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"Long COVID"
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Associations between persistent symptoms after mild COVID‐19 and long‐term health status, quality of life, and psychological distress
2022
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.
Journal Article
Swiss Recommendations for the Follow-Up and Treatment of Pulmonary Long COVID
by
Soccal, Paola M.
,
von Garnier, Christophe
,
Funke-Chambour, Manuela
in
Guidelines
,
Methods
,
Pulmonary function tests
2021
Abstract
Introduction: Emerging evidence suggests that long-term pulmonary symptoms and functional impairment occurs in a proportion of individuals following SARS-CoV-2 infection. Although the proportion of affected patients remains to be determined, physicians are increasingly being confronted with patients reporting respiratory symptoms and impairment beyond the acute phase of COVID-19. In face of limited evidence, the Swiss Society for Pulmonology established a working group to address this area of unmet need and formulated diagnostic and treatment recommendations for the care of patients with pulmonary long COVID (LC). Method: The Swiss COVID Lung Study group and Swiss Society for Pulmonology (SSP) formulated 13 questions addressing the diagnosis and treatment of pulmonary LC. A survey within the SSP special interest groups involved in care of LC patients was conducted in Switzerland. A CORE process/Delphi-like process was used to formulate recommendations. Forty experienced pulmonologists replied to the first survey and 22 completed the second follow-up survey. Agreement of ≥70% consensus led to formulation of a recommendation. Results: The participants in the survey reached consensus and formulated a strong recommendation for regarding the following points. Patients hospitalized for COVID-19 should have a pulmonary assessment including pulmonary function tests. Symptomatic subjects affected by COVID-19, including those with mild disease, should benefit from a pulmonary follow-up. Persistent respiratory symptoms after COVID-19 should be investigated by a pulmonary follow-up including plethysmography, diffusion capacity measurement, and blood gases analysis. Individuals having suffered from COVID-19 and who present with persistent respiratory symptoms should be offered a rehabilitation. Additional questions were given moderateor weak recommendations for. The panel did not reach sufficient consensus for pharmacological therapy (e.g., therapy specifically targeting lung fibrosis) to formulate recommendations for LC drug treatment. Conclusion: The formulated recommendations should serve as an interim guidance to facilitate diagnosis and treatment of patients with pulmonary LC. As new evidence emerges, these recommendations may need to be adapted.
Journal Article
Postural orthostatic tachycardia syndrome and other autonomic dysfunctions following COVID‐19: Incidence, characteristics, and associated factors
by
Jitpreeda, Amaraluk
,
Sukitpunyaroj, Damrong
,
Srisakvarakul, Chaval
in
Blood pressure
,
Blood tests
,
Cardiac arrhythmia
2024
Background Long‐COVID syndrome has become a new health concern. Many major clinical centers have experienced more patients with symptoms suggestive of autonomic dysfunction, especially postural orthostatic tachycardia syndrome (POTS) following COVID‐19. However, there is a lack of information regarding the incidence and associated factors in Asian population. Methods A retro‐prospective study was conducted to evaluate patients with symptoms suggestive of POTS or other autonomic dysfunctions. These symptoms last at least 3 months after PCR‐proven COVID‐19. Exclusion criteria were age under 18 years old, pregnancy, and pre‐COVID‐19 autonomic dysfunction symptoms. Patients with a symptom severity score greater than two were assessed with blood tests, 24‐h Holter, 24‐h ambulatory blood pressure, echocardiogram, and head‐up tilt table (HUTT). Results Seven hundred ninety‐three patients were interviewed at 146 ± 37 days after COVID‐19. The majority of patients were middle‐aged females (53%). Of those, 15 patients had the symptom severity score greater than 2. Out of those 15 patients, 12 had positive HUTT (1 demonstrating POTS, 10 neurocardiogenic syncope, and 1 orthostatic hypotension). Among those with positive HUTT patients, C‐reactive protein (CRP) was significantly higher (OR 1.01; p‐value 0.041). Fatigue and dyspnea on exertion were the two most complaint symptoms. Conclusions This study shows the incidence of autonomic dysfunction and POTS is 1.5% (12/793) and 0.1% POTS (1/793), respectively, in a primary care setting (among general post‐COVID‐19 patients). The most common symptoms for these patients were fatigue and dyspnea. Study enrollment flow and associating factors.
Journal Article
Neurological manifestations of long-COVID syndrome: a narrative review
2022
Accumulating evidence points toward a very high prevalence of prolonged neurological symptoms among coronavirus disease 2019 (COVID-19) survivors. To date, there are no solidified criteria for ‘long-COVID’ diagnosis. Nevertheless, ‘long-COVID’ is conceptualized as a multi-organ disorder with a wide spectrum of clinical manifestations that may be indicative of underlying pulmonary, cardiovascular, endocrine, hematologic, renal, gastrointestinal, dermatologic, immunological, psychiatric, or neurological disease. Involvement of the central or peripheral nervous system is noted in more than one-third of patients with antecedent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, while an approximately threefold higher incidence of neurological symptoms is recorded in observational studies including patient-reported data. The most frequent neurological manifestations of ‘long-COVID’ encompass fatigue; ‘brain fog’; headache; cognitive impairment; sleep, mood, smell, or taste disorders; myalgias; sensorimotor deficits; and dysautonomia. Although very limited evidence exists to date on the pathophysiological mechanisms implicated in the manifestation of ‘long-COVID’, neuroinflammatory and oxidative stress processes are thought to prevail in propagating neurological ‘long-COVID’ sequelae. In this narrative review, we sought to present a comprehensive overview of our current understanding of clinical features, risk factors, and pathophysiological processes of neurological ‘long-COVID’ sequelae. Moreover, we propose diagnostic and therapeutic algorithms that may aid in the prompt recognition and management of underlying causes of neurological symptoms that persist beyond the resolution of acute COVID-19. Furthermore, as causal treatments for ‘long-COVID’ are currently unavailable, we propose therapeutic approaches for symptom-oriented management of neurological ‘long-COVID’ symptoms. In addition, we emphasize that collaborative research initiatives are urgently needed to expedite the development of preventive and therapeutic strategies for neurological ‘long-COVID’ sequelae.
Journal Article
SARS-CoV-2 Reinfections and Long COVID in the Post-Omicron Phase of the Pandemic
2023
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.
Journal Article
The Conundrum of ‘Long-COVID-19ʹ: A Narrative Review
2021
COVID-19 is an ongoing pandemic with many challenges that are now extending to its intriguing long-term sequel. 'Long-COVID-19' is a term given to the lingering or protracted illness that patients of COVID-19 continue to experience even in their post-recovery phase. It is also being called 'post-acute COVID-19', 'ongoing symptomatic COVID-19', 'chronic COVID-19', 'post COVID-19 syndrome', and 'long-haul COVID-19'. Fatigue, dyspnea, cough, headache, brain fog, anosmia, and dysgeusia are common symptoms seen in Long-COVID-19, but more varied and debilitating injuries involving pulmonary, cardiovascular, cutaneous, musculoskeletal and neuropsychiatric systems are also being reported. With the data on Long-COVID-19 still emerging, the present review aims to highlight its epidemiology, protean clinical manifestations, risk predictors, and management strategies. With the re-emergence of new waves of SARS-CoV-2 infection, Long-COVID-19 is expected to produce another public health crisis on the heels of current pandemic. Thus, it becomes imperative to emphasize this condition and disseminate its awareness to medical professionals, patients, the public, and policymakers alike to prepare and augment health care facilities for continued surveillance of these patients. Further research comprising cataloging of symptoms, longer-ranging observational studies, and clinical trials are necessary to evaluate longterm consequences of COVID-19, and it warrants setting-up of dedicated, post-COVID care, multidisciplinary clinics, and rehabilitation centers. Keywords: ongoing symptomatic COVID-19, post-COVID-19 syndrome, chronic COVID, Long-COVID-19, post-COVID, Long-COVID
Journal Article
Long-COVID Symptoms in Individuals Infected with Different SARS-CoV-2 Variants of Concern: A Systematic Review of the Literature
by
Arendt-Nielsen, Lars
,
Ocampo, Miguel Joaquín
,
Velasco, Jacqueline Veronica
in
alpha
,
Cohort analysis
,
Coronaviruses
2022
The association of SARS-CoV-2 variants with long-COVID symptoms is still scarce, but new data are appearing at a fast pace. This systematic review compares the prevalence of long-COVID symptoms according to relevant SARS-CoV-2 variants in COVID-19 survivors. The MEDLINE, CINAHL, PubMed, EMBASE and Web of Science databases, as well as the medRxiv and bioRxiv preprint servers, were searched up to 25 October 2022. Case-control and cohort studies analyzing the presence of post-COVID symptoms appearing after an acute SARS-CoV-2 infection by the Alpha (B.1.1.7), Delta (B.1.617.2) or Omicron (B.1.1.529/BA.1) variants were included. Methodological quality was assessed using the Newcastle–Ottawa Scale. From 430 studies identified, 5 peer-reviewed studies and 1 preprint met the inclusion criteria. The sample included 355 patients infected with the historical variant, 512 infected with the Alpha variant, 41,563 infected with the Delta variant, and 57,616 infected with the Omicron variant. The methodological quality of all studies was high. The prevalence of long-COVID was higher in individuals infected with the historical variant (50%) compared to those infected with the Alpha, Delta or Omicron variants. It seems that the prevalence of long-COVID in individuals infected with the Omicron variant is the smallest, but current data are heterogeneous, and long-term data have, at this stage, an obviously shorter follow-up compared with the earlier variants. Fatigue is the most prevalent long-COVID symptom in all SARS-CoV-2 variants, but pain is likewise prevalent. The available data suggest that the infection with the Omicron variant results in fewer long-COVID symptoms compared to previous variants; however, the small number of studies and the lack of the control of cofounders, e.g., reinfections or vaccine status, in some studies limit the generality of the results. It appears that individuals infected with the historical variant are more likely to develop long-COVID symptomatology.
Journal Article
Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin
2021
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.
Journal Article
Post-COVID-19 Syndrome Mechanisms, Prevention and Management
by
Najafi, Majed B.
,
Javanmard, Shaghayegh H.
in
chronic covid syndrome
,
long covid
,
long haul covid
2023
As the population of patients recovering from COVID-19 grows, post COVID-19 challenges are recognizing by ongoing evidences at once. Long COVID is defined as a syndrome with a range of persistent symptoms that remain long after (beyond 12 weeks) the acute SARS-CoV-2 infection. Studies have shown that long COVID can cause multi-organ damages with a wide spectrum of manifestations. Many systems, but not limited to, including respiratory, cardiovascular, nervous, gastrointestinal, and musculoskeletal systems, are involved in long COVID. Fatigue and dyspnea are the most common symptoms of long COVID. Long COVID-19 may be driven by tissue damage caused by virus-specific pathophysiologic changes or secondary to pathological long-lasting inflammatory response because of viral persistence, immune dysregulation, and autoimmune reactions. Some risk factors like sex and age, more than five early symptoms, and specific biomarkers have been revealed as a probable long COVID predicator discussed in this review. It seems that vaccination is the only way for prevention of long COVID and it can also help patients who had already long COVID. Managing long COVID survivors recommended being in a multidisciplinary approach, and a framework for identifying those at high risk for post-acute COVID-19 must be proposed. Possible therapeutic options and useful investigation tools for follow-up are suggested in this review. In sum, as evidence and researches are regularly updated, we provide the current understanding of the epidemiology, clinical manifestation, suspected pathophysiology, associated risk factors, and treatment options of long COVID in this review.
Journal Article
Autonomic dysfunction in post-COVID patients with and witfhout neurological symptoms: a prospective multidomain observational study
by
Manganotti Paolo
,
Frezza, Nicolò Arjuna
,
Valentinotti Romina
in
Autonomic nervous system
,
Blood pressure
,
Coronary artery disease
2022
The autonomic nervous system (ANS) can be affected by COVID-19, and dysautonomia may be a possible complication in post-COVID individuals. Orthostatic hypotension (OH) and postural tachycardia syndrome (POTS) have been suggested to be common after SARS-CoV-2 infection, but other components of ANS function may be also impaired. The Composite Autonomic Symptom Scale 31 (COMPASS-31) questionnaire is a simple and validated tool to assess dysautonomic symptoms. The aim of the present study was to administer the COMPASS-31 questionnaire to a sample of post-COVID patients with and without neurological complaints. Participants were recruited among the post-COVID ambulatory services for follow-up evaluation between 4 weeks and 9 months from COVID-19 symptoms onset. Participants were asked to complete the COMPASS-31 questionnaire referring to the period after COVID-19 disease. Heart rate and blood pressure were manually taken during an active stand test for OH and POTS diagnosis. One-hundred and eighty participants were included in the analysis (70.6% females, 51 ± 13 years), and OH was found in 13.8% of the subjects. Median COMPASS-31 score was 17.6 (6.9–31.4), with the most affected domains being orthostatic intolerance, sudomotor, gastrointestinal and pupillomotor dysfunction. A higher COMPASS-31 score was found in those with neurological symptoms (p < 0.01), due to more severe orthostatic intolerance symptoms (p < 0.01), although gastrointestinal (p < 0.01), urinary (p < 0.01), and pupillomotor (p < 0.01) domains were more represented in the non-neurological symptoms group. This study confirms the importance of monitoring ANS symptoms as a possible complication of COVID-19 disease that may persist in the post-acute period.
Journal Article