Variations of the quality of care during the COVID-19 pandemic affected the mortality rate of non-COVID patients with hip fracture (preprint)

Introduction. As COVID-19 roared through the world, governments worldwide enforced containment measures that affected various treatment pathways, including those for hip fracture (HF). This study aimed to measure process and outcome indicators related to the quality of care provided to non-COVID-19 elderly patients affected by HF in Emilia-Romagna, a region of Italy severely hit by the pandemic. Methods. We collected the hospital discharge records of all patients admitted to the hospitals of Emilia-Romagna with a diagnosis of HF from January to May in the years 2019/2020. We analyzed surgery rate, surgery timeliness, length of hospital stay, timely rehabilitation, and 30-day mortality for each HF patient. We evaluated monthly data (2020 vs. 2019) with the chi-square and t-test, where appropriate. Logistic regression was used to investigate the differences in 30-day mortality. Results. Our study included 5379 patients with HF. In April and May 2020, there was a significant increase in the proportion of HF patients that did not undergo timely surgery. In March 2020, we found a significant increase in mortality (OR = 2.22). Female sex (OR = 0.52), age [≥]90 years (OR = 4.33), surgery after 48 hours (OR = 3.08) and not receiving surgery (OR = 6.19) were significantly associated with increased mortality. After adjusting for the aforementioned factors, patients hospitalized in March 2020 still suffered higher mortality (OR = 2.21). Conclusions. Our results show a reduction in the overall quality of care provided to non-COVID-19 elderly patients affected by HF. The mortality rate of patients with HF increased significantly in March 2020. Patients' characteristics and variations in processes of care partially explained this increase. Our analysis reveals the importance of including process and outcomes indicators, for both acute and post-acute care management issues, in emergency preparedness plans, to monitor healthcare systems' capacities and capabilities.

COVID-19 and regional differences in the timeliness of hip-fracture surgery: an interrupted time-series analysis (preprint)

Background. It is of great importance to examine the impact of the healthcare reorganization adopted to confront the COVID19 pandemic on the quality of care provided by healthcare systems to non COVID 19 patients. The aim of this study is to assess the impact of the COVID19 national lockdown (March 9, 2020) on the quality of care provided to patients with hip fracture (HF) in Piedmont and Emilia-Romagna, 2 large regions of northern Italy severely hit by the pandemic. Methods. We calculated the percentage of HF patients undergoing surgery within 2 days of hospital admission. An interrupted time-series analysis was performed on weekly data from December 11, 2019 to June 9, 2020 (6 months), interrupting the series in the 2nd week of March. The same data observed the year before were included as a control time series with no intervention (lockdown) in the middle of the observation period. Results. Before the lockdown, 2day surgery was 69.9% in Piedmont and 79.2% in Emilia-Romagna; after the lockdown, these proportions were equal to 69.8% (-0.1%) and 69.3% (-9.9%), respectively. While Piedmont did not experience any drop in the amount of surgery, Emilia-Romagna exhibited a significantly decline at a weekly rate of -1.29% (95% CI = -1.71 to -0.88). Divergent trend patterns in the 2 study regions reflect local differences in pandemic timing as well as in healthcare services capacity, management, and emergency preparedness.

ROCCA study protocol and interim analysis on safety of Sputnik V vaccine (Gam-COVID-Vac) in the Republic of San Marino: an observational study using active surveillance (preprint)

OBJECTIVE To assess the safety of the Sputnik V (Gam-COVID-Vac) COVID-19 vaccine through participant-based active surveillance from the Republic of San Marino vaccination campaign. DESIGN AND SETTING This is a nation-wide cohort study in the Republic of San Marino to monitor any Adverse Events Following Immunisation (AEFI) with the Sputnik V. PARTICIPANTS Adults aged 18-89 years who had at least one dose of Sputnik V administered and who responded or accessed to an e-questionnaire sent via email, QR-code or were live/phone interviewed about the 7 days after the first vaccine dose (n=2,558) and 7 days after the second dose (n=1,288). Exclusion criteria were inability to understand nor to answer the questionnaire properly. MAIN OUTCOME MEASURES Rates of overall AEFI short-term and long-term (3 months). Secondary outcomes focus on subgroups of the population presenting specific comorbidities. Being this an interim analysis, long-term data (3 months) is still being collected, especially for vulnerable populations, including subjects with comorbidities and the youngest age groups. RESULT The median age of participants was 68 years. 56% were females. After the first dose, vaccine recipients described both local and systemic reactions in 16.4% of cases, 25.8% reported systemic reactions only, and 10.2% reported local symptoms only. After the second dose, both local and systemic reactions were reported in 31.9% of cases, 18.5% reported systemic reactions only, and 16.1% reported local symptoms only. Main symptoms were local pain (24.8% for first dose and 43.8% for the second), asthenia (23.8% and 31.9%), headache (18.5% and 21.0%), and joint pain (16.5% and 21.9%). In the population over 60, recipients having reported AEFI after the first dose could be a predictor of AEFI recurrence after the second dose (p<0.001). 81.8% of those reporting second-dose AEFI, reported AEFI after the first dose, while amongst those not having reported any AEFI after the first dose, 18.2% reported AEFI after the second dose. CONCLUSION The ROCCA interim analysis confirmed a good tolerability profile in the over 60 years age group after both doses regarding short-term solicited AEFI to Sputnik V (Gam-COVID-Vac).

COVID-19 Incidence and Mortality in Pre-Dialysis Chronic Kidney Disease Patients (preprint)

Many studies reported a higher risk of COVID-19 disease among patients on dialysis or with kidney transplantation, and the poor outcome of COVID-19 in these patients. Patients in conservative management for chronic kidney disease (CKD) have received attention only recently, therefore less is known about how COVID-19 affects this population. The aim of this study was to provide evidence on COVID-19 incidence and mortality in CKD patients followed up in an integrated healthcare program and in the population living in the same catchment area.The study population included CKD patients in conservative management recruited in the Emilia-Romagna Prevention of Progressive Renal Insufficiency (PIRP) project, followed up in the 4 nephrology units (Ravenna, Forlì, Cesena and Rimini) of the Romagna Local Health Authority (Italy) and alive at 1.01.2020. We estimated the incidence of COVID-19, its related mortality and the excess mortality within the PIRP cohort as of 31.07.2020. COVID-19 incidence in CKD patients was 4.09% (193/4,716 patients), while in the general population it was 0.46% (5,195/1,125,574). The crude mortality rate among CKD patients with COVID-19 was 44.6% (86/193), compared to 4.7% (215/4,523) in CKD patients without COVID-19. The excess mortality of March-April 2020 was +69.8% than the average mortality of March-April 2015-19 in the PIRP cohort. In a cohort mostly including regularly followed up CKD patients, the incidence of COVID-19 disease and COVID-19 related mortality were about ten times higher than those of the general population. The incidence of COVID-19 among CKD patients was strongly related to the spread of the infection in the community, while its lethality is associated with the underlying kidney condition and comorbidities. For this reason, it is urgent to offer a direct protection to CKD patients by prioritizing their vaccination.

Assessing knowledge, concerns, and risk perceptions among Italian medical students during the SARS-CoV-2 pandemic. (preprint)

ABSTRACT OBJECTIVE During the first phase of COVID-19 pandemic, Italian medical students transitioned from in-person to remote learning. This study was carried out to early assess students' sources of information, perceived risk of infection, knowledge and preventive practices in order to resume academic activity. The impact of training and volunteer work was also assessed. METHODS A cross-sectional online survey was conducted in May 2020 among medical students enrolled in the School of Medicine and Surgery, Bologna University. RESULTS The analysis included 537 responses. On average students used seven sources of information on COVID-19. Scientific journals were considered the most trustworthy but they ranked only 6th in the frequency of use. Perceived risk of infection was higher for academic activities, especially in the hospital than daily living activities. Less than 50% of students reported being trained on biological risk and use of PPE. Training received was significantly associated with both perceived risk of infection and confidence in the use of PPE. Students engaged in volunteer work had higher confidence in PPE usage. INTERPRETATION Accessible scientific information and students' engagement in spreading correct knowledge play an important role in challenging misinformation during the pandemic crisis. Students showed suboptimal knowledge about PPE use, calling for additional training. We found a moderate-high perceived risk of infection that could be mitigated with specific educational programs and by promoting voluntary work. Students' engagement in public health emergencies (PHE) could potentially be beneficial for their training and as well as for the healthcare system.

Non-COVID-19 patients in times of pandemic: decreased emergency department visits and increased out-of-hospital mortality in Northern Italy (preprint)

ObjectiveThe aim of this was to assess the short-term impact of the pandemic on non-COVID-19 patients living in a one-million inhabitants area in Northern Italy (Bologna Metropolitan Area-BMA), analyzing time trends of Emergency Department (ED) visits, hospitalizations and mortality. MethodsWe conducted a retrospective observational study using data extracted from BMA healthcare informative systems. Weekly trends of ED visits, hospitalizations, in- and out-of-hospital, all-cause and cause-specific mortality between December 1st, 2019 to May 31st, 2020, were compared with those of the same period of the previous year, using Joinpoint regression models and incidence rate ratios. ResultsNon-COVID-19 ED visits and hospitalizations showed a stable trend until the first Italian case of COVID-19 has been recorded, on February 19th, 2020, when they dropped simultaneously. The reduction of ED visits was observed in all age groups and across all severity and diagnosis groups. In the lockdown period a significant increase was found in overall out-of-hospital mortality (43.2%) and cause-specific out-of-hospital mortality related to neoplasms (76.7%), endocrine, nutritional and metabolic (79.5%) as well as cardiovascular (32.7%) diseases. ConclusionsThe pandemic caused a sudden drop of ED visits and hospitalizations of non-COVID-19 patients during the lockdown period, and a concurrent increase in out-of-hospital mortality mainly driven by deaths for neoplasms, cardiovascular and endocrine diseases. The findings of this study might be useful to understand both the population reaction and the healthcare system response at the early phases of the pandemic in terms of reduced demand of care and systems capability in intercepting it.

Non-COVID-19 Patients in Times of Pandemic: Decreased Emergency Department Visits and Increased Out-of-Hospital Mortality in Northern Italy (preprint)

Background: The COVID-19 pandemic forced healthcare services organization to adjust to healthcare needs of a mutating population. In this context, our aim was to assess the short-term impact of the pandemic on non-COVID-19 patients living in a one-million inhabitants area in Northern Italy (Bologna Metropolitan Area-BMA), analyzing time trends of ED visits, hospitalizations and mortality.Methods: We conducted a retrospective observational study using data extracted from BMA healthcare informative systems. Weekly trends of ED visits, hospitalizations, in- and out-of-hospital, all-cause and cause-specific mortality between December 1st, 2019 to May 31st, 2020, were compared with those of the same period of the previous year, using Joinpoint regression models and incidence rate ratios.Findings: Non-COVID-19 ED visits and hospitalizations showed a stable trend until the first Italian case hospitalized for COVID-19 has been recorded, on February 19th, 2020, when they dropped simultaneously with the growth of the SARS-CoV-2 curve. The marked reduction of ED visits was observed in all age groups and across all severity codes and diagnosis groups. In the lockdown period a significant increase was found in overall out-of-hospital mortality (43·2%) and cause-specific out-of-hospital mortality related to neoplasms (76·7%), endocrine, nutritional and metabolic (79·5%) as well as cardiovascular (32·7%) diseases.Interpretation: Our main finding is a sudden drop of ED visits and hospitalizations of non-COVID-19 patients during the pandemic and the concurrent increase in out-of-hospital mortality, particularly for neoplasms, cardiovascular and endocrine diseases. As a second phase of the COVID-19 pandemic is currently underway, the scenario described in this study might be useful to understand both the population reaction and the healthcare system response at the early phases of the pandemic in terms of reduced demand of care and systems capability in intercepting it.Fundings: This study received no specific funding.Declaration of Interests: All the authors declare no conflict of interests.Ethics Approval Statement: The study was approved by the Emilia Romagna Ethical Committee on August 3rd, 2020.

ABO polymorphism and SARS-CoV-2 infection - a meta-analysis (preprint)

At present, existing evidence about the association between SARS-CoV-2 infection and ABO blood group polymorphism is preliminary and controversial. In this meta-analysis we investigate this association and determine SARS-CoV-2 positive individuals odds of having a specific blood group compared to controls. We performed a systematic search on MEDLINE and LitCovid databases for studies published through July 15, 2020. Seven studies met inclusion criteria for meta-analysis, including a total of 13 subgroups of populations (7503 SARS-CoV-2 positive cases and 2962160 controls). We analysed the odds of having each blood group among SARS-CoV-2 positive patients compared with controls. Random-effects models were used to obtain the overall pooled odds ratio (OR). Subgroup and sensitivity analyses were performed in order to explore the source of heterogeneity and results consistency. The results of our meta-analysis indicate that SARS-CoV-2 positive individuals are more likely to have blood group A (pooled OR 1.23, 95%CI: 1.09-1.40) and less likely to have blood group O (pooled OR=0.77, 95%CI: 0.67-0.88). Further studies are needed to investigate the mechanisms at the basis of this association, which may affect the kinetics of the pandemic according to the blood group distribution within the population.

Frauds in Scientific Research May be Overcome with Distributed Ledger Technologies (preprint)

Frauds and misconducts have been common in the history of science. Recent events connected to the COVID-19 pandemic have highlighted how the risks and consequences of this are no longer acceptable. Two papers, addressing the treatment of COVID-19, have been published in two of the most prestigious medical journals. In both, the authors declared to have analysed electronic records from a private corporation, which apparently collected data of tens of thousands of patients, coming from thousands of hospitals. Both papers have been retracted a few weeks later. When such events happen, the confidence of the population in scientific research is likely to be weakened. The objective of this paper is to highlight how the current system endangers not only the reliability of scientific research, but also the very foundations of the trust system on which modern healthcare is based. Having shed the light on the dangers of a system without appropriate monitoring, we propose to improve the research process using the promising aspects of the distributed ledger technology which, thanks to the characteristics of immutability, decentralization and transparency, appears among the best solutions to avoid the repetition of the mistakes linked to the recent and past history of research.

Patterns of COVID-19 related excess mortality in the municipalities of Northern Italy (preprint)

The Coronavirus Disease 2019 (COVID-19) spatial distribution in Italy is inhomogeneous, because of its ways of spreading from the initial hotspots. The impact of COVID-19 on mortality has been described at the regional level, while less is known about mortality in demographic subgroups within municipalities. We aimed to describe the excess mortality (EM) due to COVID-19 in the three most affected Italian regions, by estimating EM in subgroups defined by gender and age classes within each municipality from February 23 to March 31, 2020. EM varied widely among municipalities even within the same region; it was similar between genders for the [≥]75 age group, while in the other age groups it was higher in males. Thus, nearby municipalities may show a different mortality burden despite being under common regional health policies, possibly as a result of policies adopted both at the regional and at the municipality level.

Factors Associated with Access and Use of PPE during COVID-19: A Cross-sectional Study of Italian Physicians (preprint)

ObjectivesDuring the course of the Novel Coronavirus (SARS-CoV-2) pandemic, Italy has reported one of the highest number of infections. Nearly ten percent of reported coronavirus infections in Italy occurred in healthcare workers. This study aimed to understand physicians access to personal protective equipment (PPE) and to information about their use, risk perception and strategies adopted to prevent contracting the infection. MethodsWe undertook a cross-sectional, online self-reported survey implemented between March 31 and April 5 2020 of Italian physicians. ResultsResponses were received from 529 physicians, only 13% of which reported to have access to PPE every time they need them. Approximately half of the physicians reported that the information received about the use of PPE was either clear (47%) or complete (54%). Risk perception about contracting the infection was influenced by receiving adequate information on the use of PPE. Access to adequate information on the use of PPE was associated with better ability to perform donning and doffing procedures [OR=2.2 95% C.I. 1.7-2.8] and reduced perception of risk [OR=0.5, 95% C.I. 0.4-0.6]. ConclusionsResults from this rapid survey indicate that while ramping up supplies on PPE for healthcare workers is certainly of mandatory importance, adequate training and clear instructions are just as important.

How the COVID-19 pandemic is favoring the adoption of digital technologies in healthcare: a rapid literature review (preprint)

Background. Healthcare is responding to the COVID-19 pandemic through the fast adoption of digital solutions and advanced technology tools. The aim of this study is to describe which digital solutions have been reported in the scientific literature and to investigate their potential impact in the fight against the COVID-19 pandemic. Methods. We conducted a literature review searching PubMed and MedrXiv with terms considered adequate to find relevant literature on the use of digital technologies in response to COVID-19. We developed an impact score to evaluate the potential impact on COVID-19 pandemic of all the digital solutions addressed in the selected papers. Results. The search identified 269 articles, of which 145 full-text articles were assessed and 124 included in the review after screening and impact evaluation. Of selected articles, most of them addressed the use of digital technologies for diagnosis, surveillance and prevention. We report that digital solutions and innovative technologies have mainly been proposed for the diagnosis of COVID-19. In particular, within the reviewed articles we identified numerous suggestions on the use of artificial-intelligence-powered tools for the diagnosis and screening of COVID-19. Digital technologies are useful also for prevention and surveillance measures, for example through contact-tracing apps or monitoring of internet searches and social media usage. Discussion. It is worth taking advantage of the push given by the crisis, and mandatory to keep track of the digital solutions proposed today to implement tomorrow's best practices and models of care, and to be ready for any new moments of emergency.

Is There a Relationship Between Blood Group and COVID-19 Susceptibility? (preprint)

Objective: On March 11, 2020 the WHO declared that COVID-19 is pandemic. Among the risk factors for many infectious diseases, a role of the ABO blood group system is reported in the literature. We argue whether it is necessary to investigate the relationship between ABO blood groups and susceptibility to SARS-CoV-2 infection and if we should consider some blood groups as potential risk factors for COVID-19. Results: Based on the scientific evidence reported in this letter, we believe that further studies are needed to investigate how the ABO polymorphism influences the host susceptibility, individual response and clinical risk for SARS-CoV-2 infection.

COVID-19 in Italy: Is the Virus Running Through an Ancient Roman road? (preprint)

In late February 2020, Coronavirus disease-2019 (COVID-19) has aggressively spread around many bordering provinces of the three most productive regions of northern Italy (Lombardy, Veneto and Emilia Romagna). The first outbreak exploded in the municipality of Codogno (Lombardy). The province of Ferrara (Emilia Romagna) has been indicated as an anomaly due to the lower number of confirmed cases (1·065 cases per 1000 population). We argue that the spread of the virus throughout Emilia Romagna has a possible explanation in the geographical location of most of its provinces along the Via Emilia, an ancient Roman road that runs throughout the region, which we consider as a proxy for citizens’ movement, number of contacts, and social interactions. In order to test this hypothesis, we used a non-linear multiple regression analysis on aggregate province data to investigate the association between the rates of confirmed cases and the distance from the Via Emilia. The results indicate that the infection rate decreases proportionally to the distance from Via Emilia (-14% every 10 km, p<0·001). Further studies are needed, but Ferrara’s “peculiarity” might have a geographical/behavioral explanation, due to its isolation from the regional main connection routes, which are still revolving around a road built by the ancient Romans 2,000 years ago.

Forecasting COVID-19-Associated Hospitalizations under Different Levels of Social Distancing in Lombardy and Emilia-Romagna, Northern Italy: Results from an Extended SEIR Compartmental Model (preprint)

The outbreak of coronavirus disease 2019 (COVID-19) was identified in Wuhan, China, in December 2019. As of April 17, 2020, more than 2 million cases of COVID-19 have been reported worldwide. Northern Italy is one of the world’s centers of active coronavirus cases. In this study, we predicted the spread of COVID-19 and its burden on hospital care under different conditions of social distancing in Lombardy and Emilia-Romagna, the two regions of Italy most affected by the epidemic. To do this, we used a Susceptible-Exposed-Infectious-Recovered (SEIR) deterministic model, which encompasses compartments relevant to public health interventions such as quarantine. A new compartment L was added to the model for isolated infected population, i.e., individuals tested positives that do not need hospital care. We found that in Lombardy restrictive containment measures should be prolonged at least until early July to avoid a resurgence of hospitalizations; on the other hand, in Emilia-Romagna the number of hospitalized cases could be kept under a reasonable amount with a higher contact rate. Our results suggest that territory-specific forecasts under different scenarios are crucial to enhance or take new containment measures during the epidemic.

The impact of early scientific literature in response to COVID-19: a scientometric perspective (preprint)

Background. In the early phases of a new pandemic, identifying the most relevant evidence and quantifying which studies are shared the most can help researchers and policy makers. The aim of this study is to describe and quantify the impact of early scientific production in response to COVID-19 pandemic. Methods. The study consisted of: 1) review of the scientific literature produced in the first 30 days since the first COVID-19 paper was published; 2) analysis of papers' metrics with the construction of a Computed-Impact-Score (CIS) that represents a unifying score over heterogeneous bibliometric indicators. In this study we use metrics and alternative metrics collected into five separate categories. On top of those categories we compute the CIS. Highest CIS papers are further analyzed. Results. 239 papers have been included in the study. The mean of citations, mentions and social media interactions resulted in 1.63, 10 and 1250, respectively. The paper with highest CIS resulted "Clinical features of patients[...]" by Chaolin Huang et al., which rated first also in citations and mentions. This is the first paper describing patients affected by the new disease and reporting data that are clearly of great interest to both the scientific community and the general population. Conclusions. The early response of scientific literature during an epidemic does not follow a pre- established pattern. Being able to monitor how communications spread from the scientific world toward the general population using both traditional and alternative metric measures is essential, especially in the early stages of a pandemic.

Using altmetrics for detecting impactful research in quasi-zero-day time-windows: the case of COVID-19 (preprint)

On December 31st 2019, the World Health Organization (WHO) China Country Office was informed of cases of pneumonia of unknown etiology detected in Wuhan City. The cause of the syndrome was a new type of coronavirus isolated on January 7th 2020 and named Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2). SARS-CoV-2 is the cause of the coronavirus disease 2019 (COVID-19). Since January 2020 an ever increasing number of scientific works have appeared in literature. Identifying relevant research outcomes at very early stages is challenging. In this work we use COVID-19 as a use-case for investigating: (i) which tools and frameworks are mostly used for early scholarly communication; (ii) to what extent altmetrics can be used to identify potential impactful research in tight (i.e. quasi-zero-day) time-windows. A literature review with rigorous eligibility criteria is performed for gathering a sample composed of scientific papers about SARS-CoV-2/COVID-19 appeared in literature in the tight time-window ranging from January 15th 2020 to February 24th 2020. This sample is used for building a knowledge graph that represents the knowledge about papers and indicators formally. This knowledge graph feeds a data analysis process which is applied for experimenting with altmetrics as impact indicators. We find moderate correlation among traditional citation count, citations on social media, and mentions on news and blogs. This suggests there is a common intended meaning of the citational acts associated with aforementioned indicators. Additionally, we define a method that harmonises different indicators for providing a multi-dimensional impact indicator.

Analysis of the scientific literature in the first 30 Days of the novel coronavirus outbreak. (preprint)

Introduction: Recent events highlight how emerging and re-emerging pathogens are becoming global challenges for public health. In December 2019, a novel coronavirus has emerged. This has suddenly turned out into global health concern. Objectives: Aim of this research is to focus on the bibliometric aspects in order to measure what is published in the first 30-days of a global epidemic outbreak Methods: We searched PubMed database in order to find all relevant studies in the first 30-days from the first publication. Results: From the initial 442 identified articles, 234 were read in-extenso. The majority of papers come from China, UK and USA. 63.7% of the papers were commentaries, editorials and reported data and only 17.5% of the sources used data directly collected on the field. Topics mainly addressed were epidemiology, preparedness and generic discussion. NNR showed a reduction for both the objectives assessed from January to February. Conclusions: Diagnosis and effective preventive and therapeutic measures were the fields in which more research is still needed. The vast majority of scientific literature in the first 30-days of an epidemic outbreak is based on reported data rather than primary data. Nevertheless, the scientific statements and public health decisions rely on these data.