Explore the vast range of titles available.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection, the cause of coronavirus disease 2019 (COVID-19), is characterized by acute clinical pathologies, including various coagulopathies that may be accompanied by hypercoagulation and platelet hyperactivation. Recently, a new COVID-19 phenotype has been noted in patients after they have ostensibly recovered from acute COVID-19 symptoms. This new syndrome is commonly termed Long COVID/Post-Acute Sequelae of COVID-19 (PASC). Here we refer to it as Long COVID/PASC. Lingering symptoms persist for as much as 6 months (or longer) after acute infection, where COVID-19 survivors complain of recurring fatigue or muscle weakness, being out of breath, sleep difficulties, and anxiety or depression. Given that blood clots can block microcapillaries and thereby inhibit oxygen exchange, we here investigate if the lingering symptoms that individuals with Long COVID/PASC manifest might be due to the presence of persistent circulating plasma microclots that are resistant to fibrinolysis. Methods We use techniques including proteomics and fluorescence microscopy to study plasma samples from healthy individuals, individuals with Type 2 Diabetes Mellitus (T2DM), with acute COVID-19, and those with Long COVID/PASC symptoms. Results We show that plasma samples from Long COVID/PASC still contain large anomalous (amyloid) deposits (microclots). We also show that these microclots in both acute COVID-19 and Long COVID/PASC plasma samples are resistant to fibrinolysis (compared to plasma from controls and T2DM), even after trypsinisation. After a second trypsinization, the persistent pellet deposits (microclots) were solubilized. We detected various inflammatory molecules that are substantially increased in both the supernatant and trapped in the solubilized pellet deposits of acute COVID-19 and Long COVID/PASC, versus the equivalent volume of fully digested fluid of the control samples and T2DM. Of particular interest was a substantial increase in α(2)-antiplasmin (α2AP), various fibrinogen chains, as well as Serum Amyloid A (SAA) that were trapped in the solubilized fibrinolytic-resistant pellet deposits. Conclusions Clotting pathologies in both acute COVID-19 infection and in Long COVID/PASC might benefit from following a regime of continued anticlotting therapy to support the fibrinolytic system function.

Background Fibrin(ogen) amyloid microclots and platelet hyperactivation previously reported as a novel finding in South African patients with the coronavirus 2019 disease (COVID-19) and Long COVID/Post-Acute Sequelae of COVID-19 (PASC), might form a suitable set of foci for the clinical treatment of the symptoms of Long COVID/PASC. A Long COVID/PASC Registry was subsequently established as an online platform where patients can report Long COVID/PASC symptoms and previous comorbidities. Methods In this study, we report on the comorbidities and persistent symptoms, using data obtained from 845 South African Long COVID/PASC patients. By using a previously published scoring system for fibrin amyloid microclots and platelet pathology, we also analysed blood samples from 80 patients, and report the presence of significant fibrin amyloid microclots and platelet pathology in all cases. Results Hypertension, high cholesterol levels (dyslipidaemia), cardiovascular disease and type 2 diabetes mellitus (T2DM) were found to be the most important comorbidities. The gender balance (70% female) and the most commonly reported Long COVID/PASC symptoms (fatigue, brain fog, loss of concentration and forgetfulness, shortness of breath, as well as joint and muscle pains) were comparable to those reported elsewhere. These findings confirmed that our sample was not atypical. Microclot and platelet pathologies were associated with Long COVID/PASC symptoms that persisted after the recovery from acute COVID-19. Conclusions Fibrin amyloid microclots that block capillaries and inhibit the transport of O 2 to tissues, accompanied by platelet hyperactivation, provide a ready explanation for the symptoms of Long COVID/PASC. Removal and reversal of these underlying endotheliopathies provide an important treatment option that urgently warrants controlled clinical studies to determine efficacy in patients with a diversity of comorbidities impacting on SARS-CoV-2 infection and COVID-19 severity. We suggest that our platelet and clotting grading system provides a simple and cost-effective diagnostic method for early detection of Long COVID/PASC as a major determinant of effective treatment, including those focusing on reducing clot burden and platelet hyperactivation.

Background: A growing number of Coronavirus Disease-2019 (COVID-19) survivors are affected by post-acute sequelae of SARS CoV-2 infection (PACS). Using electronic health record data, we aimed to characterize PASC-associated diagnoses and develop risk prediction models. Methods: In our cohort of 63,675 patients with a history of COVID-19, 1724 (2.7%) had a recorded PASC diagnosis. We used a case–control study design and phenome-wide scans to characterize PASC-associated phenotypes of the pre-, acute-, and post-COVID-19 periods. We also integrated PASC-associated phenotypes into phenotype risk scores (PheRSs) and evaluated their predictive performance. Results: In the post-COVID-19 period, known PASC symptoms (e.g., shortness of breath, malaise/fatigue) and musculoskeletal, infectious, and digestive disorders were enriched among PASC cases. We found seven phenotypes in the pre-COVID-19 period (e.g., irritable bowel syndrome, concussion, nausea/vomiting) and sixty-nine phenotypes in the acute-COVID-19 period (predominantly respiratory, circulatory, neurological) associated with PASC. The derived pre- and acute-COVID-19 PheRSs stratified risk well, e.g., the combined PheRSs identified a quarter of the cohort with a history of COVID-19 with a 3.5-fold increased risk (95% CI: 2.19, 5.55) for PASC compared to the bottom 50%. Conclusions: The uncovered PASC-associated diagnoses across categories highlighted a complex arrangement of presenting and likely predisposing features, some with potential for risk stratification approaches.

Long COVID remains poorly characterized at the genomic level. The primary aim of this study was to examine the relationship between viral sequences and the incidence of Long COVID at a tertiary care center in Louisiana between April 2020 and December 2022. A secondary aim was analysis of the Spike protein to identify conserved regions for multivalent vaccine targets. To estimate Long COVID incidence across variants, we linked 4789 SARS-CoV-2 sequences to 3090 de-identified patient electronic health record information. The base population was defined as any patient with an International Classification of Diseases-10-Clinical Modification COVID-19 diagnosis code (U07.1) based definitions of Long COVID presentation developed by the N3C consortium. 1,554 patients (1,536 Long COVID-negative) met Long COVID definitions, with 56.3% being female, 36.1% self-reported as African American, 5.5% self-reported as Hispanic/Latino, and 54.5% had received at least one vaccine dose 14 days prior to SARS-CoV-2 collection. Long COVID-positive patients were older (mean age 43.1 years) than negative patients (35.9 years; = 0.0054) and were more likely to be female ( = 0.0001). Among unvaccinated patients, those with Long COVID were significantly younger than their vaccinated counterparts ( < 0.00001). Long COVID incidence varied by PANGO lineage, ranging between 14% in AY.13 to 67.8% in B.1.1.7. Analysis of spike protein diversity revealed eight conserved amino acid regions (Shannon entropy < 0.43), representing potential targets for vaccine design. Long COVID rates across thousands of annotated SARS-CoV-2 sequences revealed lineage-specific risk and conserved epitopes for future interventions.

Post Acute Sequelae of SARS-CoV-2 infection (PASC or Long COVID) is characterized by lingering symptomatology post-initial COVID-19 illness that is often debilitating. It is seen in up to 30–40% of individuals post-infection. Patients with Long COVID (LC) suffer from dysautonomia, malaise, fatigue, and pain, amongst a multitude of other symptoms. Fibromyalgia (FM) is a chronic musculoskeletal pain disorder that often leads to functional disability and severe impairment of quality of life. LC and FM share several clinical features, including pain that often makes them indistinguishable. The aim of this study is to develop a metabolic fingerprinting approach using portable Fourier-transform mid-infrared (FT-MIR) spectroscopic techniques to diagnose clinically similar LC and FM. Blood samples were obtained from LC (n = 50) and FM (n = 50) patients and stored on conventional bloodspot protein saver cards. A semi-permeable membrane filtration approach was used to extract the blood samples, and spectral data were collected using a portable FT-MIR spectrometer. Through the deconvolution analysis of the spectral data, a distinct spectral marker at 1565 cm−1 was identified based on a statistically significant analysis, only present in FM patients. This IR band has been linked to the presence of side chains of glutamate. An OPLS-DA algorithm created using the spectral region 1500 to 1700 cm−1 enabled the classification of the spectra into their corresponding classes (Rcv > 0.96) with 100% accuracy and specificity. This high-throughput approach allows unique metabolic signatures associated with LC and FM to be identified, allowing these conditions to be distinguished and implemented for in-clinic diagnostics, which is crucial to guide future therapeutic approaches.

Background We sought to assess whether persistent COVID‐19 symptoms beyond 6 months (Long‐COVID) among patients with mild COVID‐19 is associated with poorer health status, quality of life, and psychological distress. Methods This was a multicenter prospective cohort study that included adult outpatients with acute COVID‐19 from eight sites during 2‐week sampling periods from April 1 and July 28, 2020. Participants were contacted 6–11 months after their first positive SARS‐CoV‐2 to complete a survey, which collected information on the severity of eight COVID‐19 symptoms using a 4‐point scale ranging from 0 (not present) to 3 (severe) at 1 month before COVID‐19 (pre‐illness) and at follow‐up; the difference for each was calculated as an attributable persistent symptom severity score. A total attributable persistent COVID‐19 symptom burden score was calculated by summing the attributable persistent severity scores for all eight symptoms. Outcomes measured at long‐term follow‐up comprised overall health status (EuroQol visual analogue scale), quality of life (EQ‐5D‐5L), and psychological distress (Patient Health Questionnaire‐4). The association between the total attributable persistent COVID‐19 burden score and each outcome was analyzed using multivariable proportional odds regression. Results Of the 2092 outpatients with COVID‐19, 436 (21%) responded to the survey. The median (IQR) attributable persistent COVID‐19 symptom burden score was 2 (0, 4); higher scores were associated with lower overall health status (aOR 0.63; 95% CI: 0.57–0.69), lower quality of life (aOR: 0.65; 95%CI: 0.59–0.72), and higher psychological distress (aOR: 1.40; 95%CI, 1.28–1.54) after adjusting for age, race, ethnicity, education, and income. Conclusions In participants with mild acute COVID‐19, the burden of persistent symptoms was significantly associated with poorer long‐term health status, poorer quality of life, and psychological distress.

The coronavirus disease (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, is leading to unknown and unusual health conditions that are challenging to manage. Post-COVID-19 syndrome is one of those challenges, having become increasingly common as the pandemic evolves. The latest estimates suggest that 10 to 20% of the SARS-CoV-2 patients who undergo an acute symptomatic phase are experiencing effects of the disease beyond 12 weeks after diagnosis. Although research is beginning to examine this new condition, there are still serious concerns about the diagnostic identification, which limits the best therapeutic approach. Exercise programs and physical activity levels are well-known modulators of the clinical manifestations and prognosis in many chronic diseases. This narrative review summarizes the up-to-date evidence on post-COVID-19 syndrome to contribute to a better knowledge of the disease and explains how regular exercise may improve many of these symptoms and could reduce the long-term effects of COVID-19.

We are reviewing the current state of knowledge on the virological and immunological correlates of long COVID, focusing on recent evidence for the possible association between the increasing number of SARS-CoV-2 reinfections and the parallel pandemic of long COVID. The severity of reinfections largely depends on the severity of the initial episode; in turn, this is determined both by a combination of genetic factors, particularly related to the innate immune response, and by the pathogenicity of the specific variant, especially its ability to infect and induce syncytia formation at the lower respiratory tract. The cumulative risk of long COVID as well as of various cardiac, pulmonary, or neurological complications increases proportionally to the number of SARS-CoV-2 infections, primarily in the elderly. Therefore, the number of long COVID cases is expected to remain high in the future. Reinfections apparently increase the likelihood of long COVID, but less so if they are mild or asymptomatic as in children and adolescents. Strategies to prevent SARS-CoV-2 reinfections are urgently needed, primarily among older adults who have a higher burden of comorbidities. Follow-up studies using an established case definition and precise diagnostic criteria of long COVID in people with or without reinfection may further elucidate the contribution of SARS-CoV-2 reinfections to the long COVID burden. Although accumulating evidence supports vaccination, both before and after the SARS-CoV-2 infection, as a preventive strategy to reduce the risk of long COVID, more robust comparative observational studies, including randomized trials, are needed to provide conclusive evidence of the effectiveness of vaccination in preventing or mitigating long COVID in all age groups. Thankfully, answers not only on the prevention, but also on treatment options and rates of recovery from long COVID are gradually starting to emerge.

PurposeTo find out what is known from literature about Long COVID until January 30, 2021.MethodsWe undertook a four-step search with no language restriction. A preliminary search was made to identify the keywords. A search strategy of all electronic databases resulted in 66 eligible studies. A forward and backward search of the references and citations resulted in additional 54 publications. Non-English language articles were translated using Google Translate. We conducted our scoping review based on the PRISMA-ScR Checklist.ResultsOf 120 papers, we found only one randomized clinical trial. Of the 67 original studies, 22 were cohort, and 28 were cross-sectional studies. Of the total 120 publications, 49.1% focused on signs and symptoms, 23.3% on management, and 10.8% on pathophysiology. Ten publications focused on imaging studies. The results are also presented extensively in a narrative synthesis in separated sections (nomenclature, diagnosis, pathophysiology, risk factors, signs/symptoms, management).ConclusionsThe controversies in its definition have impaired proper recognition and management. The predominant symptoms were: fatigue, breathlessness, arthralgia, sleep difficulties, and chest pain. Recent reports also point to the risk of long-term sequela with cutaneous, respiratory, cardiovascular, musculoskeletal, mental health, neurologic, and renal involvement in those who survive the acute phase of the illness.

The pandemic of COVID-19 is the biggest public health crisis in 21 Century. Besides the acute symptoms after infection, patients and society are also being challenged by the long-term health complications associated with COVID-19, commonly known as long COVID. While health professionals work hard to find proper treatments, large amount of knowledge has been accumulated in recent years. In order to deal with long COVID efficiently, it is important for people to keep up with current progresses and take proactive actions on long COVID. For this purpose, this review will first introduce the general background of long COVID, and then discuss its risk factors, diagnostic indicators and management strategies. This review will serve as a useful resource for people to understand and prepare for long COVID that will be with us in the foreseeable future.