The significance of caloric restriction mimetics as anti-aging drugs.

Aging is an intricate process characterized by the gradual deterioration of the physiological integrity of a living organism. This unfortunate phenomenon inevitably leads to a decline in functionality and a heightened susceptibility to the ultimate fate of mortality. Therefore, it is of utmost importance to implement interventions that possess the capability to reverse or preempt age-related pathology. Caloric restriction mimetics (CRMs) refer to a class of molecules that have been observed to elicit advantageous outcomes on both health and longevity in various model organisms and human subjects. Notably, these compounds offer a promising alternative to the arduous task of adhering to a caloric restriction diet and mitigate the progression of the aging process and extend the duration of life in laboratory animals and human population. A plethora of molecular signals have been linked to the practice of caloric restriction, encompassing Insulin-like Growth Factor 1 (IGF1), Mammalian Target of Rapamycin (mTOR), the Adenosine Monophosphate-Activated Protein Kinase (AMPK) pathway, and Sirtuins, with particular emphasis on SIRT1. Therefore, this review will center its focus on several compounds that act as CRMs, highlighting their molecular targets, chemical structures, and mechanisms of action. Moreover, this review serves to underscore the significant relationship between post COVID-19 syndrome, antiaging, and importance of utilizing CRMs. This particular endeavor will serve as a comprehensive guide for medicinal chemists and other esteemed researchers, enabling them to meticulously conceive and cultivate novel molecular entities with the potential to function as efficacious antiaging pharmaceutical agents.

Endothelial dysfunction and persistent inflammation in severe post-COVID-19 patients: implications for gas exchange.

BACKGROUND: Understanding the enduring respiratory consequences of severe COVID-19 is crucial for comprehensive patient care. This study aims to evaluate the impact of post-COVID conditions on respiratory sequelae of severe acute respiratory distress syndrome (ARDS). METHODS: We examined 88 survivors of COVID-19-associated severe ARDS six months post-intensive care unit (ICU) discharge. Assessments included clinical and functional evaluation as well as plasma biomarkers of endothelial dysfunction, inflammation, and viral response. Additionally, an in vitro model using human umbilical vein endothelial cells (HUVECs) explored the direct impact of post-COVID plasma on endothelial function. RESULTS: Post-COVID patients with impaired gas exchange demonstrated persistent endothelial inflammation marked by elevated ICAM-1, IL-8, CCL-2, and ET-1 plasma levels. Concurrently, systemic inflammation, evidenced by NLRP3 overexpression and elevated levels of IL-6, sCD40-L, and C-reactive protein, was associated with endothelial dysfunction biomarkers and increased in post-COVID patients with impaired gas exchange. T-cell activation, reflected in CD69 expression, and persistently elevated levels of interferon-ß (IFN-ß) further contributed to sustained inflammation. The in vitro model confirmed that patient plasma, with altered levels of sCD40-L and IFN-ß proteins, has the capacity to alter endothelial function. CONCLUSIONS: Six months post-ICU discharge, survivors of COVID-19-associated ARDS exhibited sustained elevation in endothelial dysfunction biomarkers, correlating with the severity of impaired gas exchange. NLRP3 inflammasome activity and persistent T-cell activation indicate on going inflammation contributing to persistent endothelial dysfunction, potentially intensified by sustained viral immune response.

What is quality in long covid care? Lessons from a national quality improvement collaborative and multi-site ethnography.

BACKGROUND: Long covid (post covid-19 condition) is a complex condition with diverse manifestations, uncertain prognosis and wide variation in current approaches to management. There have been calls for formal quality standards to reduce a so-called "postcode lottery" of care. The original aim of this study-to examine the nature of quality in long covid care and reduce unwarranted variation in services-evolved to focus on examining the reasons why standardizing care was so challenging in this condition. METHODS: In 2021-2023, we ran a quality improvement collaborative across 10 UK sites. The dataset reported here was mostly but not entirely qualitative. It included data on the origins and current context of each clinic, interviews with staff and patients, and ethnographic observations at 13 clinics (50 consultations) and 45 multidisciplinary team (MDT) meetings (244 patient cases). Data collection and analysis were informed by relevant lenses from clinical care (e.g. evidence-based guidelines), improvement science (e.g. quality improvement cycles) and philosophy of knowledge. RESULTS: Participating clinics made progress towards standardizing assessment and management in some topics; some variation remained but this could usually be explained. Clinics had different histories and path dependencies, occupied a different place in their healthcare ecosystem and served a varied caseload including a high proportion of patients with comorbidities. A key mechanism for achieving high-quality long covid care was when local MDTs deliberated on unusual, complex or challenging cases for which evidence-based guidelines provided no easy answers. In such cases, collective learning occurred through idiographic (case-based) reasoning, in which practitioners build lessons from the particular to the general. This contrasts with the nomothetic reasoning implicit in evidence-based guidelines, in which reasoning is assumed to go from the general (e.g. findings of clinical trials) to the particular (management of individual patients). CONCLUSION: Not all variation in long covid services is unwarranted. Largely because long covid's manifestations are so varied and comorbidities common, generic "evidence-based" standards require much individual adaptation. In this complex condition, quality improvement resources may be productively spent supporting MDTs to optimise their case-based learning through interdisciplinary discussion. Quality assessment of a long covid service should include review of a sample of individual cases to assess how guidelines have been interpreted and personalized to meet patients' unique needs. STUDY REGISTRATION: NCT05057260, ISRCTN15022307.

Triglicerydes/high-density lipoprotein ratio as a risk factor of post-Covid-19 sinus tachycardia: A retrospective study.

Inappropriate sinus tachycardia (IST) is one of the manifestations of the post-COVID-19 syndrome (PCS), which pathogenesis remains largely unknown. This study aimed to identify potential risk factors for IST in individuals with PCS. The 1349 patients with PCS were included into the study. Clinical examination, 24H Holter ECG, 24H ambulatory blood pressure monitoring and biochemical tests were performed 12-16 weeks after the COVID-19 in all participants. IST was found in 69 (3.5%) individuals. In the clinical assessment IST patients were characterized by a higher age (p < 0.001) and lower prevalence of the diagnosed hypertension (p = 0.012), compared to remaining patients. Biochemical testing showed higher serum triglycerides (1.66 vs. 1.31 pmol/L, p = 0.007) and higher prevalence of a low high-density lipoprotein (HDL) cholesterol (24.6% vs. 15.2%, p = 0.035) in the IST group. Subsequently, the triglicerydes (TG)/HDL ratio, an indicator of insulin resistance, was significantly higher in the IST individuals (3.2 vs. 2.4, p = 0.005). 24H monitoring revealed a significantly higher minimum diastolic, maximum systolic and mean arterial blood pressure values in the IST group (p < 0.001 for all), suggesting a high prevalence of undiagnosed hypertension. A multivariate analysis confirmed the predictive value TG/HDL ratio >3 (OR 2.67, p < 0.001) as predictors of IST development. A receiver operating characteristic curve analysis of the relationship between the TG/HDL ratio and the IST risk showed that the predictive cut-off point for this parameter was 2.46 (area under the ROC curve = 0.600, p = 0.004). Based on these findings, one can conclude that insulin resistance seems to be a risk factor of IST, a common component of PCS.

Serological markers and long COVID-A rapid systematic review.

BACKGROUND: Long COVID is highly heterogeneous, often debilitating, and may last for years after infection. The aetiology of long COVID remains uncertain. Examination of potential serological markers of long COVID, accounting for clinical covariates, may yield emergent pathophysiological insights. METHODS: In adherence to PRISMA guidelines, we carried out a rapid review of the literature. We searched Medline and Embase for primary observational studies that compared IgG response in individuals who experienced COVID-19 symptoms persisting ≥12 weeks post-infection with those who did not. We examined relationships between serological markers and long COVID status and investigated sources of inter-study variability, such as severity of acute illness, long COVID symptoms assessed and target antigen(s). RESULTS: Of 8018 unique records, we identified 29 as being eligible for inclusion in synthesis. Definitions of long COVID varied. In studies that reported anti-nucleocapsid (N) IgG (n = 10 studies; n = 989 participants in aggregate), full or partial anti-Spike IgG (i.e. the whole trimer, S1 or S2 subgroups, or receptor binding domain, n = 19 studies; n = 2606 participants), or neutralizing response (n = 7 studies; n = 1123 participants), we did not find strong evidence to support any difference in serological markers between groups with and without persisting symptoms. However, most studies did not account for severity or level of care required during acute illness, and other potential confounders. CONCLUSIONS: Pooling of studies would enable more robust exploration of clinical and serological predictors among diverse populations. However, substantial inter-study variations hamper comparability. Standardized reporting practices would improve the quality, consistency and comprehension of study findings.

Symptomatic post COVID patients have impaired alveolar capillary membrane function and high VE/VCO2.

BACKGROUND: Post COVID-19 syndrome is characterized by several cardiorespiratory symptoms but the origin of patients' reported symptomatology is still unclear. METHODS: Consecutive post COVID-19 patients were included. Patients underwent full clinical evaluation, symptoms dedicated questionnaires, blood tests, echocardiography, thoracic computer tomography (CT), spirometry including alveolar capillary membrane diffusion (DM) and capillary volume (Vcap) assessment by combined carbon dioxide and nitric oxide lung diffusion (DLCO/DLNO) and cardiopulmonary exercise test. We measured surfactant derive protein B (immature form) as blood marker of alveolar cell function. RESULTS: We evaluated 204 consecutive post COVID-19 patients (56.5 ± 14.5 years, 89 females) 171 ± 85 days after the end of acute COVID-19 infection. We measured: forced expiratory volume (FEV1) 99 ± 17%pred, FVC 99 ± 17%pred, DLCO 82 ± 19%, DM 47.6 ± 14.8 mL/min/mmHg, Vcap 59 ± 17 mL, residual parenchymal damage at CT 7.2 ± 3.2% of lung tissue, peakVO2 84 ± 18%pred, VE/VCO2 slope 112 [102-123]%pred. Major reported symptoms were: dyspnea 45% of cases, tiredness 60% and fatigability 77%. Low FEV1, Vcap and high VE/VCO2 slope were associated with persistence of dyspnea. Tiredness was associated with high VE/VCO2 slope and low PeakVO2 and FEV1 while fatigability with high VE/VCO2 slope. SPB was fivefold higher in post COVID-19 than in normal subjects, but not associated to any of the referred symptoms. SPB was negatively associated to Vcap. CONCLUSIONS: In patients with post COVID-19, cardiorespiratory symptoms are linked to VE/VCO2 slope. In these patients the alveolar cells are dysregulated as shown by the very high SPB. The Vcap is low likely due to post COVID-19 pulmonary endothelial/vasculature damage but DLCO is only minimally impaired being DM preserved.

Pre-existing sleep problems as a predictor of post-acute sequelae of COVID-19.

Several months after COVID-19 many individuals still report persisting symptoms, the so-called 'post-COVID-19 syndrome'. An immunological dysfunction is one of the main pathophysiological hypotheses. As sleep is central to the functioning of the immune system, we investigated whether self-reported pre-existing sleep disturbance might be an independent risk factor for the development of post-COVID-19 syndrome. A total of 11,710 participants of a cross-sectional survey (all tested positive for severe acute respiratory syndrome coronavirus-2) were classified into probable post-COVID-19 syndrome, an intermediate group, and unaffected participants at an average of 8.5 months after infection. The case definition was based on newly occurring symptoms of at least moderate severity and ≥20% reduction in health status and/or working capacity. Unadjusted and adjusted odds ratios were calculated to investigate the association between pre-existing sleep disturbances and subsequent development of post-COVID-19 syndrome while controlling for a variety of demographic, lifestyle, and health factors. Pre-existing sleep disturbances were found to be an independent predictor of subsequent probable post-COVID-19 syndrome (adjusted odds ratio 2.7, 95% confidence interval 2.27-3.24). Sleep disturbances as part of the post-COVID-19 syndrome were reported by more than half of the participants and appeared to be a new symptom and to occur independent of a mood disorder in most cases. Recognition of disturbed sleep as an important risk factor for post-COVID-19 syndrome should promote improved clinical management of sleep disorders in the context of COVID-19. Further, it may stimulate further research on the effect of improving sleep on the prognosis of COVID-19 long-term sequelae and other post-viral conditions.

Persistent immune abnormalities discriminate post-COVID syndrome from convalescence.

BACKGROUND: Innate lymphoid cells (ILCs) are key organizers of tissue immune responses and regulate tissue development, repair, and pathology. Persistent clinical sequelae beyond 12 weeks following acute COVID-19 disease, named post-COVID syndrome (PCS), are increasingly recognized in convalescent individuals. ILCs have been associated with the severity of COVID-19 symptoms but their role in the development of PCS remains poorly defined. METHODS AND RESULTS: Here, we used multiparametric immune phenotyping, finding expanded circulating ILC precursors (ILCPs) and concurrent decreased group 2 innate lymphoid cells (ILC2s) in PCS patients compared to well-matched convalescent control groups at > 3 months after infection or healthy controls. Patients with PCS showed elevated expression of chemokines and cytokines associated with trafficking of immune cells (CCL19/MIP-3b, FLT3-ligand), endothelial inflammation and repair (CXCL1, EGF, RANTES, IL-1RA, PDGF-AA). CONCLUSION: These results define immunological parameters associated with PCS and might help find biomarkers and disease-relevant therapeutic strategies.

Inflammatory and vascular biomarkers in post-COVID-19 syndrome: A systematic review and meta-analysis of over 20 biomarkers.

Severe acute respiratory syndrome coronavirus 2 may inflict a post-viral condition known as post-COVID-19 syndrome (PCS) or long-COVID. Studies measuring levels of inflammatory and vascular biomarkers in blood, serum, or plasma of COVID-19 survivors with PCS versus non-PCS controls have produced mixed findings. Our review sought to meta-analyse those studies. A systematic literature search was performed across five databases until 25 June 2022, with an updated search on 1 November 2022. Data analyses were performed with Review Manager and R Studio statistical software. Twenty-four biomarkers from 23 studies were meta-analysed. Higher levels of C-reactive protein (Standardized mean difference (SMD) = 0.20; 95% CI: 0.02-0.39), D-dimer (SMD = 0.27; 95% CI: 0.09-0.46), lactate dehydrogenase (SMD = 0.30; 95% CI: 0.05-0.54), and leukocytes (SMD = 0.34; 95% CI: 0.02-0.66) were found in COVID-19 survivors with PCS than in those without PCS. After sensitivity analyses, lymphocytes (SMD = 0.30; 95% CI: 0.12-0.48) and interleukin-6 (SMD = 0.30; 95% CI: 0.12-0.49) were also significantly higher in PCS than non-PCS cases. No significant differences were noted in the remaining biomarkers investigated (e.g., ferritin, platelets, troponin, and fibrinogen). Subgroup analyses suggested the biomarker changes were mainly driven by PCS cases diagnosed via manifestation of organ abnormalities rather than symptomatic persistence, as well as PCS cases with duration of <6 than ≥6 months. In conclusion, our review pinpointed certain inflammatory and vascular biomarkers associated with PCS, which may shed light on potential new approaches to understanding, diagnosing, and treating PCS.

Characterisation, symptom pattern and symptom clusters from a retrospective cohort of Long COVID patients in primary care in Catalonia.

BACKGROUND: Around 10% of people infected by SARS-COV-2 report symptoms that persist longer than 3 months. Little has been reported about sex differences in symptoms and clustering over time of non-hospitalised patients in primary care settings. METHODS: This is a descriptive study of a cohort of mainly non-hospitalized patients with a persistence of symptoms longer than 3 months from the clinical onset in co-creation with the Long Covid Catalan affected group using an online survey. Recruitment was from March 2020 to June 2021. Exclusion criteria were being admitted to an ICU, < 18 years of age and not living in Catalonia. We focused on 117 symptoms gathered in 18 groups and performed cluster analysis over the first 21 days of infection, at 22-60 days, and ≥ 3 months. RESULTS: We analysed responses of 905 participants (80.3% women). Median time between symptom onset and the questionnaire response date was 8.7 months. General symptoms (as fatigue) were the most prevalent with no differences by sex, age, or wave although its frequency decreased over time (from 91.8 to 78.3%). Dermatological (52.1% in women, 28.5% in men), olfactory (34.9% women, 20.9% men) and neurocognitive symptoms (70.1% women, 55.8% men) showed the greatest differences by sex. Cluster analysis showed five clusters with a predominance of Taste & smell (24.9%) and Multisystemic clusters (26.5%) at baseline and _Multisystemic (34.59%) and Heterogeneous (24.0%) at ≥3 months. The Multisystemic cluster was more prevalent in men. The Menstrual cluster was the most stable over time, while most transitions occurred from the Heterogeneous cluster to the Multisystemic cluster and from Taste & smell to Heterogeneous. CONCLUSIONS: General symptoms were the most prevalent in both sexes at three-time cut-off points. Major sex differences were observed in dermatological, olfactory and neurocognitive symptoms. The increase of the Heterogeneous cluster might suggest an adaptation to symptoms or a non-specific evolution of the condition which can hinder its detection at medical appointments. A carefully symptom collection and patients' participation in research may generate useful knowledge about Long Covid presentation in primary care settings.

Feasibility, safety and effectiveness of prednisolone and vitamin B1, B6, and B12 in patients with post-COVID-19-syndrome (PreVitaCOV) - protocol of a randomised, double-blind, placebo-controlled multicentre trial in primary care (phase IIIb).

BACKGROUND: After infection with SARS-CoV-2 a relevant proportion of patients complains about persisting symptoms, a condition termed Post-COVID-19-syndrome (PC19S). So far, possible treatments are under investigation. Among others, neurotropic vitamins and anti-inflammatory substances are potential options. Thus, the PreVitaCOV trial aims to assess feasibility, safety, and effectiveness of treating patients in primary care with prednisolone and/or vitamin B1, B6 and B12. METHODS: The phase IIIb, multi-centre randomised, double-blind, and placebo-controlled PreVitaCOV trial has a factorial design and is planned as a two-phase approach. The pilot phase assessed feasibility and safety and was transformed into a confirmatory phase to evaluate effectiveness since feasibility was proven. Adult patients with PC19S after a documented SARS-CoV-2 infection at least 12 weeks ago are randomly assigned to 4 parallel treatments: prednisolone 20 mg for five days followed by 5 mg for 23 days (trial drug 1), B vitamins (B1 (100 mg OD), B6 (50 mg OD), and B12 (500 µg OD)) for 28 days (trial drug 2), trial drugs 1 and 2, or placebo. The primary outcome of the pilot phase was defined as the retention rate of the first 100 patients. Values of ≥ 85% were considered as confirmation of feasibility, this criterion was even surpassed by a retention rate of 98%. After transformation, the confirmatory phase proceeds by enrolling 240 additional patients. The primary outcome for the study is the change of symptom severity from baseline to day 28 as assessed by a tailored Patient Reported Outcomes Measurement Information System (PROMIS) total score referring to five symptom domains known to be typical for PC19S (fatigue, dyspnoea, cognition, anxiety, depression). The confirmatory trial is considered positive if superiority of any treatment is demonstrated over placebo operationalised by an improvement of at least 3 points on the PROMIS total score (t-score). DISCUSSION: The PreVitaCOV trial may contribute to the understanding of therapeutic approaches in PC19S in a primary care context. TRIAL REGISTRATION: EudraCT: 2022-001041-20. DRKS: DRKS00029617. CLINICALTRIALS: gov: F001AM02222_1 (registered: 05 Dec 2022).

Longitudinal course and predictors of health-related quality of life, mental health, and fatigue, in non-hospitalized individuals with or without post COVID-19 syndrome.

BACKGROUND: Long-term information on health-related quality of life (HRQOL) and mental health of non-hospitalized individuals with "post COVID-19 syndrome" (PCS) is scarce. Thus, the objectives of the present study were to compare HRQOL and mental health of individuals with and without PCS in a German sample of non-hospitalized persons after SARS-CoV-2 infection, to characterize the long-term course up to 2 years and to identify predictors for post COVID-19 impairments. METHODS: Individuals with past SARS-CoV-2 infection were examined at the University Hospital of Augsburg from November 2020 to May 2021 and completed a postal questionnaire between June and November 2022. Participants who self-reported the presence of fatigue, dyspnea on exertion, memory problems or concentration problems were classified as having PCS. HRQOL was assessed using the Veterans RAND 12-Item Health Survey, mental health was measured by the Patient Health Questionnaire and the Fatigue Asessment Scale was used to assess fatigue severity. Multivariable linear regression models with inverse probability weighting were used to determine the association between PCS and health outcomes. RESULTS: From the 304 participants (58.2% women, median age 52 years), 210 (69.1%) were classified as having PCS in median 26 months after SARS-CoV-2 infection. Persons with PCS showed significantly more often depressive and anxiety disorders. PCS was independently and significantly associated with higher levels of depression, post-traumatic stress and fatigue, as well as poorer physical and mental HRQOL in median 9 months as well as 26 months after SARS-CoV-2 infection. A large number of acute symptoms and a prior diagnosis of depression were independently associated with poor mental health and HRQOL. While post-traumatic stress and mental HRQOL improved from 9 months to 26 months post infection onset, depressiveness, fatigue and physical HRQOL remained stable in both, persons with and without PCS. CONCLUSIONS: PCS in non-hospitalized persons after SARS-CoV-2 infection is often associated with long-term impairments of mental health and HRQOL outcomes.

Characterization of cognitive symptoms in post COVID-19 patients.

Cognitive symptoms (CS) belong to the most common manifestations of the Post COVID-19 (PC) condition. We sought to objectify CS in PC patients using routine diagnostic assessments: neurocognitive testing (NCT) and brain imaging (BI). Further, we investigated possible associations of CS with patient reported outcomes (PROs), and risk factors for developing CS. Clinical data and PROs of 315 PC patients were assessed at a mean of 6 months after SARS-CoV-2 infection. 231 (73.3%) patients reported any sort of CS. Among them, 78 underwent NCT and 55 received BI. In NCT, the cognitive domains most affected were the working memory, attention, and concentration. Nonetheless, pathological thresholds were exceeded only in few cases. Neurocognitive performance did not differ significantly between patients complaining of severe (n = 26) versus non-severe (n = 52) CS. BI findings were abnormal in 8 (14.5%) cases with CS but were most likely not related to PC. Patients reporting high severity of CS scored worse in the PHQ-9, FSS, WHOQOL-BREF, were more likely to report impaired sleep, and had a higher prevalence of psychiatric diagnoses. Overall, NCT could confirm mild impairment in some but not all PC patients with CS, while BI studies were abnormal in only few cases. CS severity did not affect NCT results, but severe CS were associated with symptoms of depression (PHQ-9), fatigue (FSS), reduced quality of life (WHOQOL-BREF) and higher prevalence of psychiatric illnesses. These findings support the importance of NCT, BI, and neuro-psychological assessment in the work-up of PC patients reporting CS. TRIAL REGISTRATION: Trial registration number and date of registration: DRKS00030974, 22 Dec 2022, retrospectively registered.

Headache severity in patients with post COVID-19 condition: a case-control study.

Post COVID-19 conditions (PCC) present with a wide range of symptoms. Headache is one of the most frequently reported neurological symptoms by patients with PCC. We aimed to assess the prevalence of headache in patients with PCC who attended the Post-COVIDLMU outpatient department at LMU University Hospital in Munich. We hypothesized that headaches occur more frequently in patients with PCC than in the control group. Patients answered a questionnaire containing sociodemographic characteristics, their current symptoms, and prior psychiatric and somatic diagnoses, the WHO Quality of Life assessment (WHOQOL-BREF), 9-item Patient Health Questionnaire (PHQ-9), and the Fatigue Severity Scale (FSS). 188 PCC patients were included in this study and compared to a control group of patients with a history of COVID-19 or a different infectious disease - but no consecutive post-infectious condition (nc=27). 115 (61%) of our PCC patients were female. The median age was 41 years. 60 (32%, p = 0.001) had a pre-existing psychiatric diagnosis. PCC was associated with worse outcomes in all four domains of the WHOQOL-BREF (p < 0.001), high levels of fatigue (FSS; p < 0.001), and a higher likeliness for symptoms of depression (PHQ-9; p < 0.001). We were able to confirm that psychiatric disorders are more frequently associated with headaches in PCC patients. Headache should be assessed and treated in the context of PCC not only by neurologists but by multi-professional teams and regarding all PCC symptoms.

The global prevalence of depression, anxiety, and sleep disorder among patients coping with Post COVID-19 syndrome (long COVID): a systematic review and meta-analysis.

BACKGROUND: Post COVID-19 syndrome, also known as "Long COVID," is a complex and multifaceted condition that affects individuals who have recovered from SARS-CoV-2 infection. This systematic review and meta-analysis aim to comprehensively assess the global prevalence of depression, anxiety, and sleep disorder in individuals coping with Post COVID-19 syndrome. METHODS: A rigorous search of electronic databases was conducted to identify original studies until 24 January 2023. The inclusion criteria comprised studies employing previously validated assessment tools for depression, anxiety, and sleep disorders, reporting prevalence rates, and encompassing patients of all age groups and geographical regions for subgroup analysis Random effects model was utilized for the meta-analysis. Meta-regression analysis was done. RESULTS: The pooled prevalence of depression and anxiety among patients coping with Post COVID-19 syndrome was estimated to be 23% (95% CI: 20%-26%; I2 = 99.9%) based on data from 143 studies with 7,782,124 participants and 132 studies with 9,320,687 participants, respectively. The pooled prevalence of sleep disorder among these patients, derived from 27 studies with 15,362 participants, was estimated to be 45% (95% CI: 37%-53%; I2 = 98.7%). Subgroup analyses based on geographical regions and assessment scales revealed significant variations in prevalence rates. Meta-regression analysis showed significant correlations between the prevalence and total sample size of studies, the age of participants, and the percentage of male participants. Publication bias was assessed using Doi plot visualization and the Peters test, revealing a potential source of publication bias for depression (p = 0.0085) and sleep disorder (p = 0.02). However, no evidence of publication bias was found for anxiety (p = 0.11). CONCLUSION: This systematic review and meta-analysis demonstrate a considerable burden of mental health issues, including depression, anxiety, and sleep disorders, among individuals recovering from COVID-19. The findings emphasize the need for comprehensive mental health support and tailored interventions for patients experiencing persistent symptoms after COVID-19 recovery.

Clinical characteristics and effects of inhaled corticosteroid in patients with post-COVID-19 chronic cough during the Omicron variant outbreak.

BACKGROUND: Chronic cough is a common symptom in patients post the coronavirus disease 2019 (COVID-19). In this study, we aimed to investigate the efficacy of inhaled corticosteroids (ICS) and the clinical characteristics of patients with post-COVID-19 chronic cough during the Omicron era. METHODS: An ambispective, longitudinal cohort study was conducted that included patients with post-COVID-19 who attended the respiratory clinic at our hospital between January 1, 2023, and March 31, 2023 with a complaint of persistent cough lasting more than 8 weeks. At 30 and 60 days after the first clinic visit for post-COVID-19 chronic cough, enrolled patients were prospectively followed up. We compared the changes in symptoms and pulmonary function between patients receiving ICS treatment (ICS group) and those not receiving ICS treatment (NICS group) at the two visits. RESULTS: A total of 104 patients with post-COVID-19 chronic cough were enrolled in this study (ICS group, n = 51; NICS group, n = 53). The most common symptoms accompanying post-COVID-19 chronic cough were sputum (58.7%, 61/104) and dyspnea (48.1%, 50/104). Seventy-one (82.6%, 71/86) patients had airway hyperresponsiveness, and 49 patients (47.1%, 49/104) were newly diagnosed with asthma. Most patients (95.2%, 99/104) exhibited improvement at 60 days after the first visit. The pulmonary function parameters of the patients in the ICS group were significantly improved compared to the baseline values (P < 0.05), and the improvement in the FEV1/FVC was significantly greater than that in the NICS group (P = 0.003) after 60 days. CONCLUSIONS: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may contribute to the pathogenesis of asthma, which could be the underlying cause of persistent cough post-COVID-19 infection. Post-COVID-19 chronic cough during the Omicron era was often accompanied by sputum, dyspnea, and airway hyperresponsiveness. ICS treatment did not have a significant impact on symptom management of post-COVID-19 chronic cough; however, it can improve impaired lung function in in these individuals.

Function and activity capacity at 1 year after the admission to intensive care unit for COVID-19.

OBJECTIVE: To describe hand grip strength, walking speed, functional mobility, and postural control at one year following intensive care unit admission for COVID-19, and to find any predictors that are associated with impaired hand grip strength, walking speed, functional mobility, or postural control at the 1-year follow-up. DESIGN: Retrospective cross-sectional and longitudinal observational study. SETTING: Intensive care unit and outpatient research clinic at Sahlgrenska University Hospital. PARTICIPANTS: Of the 105 individuals in "The Gothenburg Recovery and Rehabilitation after COVID-19 and Intensive Care Unit" cohort, 78 participated in this study. MAIN MEASURES: Descriptive statistics for hand grip strength, walking speed, functional mobility, and postural control were presented and binary logistic regressions were performed to find their significant predictors. RESULTS: At 1-year following intensive care unit admission for COVID-19, impaired hand grip strength was found in 24.4% for the right hand and 23.1% for the left hand. Walking speed, functional mobility, and postural control were found to be impaired in 29.5%, 21.8%, and 5.1%, respectively. For impaired walking speed, longer length of stay at intensive care unit and presence of diabetes mellitus were risk factors. Diabetes mellitus was found to be the risk factor for impaired functional mobility. CONCLUSION: In this study, 45% of the participants showed impairment in function, activity capacity or both. These results suggest that individuals who recovered after intensive care unit admission for COVID-19 would benefit from receiving long-term follow-up to enable identification of those with need of physical health assistance and rehabilitation.

COVID-19-associated costs and mortality in Germany: an incidence-based analysis from a payer's perspective.

BACKGROUND: This study aims to estimate average COVID-19-associated healthcare costs per capita in Germany from a payer perspective. In addition, insights into COVID-19-associated mortality should be gained. METHODS: For this purpose, a retrospective longitudinal analysis using health insurance claims data was performed. Patients affected by COVID-19 in Q1/2021 (investigation group (IG)) were compared to a matched non-COVID-19 control group (CG) (1:1 propensity score matching (PSM)). Mean values of healthcare costs in 2020 and 2021 were computed for both groups and then separated by age and by development of Post-COVID-19 Syndrome (PCS). Group differences were examined using Mann-Whitney U test (α = 0.05). Difference-in-Differences approach (DiD) was used to estimate average cost effects of COVID-19 in 2021. Concerning mortality, the number of deaths in 2021 was compared between IG and CG using χ2 test of independence. RESULTS: A total of 8,014 insurants were included (n = 4,007 per group; n = 536 per group examining PCS patients only). Total healthcare costs varied a lot in the sample, were comparable between IG and CG in 2020, but were significantly higher in the IG in 2021 (DiD estimate = € 1,063 (in total); € 3,242 (PCS group)). This was more pronounced in the older age groups. High hospital costs of a minority of patients were the most influential driver of COVID-19-associated healthcare costs. Mortality was more than doubled in the IG (tripled in patients aged ≥ 60). CONCLUSIONS: COVID-19 is associated with significantly increased healthcare costs and mortality, especially in older age groups. The additional development of PCS further increases the costs of COVID-19.

Examining the long-term effects of COVID-19 in surgical nurses: Case of Aegean Region.

PURPOSE: To examine the long-term effects of COVID-19 on surgical nurses. BACKGROUND: Individuals contaminated with COVID-19 may face several metabolic or psychological issues, primarily in the respiratory, cardiovascular, nervous, musculoskeletal and renal systems during the late period. However, the long-term epidemiology is still not clear. DESIGN: Descriptive cross-sectional study. METHODS: The study included nurses (n = 509) who had been diagnosed with COVID-19 at least 12 weeks before and worked in surgical departments. We collected the study data via an online survey using the snowball sampling method between December 2021 and May 2022. This study followed the Reporting of Observational Studies in Epidemiology Guideline. RESULTS: The mean age of the nurses was 31.66 ± 8.74 years. Nurses stated that they were diagnosed with COVID-19 approximately 36 weeks before participating in this study. We found that the nurses mostly experienced palpitation (83.5%), headache (73.5%), dyspnea (64.1%), anosmia (57.6%), arthralgia (55.7%) and burnout (58.4%) during the late period after COVID-19. CONCLUSION: The long-term effects of COVID-19 were related to multiple organ dysfunctions. NO PATIENT OR PUBLIC CONTRIBUTION: Since the study was conducted with healthy individuals who had previously experienced COVID-19, there is no patient contribution. RELEVANCE TO CLINICAL PRACTICE: This study focuses on the long-term effects of COVID-19 on nurses. The results support the long-term effects of COVID-19 and are thought to contribute to the literature.

Long-term health consequences of COVID-19 in survivors hospitalised at a tertiary care hospital and their correlation with acute COVID-19 severity and associated risk factors.

OBJECTIVES: To determine post-COVID syndromes in the Indian population, correlating a wide spectrum of post-COVID manifestations with acute disease severity and associated risk factors. BACKGROUND: Post-COVID Syndrome (PCS) is defined as signs and symptoms that develop during or after acute COVID-19 infection. DESIGN OF STUDY: This is a prospective observational cohort with repetitive measurements. METHODS: The study followed RT-PCR confirmed COVID-19-positive survivors discharged from HAHC Hospital, New Delhi, for a period of 12 weeks. The patients were interviewed over the phone at 4 weeks and 12 weeks from the onset of symptoms for evaluation of clinical symptoms and health-related quality of life parameters. RESULTS: A total of 200 patients completed the study. At the baseline, 50% of the patients were categorised as severe based on their acute infection assessment. At 12 weeks after symptom onset, fatigue (23.5%), hair loss (12.5%) and dyspnea (9%) were the main persistent symptoms. The incidence of hair loss (12.5%), memory loss (4.5%) and brain fog (5%) were found to be increased as compared to the acute infection period. Severity of the acute COVID infection behaved as an independent predictor for the development of PCS, with high odds of experiencing persistent cough (OR = 13.1), memory loss (OR = 5.2) and fatigue (OR = 3.3). Further, 30% of subjects in the severe group experienced statistically significant fatigue at 12 weeks (p < .05). CONCLUSION: From the results of our study, it can be concluded that there is a huge disease burden of post-COVID Syndrome (PCS). The PCS comprised multisystem symptoms ranging from serious complaints of dyspnea, memory loss and brain fog to non-serious complaints of fatigue and hair loss. Severity of the acute COVID infection behaved as an independent predictor for the development of PCS. Our findings strongly recommend vaccination against COVID-19, for protection from disease severity as well as prevention of PCS. RELEVANCE TO CLINICAL PRACTICE: The findings of our study support the multidisciplinary approach required for the management of PCS with a team comprising of physicians, nurses, physiotherapists and psychiatrists working in close coordination for the rehabilitation of these patients. As nurses are considered the most trusted professionals in the community and the class of health workers associated with rehabilitation, focus should be given to educating them on PCS, which would prove to be an important strategy for efficient monitoring and long-term management of COVID-19 survivors.