Search Results (25)

Background/Objectives: This study aimed to evaluate sociodemographic factors, features of the acute infection, and post-infection health status in survivors of COVID-19, assessing their association with post-acute COVID-19 syndrome (PACS). Methods: A multidisciplinary public clinic in Brazil assessed COVID-19 survivors between June 2020 and February 2022. Patients were classified as having PACS or subacute infection (SI). Data on the history of the acute infection, current symptoms, physical examination, and laboratory findings were collected and analyzed using multivariate models with PACS as the outcome. Results: Among the 113 participants, 63.71% were diagnosed with PACS at a median of 130 days (IQR: 53–196) following acute symptom onset. Admission to the intensive care unit was more frequent among individuals with PACS than those with SI (83.3% vs. 65.0% respectively; p = 0.037). Symptoms significantly more prevalent in the PACS group when compared to the SI cohort included hair loss (44.4% vs. 17.1% respectively; p = 0.004), lower limb paresthesia (34.7% vs. 9.8% respectively; p = 0.003), and slow thinking speed (28.2% vs. 0.0% respectively; p < 0.001). Logistic regression revealed that only the time interval between the onset of acute symptoms and the clinical evaluation was independently associated with a PACS diagnosis (β = 0.057; 95% CI: 1.03–1.08; p < 0.001). Conclusions: Patients with PACS had a higher frequency of intensive care unit admission compared to those with subacute infection. However, in the multivariate analysis, the severity of the acute infection did not predict the final diagnosis of PACS, which was associated only with the time elapsed since symptom onset. Full article

Background: Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, long COVID (LC) has become a significant global health burden. While knowledge about LC is accumulating, studies on its prevention are still lacking. Methods: We conducted a systematic review following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to investigate prevention options for LC. We identified fifteen articles on vaccines, seven on antivirals, and six on other interventions after searching for articles in the PubMed/MEDLINE database using the MeSH terms. Results: Most vaccine-related studies demonstrated a protective effect of COVID-19 vaccines against developing LC. Our review found an equivocal effect of antivirals, while metformin had a protective effect in outpatients and corticosteroids were protective in hospitalized patients against LC. Conversely, COVID-19 convalescent plasma and multiple micronutrient supplement did not confer any protection against LC. Conclusions: COVID-19 vaccination is vital as it not only prevents COVID-19 but also reduces the severity of illness and may help prevent LC. Further studies are warranted to shed light on preventive strategies for long COVID. Full article

The COVID-19 pandemic, driven by SARS-CoV-2, has led to a global health crisis, highlighting the virus’s unique molecular mechanisms that distinguish it from other respiratory pathogens. It is known that the Hypoxia-Inducible Factor 1α (HIF-1α) activates a complex network of intracellular signaling pathways regulating cellular energy metabolism, angiogenesis, and cell survival, contributing to the wide range of clinical manifestations of COVID-19, including Post-Acute COVID-19 Syndrome (PACS). Emerging evidence suggests that dysregulation of HIF-1α is a key driver of systemic inflammation, silent hypoxia, and pathological tissue remodeling in both the acute and post-acute phases of the disease. This scoping review was conducted following PRISMA-ScR guidelines and registered in INPLASY. It involved a literature search in Scopus and PubMed, supplemented by manual reference screening, with study selection facilitated by Rayyan software. Our analysis clarifies the dual role of HIF-1α, which may either worsen inflammatory responses and viral persistence or support adaptive mechanisms that reduce cellular damage. The potential for targeting HIF-1α therapeutically in COVID-19 is complex, requiring further investigation to clarify its precise role and translational applications. This review deepens the molecular understanding of SARS-CoV-2-induced cellular and tissue dysfunction in hypoxia, offering insights for improving clinical management strategies and addressing long-term sequelae. Full article

Background: COVID-19 infection can have a protracted course in many survivors, with varied sociodemographic and medical characteristics, exhibiting a plethora of symptoms that have consequential impacts on their quality of life. This study sought to gather pertinent data about the prevalence of Long-Haul COVID (LC), the predisposing factors to this condition and the burden on the quality of life of Mauritian survivors. Research Setting: A cross-sectional study was performed using an adapted online questionnaire, using two definitions of Long COVID, namely the WHO and NICE, SIGN and RCGP definitions. Associations between LC and categorical variables were employed to explore relationships between LC and ratio (FAS, FSS, PCS-12, MCS-12) variables. Simple and multivariable logistic regression models were used to assess the predictors and outcomes associated with LC. Findings: Of 285 Mauritians with a confirmed history of COVID-19 infection, 64.2% developed Long COVID (WHO LC-38.9%, NICE, SIGN and RCGP LC-55.8%). The most prevalent symptoms were fatigue or muscle weakness (88.0%), cough (57.4%), difficulty concentrating (55.2%), trouble remembering or memorising (49.7%), insomnia or sleep disturbance (43.7%), amongst others. Statistically significant associations were determined between LC and age, gender, vaccination status, severity of acute illness, reinfections, self-perception of disease and having more than five acute symptoms. Long COVID positively correlated with fatigue. Both Long COVID and severe fatigue (F = 73.266, p < 0.001) negatively impacted PCS-12. Fatigue had no significant impact on MCS-12. Conclusions: This study demonstrated the presence of Long COVID in the Mauritian population. Long COVID manifests as a complex and long-lasting affliction that affects even young adults with disabling outcomes, owing to multiple lingering symptoms but, most importantly, fatigue. The latter brings about distressing declines in physical and overall quality of life that thump both individual and societal health and productivity. Full article

Post-acute COVID-19 syndrome (PACS) is characterized by the persistence of one or more symptoms after the acute phase, leading to physical disabilities. This study aims to investigate whether the functional capacity and respiratory function 120 days post-COVID-19 differed according to the level of respiratory support needed during hospitalization in acute COVID-19 in the pre-vaccine rollout period. We followed up with 118 COVID-19 hospitalized patients in the acute phase until 120 days post-acute disease, with patients split into a Non-Invasive Oxygen Therapy Group (OTG, n = 72), Invasive Mechanical Ventilation Group (IMV, n = 12), and Room Air Group (RAG, n = 34), assessing the body composition, respiratory muscle strength, pulmonary function, functional capacity, and muscle strength at the follow-up visit. In total, 54 individuals (45.8%) were female, with a median age of 48 years old (IQR: 41–58). We found that the group with IMV was older (p < 0.001), had more admissions to the ICU (p < 0.001), and had longer hospital stays (p < 0.001). There were no statistically significant differences between groups (OTG, IMV, and RAG) for the spirometry function (p = 0.31), DASI score (p = 0.77), manovacuometry (MIP p = 0.74; MEP p = 0.23), 6MWT (p = 0.43), and handgrip (p = 0.19) outcomes. At D120, the IMV group had an important loss of body muscle mass (BMM) and a higher BMM than RAG (p = 0.02). Reduction in MIP (p = 0.01) and MEP (p = 0.02) in the IMV group and OTG group when compared to the RAG was also observed. Functional outcomes at 120 days from COVID-19 hospitalization were not found to be associated with the levels of oxygen supplementation during acute disease in this group of participants. Full article

Objectives: Chronic pain is a common symptom in Post-Acute COVID-19 Syndrome (PACS), affecting 11–60% of patients, but the link between COVID-19 and chronic pain remains unclear. This study assesses healthcare resource utilization (HRU) for pain management among French COVID-19 survivors, using the National French Claims Database (SNDS). We analyzed medical consultations, rehabilitation services, diagnostic procedures, and medication dispensing to identify PACS-related pain patterns and their impact on the healthcare system. Methods: The cohort included 68,822 patients hospitalized during the first COVID-19 wave (March–June 2020), with 13,939 ICU survivors. HRU was assessed for six months pre- and post-hospitalization in four areas: (1) medical consultations and rehabilitation; (2) pain-related medication dispensing; (3) neuropathic diagnostic procedures; (4) hospital admissions for chronic pain. A post–pre ratio (PP-Ratio) compared post-COVID to pre-COVID HRU. Results: Significant changes in HRU were observed, particularly for ICU survivors. Neurology consultations (PP-Ratio 1.41) and outpatient physical therapy (PP-Ratio 1.69) increased. Dispensing of strong opioids, antiepileptics, anxiolytics, and hypnotics rose, while NSAID use decreased. Hospitalizations for chronic pain also increased (PP-Ratio 1.52). Similar trends were seen among ICU survivors, with notable increases in opioid and antiepileptic use. No distinct PACS-related pain patterns emerged. Conclusions: Non-specific increases in HRU for pain management were found following COVID-19 hospitalization, likely due to disease severity and ICU care rather than PACS-related chronic pain. Further research is needed to explore long-term pain outcomes in this population. Full article

Although the impact of post-acute COVID-19 syndrome (PACS) on patients and public health is undeniably significant, its etiology remains largely unclear. Much research has been conducted on the pathophysiology, shedding light on various aspects; however, due to the multitude of symptoms and clinical conditions that directly or indirectly define PACS, it is challenging to establish definitive causations. In this exploration, through systematically reviewing the latest pathophysiological findings related to the neurological symptoms of the syndrome, we aim to examine how psychosocial and neuropsychological symptoms may overlap with neurological ones, and how they may not only serve as risk factors but also contribute to the persistence of some primary symptoms of the disorder. Findings from our synthesis suggest that psychological and psychosocial factors, such as anxiety, depression, and loneliness, may interact with neurological symptoms in a self-reinforcing feedback loop. This cycle seems to be affecting both physical and psychological distress, potentially increasing the persistence and severity of PACS symptoms. By pointing out this interaction, in this review study, we attempt to offer a new perspective on the interconnected nature of psychological, psychosocial, and neurological factors, emphasizing the importance of integrated treatment approaches to disrupt this cycle and improve outcomes when possible. Full article

Background/Objectives: Clinical studies show that SARS-CoV-2 vaccination sometimes entails a severe and disabling chronic syndrome termed post-acute-COVID-19-vaccination syndrome (PACVS). PACVS shares similarities with long COVID. Today, PACVS is still not officially recognised as a disease. In contrast, long COVID was registered by health authorities in December 2021. Here, we address possible reasons for that discrepancy. Methods: We analyse whether common symptoms of PACVS have been registered by European pharmacovigilance as adverse vaccination reactions and which consequences have been drawn thereof. Results: (i) PACVS is distinguished from normal vaccination reactions solely by prolonged duration. (ii) Symptom duration is poorly monitored by post-authorisation pharmacovigilance. (iii) PACVS-specific signals were faithfully recorded by pharmacovigilance systems but have not prompted appropriate reactions of health authorities. (iv) The most widely applied SARS-CoV-2 mRNA-vaccine has been modified after roll-out without renewed phase III evaluation; the modification has increased DNA contaminations suspected to extend the spectrum of adverse events. (v) Crossing of pharmacovigilance data with corresponding estimates of applied vaccine doses suggest a PACVS prevalence of 0.003% in the general population. In contrast, occupational surveillance studies suggest a PACVS prevalence of 0.9% in young and middle-aged persons. Conclusions: (a) Denial of official recognition of PACVS is unjustified. (b) PACVS seems to target preferentially young and middle-aged persons. (c) Without official disease recognition, access to public healthcare and welfare services is made difficult for PACVS-affected persons, which creates considerable socio-economic problems. (d) Without official disease recognition, development and evaluation of PACVS therapies is impaired. Full article

The coronavirus disease 2019 (COVID-19) survivors are frequently observed to present persistent symptoms constituting what has been called “post-acute COVID-19 syndrome” (PACS) or “long COVID-19”. Some clinical risk factors have been identified to be associated with PACS development; however, specific mechanisms responsible for PACS pathology remain unknown. This study investigates clinical, immunological, and metabolomic risk factors associated with post-acute COVID-19 syndrome (PACS) in 51 patients, assessed 7–19 months after acute infection. Among the participants, 62.7% were male and 37.2% were female, with an average age of 47.8 years. At the follow-up, 37.2% met the criteria for PACS, revealing significant differences in immunological and metabolomic profiles at the time of acute infection. Patients with PACS were characterized by elevated levels of mature low-density granulocytes (LDGs), interleukin-8 (IL-8), pyruvate, pseudouridine, and cystine. Baseline multivariate analysis showed increased pyruvate and decreased alpha tocopherol levels. At follow-up, there was a decrease in absolute B lymphocytes and an increase in non-classical monocytes and 3-hydroxyisovaleric acid levels. These findings suggest that specific immunological and metabolomic markers during acute infection can help identify patients at higher risk of developing persistent PACS. Full article

Impaired lung gas exchange is commonly seen in patients with pulmonary involvement related to SARS-CoV-2 acute infection or post-acute COVID-19 syndrome (PACS). The primary aim of our study was to assess lung gas transfer, measuring the pulmonary diffusion capacity for nitric oxide (D_LNO) and carbon monoxide (D_LCO) in all COVID-19 patients. Our secondary aim was to decipher the respective roles of perturbed lung membrane conductance (D_M) and reduced pulmonary capillary volume (V_C) in patients with impaired lung gas exchange. From May to October 2020, we measured D_LNO-D_LCO in 118 patients during their post-COVID-19 period (4.6 months after infection) to decipher alveolo-capillary gas transfer disturbances. D_LNO-D_LCO measurement was also performed in 28 healthy non-smokers as controls. Patients were classified into three groups according to the severity (mild, moderate, and severe) of acute COVID-19 infection. Patients with mild COVID-19 had normal lung volumes and airways expiratory flows but impaired pulmonary gas exchange, as shown by the significant decreases in D_LNO, D_LCO, D_M, and V_C as compared with controls. V_C was significantly impaired and the D_LNO/D_LCO ratio was increased in patients with moderate (n = 4, 11%) and severe COVID-19 (n = 23, 49%). Abnormal membrane conductance was also seen in all three groups of post-COVID-19 patients. These findings suggest a persistent alveolo-capillary gas transfer defect, implying not only reduced membrane conductance but also abnormal pulmonary vascular capacitance in all PACS patients, even those with a milder form of COVID-19 infection. Full article

Coronavirus disease (COVID-19) is an infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can be asymptomatic or present with multiple organ dysfunction. Many infected individuals have chronic alterations associated with neuropsychiatric, endocrine, gastrointestinal, and musculoskeletal symptoms, even several months after disease onset, developing long-COVID or post-acute COVID-19 syndrome (PACS). Microbiota dysbiosis contributes to the onset and progression of many viral diseases, including COVID-19 and post-COVID-19 manifestations, which could serve as potential diagnostic and prognostic biomarkers. This review aimed to discuss the most recent findings on gut microbiota dysbiosis and its relationship with the sequelae of PACS. Elucidating these mechanisms could help develop personalized and non-invasive clinical strategies to identify individuals at a higher risk of experiencing severe disease progression or complications associated with PACS. Moreover, the review highlights the importance of targeting the gut microbiota composition to avoid dysbiosis and to develop possible prophylactic and therapeutic measures against COVID-19 and PACS in future studies. Full article

A substantial fraction of the 15% with double-jointedness or hypermobility have the traditionally ascertained joint-skeletal, cutaneous, and cardiovascular symptoms of connective tissue dysplasia and its particular manifestation as Ehlers–Danlos syndrome (EDS). The holistic ascertainment of 120 findings in 1261 EDS patients added neuro-autonomic symptoms like headaches, muscle weakness, brain fog, chronic fatigue, dyspnea, and bowel irregularity to those of arthralgia and skin laxity, 15 of these symptoms shared with those of post-infectious SARS-CoV-2 (long COVID-19). Underlying articulo-autonomic mechanisms guided a clinical qualification protocol that qualified DNA variants in 317 genes as having diagnostic utility for EDS, six of them identical (F2-LIFR-NLRP3-STAT1-T1CAM1-TNFRSF13B) and eighteen similar to those modifying COVID-19 severity/EDS, including ADAMTS13/ADAMTS2-C3/C1R-IKBKG/IKBKAP-PIK3C3/PIK3R1-POLD4/POLG-TMPRSS2/TMPRSS6-WNT3/WNT10A. Also, contributing to EDS and COVID-19 severity were forty and three genes, respectively, impacting mitochondrial functions as well as parts of an overlapping gene network, or entome, that are hypothesized to mediate the cognitive–behavioral, neuro-autonomic, and immune-inflammatory alterations of connective tissue in these conditions. The further characterization of long COVID-19 natural history and genetic predisposition will be necessary before these parallels to EDS can be carefully delineated and translated into therapies. Full article

Concentration and memory impairment (named “brain fog”) represents a frequent and disabling neuropsychological sequela in post-acute COVID-19 syndrome (PACS) patients. The aim of this study was to assess whether neurocognitive function could improve after a multidisciplinary rehabilitation program enhanced with individualized neuropsychological treatment. A prospective monocentric registry of PACS patients consecutively admitted to our Rehabilitation Unit was created. The Montreal Cognitive Assessment (MoCA) was used to assess cognitive impairment at admission and discharge. A total of sixty-four (64) PACS patients, fifty-six (56) of them with brain fog, were treated with a day-by-day individualized psychological intervention of cognitive stimulation (45 min) on top of a standard in-hospital rehabilitation program. The mean duration of the acute-phase hospitalization was 55.8 ± 25.8 days and the mean in-hospital rehabilitation duration was 30 ± 10 days. The mean age of the patients was 67.3 ± 10.4 years, 66% of them were male, none had a previous diagnosis of dementia, and 66% of the entire sample had experienced severe COVID-19. At admission, only 12% of the patients had normal cognitive function, while 57% showed mild, 28% moderate, and 3% severe cognitive impairment. After psychological treatment, a significant improvement in the MoCA score was found (20.4 ± 5 vs. 24.7 ± 3.7; p < 0.0001) as a result of significant amelioration in the following domains: attention task (p = 0.014), abstract reasoning (p = 0.003), language repetition (p = 0.002), memory recall (p < 0.0001), orientation (p < 0.0001), and visuospatial abilities (p < 0.0001). Moreover, the improvement remained significant after multivariate analysis adjusted for several confounding factors. Finally, at discharge, 43% of the patients with cognitive impairment normalized their cognitive function, while 4.7% were discharged with residual moderate cognitive impairment. In conclusion, our study provides evidence of the effects of multidisciplinary rehabilitation enhanced with neuropsychological treatment on improvement in the cognitive function of post-acute COVID-19 patients. Full article

Introduction: A likely mechanism of Long COVID (LC) is dysautonomia, manifesting as orthostatic intolerance (OI). In our LC service, all patients underwent a National Aeronautics and Space Administration (NASA) Lean Test (NLT), which can detect OI syndromes of Postural Tachycardia Syndrome (PoTS) or Orthostatic Hypotension (OH) in a clinic setting. Patients also completed the COVID-19 Yorkshire Rehabilitation Scale (C19-YRS), a validated LC outcome measure. Our objectives in this retrospective study were (1) to report on the findings of the NLT; and (2) to compare findings from the NLT with LC symptoms reported on the C19-YRS. Methods: NLT data, including maximum heart rate increase, blood pressure decrease, number of minutes completed and symptoms experienced during the NLT were extracted retrospectively, together with palpitation and dizziness scores from the C19-YRS. Mann-Witney U tests were used to examine for statistical difference in palpitation or dizziness scores between patients with normal NLT and those with abnormal NLT. Spearman’s rank was used to examine the correlation between the degree of postural HR and BP change with C19-YRS symptom severity score. Results: Of the 100 patients with LC recruited, 38 experienced symptoms of OI during the NLT; 13 met the haemodynamic screening criteria for PoTS and 9 for OH. On the C19-YRS, 81 reported dizziness as at least a mild problem, and 68 for palpitations being at least a mild problem. There was no significant statistical difference between reported dizziness or palpitation scores in those with normal NLT and those with abnormal NLT. The correlation between symptom severity score and NLT findings was <0.16 (poor). Conclusions: We have found evidence of OI, both symptomatically and haemodynamically in patients with LC. The severity of palpitations and dizziness reported on the C19-YRS does not appear to correlate with NLT findings. We would recommend using the NLT in all LC patients in a clinic setting, regardless of presenting LC symptoms, due to this inconsistency. Full article

COVID-19 impacted the entire world’s population, frequently resulting in long-lasting neuropsychiatric complications. Furthermore, social distancing, lockdowns and fear for one’s personal health worsen individual psychological wellbeing, especially in children and adolescents. Herein, we discuss the results of studies that specifically reported data about the impact of the COVID-19 pandemic or infection on children with Pediatric Acute-Onset Neuropsychiatric Disorders (PANS). Furthermore, we present the cases of five adolescents with PANS whose symptomatology increased following SARS-CoV-2 infection. What emerged from this study was that COVID-19 resulted in the exacerbation of obsessions, tics, anxiety and mood symptoms and decreased wellbeing. Moreover, new symptoms, as well as new PANS cases, are reported to have arisen after COVID-19 infection. Here, we hypothesize that the pathogenic mechanisms of silent viruses, such as the Epstein–Barr virus, are related to neuroinflammation, immune responses and reactivation, with additional roles played by social-isolation-related inflammatory processes. The discussion of PANS, which represents a model of immune-mediated neuropsychiatric manifestations, is particularly relevant, with the aim of uncovering the mechanisms that lead to neuropsychiatric Post-Acute COVID-19 Syndrome (PACS). Prospects for future studies and treatment implications are discussed. Full article