Post-COVID Trajectory of Pentraxin 3 Plasma Levels Over 6 Months and Their Association with the Risk of Developing Post-Acute Depression and Anxiety.

BACKGROUND AND OBJECTIVES: Clinical manifestations of coronavirus disease 2019 (COVID-19) often persist after acute disease resolution. Underlying molecular mechanisms are unclear. The objective of this original article was to longitudinally measure plasma levels of markers of the innate immune response to investigate whether they associate with and predict post-COVID symptomatology. METHODS: Adult patients with previous severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection during the first pandemic wave who underwent the 6-month multidisciplinary follow-up were included. Plasma levels of pentraxin 3 (PTX3), the complement components C3a and C5a, and chitinase-3 like-protein-1 (CHI3L1) were measured at hospital admission during acute disease (baseline) and at 1 and 6 months after hospital discharge. Associations with post-COVID-19 sequelae at 6 months were investigated using descriptive statistic and multiple regression models. RESULTS: Ninety-four COVID-19 patients were included. Baseline PTX3, C5a, C3a, and CHI3L1 did not predict post-COVID-19 sequelae. The extent of the reduction of PTX3 over time (delta PTX3) was associated with lower depressive and anxiety symptoms at 6 months (both p < 0.05). When entering sex, age, need for intensive care unit or non-invasive ventilation during hospital stay, psychiatric history, and baseline PTX3 as nuisance covariates into a generalized linear model (GLM), the difference between baseline and 6-month PTX3 levels (delta PTX3) significantly predicted depression (χ2 = 4.66, p = 0.031) and anxiety (χ2 = 4.68, p = 0.031) at 6 months. No differences in PTX3 levels or PTX3 delta were found in patients with or without persistent or new-onset other COVID-19 symptoms or signs at 6 months. Plasma levels of C3a, C5a, and CHI3L1 did not correlate with PTX3 levels at either time point and failed to associate with residual or de novo respiratory or systemic clinical manifestations of the disease at 6 months. CONCLUSIONS: A lower reduction of plasma PTX3 after acute COVID-19 associates with the presence of depression and anxiety, suggesting an involvement of inflammation in post-COVID-19 psychopathology and a potential role of PTX3 as a biomarker.

Universal screening for early detection of chronic autoimmune, metabolic and cardiovascular diseases in the general population using capillary blood (UNISCREEN): low-risk interventional, single-centre, pilot study protocol.

INTRODUCTION: Chronic autoimmune (type 1 diabetes and coeliac disease) and metabolic/cardiovascular (type 2 diabetes, dyslipidaemia, hypertension) diseases are highly prevalent across all age ranges representing a major public health burden. Universal screening for prediction/early identification of these conditions is a potential tool for reducing their impact on the general population. The aim of this study is to assess whether universal screening using capillary blood sampling is feasible at a population-based level. METHODS AND ANALYSIS: This is a low-risk interventional, single-centre, pilot study for a population-based screening programme denominated UNISCREEN. Participants are volunteers aged 1-100 who reside in the town of Cantalupo (Milan, Italy) undergoing: (1) interview collecting demographics, anthropometrics and medical history; (2) capillary blood collection for measurement of type 1 diabetes and coeliac disease-specific autoantibodies and immediate measurement of glucose, glycated haemoglobin and lipid panel by point-of-care devices; (3) venous blood sampling to confirm autoantibody-positivity; (4) blood pressure measurement; (5) fulfilment of a feasibility and acceptability questionnaire. The outcomes are the assessment of feasibility and acceptability of capillary blood screening, the prevalence of presymptomatic type 1 diabetes and undiagnosed coeliac disease, distribution of glucose categories, lipid panel and estimate of cardiovascular risk in the study population. With approximately 3000 inhabitants, the screened population is expected to encompass at least half of its size, approaching nearly 1500 individuals. ETHICS AND DISSEMINATION: This protocol and the informed consent forms have been reviewed and approved by the San Raffaele Hospital Ethics Committee (approval number: 131/INT/2022). Written informed consent is obtained from all study participants or their parents if aged <18. Results will be published in scientific journals and presented at meetings. CONCLUSIONS: If proven feasible and acceptable, this universal screening model would pave the way for larger-scale programmes, providing an opportunity for the implementation of innovative public health programmes in the general population. TRIAL REGISTRATION NUMBER: NCT05841719.

Micronized/ultramicronized palmitoylethanolamide improves depression and fatigue in coronavirus disease 2019 (COVID-19) survivors.

Coronavirus disease 2019 (COVID-19) may lead to neuropsychiatric sequelae. Palmitoylethanolamide (PEA) is an anti-inflammatory and neuroprotective amide used in depressive syndromes. Here we investigate whether micronized/ultramicronized (m/um) PEA improves neuropsychiatric sequelae in COVID-19 survivors. Patients evaluated at our post-COVID-19 outpatient clinic between February and August 2021 and presenting neuropsychiatric manifestations (n = 98) were offered treatment with m/umPEA 600 mg twice daily for 3 months. Those accepting m/umPEA therapy (n = 57) were compared with those who did not (n = 41), in terms of depression, fatigue, chronic pain and subjective well-being, through validated scales administered pre- and posttreatment. The two groups did not differ in terms of demographics, comorbidities, psychiatric history, antidepressant therapy, acute COVID-19 severity and baseline neuropsychiatric status. Patients receiving m/umPEA showed a greater improvement in depression and fatigue (both P < 0.05). Conversely, no association was found with changes in chronic pain or subjective well-being. At multivariable logistic regression, m/umPEA predicted neuropsychiatric improvement independently of age, sex and baseline neuropsychiatric status. Worse pretreatment fatigue and subjective well-being identified those who most likely benefited from treatment. In conclusion, despite its retrospective nature, our study suggests that m/umPEA may improve depression and fatigue in COVID-19 survivors, justifying future research in this setting.

Longitudinal Changes in Physical Function and Their Impact on Health Outcomes in COVID-19 Patients.

BACKGROUND: Coronavirus disease (COVID-19) is correlated with a variety of long-term sequelae that affect different aspects of health, including physical function. This study investigated the longitudinal changes in handgrip strength (HGS) over six months post-hospital discharge in COVID-19 patients and explores the associations between HGS, health-related quality of life, dyspnoea, exercise capacity, and body mass index (BMI). METHODS: Adult COVID-19 patients were followed up at one, three, and six months after hospital discharge. HGS, BMI, exercise capacity, and health-related quality of life were assessed. Data from patients with HGS measurements at all three time points were analysed. RESULTS: Low HGS was prevalent one month post-discharge (35%). Participants with low HGS exhibited more severe disease (30.5% vs. 5.9% were admitted to the intensive care unit, p < 0.01), longer hospital stays (median [IQR] 21 [10.0; 40.5] vs. 12.0 [8.0; 20.0] days, p < 0.01), greater weight loss (-5.7 [-9.1; -0.6] vs. -3.2 [-5.7; -0.0] kg, p = 0.004), and reduced exercise capacity (6 min walking test [6 MWT], 95.7 [84.0; 102.0] vs. 100.0 [92.9; 105.0]% predicted, p = 0.007). Those with persistently low HGS (40% of the initial low HGS group) had worse exercise capacity (6-MWT 93.3 [78.3; 101.0] vs. 101.0 [95.0; 107.0]% predicted, p < 0.001), more dyspnoea (29.0% vs. 2.0% of participants, p < 0.001), poorer quality of life (visual analogue scale score, 75 [50; 75] vs. 85 [75; 95], p < 0.001), and higher rates of problems in various health dimensions. HGS at 1 month was the only significant predictor of HGS improvement from 1 month to 6 months (odds ratio [95% CI] 1.11 [1.03; 1.20], p = 0.008). CONCLUSIONS: This study highlights the prevalence of reduced physical function among COVID-19 survivors and emphasises the importance of early identification and intervention to optimise their long-term health. Monitoring HGS, a simple and reliable tool, can provide valuable insights into patients' overall physical function, aiding in tailored care and improved outcomes.

Prevalence of Long COVID-19 Symptoms After Hospital Discharge in Frail and Robust Patients.

Background: A motley postacute symptomatology may develop after COVID-19, irrespective of the acute disease severity, age, and comorbidities. Frail individuals have reduced physiological reserves and manifested a worse COVID-19 course, during the acute setting. However, it is still unknown, whether frailty may subtend some long COVID-19 manifestations. We explored the prevalence of long COVID-19 disturbs in COVID-19 survivals. Methods: This was an observational study. Patients aged 65 years or older were followed-up 1, 3, and 6 months after hospitalization for COVID-19 pneumonia. Results: A total of 382 patients were enrolled. Frail patients were more malnourished (median Mini Nutritional Assessment Short Form score 8 vs. 9, p = 0.001), at higher risk of sarcopenia [median Strength, Assistance with walking, Rising from a chair, Climbing stairs, and Falls (SARC-F) score 3 vs. 1.5, p = 0.003], and manifested a worse physical performance [median Short Physical Performance Battery (SPPB) score 10 vs. 11, p = 0.0007] than robust individuals, after hospital discharge following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. Frailty was significantly associated with: (i) confusion, as a presenting symptom of COVID-19 [odds ratio (OR) 77.84, 95% CI 4.23-1432.49, p = 0.003]; (ii) malnutrition (MNA-SF: adjusted B -5.63, 95% CI -8.39 to -2.87, p < 0.001), risk of sarcopenia (SARC-F: adjusted B 9.11, 95% CI 3.10-15.13, p = 0.003), impaired muscle performance (SPPB: B -3.47, 95% CI -6.33 to -0.61, p = 0.02), complaints in mobility (adjusted OR 1674200.27, 95% CI 4.52-619924741831.25, p = 0.03), in self-care (adjusted OR 553305.56, 95% CI 376.37-813413358.35, p < 0.001), and in performing usual activities of daily living (OR 71.57, 95% CI 2.87-1782.53, p = 0.009) at 1-month follow-up; (iii) dyspnea [modified Medical Research Council (mMRC): B 4.83, 95% CI 1.32-8.33, p = 0.007] and risk of sarcopenia (SARC-F: B 7.12, 95% CI 2.17-12.07, p = 0.005) at 3-month follow-up; and (iv) difficulties in self-care (OR 2746.89, 95% CI 6.44-1172310.83, p = 0.01) at the 6-month follow-up. In a subgroup of patients (78 individuals), the prevalence of frailty increased at the 1-month follow-up compared to baseline (p = 0.009). Conclusion: The precocious identification of frail COVID-19 survivors, who manifest more motor and respiratory complaints during the follow-up, could improve the long-term management of these COVID-19 sequelae.

Evaluation of Muscle Mass and Stiffness with Limb Ultrasound in COVID-19 Survivors.

BACKGROUND: acute illnesses, like COVID-19, can act as a catabolic stimulus on muscles. So far, no study has evaluated muscle mass and quality through limb ultrasound in post-COVID-19 patients. METHODS: cross sectional observational study, including patients seen one month after hospital discharge for SARS-CoV-2 pneumonia. The patients underwent a multidimensional evaluation. Moreover, we performed dominant medial gastrocnemius ultrasound (US) to characterize their muscle mass and quality. RESULTS: two hundred fifty-nine individuals (median age 67, 59.8% males) were included in the study. COVID-19 survivors with reduced muscle strength had a lower muscle US thickness (1.6 versus 1.73 cm, p =0.02) and a higher muscle stiffness (87 versus 76.3, p = 0.004) compared to patients with normal muscle strength. Also, patients with reduced Short Physical Performance Battery (SPPB) scores had a lower muscle US thickness (1.3 versus 1.71 cm, p = 0.01) and a higher muscle stiffness (104.9 versus 81.07, p = 0.04) compared to individuals with normal SPPB scores. The finding of increased muscle stiffness was also confirmed in patients with a pathological value (≥ 4) at the sarcopenia screening tool SARC-F (103.0 versus 79.55, p < 0.001). Muscle stiffness emerged as a significant predictor of probable sarcopenia (adjusted OR 1.02, 95% C.I. 1.002 - 1.04, p = 0.03). The optimal ultrasound cut-offs for probable sarcopenia were 1.51 cm for muscle thickness (p= 0.017) and 73.95 for muscle stiffness (p = 0.004). DISCUSSION: we described muscle ultrasound characteristics in post COVID-19 patients. Muscle ultrasound could be an innovative tool to assess muscle mass and quality in this population. Our preliminary findings need to be confirmed by future studies comparing muscle ultrasound with already validated techniques for measuring muscle mass and quality.

Exercise for slowing the progression of atherosclerotic process: effects on inflammatory markers.

Atherosclerosis is a dynamic process driven by all cardiovascular risk factors that can be briefly divided into an early and a late phase. Inflammation is one of the fundamental substrates that initiates the atherosclerotic process in the early stages and promotes and maintains it in the final stages. In the last decades, clinical and experimental data have shown that inflammation is supported by mediators that respond to physical activity. The present review aimed at investigating the effect of physical exercise on inflammatory mediators, both the positive ones that have a proinflammatory effect (interleukin 6, c-reactive protein and tumor necrosis factor α, interferon γ, high-mobility group box-1), and the negative ones which have an anti-inflammatory effect (interleukin 10). Pooled data support the evidence that physical exercise can directly modulate the activity of inflammatory cytokines slowing down or preventing the formation of the atherosclerotic stage.