Inadequate Physical Activity Is Associated with Worse Physical Function in a Sample of COVID-19 Survivors with Post-Acute Symptoms.

Background-Patients affected by Long COVID often report shorter times spent doing physical activity (PA) after COVID-19. The aim of the present study was to evaluate potential associations between PA levels and parameters of physical function in a cohort of COVID-19 survivors with post-acute symptoms, with a particular focus on individuals aged 65 and older. Materials and methods-PA levels before and after COVID-19 were assessed in a sample of patients that had recovered from COVID-19 and were admitted to a post-acute outpatient service at the Fondazione Policlinico Universitario Agostino Gemelli IRCCS (Rome, Italy). Participation in PA was operationalized as the engagement in leisure-time PA for at least 150 min per week in the last 3 months. Self-rated health and measures of physical performance and muscle strength were assessed. Results-Mean age of 1846 participants was 55.2 ± 14.4 years and 47% were women. Before COVID-19, inactivity was detected in 47% of the whole study population; only 28% maintained pre-COVID-19 PA engagement. Inactivity was more frequent in women. The stopping of physical activity was associated with increased BMI and CRP levels, lower vitamin D levels and a higher prevalence of post-COVID-19 fatigue, dyspnea, arthralgia, and myalgia. Active participants had higher handgrip strength and performed better on both the six-minute walking test (6MWT) and at the one-minute sit-to-stand test (1MSTST). In particular, at the 6MWT, participants 65 and older that were still active after COVID-19 walked 32 m more than sedentary peers. Moreover, the distance covered was 28 m more than those who were active only before COVID-19 (p = 0.05). Formerly active subjects performed similarly at the 6MWT to inactive participants. PA was associated with better self-rated health. Conclusions-Our findings reveal that inactivity is frequent in the post-acute COVID-19 phase. Stopping physical activity after COVID-19 results in measures of performance that are comparable to those who were never active. Relevant differences in the distance covered at the 6MWT were found between older active subjects and their sedentary peers.

Use of First-Line Oral Analgesics during and after COVID-19: Results from a Survey on a Sample of Italian 696 COVID-19 Survivors with Post-Acute Symptoms.

Background-Analgesics could be used to manage painful symptoms during and after COVID-19. Materials and methods-Persistence of painful symptoms was assessed during and after COVID-19 in a sample of patients admitted to a post-acute COVID-19 outpatient service in Rome, Italy. Data on type and frequency of use of first-line analgesics were collected. Pain severity was evaluated with a numeric rating scale (NRS) from 0 to 10. Results-Mean age of 696 participants was 57.1 ± 20.3 years and 61.7% were women. During COVID-19, the most prevalent symptoms were fever, fatigue, arthralgia, myalgia and headache. Acetaminophen was used by 40% of the sample. Only 6.7% needed to continue analgesic therapy after COVID-19. Frequent causes of analgesics consumption were persistent arthralgia and myalgia. The most common analgesics used amongst those who continued taking analgesics in the post-acute phase of COVID-19 were the following: acetaminophen (31%), ibuprofen (31%) and other non-steroidal anti-inflammatory drug (NSAID) (29.5%); in older subjects the most common analgesic used was acetaminophen (54%). Most of the subjects in this group said there was an improvement in pain perception after taking analgesic therapy (84%). Conclusions-Use of analgesics in the post-acute COVID-19 is common in subjects with persistent arthralgia and myalgia, and common analgesics were acetaminophen and ibuprofen. Further research on the safety and efficacy of those medications in COVID-19 is warranted.

Effects of l-Arginine Plus Vitamin C Supplementation on l-Arginine Metabolism in Adults with Long COVID: Secondary Analysis of a Randomized Clinical Trial.

Altered l-arginine metabolism has been described in patients with COVID-19 and has been associated with immune and vascular dysfunction. In the present investigation, we determined the serum concentrations of l-arginine, citrulline, ornithine, monomethyl-l-arginine (MMA), and symmetric and asymmetric dimethylarginine (SDMA, ADMA) in adults with long COVID at baseline and after 28-days of l-arginine plus vitamin C or placebo supplementation enrolled in a randomized clinical trial, compared with a group of adults without previous history of SARS-CoV-2-infection. l-arginine-derived markers of nitric oxide (NO) bioavailability (i.e., l-arginine/ADMA, l-arginine/citrulline+ornithine, and l-arginine/ornithine) were also assayed. Partial least squares discriminant analysis (PLS-DA) models were built to characterize systemic l-arginine metabolism and assess the effects of the supplementation. PLS-DA allowed discrimination of participants with long COVID from healthy controls with 80.2 ± 3.0% accuracy. Lower markers of NO bioavailability were found in participants with long COVID. After 28 days of l-arginine plus vitamin C supplementation, serum l-arginine concentrations and l-arginine/ADMA increased significantly compared with placebo. This supplement may therefore be proposed as a remedy to increase NO bioavailability in people with long COVID.

Inflammaging at the Time of COVID-19.

Severe coronavirus disease 2019 (COVID-19) is associated with overproduction of proinflammatory cytokines. The ensuing cytokine storm contributes to the development of severe pneumonia and, possibly, to long-term symptom persistence (long COVID). The chronic state of low-grade inflammation that accompanies aging (inflammaging) might predispose older adults to severe COVID-19. Inflammaging may also contribute to symptom persistence following acute COVID-19. Antiinflammatory drugs and immunomodulatory agents can achieve significant therapeutic gain during acute COVID-19. Lifestyle interventions (eg, physical activity, diet) may be proposed as strategies to counteract inflammation and mitigate long-term symptom persistence.

Health trajectories in older patients hospitalized for COVID-19: Results from the GeroCovid multicenter study.

BACKGROUND: COVID-19 has disproportionately affected older adults. Yet, healthcare trajectories experienced by older persons hospitalized for COVID-19 have not been investigated. This study aimed at estimating the probabilities of transitions between severity states in older adults admitted in COVID-19 acute wards and at identifying the factors associated with such dynamics. METHODS: COVID-19 patients aged ≥60 years hospitalized between March and December 2020 were involved in the multicentre GeroCovid project-acute wards substudy. Sociodemographic and health data were obtained from medical records. Clinical states during hospitalization were categorized on a seven-category scale, ranging from hospital discharge to death. Based on the transitions between these states, first, we defined patients' clinical course as positive (only improvements), negative (only worsening), or fluctuating (both improvements and worsening). Second, we focused on the single transitions between clinical states and estimated their probability (through multistage Markov modeling) and associated factors (with proportional intensity models). RESULTS: Of the 1024 included patients (mean age 78.1 years, 51.1% women), 637 (62.2%) had a positive, 66 (6.4%) had a fluctuating, and 321 (31.3%) had a negative clinical course. Patients with a fluctuating clinical course were younger, had better mobility and cognitive levels, fewer diseases, but a higher prevalence of cardiovascular disease and obesity. Considering the single transitions, the probability that older COVID-19 patients experienced clinical changes was higher within a 10-day timeframe, especially for milder clinical states. Older age, male sex, lower mobility level, multimorbidity, and hospitalization during the COVID-19 first wave (compared with the second one) were associated with an increased probability of progressing towards worse clinical states or with a lower recovery. CONCLUSION: COVID-19 in older inpatients has a complex and dynamic clinical course. Identifying individuals more likely to experience a fluctuating clinical course and sudden worsening may help organize healthcare resources and clinical management across settings at different care intensity levels.

Effects of l-Arginine Plus Vitamin C Supplementation on Physical Performance, Endothelial Function, and Persistent Fatigue in Adults with Long COVID: A Single-Blind Randomized Controlled Trial.

Long COVID, a condition characterized by symptom and/or sign persistence following an acute COVID-19 episode, is associated with reduced physical performance and endothelial dysfunction. Supplementation of l-arginine may improve endothelial and muscle function by stimulating nitric oxide synthesis. A single-blind randomized, placebo-controlled trial was conducted in adults aged between 20 and 60 years with persistent fatigue attending a post-acute COVID-19 outpatient clinic. Participants were randomized 1:1 to receive twice-daily orally either a combination of 1.66 g l-arginine plus 500 mg liposomal vitamin C or a placebo for 28 days. The primary outcome was the distance walked on the 6 min walk test. Secondary outcomes were handgrip strength, flow-mediated dilation, and fatigue persistence. Fifty participants were randomized to receive either l-arginine plus vitamin C or a placebo. Forty-six participants (median (interquartile range) age 51 (14), 30 [65%] women), 23 per group, received the intervention to which they were allocated and completed the study. At 28 days, l-arginine plus vitamin C increased the 6 min walk distance (+30 (40.5) m; placebo: +0 (75) m, p = 0.001) and induced a greater improvement in handgrip strength (+3.4 (7.5) kg) compared with the placebo (+1 (6.6) kg, p = 0.03). The flow-mediated dilation was greater in the active group than in the placebo (14.3% (7.3) vs. 9.4% (5.8), p = 0.03). At 28 days, fatigue was reported by two participants in the active group (8.7%) and 21 in the placebo group (80.1%; p < 0.0001). l-arginine plus vitamin C supplementation improved walking performance, muscle strength, endothelial function, and fatigue in adults with long COVID. This supplement may, therefore, be considered to restore physical performance and relieve persistent symptoms in this patient population.

Fatigue in Covid-19 survivors: The potential impact of a nutritional supplement on muscle strength and function.

BACKGROUND: Fatigue with reduced tolerance to exercise is a common persistent long-lasting feature amongst COVID-19 survivors. The assessment of muscle function in this category of patients is often neglected. AIM: To evaluate the potential impact of a daily supplementation based on amino acids, minerals, vitamins, and plant extracts (Apportal®) on muscle function, body composition, laboratory parameters and self-rated health in a small group of COVID-19 survivors affected by fatigue. METHODS: Thirty participants were enrolled among patients affected by physical fatigue during or after acute COVID-19 and admitted to the post-COVID-19 outpatient service at Fondazione Policlinico Gemelli in Rome between 1st March 2021 and 30th April 2021. All participants were evaluated at first visit (t0) and at control visit (t1), after taking a daily sachet of Apportal® for 28 days. Muscle function was analyzed using hand grip strength test, exhaustion strength time and the number of repetitions at one-minute chair stand test. Body composition was assessed with bioelectrical impedance analysis (BIA). Laboratory parameters, including standard blood biochemistry and ferritin levels, were evaluated at the first visit and during the control visit. A quick evaluation of self-rated health, before COVID-19, at t0 and t1, was obtained through a visual analogue scale (VAS). RESULTS: Participants aged 60 years and older were 13 (43%). Females represented the 70% of the study sample. Participants hospitalized for COVID-19 with low-flow oxygen supplementation represented the 43.3% of the study sample while 3.3% received noninvasive ventilation (NIV) or invasive ventilation. Hand grip strength improved from 26.3 Kg to 28.9 Kg (p < 0.05) at t1 as compared to t0. The mean time of strength exhaustion increased from 31.7 s (sec) at t0 to 47.5 s at t1 (p < 0.05). Participants performed a higher number of repetitions (28.3 vs. 22.0; p < 0.05) during the one-minute chair stand test at t1 as compared to t0. A trend, although not significant, in reduction of ferritin levels was found after nutritional supplementation (94.4 vs. 84.3, respectively; p = 0.01). The self-rated health status increased by at least 13 points (t0, mean 57.6 ± 5.86; t1, mean 71.4 ± 6.73; p < 0.05). CONCLUSIONS: After 28 days of nutritional supplementation with Apportal® in COVID-19 survivors affected by fatigue with reduced tolerance to exercise, we found a significant improvement in means of muscle strength and physical performance, associated with enhancement of self-rated health status between t0 and t1.

Lifestyle Changes and Psychological Well-Being in Older Adults During COVID-19 Pandemic.

COVID-19 pandemic forced countries to adopt strategies aimed at responding to the health emergency by containing contagion. Lockdowns have ensured the achievement of this goal but imposed substantial restrictions to the freedom of movement and resulted in social isolation for a large share of vulnerable people. The aim of the present study was to evaluate the impact of COVID-19 pandemic and associated emergency restriction measures on the quality of life, lifestyle habits, and psychosocial status in older adults.

Nutraceuticals and Dietary Supplements for Older Adults with Long COVID-19.

The persistence of COVID-19 symptoms weeks or months after an initial SARS-CoV-2 infection has become one of the most burdensome legacies of the pandemic. This condition, known as long COVID syndrome, affects many persons of all age groups and is associated with substantial reductions of quality of life. Several mechanisms may be involved in long COVID syndrome, including chronic inflammation, metabolic perturbations, endothelial dysfunction, and gut dysbiosis. These pathogenic mechanisms overlap with those of the aging process and may aggravate pre-existing degenerative conditions. This review discusses bioactive foods, supplements, and nutraceuticals as possible interventions against long COVID syndrome.

Sarcopenia as potential biological substrate of long COVID-19 syndrome: prevalence, clinical features, and risk factors.

BACKGROUND: Severe clinical pictures and sequelae of COVID-19 disease are immune mediated and characterized by a 'cytokine storm'. Skeletal muscle has emerged as a potent regulator of immune system function. The aim of the present study is to define the prevalence of sarcopenia among COVID-19 survivors and the negative impact of sarcopenia on the post-acute COVID-19 syndrome and its related risk factors. METHODS: A total of 541 subjects recovered from COVID-19 disease were enrolled in the Gemelli Against COVID-19 Post-Acute Care between April 2020 and February 2021. They underwent a multidisciplinary clinical evaluation and muscle strength and physical performance assessment. RESULTS: Mean age was 53.1 years (SD 15.2, range from 18 to 86 years), and 274 (51%) were women. The prevalence of sarcopenia was 19.5%, and it was higher in patients with a longer hospital stay and lower in patients who were more physically active and had higher levels of serum albumin. Patients with sarcopenia had a higher number of persistent symptoms than non-sarcopenic patients (3.8 ± 2.9 vs. 3.2 ± 2.8, respectively; P = 0.06), in particular fatigue, dyspnoea, and joint pain. CONCLUSIONS: Sarcopenia identified according to the EWGSOP2 criteria is high in patients recovered from COVID-19 acute illness, particularly in those who had experienced the worst clinical picture reporting the persistence of fatigue and dyspnoea. Our data suggest that sarcopenia, through the persistence of inflammation, could be the biological substrate of long COVID-19 syndrome. Physical activity, especially if associated with adequate nutrition, seems to be an important protective factor.

Effects of a New Multicomponent Nutritional Supplement on Muscle Mass and Physical Performance in Adult and Old Patients Recovered from COVID-19: A Pilot Observational Case-Control Study.

OBJECTIVE: The purpose of the present study was to assess the effect of a specific oral nutritional supplement among patients recovered from COVID-19 but suffering symptoms of fatigue. METHODS: This is an observational case-control study involving a sample of 66 COVID-19 survivors divided in two groups, 33 subjects in the intervention group who received the nutritional supplement and 33 subjects in the control group. The nutritional supplement received by subjects in the active group was based on amino acids; vitamin B6 and B1; and malic, succinic and citric acids. After an 8-week follow-up, the main outcomes considered were skeletal muscle index (measured by bioelectrical impedance analysis), physical performance measures (handgrip strength, one-minute chair-stand test, six-minute walking test), and quality of life (using EuroQol visual analogue scale). RESULTS: All the considered areas increased significantly in the subjects receiving the active treatment with oral nutritional supplement in comparison with the baseline values. After adjusting for age, gender, and baseline values, skeletal muscle index, handgrip strength test, the one-minute chair-stand test, and six-minute walking test values were higher among participants in the treatment group compared with subjects in control group. The oral nutritional supplement significantly improved the handgrip strength; similarly, participants in the active group showed a higher improvement in skeletal muscle index, the one-minute chair-stand test, the six-minute walking test, and in quality of life. CONCLUSION: The nutritional supplement containing nine essential amino acids plus cysteine; vitamin B6 and B1; and malic, succinic and citric acids had a positive effect on nutritional status, functional recovery, and quality of life in COVID-19 survivors still suffering from fatigue. Additional controlled clinical trials are required to corroborate these results.

Inflamm-aging at the time of COVID-19

Synopsis Severe COVID-19 is associated with overproduction of pro-inflammatory cytokines. The ensuing cytokine storm contributes to the development of severe pneumonia and, possibly, to long-term symptom persistence (long COVID). The chronic state of low-grade inflammation that accompanies aging (inflamm-aging) might predispose older adults to severe COVID-19. Inflamm-aging may also contribute to symptom persistence following acute COVID-19. Anti-inflammatory drugs and immunomodulatory agents can achieve significant therapeutic gain during acute COVID-19. Lifestyle interventions (e.g., physical activity, diet) may be proposed as strategies to counteract inflammation and mitigate long-term symptom persistence.

Prevalence and Predictors of Persistence of COVID-19 Symptoms in Older Adults: A Single-Center Study.

OBJECTIVES: Symptom persistence weeks after laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance is a relatively common long-term complication of Coronavirus disease 2019 (COVID-19). Little is known about this phenomenon in older adults. The present study aimed at determining the prevalence of persistent symptoms among older COVID-19 survivors and identifying symptom patterns. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: We analyzed data collected in people 65 years and older (n = 165) who were hospitalized for COVID-19 and then admitted to the Day Hospital Post-COVID 19 of the Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS (Rome, Italy) between April and December 2020. All patients tested negative for SARS-CoV-2 and met the World Health Organization criteria for quarantine discontinuation. MEASURES: Patients were offered multidisciplinary individualized assessments. The persistence of symptoms was evaluated on admission using a standardized questionnaire. RESULTS: The mean age was 73.1 ± 6.2 years (median 72, interquartile range 27), and 63 (38.4%) were women. The average time elapsed from hospital discharge was 76.8 ± 20.3 days (range 25-109 days). On admission, 137 (83%) patients reported at least 1 persistent symptom. Of these, more than one-third reported 1 or 2 symptoms and 46.3% had 3 or more symptoms. The rate of symptom persistence was not significantly different when patients were stratified according to median age. Compared with those with no persistent symptoms, patients with symptom persistence reported a greater number of symptoms during acute COVID-19 (5.3 ± 3.0 vs 3.3 ± 2.0; P < .001). The most common persistent symptoms were fatigue (53.1%), dyspnea (51.5%), joint pain (22.2%), and cough (16.7%). The likelihood of symptom persistence was higher in those who had experienced fatigue during acute COVID-19. CONCLUSIONS AND IMPLICATIONS: Persistent symptoms are frequently experienced by older adults who have been hospitalized for COVID-19. Follow-up programs should be implemented to monitor and care for long-term COVID-19-related health issues.