Dementia, infections and vaccines: 30 years of controversy.

This paper reports the proceedings of a virtual meeting convened by the European Interdisciplinary Council on Ageing (EICA), to discuss the involvement of infectious disorders in the pathogenesis of dementia and neurological disorders leading to dementia. We recap how our view of the infectious etiology of dementia has changed over the last 30 years in light of emerging evidence, and we present evidence in support of the implication of infection in dementia, notably Alzheimer's disease (AD). The bacteria and viruses thought to be responsible for neuroinflammation and neurological damage are reviewed. We then review the genetic basis for neuroinflammation and dementia, highlighting the genes that are currently the focus of investigation as potential targets for therapy. Next, we describe the antimicrobial hypothesis of dementia, notably the intriguing possibility that amyloid beta may itself possess antimicrobial properties. We further describe the clinical relevance of the gut-brain axis in dementia, the mechanisms by which infection can move from the intestine to the brain, and recent findings regarding dysbiosis patterns in patients with AD. We review the involvement of specific pathogens in neurological disorders, i.e. SARS-CoV-2, human immunodeficiency virus (HIV), herpes simplex virus type 1 (HSV1), and influenza. Finally, we look at the role of vaccination to prevent dementia. In conclusion, there is a large body of evidence supporting the involvement of various infectious pathogens in the pathogenesis of dementia, but large-scale studies with long-term follow-up are needed to elucidate the role that infection may play, especially before subclinical or clinical disease is present.

Changes in sleep quality and sleep disturbances in the general population from before to during the COVID-19 lockdown: A systematic review and meta-analysis

Introduction This systematic review and meta-analysis aims to explore changes in sleep quality and sleep disturbances in the general population from before to during the COVID-19 lockdown. Methods The protocol was registered in PROSPERO (CRD42021256378) and the PRISMA guidelines were followed. The major databases and gray literature were systematically searched from inception to 28/05/2021 to identify observational studies evaluating sleep changes in the general population during the lockdown with respect to the pre-lockdown period. A random effects meta-analysis was undertaken for studies reporting (a) the means of the Pittsburgh Sleep Quality Index (PSQI) global scores or the means of the sleep onset latency (SOL) times (minutes - min) before and during the lockdown, (b) the percentages of poor sleep quality before and during the lockdown, or (c) the percentages of changes in sleep quality. Subgroup analysis by risk of bias and measurement tool utilized was carried out. A narrative synthesis on sleep efficiency, sleep disturbances, insomnia and sleep medication consumption was also performed. Results Sixty-three studies were included. A decline in sleep quality, reflected in a pooled increase in the PSQI global scores (standardized mean difference (SMD) = 0.26;95% CI 0.17–0.34) and in SOL (SMD = 0.38 min;95% CI 0.30–0.45) were found. The percentage of individuals with poor sleep quality increased during the lockdown (pooled relative risk 1.4;95% CI 1.24–1.61). Moreover, 57.3% (95% CI 50.01–61.55) of the individuals reported a change in sleep quality;in 37.3% (95% CI 34.27–40.39) of these, it was a worsening. The studies included in the systematic review reported a decrease in sleep efficiency and an increase in sleep disturbances, insomnia, and in sleep medication consumption. Discussion Timely interventions are warranted in view of the decline in sleep quality and the increase in sleep disturbances uncovered and their potentially negative impact on health. Further research and in particular longitudinal studies using validated instruments examining the long-term impact of the lockdown on sleep variables is needed. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021256378, identifier CRD42021256378.

Association Between Smoking and SARS-CoV-2 Infection: Cross-sectional Study of the EPICOVID19 Internet-Based Survey.

BACKGROUND: Several studies have reported a low prevalence of current smoking among hospitalized COVID-19 cases; however, no definitive conclusions can be drawn. OBJECTIVE: We investigated the association of tobacco smoke exposure with nasopharyngeal swab (NPS) test results for SARS-CoV-2 infection and disease severity accounting for possible confounders. METHODS: The nationwide, self-administered, cross-sectional web-based Italian National Epidemiological Survey on COVID-19 (EPICOVID19) was administered to an Italian population of 198,822 adult volunteers who filled in an online questionnaire between April 13 and June 2, 2020. For this study, we analyzed 6857 individuals with known NPS test results. The associations of smoking status and the dose-response relationship with a positive NPS test result and infection severity were calculated as odds ratios (ORs) with 95% CIs by means of logistic and multinomial regression models adjusting for sociodemographic, clinical, and behavioral characteristics. RESULTS: Out of the 6857 individuals (mean age 47.9 years, SD 14.1; 4516/6857, 65.9% female), 63.2% (4334/6857) had never smoked, 21.3% (1463/6857) were former smokers, and 15.5% (1060/6857) were current smokers. Compared to nonsmokers, current smokers were younger, were more educated, were less affected by chronic diseases, reported COVID-19-like symptoms less frequently, were less frequently hospitalized, and less frequently tested positive for COVID-19. In multivariate analysis, current smokers had almost half the odds of a positive NPS test result (OR 0.54, 95% CI 0.45-0.65) compared to nonsmokers. We also found a dose-dependent relationship with tobacco smoke: mild smokers (adjusted OR [aOR] 0.76, 95% CI 0.55-1.05), moderate smokers (aOR 0.56, 95% CI 0.42-0.73), and heavy smokers (aOR 0.38, 95% CI 0.27-0.53). This inverse association also persisted when considering the severity of the infection. Current smokers had a statistically significantly lower probability of having asymptomatic (aOR 0.50, 95% CI 0.27-0.92), mild (aOR 0.65, 95% CI 0.53-0.81), and severe infections (aOR 0.27, 95% CI 0.17-0.42) compared to those who never smoked. CONCLUSIONS: Current smoking was negatively associated with SARS-CoV-2 infection with a dose-dependent relationship. Ad hoc experimental studies are needed to elucidate the mechanisms underlying this association. TRIAL REGISTRATION: ClinicalTrials.gov NCT04471701; https://clinicaltrials.gov/ct2/show/NCT04471701.

Diabetes Affects Antibody Response to SARS-CoV-2 Vaccination in Older Residents of Long-Term Care Facilities: Data From the GeroCovid Vax Study.

OBJECTIVE: Type 2 diabetes may affect the humoral immune response after vaccination, but data concerning coronavirus disease 19 (COVID-19) vaccines are scarce. We evaluated the impact of diabetes on antibody response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in older residents of long-term care facilities (LTCFs) and tested for differences according to antidiabetic treatment. RESEARCH DESIGN AND METHODS: For this analysis, 555 older residents of LTCFs participating in the GeroCovid Vax study were included. SARS-CoV-2 trimeric S immunoglobulin G (anti-S IgG) concentrations using chemiluminescent assays were tested before the first dose and after 2 and 6 months. The impact of diabetes on anti-S IgG levels was evaluated using linear mixed models, which included the interaction between time and presence of diabetes. A second model also considered diabetes treatment: no insulin therapy (including dietary only or use of oral antidiabetic agents) and insulin therapy (alone or in combination with oral antidiabetic agents). RESULTS: The mean age of the sample was 82.1 years, 68.1% were women, and 25.2% had diabetes. In linear mixed models, presence of diabetes was associated with lower anti-S IgG levels at 2 (ß = -0.20; 95% CI -0.34, -0.06) and 6 months (ß = -0.22; 95% CI -0.37, -0.07) after the first vaccine dose. Compared with those without diabetes, residents with diabetes not using insulin had lower IgG levels at 2- and 6-month assessments (ß = -0.24; 95% CI -0.43, -0.05 and ß = -0.30; 95% CI -0.50, -0.10, respectively), whereas no differences were observed for those using insulin. CONCLUSIONS: Older residents of LTCFs with diabetes tended to have weaker antibody response to COVID-19 vaccination. Insulin treatment might buffer this effect and establish humoral immunity similar to that in individuals without diabetes.

Influenza Vaccination and COVID-19 Outcomes in People Older than 50 Years: Data from the Observational Longitudinal SHARE Study.

Existing literature on the association between influenza vaccination and COVID-19 infection/outcomes is conflicting. Therefore, we aimed to investigate the association between influenza vaccination and COVID-19 outcomes in a large cohort of adults who participated in the SHARE (Survey of Health, Ageing, and Retirement in Europe). Information regarding influenza vaccination in the previous year, and medical and demographic characteristics, were self-reported. Positivity for COVID-19, symptomatology, and hospitalization were also ascertained using self-reported information. An adjusted logistic regression analysis (including 15 baseline factors or propensity score) was used to assess the association between influenza vaccination and COVID-19 outcomes. A total of 48,408 participants (mean age 67 years; 54.1% females) were included. The prevalence of influenza vaccination was 38.3%. After adjusting for 15 potential confounders, influenza vaccination was significantly associated with a lower risk of positivity for COVID-19 (OR = 0.95; p < 0.0001), symptomatic forms (OR = 0.87; p < 0.0001), and hospitalization for COVID-19 (OR = 0.95; p < 0.0001). The results were similar when using a propensity score approach. In conclusion, influenza vaccination may be beneficial for the prevention of COVID-19, as the present study found that influenza vaccination was associated with a small/moderate lower risk of COVID-19 infection and adverse outcomes.

Multidimensional Frailty and Vaccinations in Older People: A Cross-Sectional Study.

It is known that influenza, herpes zoster, pneumococcal and pertussis infections may increase morbidity and mortality in older people. Vaccinations against these pathogens are effective in older adults. Frailty seems to be an important determinant of vaccination rates, yet data supporting this association are still missing. Therefore, we aimed to investigate the prevalence of four recommended vaccinations (influenza, herpes zoster, pneumococcal and diphtheria-tetanus-pertussis) and the association with multidimensional frailty assessed using a self-reported comprehensive geriatric assessment tool, i.e., the multidimensional prognostic index (SELFY-MPI). Older participants visiting the outpatient clinic of Azienda Ospedaliera Universitaria, Palermo, Italy were included. The SELFY-MPI questionnaire score was calculated based on eight different domains, while the vaccination status was determined using self-reported information. We included 319 participants from the 500 initially considered (63.8%). Vaccination against influenza was observed in 70.5% of the cases, whilst only 1.3% received the vaccination against diphtheria-tetanus-pertussis. Participants with higher SELFY-MPI scores were more likely to report vaccination against pneumococcus (45.6 vs. 28.3%, p = 0.01), whilst no significant differences were observed for the other vaccinations. In conclusion, the coverage of recommended vaccinations is low. Higher SELFY-MPI scores and vaccination status, particularly anti-pneumococcus, appear to be associated, but future studies are urgently needed for confirming that frailty is associated with vaccination status in older people.

Influenza Vaccination Uptake in the General Italian Population during the 2020-2021 Flu Season: Data from the EPICOVID-19 Online Web-Based Survey.

To assess influenza vaccine uptake during the 2020/2021 flu season and compare it with that of the 2019/2020 flu season among respondents to the second phase of the web-based EPICOVID-19 survey, we performed an observational web-based nationwide online survey (January-February 2021) in which respondents to the first survey (April-June 2020) were contacted and asked to complete a second questionnaire. Factors associated with vaccine uptake in the 2020/2021 flu season were assessed by applying a multivariable multinomial logistic regression model. Out of the 198,822 respondents to the first survey, 41,473 (20.9%) agreed to fill out the follow-up questionnaire; of these, 8339 (20.1%) were vaccinated only during the 2020/2021 season, 8828 (21.3%) were vaccinated during both seasons and 22,710 (54.8%) were vaccinated in neither season. Educational level (medium (aOR 1.33 95%CI 1.13-1.56) and high (aOR 1.69 95%CI 1.44-1.97) vs. low) and socio-economic deprivation according to SES scoring (1 point aOR 0.83 (95%CI 0.78-0.89), 2 aOR 0.68 (95%CI 0.60-0.77) points or ≥3 points aOR 0.42 (95%CI 0.28-0.45) vs. 0 points) were found to be associated with flu vaccine uptake. Our study shows that social determinants seemed to affect flu vaccination uptake and identifies specific categories of the population to target during future influenza vaccination campaigns.

Epidemiology of SARS-CoV-2 Infection in Italy Using Real-World Data: Methodology and Cohort Description of the Second Phase of Web-Based EPICOVID19 Study.

Digital technologies have been extensively employed in response to the SARS-CoV-2 pandemic worldwide. This study describes the methodology of the two-phase internet-based EPICOVID19 survey, and the characteristics of the adult volunteer respondents who lived in Italy during the first (April-May 2020) and the second wave (January-February 2021) of the epidemic. Validated scales and ad hoc questionnaires were used to collect socio-demographic, medical and behavioural characteristics, as well as information on COVID-19. Among those who provided email addresses during phase I (105,355), 41,473 participated in phase II (mean age 50.7 years ± 13.5 SD, 60.6% females). After a median follow-up of ten months, 52.8% had undergone nasopharyngeal swab (NPS) testing and 13.2% had a positive result. More than 40% had undergone serological test (ST) and 11.9% were positive. Out of the 2073 participants with at least one positive ST, 72.8% had only negative results from NPS or never performed it. These results indicate that a large fraction of individuals remained undiagnosed, possibly contributing to the spread of the virus in the community. Participatory online surveys offer a unique opportunity to collect relevant data at individual level from large samples during confinement.

Sex- and gender-related differences linked to SARS-CoV-2 infection among the participants in the web-based EPICOVID19 survey: the hormonal hypothesis.

Objective To investigate sex- and gender-based differences linked to SARS-COV-2 infection and to explore the role of hormonal therapy (HT) in females. Study design Data from the self-administered, cross-sectional, web-based EPICOVID19 survey of 198,822 adults living in Italy who completed an online questionnaire during the first wave of the epidemic in Italy (April-May 2020) were analyzed. Main outcomes measures Multivariate binary logistic and multinomial regression models were respectively used to estimate the odds ratios (ORs) with 95% confidence intervals (CIs) for positive nasopharyngeal swab (NPS) test results and severe SARS-CoV-2 infection. Results The data from 6,873 participants (mean age 47.9 ± 14.1 years, 65.8% females) who had a known result from an NPS test were analyzed. According to the multivariate analysis, females had lower odds of a positive result from the NPS test (aOR 0.75, 95%CI 0.66-0.85) and of having a severe infection (aOR 0.46, 95%CI 0.37-0.57) than did their male counterparts. These differences were greater with decreasing age in both sexes. In addition, females aged ≥60 years receiving HT (N = 2,153, 47.6%) had a 46% lower probability of having a positive NPS test (aOR 0.54, 95%CI 0.36-0.80) than their same-aged peers who had never used HT; there were no differences in the younger age groups with respect to HT status. Conclusion Female sex was associated with an age-dependent lower risk of having a severe SARS-CoV-2 infection than their male counterparts. Age seemed to modify the relationship between HT status and infection: while the two were not related among younger participants, it was negative in the older ones. Future prospective studies are needed to elucidate the potential protective role sex hormones may play. Trial registration ClinicalTrials.gov NCT04471701.

Accessibility to SARS-CoV-2 swab test during the Covid-19 pandemic: Did age make the difference?

Although COVID-19 affects older people more severely, health policies during the first wave of the pandemic often prioritized younger individuals. We investigated whether age had influenced the access to a diagnostic test for SARS-CoV-2 infection and whether clinical complexity and healthcare resources availability could have impacted such differences. This work included 126,741 Italian participants in the EPICOVID19 web-based survey, who reported having had contacts with known/suspected COVID-19 cases (epidemiological criterion) and/or COVID-19-like signs/symptoms (clinical criterion) from February to June 2020. Data on sociodemographic, medical history and access to SARS-CoV-2 nasopharyngeal swab (NPS) were collected. Logistic regressions estimated the probability of accessing NPS as a function of age and the possible modifying effect of chronic diseases' number and residential areas in such association. A total of 6136 (4.8%) participants had undergone an NPS. Older participants had lower NPS frequencies than the younger ones when reporting epidemiological (14.9% vs. 8.8%) or both epidemiological and clinical criteria (17.5% vs. 13.7%). After adjustment for potential confounders, including epidemiological and clinical criteria, the chance of NPS access decreased by 29% (OR=0.71, 95%CI:0.63-0.79) in older vs. younger individuals. Such disparity was accentuated in areas with greater healthcare resources. In conclusion, in the first wave of the pandemic, age may have affected the access to COVID-19 diagnostic testing, disadvantaging older people.

Manifesto on the Value of Adult Immunization: "We Know, We Intend, We Advocate".

Immunization through vaccination is a milestone achievement that has made a tremendous contribution to public health. Historically, immunization programs aimed firstly to protect children, who were disproportionally affected by infectious diseases. However, vaccine-preventable diseases can have significant impacts on adult mortality, health, and quality of life. Despite this, adult vaccinations have historically been overlooked in favor of other health priorities, because their benefits to society were not well recognized. As the general population is aging, the issue of vaccination in older adults is gaining importance. In high-income countries, recommendations for the routine vaccination of older adults have been gradually introduced. The Italian National Immunization Plan is considered to be among the most advanced adult vaccination plans in Europe. However, available data indicate there is low adherence to vaccination recommendations in Italy. The COVID-19 pandemic has exposed the damage that can be caused by an infectious disease, especially among adults and individuals with comorbidities. The aim of this "Manifesto", therefore, is to provide an overview of the existing evidence on the value of adult vaccination, in the Italian context, with a call to action to healthcare providers and health authorities.

Prevalence of unwillingness and uncertainty to vaccinate against COVID-19 in older people: A systematic review and meta-analysis.

The coronavirus disease 2019 (COVID-19) has been shown to have more severe health outcomes in older people specifically in relation to mortality and disability. Vaccination seems to be efficacious and safe for preventing the negative consequences of COVID-19, but vaccine hesitancy seems to be high in older adults. We therefore aimed to investigate the prevalence of unwillingness and the uncertainty to vaccinate against COVID-19 in older people and the factors that can be associated with the unwillingness to vaccinate. For this work, we searched several databases until 18th June 2021 for studies reporting the prevalence of unwillingness and the uncertainty to vaccinate against COVID-19 in people aged >60 years. A meta-analysis of the prevalence, with the correspondent 95% confidence intervals (CIs), was proposed. Factors that can be associated with the unwillingness to vaccinate against COVID-19 were explored through multivariable analyses and reported as odds ratios (ORs). Among 662 papers initially screened, we included 15 studies for a total of 9753 older adults. The prevalence of unwillingness to vaccinate against COVID-19 in older people was 27.03% (95%CI: 15.10-38.95%), whilst the correspondent figure of uncertainty was 19.33% (95%CI: 12.28-26.39). The risk of being unvaccinated was significantly higher in Hispanics (OR=1.197; 95%CI: 1.010-1.418) and in case of low education (OR=1.678; 95%CI: 1.170-2.408) and low income (OR=1.287; 95%CI: 1.127-1.469). In conclusion, the hesitancy for COVID-19 vaccination is a relevant problem in older people, particularly in those with a low income, a low level of education, and in Hispanics living in the United States.

Underrepresentation of older adults in clinical trials on COVID-19 vaccines: A systematic review.

During the COVID-19 pandemic older subjects have been disproportionately affected by the disease. Vaccination is a fundamental intervention to prevent the negative consequences of COVID-19, but it is not known if the needs and vulnerabilities of older people are adequately addressed by their inclusion in randomized clinical trials (RCTs) evaluating the efficacy of vaccines for COVID-19. Given this background, we aimed to evaluate if current and ongoing phase II-III RCTs evaluating the efficacy of COVID-19 vaccines included a representative sample of older people. A systematic literature search in PubMed and Clinicaltrials.gov was performed until May 01st, 2021. Among 474 abstracts initially retrieved, 20 RCTs (ten already published, ten ongoing) were included. In the ten studies already published, the mean age of participants was 45.2 ± 11.9 years and only 9.83% of the participants were more than 65 years, 1.66% more than 75 years and less than 1% (0.55%) more than 85 years. In the ten ongoing RCTs, many of the studies aimed at including participants older than 18 years, with one study including participants between 18 and 84 years, and two between 21 and 100 years. In conclusion, our systematic review demonstrates that in published and ongoing phase II-III randomized clinical trials evaluating the efficacy of COVID-19 vaccines only a tiny fraction of the most vulnerable group of older people was included, although they clearly were the first population that had to be vaccinated.

Fostering healthy aging: The interdependency of infections, immunity and frailty.

Untangling the interdependency of infections, immunity and frailty may help to clarify their roles in the maintenance of health in aging individuals, and the recent COVID-19 pandemic has further highlighted such priority. In this scoping review we aimed to systematically collect the evidence on 1) the impact of common infections such as influenza, pneumonia and varicella zoster on frailty development, and 2) the role played by frailty in the response to immunization of older adults. Findings are discussed under a unifying framework to identify knowledge gaps and outline their clinical and public health implications to foster a healthier aging. Twenty-nine studies (113,863 participants) selected to answer the first question provided a moderately strong evidence of an association between infections and physical as well as cognitive decline - two essential dimensions of frailty. Thirteen studies (34,520 participants) investigating the second aim, showed that frailty was associated with an impaired immune response in older ages, likely due to immunosenescence. However, the paucity of studies, the absence of tools to predict vaccine efficacy, and the lack of studies investigating the efficacy of newer vaccines in presence of frailty, strongly limit the formulation of more personalized immunization strategies for older adults. The current evidence suggests that infections and frailty repeatedly cross each other pathophysiological paths and accelerate the aging process in a vicious circle. Such evidence opens to several considerations. First, the prevention of both conditions pass through a life course approach, which includes several individual and societal aspects. Second, the maintenance of a well-functioning immune system may be accomplished by preventing frailty, and vice versa. Third, increasing the adherence to immunization may delay the onset of frailty and maintain the immune system homeostasis, beyond preventing infections.

Dexamethasone and oxygen therapy in care home residents with diabetes: a management guide and algorithm for treatment: a rapid response action statement from the European Diabetes Working Party for Older People (EDWPOP) and European Geriatric Medicine Society (EuGMS).

This statement addresses the need to provide clinically relevant and practical guidance for long-term care staff working in care homes and other stakeholders engaged in the care of residents who require consideration for dexamethasone and oxygen therapy. It had been provided following a series of consensus discussions between the EDWPOP and the EuGMS in January and February 2021. Its main aim is to minimise morbidity and mortality from serious acute illnesses including COVID-19 requiring these treatments within the long-term care sector.

Increase in Frailty in Nursing Home Survivors of Coronavirus Disease 2019: Comparison With Noninfected Residents.

OBJECTIVES: Institutionalized older adults have a high prevalence of frailty and disability, which may make them more vulnerable to the negative consequences of coronavirus disease 2019 (COVID-19). We investigated the impact of COVID-19 on the level of frailty, physical, and cognitive performance in nursing home residents. DESIGN: Nested case-control study. SETTING AND PARTICIPANTS: The study included nursing home residents who were infected with COVID-19 (case group, n = 76), matched by age to a control group (n = 76). METHODS: Participants' sociodemographic and medical data were collected, and they were also assessed for physical function (handgrip and walking speed), cognitive performance (Mini-Mental State Examination) and frailty (Frail-NH scale) before the first wave of the COVID-19 pandemic (October to December 2019, pre-COVID-19) and after (June to July 2020, post-COVID-19). COVID-19 symptoms and clinical course were recorded for the cases. RESULTS: Between the pre- and post-COVID-19 assessments, we found a 19% greater deterioration in handgrip, a 22% greater decrease in walking speed, and a 21% greater increase in Frail-NH scores in cases compared with controls. In both cases and controls, on the other hand, there was a significant 10% decrease in Mini-Mental State Examination scores over the study period. Multivariable logistic regression showed that COVID-19 survivors had a 4-fold increased chance of developing frailty compared with controls (odds ratio 4.95, 95% confidence interval 1.13-21.6, P = .03), but not cognitive decline. CONCLUSIONS AND IMPLICATIONS: COVID-19 can accelerate the aging process of institutionalized older adults in terms of physical performance and frailty by around 20%. However, we found similar levels of decline in cognitive performance in both cases and controls, likely because of the burden of social isolation and containment measures on neuropsychological health.

The potential long-term impact of the COVID-19 outbreak on patients with non-communicable diseases in Europe: consequences for healthy ageing.

The early stages of the COVID-19 pandemic have focused on containing SARS-CoV-2 infection and identifying treatment strategies. While controlling this communicable disease is of utmost importance, the long-term effect on individuals with non-communicable diseases (NCD) is significant. Although certain NCDs appear to increase the severity of COVID-19 and mortality risk, SARS-CoV-2 infection in survivors with NCDs may also affect the progression of their pre-existing clinical conditions. Infection containment measures will have substantial short- and long-term consequences; social distancing and quarantine restrictions will reduce physical activity and increase other unhealthy lifestyles, thus increasing NCD risk factors and worsening clinical symptoms. Vitamin D levels might decrease and there might be a rise in mental health disorders. Many countries have made changes to routine management of NCD patients, e.g., cancelling non-urgent outpatient visits, which will have important implications for NCD management, diagnosis of new-onset NCDs, medication adherence, and NCD progression. We may have opportunities to learn from this unprecedented crisis on how to leverage healthcare technologies and improve procedures to optimize healthcare service provision. This article discusses how the COVID-19 outbreak and related infection control measures could hit the most frail individuals, worsening the condition of NCD patients, while further jeopardizing the sustainability of the healthcare systems. We suggest ways to define an integrated strategy that could involve both public institutional entities and the private sector to safeguard frail individuals and mitigate the impact of the outbreak.

Age-Related Changes in Clinical Presentation of Covid-19: the EPICOVID19 Web-Based Survey.

BACKGROUND: The influence of aging and multimorbidity on Covid-19 clinical presentation is still unclear. OBJECTIVES: We investigated whether the association between symptoms (or cluster of symptoms) and positive SARS-CoV-2 nasopharyngeal swab (NPS) was different according to patients' age and presence of multimorbidity. METHODS: The study included 6680 participants in the EPICOVID19 web-based survey, who reported information about symptoms from February to June 2020 and who underwent at least one NPS. Symptom clusters were identified through hierarchical cluster analysis. The associations between symptoms (and clusters of symptoms) and positive NPS were investigated through multivariable binary logistic regression in the sample stratified by age (<65 vs ≥65 years) and number of chronic diseases (0 vs 1 vs ≥2). RESULTS: The direct association between taste/smell disorders and positive NPS was weaker in older and multimorbid patients than in their younger and healthier counterparts. Having reported no symptoms reduced the chance of positive NPS by 86% in younger (95%CI: 0.11-0.18), and by 46% in older participants (95%CI: 0.37-0.79). Of the four symptom clusters identified (asymptomatic, generic, flu-like, and combined generic and flu-like symptoms), those associated with a higher probability of SARS-CoV-2 infection were the flu-like for older people, and the combined generic and flu-like for the younger ones. CONCLUSIONS: Older age and pre-existing chronic diseases may influence the clinical presentation of Covid-19. Symptoms at disease onset tend to aggregate differently by age. New diagnostic algorithms considering age and chronic conditions may ease Covid-19 diagnosis and optimize health resources allocation. TRIAL REGISTRATION: NCT04471701 (ClinicalTrials.gov).

Rapid COVID-19 Screening Based on Self-Reported Symptoms: Psychometric Assessment and Validation of the EPICOVID19 Short Diagnostic Scale.

BACKGROUND: Confirmed COVID-19 cases have been registered in more than 200 countries, and as of July 28, 2020, over 16 million cases have been reported to the World Health Organization. This study was conducted during the epidemic peak of COVID-19 in Italy. The early identification of individuals with suspected COVID-19 is critical in immediately quarantining such individuals. Although surveys are widely used for identifying COVID-19 cases, outcomes, and associated risks, no validated epidemiological tool exists for surveying SARS-CoV-2 infection in the general population. OBJECTIVE: We evaluated the capability of self-reported symptoms in discriminating COVID-19 to identify individuals who need to undergo instrumental measurements. We defined and validated a method for identifying a cutoff score. METHODS: Our study is phase II of the EPICOVID19 Italian national survey, which launched in April 2020 and included a convenience sample of 201,121 adults who completed the EPICOVID19 questionnaire. The Phase II questionnaire, which focused on the results of nasopharyngeal swab (NPS) and serological tests, was mailed to all subjects who previously underwent NPS tests. RESULTS: Of 2703 subjects who completed the Phase II questionnaire, 694 (25.7%) were NPS positive. Of the 472 subjects who underwent the immunoglobulin G (IgG) test and 421 who underwent the immunoglobulin M test, 22.9% (108/472) and 11.6% (49/421) tested positive, respectively. Compared to NPS-negative subjects, NPS-positive subjects had a higher incidence of fever (421/694, 60.7% vs 391/2009, 19.5%; P<.001), loss of taste and smell (365/694, 52.6% vs 239/2009, 11.9%; P<.001), and cough (352/694, 50.7% vs 580/2009, 28.9%; P<.001). With regard to subjects who underwent serological tests, IgG-positive subjects had a higher incidence of fever (65/108, 60.2% vs 43/364, 11.8%; P<.001) and pain in muscles/bones/joints (73/108, 67.6% vs 71/364, 19.5%; P<.001) than IgG-negative subjects. An analysis of self-reported COVID-19 symptom items revealed a 1-factor solution, the EPICOVID19 diagnostic scale. The following optimal scores were identified: 1.03 for respiratory problems, 1.07 for chest pain, 0.97 for loss of taste and smell 0.97, and 1.05 for tachycardia (ie, heart palpitations). These were the most important symptoms. For adults aged 18-84 years, the cutoff score was 2.56 (sensitivity: 76.56%; specificity: 68.24%) for NPS-positive subjects and 2.59 (sensitivity: 80.37%; specificity: 80.17%) for IgG-positive subjects. For subjects aged ≥60 years, the cutoff score was 1.28, and accuracy based on the presence of IgG antibodies improved (sensitivity: 88.00%; specificity: 89.58%). CONCLUSIONS: We developed a short diagnostic scale to detect subjects with symptoms that were potentially associated with COVID-19 from a wide population. Our results support the potential of self-reported symptoms in identifying individuals who require immediate clinical evaluations. Although these results come from the Italian pandemic period, this short diagnostic scale could be optimized and tested as a screening tool for future similar pandemics.