Clinical Outcomes in the Second versus First Pandemic Wave in Italy: Impact of Hospital Changes and Reorganization

The region of Lombardy was the epicenter of the COVID-19 outbreak in Italy. Emergency Hospital 19 (EH19) was built in the Milan metropolitan area during the pandemic’s second wave as a facility of Humanitas Clinical and Research Center (HCRC). The present study aimed to assess whether the implementation of EH19 was effective in improving the quality of care of COVID-19 patients during the second wave compared with the first one. The demographics, mortality rate, and in-hospital length of stay (LOS) of two groups of patients were compared: the study group involved patients admitted at HCRC and managed in EH19 during the second pandemic wave, while the control group included patients managed exclusively at HCRC throughout the first wave. The study and control group included 903 (56.7%) and 690 (43.3%) patients, respectively. The study group was six years older on average and had more pre-existing comorbidities. EH19 was associated with a decrease in the intensive care unit admission rate (16.9% vs. 8.75%, p <0.001), and an equal decrease in invasive oxygen therapy (3.8% vs. 0.23%, p <0.001). Crude mortality was similar but overlap propensity score weighting revealed a trend toward a potential small decrease. The adjusted difference in LOS was not significant. The implementation of an additional COVID-19 hospital facility was effective in improving the overall quality of care of COVID-19 patients during the first wave of the pandemic when compared with the second. Further studies are necessary to validate the suggested approach.

Short-term health-related quality of life, physical function and psychological consequences of severe COVID-19.

BACKGROUND: Survivors of severe COVID-19 are at risk of impaired health-related quality of life (HRQoL) and persistent physical and psychological disability after ICU and hospital discharge. The subsequent social burden is a major concern. We aimed to assess the short-term HRQoL, physical function and prevalence of post-traumatic stress symptoms of invasively mechanically ventilated COVID-19 patients treated in our ICU. METHODS: Prospective, observational cohort study in a follow-up clinic. Patients completed a 6-min walking test (6MWT) to assess their cardio-pulmonary function around 2 months (early follow-up) from hospital discharge, the EQ-5D-5L questionnaire for quality of life assessment around 2 months and at 6 months from hospital discharge and an anonymous web-based Impact of Event Scale-Revised (IES-R) questionnaire for Post-Traumatic Stress symptoms at 2 months. RESULTS: 47 patients attended our follow-up program, mean age 59 ± 10 years, median pre-morbid Clinical Frailty Scale (CFS) 2 [2-3]. The median distance walked in 6 min was 470 [406-516] m, 83 [67-99]% of the predicted value. Overall 1 out 3 patients and 4/18 (22%) among those with a good functional baseline prior to COVID-19 (CFS of 1 or 2) had lower (84%) than predicted 6MWT. EQ-5D-5L quality of life VAS was 80 [70-90] out of 100 at early follow-up with a slight improvement to 85 [77.5-90] at 6 months. Mobility, self-care and usual activities improved between the two timepoints, while pain/discomfort and depression/anxiety did not improve or got worse. The IES-R total score was greater than the threshold for concern of 1.6 in 27/41(66%) respondents. CONCLUSIONS: Patients recovering from severe COVID-19 requiring invasive mechanical ventilation surviving hospital discharge present with early mild to moderate functional impairment, mildly reduced quality of life from hospital discharge with an overall improvement of mobility, self-care and the ability of performing usual activities, while a worsening of pain and depression/anxiety symptoms at 6 months and a large proportion of symptoms of post-traumatic distress soon after hospital discharge.

Health Communication in COVID-19 Era: Experiences from the Italian VaccinarSì Network Websites.

In 2013, in a bid to combat Vaccine Hesitancy (VH) and provide information on vaccines by communicating with the general public and the health community (e.g., healthcare workers and public health operators), the Italian Society of Hygiene and Preventive Medicine (S.It.I.) published the national website "VaccinarSì". The project was subsequently extended to ten Italian Regions. This led to the creation of the VaccinarSì Network, whose websites are publicly owned. The aim of this work was to present the framework of the websites of the VaccinarSì Network and to analyse user behaviour in the pre-COVID-19-era (dating from each website's publication until 31 January 2020) and in the COVID-19-era (from 1 February 2020 to 31 January 2021). Some metrics such as the number of visits to the site (sessions, number of users and average session duration), user behaviour (pages viewed, bounce rate and organic search) and the session acquisition path (direct traffic, referrals and social traffic) were searched, extrapolated and processed with Google Analytics. Qualitative and normally distributed quantitative variables were summarised with their absolute (relative) frequencies and means. Statistical differences between the means of the two periods were evaluated through paired t-test. A two-tailed p-value less than 0.05 was considered to be statistically significant. When the total values recorded over the period were compared, an overall increase in metrics was observed-the number of individual users, visits and individual pageviews rose in a statistically significant way. Our study aimed to highlight how combining disciplines such as health education and digital communication via Information and Communication Technologies (ICT) represents the best strategy to support citizens. This approach gives them the tools to become independent and responsible players that are capable of voluntarily and consciously choosing to adhere to vaccination programs. The VaccinarSì Network's goal for the future is to reach an even wider audience. By building each user's critical knowledge, this network enables users to be active components of a wider, more empowered community.

The role of anti-hypertensive treatment, comorbidities and early introduction of LMWH in the setting of COVID-19: A retrospective, observational study in Northern Italy.

BACKGROUND: There is a great deal of debate about the role of cardiovascular comorbidities and the chronic use of antihypertensive agents (such as ACE-I and ARBs) on mortality on COVID-19 patients. Of note, ACE2 is responsible for the host cell entry of the virus. METHODS: We extracted data on 575 consecutive patients with laboratory-confirmed SARS-CoV-2 infection admitted to the Emergency Department (ED) of Humanitas Center, between February 21 and April 14, 2020. The aim of the study was to evaluate the role of chronic treatment with ACE-I or ARBs and other clinical predictors on in-hospital mortality in a cohort of COVID-19 patients. RESULTS: Multivariate analysis showed that a chronic intake of ACE-I was associated with a trend in reduction of mortality (OR: 0.53; 95% CI: 0.27-1.03; p = 0.06), differently from a chronic intake of ARB (OR: 1.1; 95% CI: 0.5-2.8; p=0.8). Increased age (ORs ranging from 3.4 to 25.2 and to 39.5 for 60-70, 70-80 and >80 years vs <60) and cardiovascular comorbidities (OR: 1.90; 95% CI: 1.1-3.3; p = 0.02) were confirmed as important risk factors for COVID-19 mortality. Timely treatment with low-molecular-weight heparin (LMWH) in ED was found to be protective (OR: 0.36; 95% CI: 0.21-0.62; p < 0.0001). CONCLUSIONS: This study can contribute to understand the reasons behind the high mortality rate of patients in Lombardy, a region which accounts for >50% of total Italian deaths. Based on our findings, we support that daily intake of antihypertensive medications in the setting of COVID-19 should not be discontinued and that a timely LMWH administration in ED has shown to decrease in-hospital mortality.

Macrophage expression and prognostic significance of the long pentraxin PTX3 in COVID-19.

Long pentraxin 3 (PTX3) is an essential component of humoral innate immunity, involved in resistance to selected pathogens and in the regulation of inflammation1-3. The present study was designed to assess the presence and significance of PTX3 in Coronavirus Disease 2019 (COVID-19)4-7. RNA-sequencing analysis of peripheral blood mononuclear cells, single-cell bioinformatics analysis and immunohistochemistry of lung autopsy samples revealed that myelomonocytic cells and endothelial cells express high levels of PTX3 in patients with COVID-19. Increased plasma concentrations of PTX3 were detected in 96 patients with COVID-19. PTX3 emerged as a strong independent predictor of 28-d mortality in multivariable analysis, better than conventional markers of inflammation, in hospitalized patients with COVID-19. The prognostic significance of PTX3 abundance for mortality was confirmed in a second independent cohort (54 patients). Thus, circulating and lung myelomonocytic cells and endothelial cells are a major source of PTX3, and PTX3 plasma concentration can serve as an independent strong prognostic indicator of short-term mortality in COVID-19.

Interleukin-6 receptor blocking with intravenous tocilizumab in COVID-19 severe acute respiratory distress syndrome: A retrospective case-control survival analysis of 128 patients.

In cases of COVID-19 acute respiratory distress syndrome, an excessive host inflammatory response has been reported, with elevated serum interleukin-6 levels. In this multicenter retrospective cohort study we included adult patients with COVID-19, need of respiratory support, and elevated C-reactive protein who received intravenous tocilizumab in addition to standard of care. Control patients not receiving tocilizumab were matched for sex, age and respiratory support. We selected survival as the primary endpoint, along with need for invasive ventilation, thrombosis, hemorrhage, and infections as secondary endpoints at 30 days. We included 64 patients with COVID-19 in the tocilizumab group and 64 matched controls. At baseline the tocilizumab group had longer symptom duration (13 ± 5 vs. 9 ± 5 days) and received hydroxychloroquine more often than controls (100% vs. 81%). The mortality rate was similar between groups (27% with tocilizumab vs. 38%) and at multivariable analysis risk of death was not significantly influenced by tocilizumab (hazard ratio 0.61, 95% confidence interval 0.33-1.15), while being associated with the use at baseline of non invasive mechanical or invasive ventilation, and the presence of comorbidities. Among secondary outcomes, tocilizumab was associated with a lower probability of requiring invasive ventilation (hazard ratio 0.36, 95% confidence interval 0.16-0.83; P = 0.017) but not with the risk of thrombosis, bleeding, or infections. The use of intravenous tocilizumab was not associated with changes in 30-day mortality in patients with COVID-19 severe respiratory impairment. Among the secondary outcomes there was less use of invasive ventilation in the tocilizumab group.

Genomewide Association Study of Severe Covid-19 with Respiratory Failure.

BACKGROUND: There is considerable variation in disease behavior among patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19). Genomewide association analysis may allow for the identification of potential genetic factors involved in the development of Covid-19. METHODS: We conducted a genomewide association study involving 1980 patients with Covid-19 and severe disease (defined as respiratory failure) at seven hospitals in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe. After quality control and the exclusion of population outliers, 835 patients and 1255 control participants from Italy and 775 patients and 950 control participants from Spain were included in the final analysis. In total, we analyzed 8,582,968 single-nucleotide polymorphisms and conducted a meta-analysis of the two case-control panels. RESULTS: We detected cross-replicating associations with rs11385942 at locus 3p21.31 and with rs657152 at locus 9q34.2, which were significant at the genomewide level (P<5×10-8) in the meta-analysis of the two case-control panels (odds ratio, 1.77; 95% confidence interval [CI], 1.48 to 2.11; P = 1.15×10-10; and odds ratio, 1.32; 95% CI, 1.20 to 1.47; P = 4.95×10-8, respectively). At locus 3p21.31, the association signal spanned the genes SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6 and XCR1. The association signal at locus 9q34.2 coincided with the ABO blood group locus; in this cohort, a blood-group-specific analysis showed a higher risk in blood group A than in other blood groups (odds ratio, 1.45; 95% CI, 1.20 to 1.75; P = 1.48×10-4) and a protective effect in blood group O as compared with other blood groups (odds ratio, 0.65; 95% CI, 0.53 to 0.79; P = 1.06×10-5). CONCLUSIONS: We identified a 3p21.31 gene cluster as a genetic susceptibility locus in patients with Covid-19 with respiratory failure and confirmed a potential involvement of the ABO blood-group system. (Funded by Stein Erik Hagen and others.).

High mortality in COVID-19 patients with mild respiratory disease.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected 189 000 people in Italy, with more than 25 000 deaths. Several predictive factors of mortality have been identified; however, none has been validated in patients presenting with mild disease. METHODS: Patients with a diagnosis of interstitial pneumonia caused by SARS-CoV-2, presenting with mild symptoms, and requiring hospitalization in a non-intensive care unit with known discharge status were prospectively collected and retrospectively analysed. Demographical, clinical and biochemical parameters were recorded, as need for non-invasive mechanical ventilation and admission in intensive care unit. Univariate and multivariate logistic regression analyses were used to identify independent predictors of death. RESULTS: Between 28 February and 10 April 2020, 229 consecutive patients were included in the study cohort; the majority were males with a mean age of 60 years. 54% of patients had at least one comorbidity, with hypertension being the most commonly represented, followed by diabetes mellitus. 196 patients were discharged after a mean of 9 days, while 14.4% died during hospitalization because of respiratory failure. Age higher than 75 years, low platelet count (<150 × 103 /mm3 ) and higher ferritin levels (>750 ng/mL) were independent predictors of death. Comorbidities were not independently associated with in-hospital mortality. CONCLUSIONS: In-hospital mortality of patients with COVID-19 presenting with mild symptoms is high and is associated with older age, platelet count and ferritin levels. Identifying early predictors of outcome can be useful in the clinical practice to better stratify and manage patients with COVID-19.

Early Predictors of Clinical Deterioration in a Cohort of 239 Patients Hospitalized for Covid-19 Infection in Lombardy, Italy.

We described features of hospitalized Covid-19 patients and identified predictors of clinical deterioration. We included patients consecutively admitted at Humanitas Research Hospital (Rozzano, Milan, Italy); retrospectively extracted demographic; clinical; laboratory and imaging findings at admission; used survival methods to identify factors associated with clinical deterioration (defined as intensive care unit (ICU) transfer or death), and developed a prognostic index. Overall; we analyzed 239 patients (29.3% females) with a mean age of 63.9 (standard deviation [SD]; 14.0) years. Clinical deterioration occurred in 70 patients (29.3%), including 41 (17.2%) ICU transfers and 36 (15.1%) deaths. The most common symptoms and signs at admission were cough (77.8%) and elevated respiratory rate (34.1%), while 66.5% of patients had at least one coexisting medical condition. Imaging frequently revealed ground-glass opacity (68.9%) and consolidation (23.8%). Age; increased respiratory rate; abnormal blood gas parameters and imaging findings; coexisting coronary heart disease; leukocytosis; lymphocytopenia; and several laboratory parameters (elevated procalcitonin; interleukin-6; serum ferritin; C-reactive protein; aspartate aminotransferase; lactate dehydrogenase; creatinine; fibrinogen; troponin-I; and D-dimer) were significant predictors of clinical deterioration. We suggested a prognostic index to assist risk-stratification (C-statistic; 0.845; 95% CI; 0.802‒0.887). These results could aid early identification and management of patients at risk, who should therefore receive additional monitoring and aggressive supportive care.