Anemia as a risk factor for disease progression in patients admitted for COVID-19: data from a large, multicenter cohort study.

In respiratory infections, anemia is both a consequence of acute inflammation and a predictor of poor clinical outcomes. There are few studies investigating the role of anemia in COVID-19, suggesting a potential role in predicting disease severity. In this study, we aimed to assess the association between the presence of anemia at admission and incidence of severe disease and death in patients hospitalized for COVID-19. Data from all adult patients admitted for COVID-19 in University Hospital "P. Giaccone" Palermo, and University Hospital of Bari, Italy, were retrospectively collected from 1st of September 2020 to 31 August 2022. The association between anemia (defined as Hb < 13 g/dl and < 12 g/dl in males and females, respectively), in-hospital mortality and severe COVID-19 was tested using a Cox's regression analysis. Severe COVID-19 forms were defined as admission to intensive or sub-intensive care unit or a qSOFAscore ≥ 2 or CURB65scores ≥ 3. p values were calculated using the Student's t test for continuous variables and the Mantel-Haenszel Chi-square test for categorical ones. The association between anemia and the mortality was made using a Cox's regression analysis, adjusted, in two models, for the potential confounders and using a propensity score. Among the 1562 patients included in the analysis, prevalence of anemia was 45.1% (95% CI 43-48%). Patients with anemia were significantly older (p < 0.0001), reported more co-morbidities, and presented higher baseline levels of procalcitonin, CRP, ferritin and IL-6. Overall, the crude incidence of mortality was about four times higher in patients with anemia compared to those without. After adjusting for 17 potential confounders, the presence of anemia significantly increased the risk of death (HR = 2.68; 95% CI: 1.59-4.52) and of risk of severe COVID-19 (OR = 2.31; 95% CI: 1.65-3.24). The propensity score analysis substantially confirmed these analyses. Our study provides evidence that, in patients hospitalized for COVID-19, anemia is both associated with a more pronounced baseline pro-inflammatory profile and higher incidence of in-hospital mortality and severe disease.

Stool Xpert MTB/RIF as a possible diagnostic alternative to sputum in Africa: a systematic review and meta-analysis.

Introduction: Worldwide, COVID-19 pandemic lead to a large fall in the number of newly reported TB cases. In sub-Saharan Africa, microbiological diagnosis of TB is generally based on smear microscopy and Xpert MTB/RIF on sputum samples, but good quality sputum samples are often difficult to obtain, leading clinicians to rely on more invasive procedures for diagnosis. Aim of this study was to investigate pooled sensitivity and specificity of Xpert MTB/RIF on stool samples compared to respiratory microbiological reference standards in African countries. Methods: Four investigators independently searched PubMed, SCOPUS, and Web of Science until 12th October 2022, then screened titles and abstracts of all potentially eligible articles. The authors applied the eligibility criteria, considered the full texts. All the studies reported the data regarding true positive (TP), true negative (TN), false positive (FP) and false negative (FN). Risk of bias and applicability concerns were assessed with the Quadas-2 tool. Results: overall, among 130 papers initially screened, we evaluated 47 works, finally including 13 papers for a total of 2,352 participants, mainly children. The mean percentage of females was 49.6%, whilst the mean percentage of patients reporting HIV was 27.7%. Pooled sensitivity for Xpert MTB/RIF assay for detecting pulmonary tuberculosis was 68.2% (95%CI: 61.1-74.7%) even if characterized by a high heterogeneity (I2=53.7%). Specificity was almost 100% (99%, 95%CI: 97-100%; I2 = 45.7%). When divided for reference standard, in the six studies using sputum and nasogastric aspirate the accuracy was optimal (AUC = 0.99, SE = 0.02), whilst in the studies using only sputum for tuberculosis detection the AUC was 0.85 (with a SE = 0.16). The most common source of bias was exclusion of enrolled patients in the analysis. Conclusions: Our study confirms that, in Africa, stool Xpert MTB/RIF may be a useful rule-in test for children above and below 5 years of age under evaluation for pulmonary tuberculosis. Sensitivity increased substantially when using both sputum and nasogastric aspirate as reference samples.

The Role of Multidimensional Prognostic Index to Identify Hospitalized Older Adults with COVID-19 Who Can Benefit from Remdesivir Treatment: An Observational, Prospective, Multicenter Study.

BACKGROUND: Data regarding the importance of multidimensional frailty to guide clinical decision making for remdesivir use in older patients with coronavirus disease 2019 (COVID-19) are largely unexplored. OBJECTIVE: The aim of this research was to evaluate if the Multidimensional Prognostic Index (MPI), a multidimensional frailty tool based on the Comprehensive Geriatric Assessment (CGA), may help physicians in identifying older hospitalized patients affected by COVID-19 who might benefit from the use of remdesivir. METHODS: This was a multicenter, prospective study of older adults hospitalized for COVID-19 in 10 European hospitals, followed-up for 90 days after hospital discharge. A standardized CGA was performed at hospital admission and the MPI was calculated, with a final score ranging between 0 (lowest mortality risk) and 1 (highest mortality risk). We assessed survival with Cox regression, and the impact of remdesivir on mortality (overall and in hospital) with propensity score analysis, stratified by MPI = 0.50. RESULTS: Among 496 older adults hospitalized for COVID-19 (mean age 80 years, female 59.9%), 140 (28.2% of patients) were treated with remdesivir. During the 90 days of follow-up, 175 deaths were reported, 115 in hospital. Remdesivir treatment significantly reduced the risk of overall mortality (hazard ratio [HR] 0.54, 95% confidence interval CI 0.35-0.83 in the propensity score analysis) in the sample as whole. Stratifying the population, based on MPI score, the effect was observed only in less frail participants (HR 0.47, 95% CI 0.22-0.96 in propensity score analysis), but not in frailer subjects. In-hospital mortality was not influenced by remdesivir use. CONCLUSIONS: MPI could help to identify less frail older adults hospitalized for COVID-19 who could benefit more from remdesivir treatment in terms of long-term survival.

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.

Prognostic Value of Magnesium in COVID-19: Findings from the COMEPA Study.

Magnesium (Mg) plays a key role in infections. However, its role in coronavirus disease 2019 (COVID-19) is still underexplored, particularly in long-term sequelae. The aim of the present study was to examine the prognostic value of serum Mg levels in older people affected by COVID-19. Patients were divided into those with serum Mg levels ≤1.96 vs. >1.96 mg/dL, according to the Youden index. A total of 260 participants (mean age 65 years, 53.8% males) had valid Mg measurements. Serum Mg had a good accuracy in predicting in-hospital mortality (area under the curve = 0.83; 95% CI: 0.74-0.91). Low serum Mg at admission significantly predicted in-hospital death (HR = 1.29; 95% CI: 1.03-2.68) after adjusting for several confounders. A value of Mg ≤ 1.96 mg/dL was associated with a longer mean length of stay compared to those with a serum Mg > 1.96 (15.2 vs. 12.7 days). Low serum Mg was associated with a higher incidence of long COVID symptomatology (OR = 2.14; 95% CI: 1.30-4.31), particularly post-traumatic stress disorder (OR = 2.00; 95% CI: 1.24-16.40). In conclusion, low serum Mg levels were significant predictors of mortality, length of stay, and onset of long COVID symptoms, indicating that measuring serum Mg in COVID-19 may be helpful in the prediction of complications related to the disease.

Association between multidimensional prognostic index (MPI) and infections in a population of older people affected by COVID-19.

BACKGROUND: Only limited studies analyzed a possible relationship between frailty and infections. Our aim was to investigate the possible association between higher multidimensional prognostic index (MPI) values, a tool for evaluating multidimensional frailty, and the prevalence of infectious diseases, including antibiotics' cost and the prevalence of MDR (multidrug resistance) pathogens. METHODS: Older patients, affected by COVID-19, were enrolled in the hospital of Palermo over four months. RESULTS: 112 participants (mean age 77.6, 55.4% males) were included. After adjusting for potential confounders, frailer participants had a higher odds of any positivity to pathogens (prevalence: 61.5%, odds ratio = 15.56, p < 0.0001) compared to a prevalence of 8.6% in more robust, including MDR, and a higher costs in antibiotics. CONCLUSIONS: Higher MPI values, indicating frailer subjects, were associated with a higher prevalence of infections, particularly of MDR pathogens, and a consequent increase in antibiotics' cost.

Mediterranean diet in the management and prevention of obesity.

The current pandemic of obesity represents a major global public health problem, mainly due to its association with chronic non-communicable disabling conditions and with increased mortality. Population aging increases the chances of non-communicable chronic diseases allowing a longer exposure to risk factors for these disabling conditions. Obesity is a major risk factor contributing to pathological aging. Numerous epidemiological studies have shown that the risk of death due to cardiovascular disease and cancer increases progressively as overweight and obesity rise. Nutrition research is now focused on the effects of combinations of foods in dietary patterns instead of those of single nutrients or foods. The dietary model with the largest body of evidence of health benefit is that traditionally followed by inhabitants of some Mediterranean countries. There is evidence confirming the inverse association of adhering to Mediterranean diet with overweight and obesity. Four meta-analyses of randomized controlled trials, including up to 16 trials, have shown a greater reduction of body weight and BMI with MedDiet compared to other diets, while a meta-analysis of 7 prospective cohort studies, found a reduced risk of becoming obese and gaining weight over time associated with a higher adherence to MedDiet. This narrative review examines studies reporting inverse associations of a higher adherence to the MedDiet with overweight/obesity and with age-associated chronic diseases related to obesity.

Can Baseline IL-6 Levels Predict Long COVID in Subjects Hospitalized for SARS-CoV-2 Disease?

The immune response to infection plays a crucial role in the pathogenesis of COVID-19, but several patients develop a wide range of persistent symptoms, which is becoming a major global health and economic burden. However, reliable indicators are not yet available to predict the persistence of symptoms typical of the so-called long COVID. Our study aims to explore an eventual role of IL-6 levels as a marker of long COVID. Altogether, 184 patients admitted to the COVID Medicine Unit of the University Hospital in Palermo, Italy, from the 1st of September 2020, were analyzed. Patients were divided into two groups according to the IL-6 serum levels (normal or elevated), considering the serum IL-6 levels measured during the first four days of hospitalization. In our study, higher serum IL-6 levels were associated with a doubled higher risk of long COVID (OR = 2.05; 95% CI: 1.04-4.50) and, in particular, they were associated with a higher incidence of mobility decline (OR = 2.55; 95% CI: 1.08-9.40) and PTSD (OR = 2.38; 95% CI: 1.06-8.61). The analysis of our case series confirmed the prominent role of IL-6 levels in response to SARS-CoV-2 infection, as predictors not only of COVID-19 disease severity and unfavorable outcomes, but also long COVID development trends.

Older People Hospitalized for COVID-19: Prognostic Role of Multidimensional Prognostic Index and Other Prognostic Scores.

During the SARS-CoV-2 pandemic, frailty and patients' poor outcomes seem to be closely related. However, there is no clear indication of the significance of this connection and the most adequate risk index in clinical practice. In this study, we compared a short version of MPI (multidimensional prognostic index) and other two prognostic scores for COVID-19 as potential predictors of poor patient outcomes. The patients were consecutively enrolled in the hospital of Palermo for COVID-19. The accuracy of Brief-MPI, 4C score and COVID-GRAM score in points was evaluated using the area under the curve (AUC) with 95% CI, taking mortality or sub-ICU admission as outcome. The study included 112 participants (mean age 77.6, 55.4% males). During a mean of 16 days of hospitalization, Brief-MPI significantly increased by 0.03 ± 0.14 (p = 0.04), whilst COVID-GRAM did not. Brief-MPI, 4C score and COVID-GRAM scores had good accuracy in predicting negative outcomes (AUC > 0.70 for all three scores). Brief-MPI was significantly associated with an increased mortality/ICU admission risk, indicating the importance of multidimensional impairment in clinical decision-making with an accuracy similar to other prognostic scores commonly used in COVID-19 study, providing information regarding domains for which interventions can be proposed.

Incidence of long COVID-19 in people with previous SARS-Cov2 infection: a systematic review and meta-analysis of 120,970 patients

The long-term consequences of the coronavirus disease 19 (COVID-19) are likely to be frequent but results hitherto are inconclusive. Therefore, we aimed to define the incidence of long-term COVID signs and symptoms as defined by the World Health Organization, using a systematic review and meta-analysis of observational studies. A systematic search in several databases was carried out up to 12 January 2022 for observational studies reporting the cumulative incidence of long COVID signs and symptoms divided according to body systems affected. Data are reported as incidence and 95% confidence intervals (CIs). Several sensitivity and meta-regression analyses were performed. Among 11,162 papers initially screened, 196 were included, consisting of 120,970 participants (mean age: 52.3 years;48.8% females) who were followed-up for a median of six months. The incidence of any long COVID symptomatology was 56.9% (95% CI 52.2–61.6). General long COVID signs and symptoms were the most frequent (incidence of 31%) and digestive issues the least frequent (7.7%). The presence of any neurological, general and cardiovascular long COVID symptomatology was most frequent in females. Higher mean age was associated with higher incidence of psychiatric, respiratory, general, digestive and skin conditions. The incidence of long COVID symptomatology was different according to continent and follow-up length. Long COVID is a common condition in patients who have been infected with SARS-CoV-2, regardless of the severity of the acute illness, indicating the need for more cohort studies on this topic.

Incidence of long COVID-19 in people with previous SARS-Cov2 infection: a systematic review and meta-analysis of 120,970 patients.

The long-term consequences of the coronavirus disease 19 (COVID-19) are likely to be frequent but results hitherto are inconclusive. Therefore, we aimed to define the incidence of long-term COVID signs and symptoms as defined by the World Health Organization, using a systematic review and meta-analysis of observational studies. A systematic search in several databases was carried out up to 12 January 2022 for observational studies reporting the cumulative incidence of long COVID signs and symptoms divided according to body systems affected. Data are reported as incidence and 95% confidence intervals (CIs). Several sensitivity and meta-regression analyses were performed. Among 11,162 papers initially screened, 196 were included, consisting of 120,970 participants (mean age: 52.3 years; 48.8% females) who were followed-up for a median of six months. The incidence of any long COVID symptomatology was 56.9% (95% CI 52.2-61.6). General long COVID signs and symptoms were the most frequent (incidence of 31%) and digestive issues the least frequent (7.7%). The presence of any neurological, general and cardiovascular long COVID symptomatology was most frequent in females. Higher mean age was associated with higher incidence of psychiatric, respiratory, general, digestive and skin conditions. The incidence of long COVID symptomatology was different according to continent and follow-up length. Long COVID is a common condition in patients who have been infected with SARS-CoV-2, regardless of the severity of the acute illness, indicating the need for more cohort studies on this topic.

Interventions for Improving Long COVID-19 Symptomatology: A Systematic Review.

INTRODUCTION: Although the understanding of several aspects of long COVID-19 syndrome is increasing, there is limited literature regarding the treatment of these signs and symptoms. The aim of our systematic review was to understand which therapies have proved effective against the symptoms of long COVID-19. METHODS: A systematic search for randomized controlled or clinical trials in several databases was conducted through 15 May 2022. Specific inclusion criteria included: (1) intervention studies, either randomized controlled (RCTs) or clinical trials; (2) diagnosis of long COVID-19, according to the World Health Organization criteria; (3) presence of long COVID-19 for at least 12 weeks after SARS-CoV-2 infection. RESULTS: We initially found 1638 articles to screen. After removing 1602 works based on their title/abstract, we considered 35 full texts, and among them, two intervention studies were finally included. The first RCT focused on the greater improvement of treatment combining olfactory rehabilitation with oral supplementation with Palmitoylethanolamide and Luteolin in patients with olfactory dysfunction after COVID-19. The second study evaluated the positive impact of aromatherapy vs. standard care in adult females affected by fatigue. CONCLUSION: Our systematic review found only two intervention studies focused on patients affected by long COVID-19. More intervention studies are needed to investigate potentially positive interventions for long COVID-19 symptoms.

Human Monkeypox: A Comprehensive Narrative Review and Analysis of the Public Health Implications.

Recently, numerous cases of monkeypox were reported from several non-endemic countries in Europe, North America, and Oceania, suggesting an unusual and alarming public health issue, particularly considering that the disease is not directly related to human or animal travels. Attention is currently being drawn to this phenomenon since more than 70% of the global population is no longer vaccinated against smallpox. Indeed, the smallpox vaccination also confers some indirect degree of protection against other poxviruses, including monkeypox. We performed a narrative review to describe the existing literature with regard to monkeypox using the MEDLINE, EMBASE, and Scopus databases. This review aims to provide updated evidence of findings on the epidemiology, clinical features, diagnosis, management, and prevention of monkeypox, also considering the concurrent zoonotic pandemic caused by the COVID-19 coronavirus, SARS-CoV-2.

Frailty trajectories in community-dwelling older adults during COVID-19 pandemic: The PRESTIGE study.

BACKGROUND: Frailty has been recognized as potential surrogate of biological age and relevant risk factor for COVID-19 severity. Thus, it is important to explore the frailty trajectories during COVID-19 pandemic and understand how COVID-19 directly and indirectly impacts on frailty condition. METHODS: We enrolled 217 community-dwelling older adults with available information on frailty condition as assessed by multidimensional frailty model both at baseline and at one-year follow-up using Multidimensional Prognostic Index (MPI) tools. Pre-frail/frail subjects were identified at baseline as those with MPI score >0.33 (MPI grades 2-3). Frailty worsening was defined by MPI difference between 12 months follow-up and baseline ≥0.1. Multivariable logistic regression was modelled to identify predictors of worsening of frailty condition. RESULTS: Frailer subjects at baseline (MPI grades 2-3 = 48.4%) were older, more frequently female and had higher rates of hospitalization and Sars-CoV-2 infection compared to robust ones (MPI grade 1). Having MPI grades 2-3 at baseline was associated with higher risk of further worsening of frailty condition (adjusted odd ratio (aOR): 13.60, 95% confidence interval (CI): 4.01-46.09), independently by age, gender and Sars-CoV-2 infection. Specifically, frail subjects without COVID-19 (aOR: 14.84, 95% CI: 4.26-51.74) as well as those with COVID-19 (aOR: 12.77, 95% CI: 2.66-61.40, p = 0.001) had significantly higher risk of worsening of frailty condition. CONCLUSIONS: Effects of COVID-19 pandemic among community-dwelling frailer individuals are far beyond the mere infection and disease, determining a significant deterioration of frailty status both in infected and non-infected subjects.

Can the Multidimensional Prognostic Index Improve the Identification of Older Hospitalized Patients with COVID-19 Likely to Benefit from Mechanical Ventilation? An Observational, Prospective, Multicenter Study.

OBJECTIVE: Data on prognostic tools for indicating mechanical ventilation in older people with COVID-19 are still limited. The aim of this research was to evaluate if the Multidimensional Prognostic Index (MPI), based on the Comprehensive Geriatric Assessment (CGA), may help physicians in identifying older hospitalized patients affected by COVID-19 who might benefit from mechanical ventilation. DESIGN: Longitudinal, multicenter study. SETTINGS AND PARTICIPANTS: 502 older people hospitalized for COVID-19 in 10 European hospitals. METHODS: MPI was calculated using 8 different domains typical of the CGA. A propensity score, Cox's regression analysis was used for assessing the impact of mechanical ventilation on rehospitalization/mortality for 90 days' follow-up, stratified by MPI = 0.50. The accuracy of MPI in predicting negative outcomes (ie, rehospitalization/mortality) was assessed using the area under the curve (AUC), and the discrimination with several indexes like the Net Reclassification Improvement (NRI) and the Integrated Discrimination Improvement (IDI). RESULTS: Among 502 older people hospitalized for COVID-19 (mean age: 80 years), 152 were treated with mechanical ventilation. In the propensity score analysis, during the 90-day follow-up period, there were 44 rehospitalizations and 95 deaths. Mechanical ventilation in patients with MPI values ≥ 0.50, indicating frailer participants, was associated with a higher risk of rehospitalization/mortality (hazard ratio 1.56, 95% CI 1.09-2.23), whereas in participants with MPI values < 0.50 this association was not significant. The accuracy of the model including age, sex, respiratory parameters, and MPI was good (AUC = 0.783) as confirmed by an NRI of 0.2756 (P < .001) and an IDI of 0.1858 (P < .001), suggesting a good discrimination of the model in predicting negative outcomes. CONCLUSIONS AND IMPLICATIONS: MPI could be useful for better individualizing older people hospitalized by COVID-19 who could benefit from mechanical ventilation.

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.