viral variants and vaccination in several European and non-European countries will help us to better understand risk factors for disease severity and the interplay between SARS CoV-2 variants, immune responses and vaccine efficacy. The main strengths of this study are the large sample size, the long study duration covering different waves of COVID-19 and the collection of biological samples that allows future research. TRIAL REGISTRATION: The trial has been registered on ClinicalTrials.gov. The unique identifier assigned to this trial is NCT05463380.

EuCARE-POSTCOVID Study: a multicentre cohort study on long-term post-COVID-19 manifestations.

BACKGROUND: Post-COVID-19 condition refers to persistent or new onset symptoms occurring three months after acute COVID-19, which are unrelated to alternative diagnoses. Symptoms include fatigue, breathlessness, palpitations, pain, concentration difficulties ("brain fog"), sleep disorders, and anxiety/depression. The prevalence of post-COVID-19 condition ranges widely across studies, affecting 10-20% of patients and reaching 50-60% in certain cohorts, while the associated risk factors remain poorly understood. METHODS: This multicentre cohort study, both retrospective and prospective, aims to assess the incidence and risk factors of post-COVID-19 condition in a cohort of recovered patients. Secondary objectives include evaluating the association between circulating SARS-CoV-2 variants and the risk of post-COVID-19 condition, as well as assessing long-term residual organ damage (lung, heart, central nervous system, peripheral nervous system) in relation to patient characteristics and virology (variant and viral load during the acute phase). Participants will include hospitalised and outpatient COVID-19 patients diagnosed between 01/03/2020 and 01/02/2025 from 8 participating centres. A control group will consist of hospitalised patients with respiratory infections other than COVID-19 during the same period. Patients will be followed up at the post-COVID-19 clinic of each centre at 2-3, 6-9, and 12-15 months after clinical recovery. Routine blood exams will be conducted, and patients will complete questionnaires to assess persisting symptoms, fatigue, dyspnoea, quality of life, disability, anxiety and depression, and post-traumatic stress disorders. DISCUSSION: This study aims to understand post-COVID-19 syndrome's incidence and predictors by comparing pandemic waves, utilising retrospective and prospective data. Gender association, especially the potential higher prevalence in females, will be investigated. Symptom tracking via questionnaires and scales will monitor duration and evolution. Questionnaires will also collect data on vaccination, reinfections, and new health issues. Biological samples will enable future studies on post-COVID-19 sequelae mechanisms, including inflammation, immune dysregulation, and viral reservoirs. TRIAL REGISTRATION: This study has been registered with ClinicalTrials.gov under the identifier NCT05531773.

Quantitative Chest CT Analysis to Measure Short-Term Sequelae of COVID-19 Pneumonia: A Monocentric Prospective Study.

(1) Background: Quantitative CT analysis (QCT) has demonstrated promising results in the prognosis prediction of patients affected by COVID-19. We implemented QCT not only at diagnosis but also at short-term follow-up, pairing it with a clinical examination in search of a correlation between residual respiratory symptoms and abnormal QCT results. (2) Methods: In this prospective monocentric trial performed during the "first wave" of the Italian pandemic, i.e., from March to May 2020, we aimed to test the relationship between %deltaCL (variation of %CL-compromised lung volume) and variations of symptoms-dyspnea, cough and chest pain-at follow-up clinical assessment after hospitalization. (3) Results: 282 patients (95 females, 34%) with a median age of 60 years (IQR, 51-69) were included. We reported a correlation between changing lung abnormalities measured by QCT, and residual symptoms at short-term follow up after COVID-19 pneumonia. Independently from age, a low percentage of surviving patients (1-4%) may present residual respiratory symptoms at approximately two months after discharge. QCT was able to quantify the extent of residual lung damage underlying such symptoms, as the reduction of both %PAL (poorly aerated lung) and %CL volumes was correlated to their disappearance. (4) Conclusions QCT may be used as an objective metric for the measurement of COVID-19 sequelae.

Female gender is associated with long COVID syndrome: a prospective cohort study.

OBJECTIVE: We explored the association between female gender and long COVID syndrome, defined as persistence of physical and/or psychological symptoms for more than 4 weeks after recovery from acute COVID-19 disease. The secondary aim was to identify predictors of long COVID syndrome by multivariable logistic regression analysis. METHODS: This was a single-centre prospective cohort study conducted at San Paolo Hospital in Milan, Italy. We enrolled adult patients who were evaluated at the post-COVID outpatient service of our Infectious Diseases Unit between 15 April 2020 and 15 December 2020. Participants were individuals who had clinically recovered from COVID-19 and in whom virological clearance had occurred. Previous infection by SARS-CoV-2 was microbiologically documented by positivity using a reverse-transcriptase polymerase chain reaction (RT-PCR) assay of nasopharyngeal swab. All enrolled patients underwent blood tests and a comprehensive medical examination at follow-up. Individuals were interviewed about resolved and persisting symptoms and were asked to fill in two questionnaires to allow assessment of the Hospital Anxiety and Depression symptoms (HADS) score and of the Impact of Event Scale-Revised (IES-R) score. RESULTS: A total of 377 patients were enrolled in the study. The median time from symtpom onset to virological clerance was 44 (37-53) days. A diagnosis of long COVID syndrome was made in 260/377 (69%) patients. The most common reported symptoms were fatigue (149/377, 39.5%), exertional dyspnoea (109/377, 28.9%), musculoskeletal pain (80/377, 21.2%) and "brain fog" (76/377, 20.2%). Anxiety symptoms were ascertained in 71/377 (18.8%) individuals, whereas 40/377 (10.6%) patients presented symptoms of depression. Post-traumatic stress disorder (defined by a pathological IES-R score) was diagnosed in one-third of patients (85/275, 31%). Female gender was independently associated with long COVID syndrome at multivariable analysis (AOR 3.3 vs. males, 95% CI 1.8-6.2, p < 0.0001). Advanced age (adjusted (A)OR 1.03 for 10 years older, 95% CI 1.01-1.05, p 0.01) and active smoking (AOR 0.19 for former smokers vs. active smokers, 95% CI 0.06-0.62, p 0.002) were also associated with a higher risk of long COVID, while no association was found between severity of disease and long COVID (AOR 0.67 for continuous positive airway pressure (CPAP)/non-invasive mechanical ventilation (NIMV)/orotracheal intubation (OTI) vs. no 02 therapy, 95% CI 0.29-1.55, p 0.85). DISCUSSION: Factors that were found to be associated with a higher risk of developing "long COVID" syndrome were female gender, older age and active smoking, but not severity of the acute disease. Individuals affected by SARS-CoV-2 infection with the aforementioned features should be early identified and involved in follow-up programmes.

Declining Mortality Rate of Hospitalised Patients in the Second Wave of the COVID-19 Epidemics in Italy: Risk Factors and the Age-Specific Patterns.

BACKGROUND: Mortality rate from COVID-19 in Italy is among the world's highest. We aimed to ascertain whether there was any reduction of in-hospital mortality in patients hospitalised for COVID-19 in the second-wave period (October 2020-January 2021) compared to the first one (February-May 2020); further, we verified whether there were clusters of hospitalised patients who particularly benefitted from reduced mortality rate. METHODS: Data collected related to in-patients' demographics, clinical, laboratory, therapies and outcome. Primary end-point was time to in-hospital death. Factors associated were evaluated by uni- and multivariable analyses. A flow diagram was created to determine the rate of in-hospital death according to individual and disease characteristics. RESULTS: A total of 1561 patients were included. The 14-day cumulative incidence of in-hospital death by competing risk regression was of 24.8% (95% CI: 21.3-28.5) and 15.9% (95% CI: 13.7-18.2) in the first and second wave. We observed that the highest relative reduction of death from first to second wave (more than 47%) occurred mainly in the clusters of patients younger than 70 years. CONCLUSIONS: Progress in care and supporting therapies did affect population over 70 years to a lesser extent. Preventive and vaccination campaigns should focus on individuals whose risk of death from COVID-19 remains high.

Incidence, Risk Factors and Impact on Clinical Outcomes of Bloodstream Infections in Patients Hospitalised with COVID-19: A Prospective Cohort Study.

With the aim of describing the burden and epidemiology of community-acquired/healthcare-associated and hospital-acquired bloodstream infections (CA/HCA-BSIs and HA-BSIs) in patients hospitalised with COVID-19, and evaluating the risk factors for BSIs and their relative impact on mortality, an observational cohort study was performed on patients hospitalised with COVID-19 at San Paolo Hospital in Milan, Italy from 24 February to 30 November 2020. Among 1351 consecutive patients hospitalised with COVID-19, 18 (1.3%) had CA/HCA-BSI and 51 (3.8%) HA-BSI for a total of 82 episodes of BSI. The overall incidence of HA-BSI was 3.3/1000 patient-days (95% CI 2.4-4.2). Patients with HA-BSI had a longer hospital stay compared to CA/HCA-BSI and no-BSI groups (27 (IQR 21-35) vs. 12 (7-29) vs. 9 (5-17) median-days, p < 0.001) but a similar in-hospital mortality (31% vs. 33% vs. 25%, p = 0.421). BSI was not associated with an increased risk of mortality (CA/HCA-BSI vs. non-BSI aOR 1.27 95% CI 0.41-3.90, p = 0.681; HA-BSI vs. non-BSI aOR 1.29 95% CI 0.65-2.54, p = 0.463). Upon multivariate analysis, NIMV/CPAP (aOR 2.09, 95% CI 1.06-4.12, p = 0.034), IMV (aOR 5.13, 95% CI 2.08-12.65, p < 0.001) and corticosteroid treatment (aOR 2.11, 95% CI 1.06-4.19, p = 0.032) were confirmed as independent factors associated with HA-BSI. Development of HA-BSI did not significantly affect mortality. Patients treated with corticosteroid therapy had double the risk of developing BSI.