Tag: covid-19

Differential diagnosis and pathogenesis of the neurological signs and symptoms in COVID-19 and long-COVID syndrome

Abstract:

Neurological features have now been reported very frequently in the ongoing COVID-19 pandemic caused by SARS-CoV-2. The neurological deficits associated features are observed in both acute and chronic stages of COVID-19 and they appear to overlap with wide-ranging symptoms that can be attributed to being of non-neural origins, thus obscuring the definitive diagnosis of neuro-COVID.

The pathogenetic factors acting in concert to cause neuronal injury are now emerging, with SARS-CoV-2 directly affecting the brain coupled with the neuroinflammatory factors have been implicated in the causation of disabilities in acute COVID-19 and patients with Long-COVID syndrome. As the differentiation between a neural origin and other organ-based causation of a particular neurological feature is of prognostic significance, it implores a course of action to this covert, yet important neurological challenge.

Source: Baig AM. Differential diagnosis and pathogenesis of the neurological signs and symptoms in COVID-19 and long-COVID syndrome. CNS Neurosci Ther. 2022 Sep 19. doi: 10.1111/cns.13957. Epub ahead of print. PMID: 36117492. https://onlinelibrary.wiley.com/doi/10.1111/cns.13957 (Full text)

Memory alterations after COVID-19 infection: a systematic review

Abstract:

SARS-CoV-2 infection has a wide range of both acute and long-term symptoms. Memory alterations have been frequently reported in studies that explore cognition. The main objective of the systematic review is to update and further analyze the existing evidence of objective memory impairments in long-COVID-19 considering sample and study design characteristics, as well as to explore associations between memory performance and their epidemiological, clinical, and pathological features.

A total of 13 studies were identified by searching in PubMed, Web of Science, and PsycInfo databases up to May 6, 2022. Most studies evaluated verbal component of memory in the short-term and long-term recall up to 30 min and mainly performed a single assessment completed at 4-6 months after the infection. The samples mainly consisted of middle-aged adults that required hospitalization. Samples were not stratified by sex, age, and severity.

Poor verbal learning was reported in most cases (6-58%), followed by deficits in long-term (4-58%) and short-term (4-37%) verbal memory. Visuospatial component of memory was studied less than verbal component, showing impairment of long-term retention of visual items (10-49%). COVID-19 severity in the acute stage was not systematically associated with poor memory performance. Verbal memory deficits were associated with anxiety and depression.

The existing literature on objective memory assessment in long-COVID suggests further research is warranted to confirm memory dysfunction in association with epidemiological, pathological, and clinical factors, using both verbal and visuospatial tests, and exploring in deep long-term memory deficits.

Source: Llana T, Zorzo C, Mendez-Lopez M, Mendez M. Memory alterations after COVID-19 infection: a systematic review. Appl Neuropsychol Adult. 2022 Sep 15:1-14. doi: 10.1080/23279095.2022.2123739. Epub ahead of print. PMID: 36108666.  https://pubmed.ncbi.nlm.nih.gov/36108666/

Targeting endothelial dysfunction and oxidative stress in Long-COVID

Comment:

We thank Dr. Hsu and Dr. Lai for their interest in our work on COVID-19 and Long-COVID.

We fully agree with them on the fact that several factors need to be pondered in order to evaluate the risk of developing Long-COVID , . However, we respectfully believe that these considerations are not pertinent to our study . Indeed, we designed the LINCOLN (l-Arginine and Vitamin C improves Long-COVID) survey to determine whether a supplementation combining l-Arginine (to improve endothelial function) and Vitamin C (to reduce oxidation) could have favorable effects in patients with Long-COVID . Thus, in our study we did not assess the risk of developing Long-COVID; in fact, as clearly specified in our article, all the enrolled patients had Long-COVID when the survey was administered. Nevertheless, potential differences in health conditions between the group that had received l-Arginine + Vitamin C and the group that had received the alternative treatment were ruled out by their family physicians. When comparing the two groups, we did not observe any significant difference in terms of age, sex, hospitalization due to COVID-19, and time from SARS-Cov-2 negativization. Moreover, bearing in mind the limitations that all surveys have, we had concluded our article stating that further dedicated interventional studies were warranted to endorse our findings.

Of note, we have previously conducted a randomized, double-blind, placebo-controlled, parallel-group, clinical trial testing the effects of l-Arginine oral supplementation in patients hospitalized for COVID-19, demonstrating that this treatment significantly decreases the length of hospitalization and reduces the respiratory support . Additionally, we have identified endothelial exosomes enriched in miR-24 as a reliable biomarker to predict cerebrovascular complications of COVID-19 , corroborating the fundamental role of endothelial dysfunction in the pathobiology of COVID-19 and its clinical sequelae .

Source: Trimarco V, Izzo R, Mone P, Trimarco B, Santulli G. Targeting endothelial dysfunction and oxidative stress in Long-COVID. Pharmacol Res. 2022 Sep 13;184:106451. doi: 10.1016/j.phrs.2022.106451. Epub ahead of print. PMID: 36108875; PMCID: PMC9467917. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9467917/ (Full text)

Low Prevalence of Interferon-α Autoantibodies in People Experiencing Long COVID Symptoms

Abstract:

Interferon (IFN)-specific autoantibodies have been implicated in severe COVID-19 and have been proposed as a potential driver of the persistent symptoms characterizing Long COVID, a type of post-acute sequelae of SARS-CoV-2 infection (PASC). We report than only two of 215 SARS-CoV-2 convalescent participants tested over 394 timepoints, including 121 people experiencing Long COVID symptoms, had detectable IFN-α2 antibodies. Both had been hospitalized during the acute phase of the infection. These data suggest that persistent anti-IFN antibodies, although a potential driver of severe COVID-19, are unlikely to contribute to Long COVID symptoms in the post-acute phase of the infection.

Source: Peluso MJ, Mitchell A, Wang CY, Takahashi S, Hoh R, Tai V, Durstenfeld MS, Hsue PY, Kelly JD, Martin JN, Wilson MR, Greenhouse B, Deeks SG, DeRisi JL, Henrich TJ. Low Prevalence of Interferon-α Autoantibodies in People Experiencing Long COVID Symptoms. J Infect Dis. 2022 Sep 12:jiac372. doi: 10.1093/infdis/jiac372. Epub ahead of print. PMID: 36089700.  https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiac372/6696027 (Full text available as PDF file)

Post-acute COVID syndrome (long COVID): What should radiographers know and the potential impact for imaging services

Abstract:

Objectives: The COVID-19 pandemic caused an unprecedented health crisis resulting in over 6 million deaths worldwide, a figure, which continues to grow. In addition to the excess mortality, there are individuals who recovered from the acute stages, but suffered long-term changes in their health post COVID-19, commonly referred to as long COVID. It is estimated there are currently 1.8 million long COVID sufferers by May 2022 in the UK alone. The aim of this narrative literature review is to explore the signs, symptoms and diagnosis of long COVID and the potential impact on imaging services.

Key findings: Long COVID is estimated to occur in 9.5% of those with two doses of vaccination and 14.6% if those with a single dose or no vaccination. Long COVID is defined by ongoing symptoms lasting for 12 or more weeks post acute infection. Symptoms are associated with reductions in the quality of daily life and may involve multisystem manifestations or present as a single symptom.

Conclusion: The full impact of long COVID on imaging services is yet to be realised, but there is likely to be significant increased demand for imaging, particularly in CT for the assessment of lung disease. Educators will need to include aspects related to long COVID pathophysiology and imaging presentations in curricula, underpinned by the rapidly evolving evidence base.

Implications for practice: Symptoms relating to long COVID are likely to become a common reason for imaging, with a particular burden on Computed Tomography services. Planning, education and updating protocols in line with a rapidly emerging evidence base is going to be essential.

Source: Alghamdi F, Owen R, Ashton REM, Obotiba AD, Meertens RM, Hyde E, Faghy MA, Knapp KM, Rogers P, Strain WD. Post-acute COVID syndrome (long COVID): What should radiographers know and the potential impact for imaging services. Radiography (Lond). 2022 Sep 12:S1078-8174(22)00119-5. doi: 10.1016/j.radi.2022.08.009. Epub ahead of print. PMID: 36109264; PMCID: PMC9468096. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9468096/ (Full text)

What we already know about the Post-COVID-19 Syndrome: A narrative review

Abstract:

As an increasingly number of patients recover from the acute COVID-19 disease, it has been observed that many face long lasting symptoms, referred as the Post-COVID-19 Syndrome. This article covers the most common signs and symptoms of this syndrome, its general aspects, and important complementary exams related to the disease. The manuscript is a narrative review, gathering new evidence published about the topic.

The most common symptoms of the Post-COVID-19 Syndrome are chronic fatigue, breathlessness, depression or anxiety, pain, cough and alopecia, and many of them are still present 6 months after hospital discharge from the acute disease, depending on the gravity of the illness. It is important for patients to maintain medical follow-up to access severity of the symptoms and choose whether further investigation is necessary. There are some treatments available to some minimize the long-lasting burden of the syndrome, and the physician should access the need for treatment with the patient.

As a new disease, there is a lot of new evidence being produced rapidly, but no up-to-date protocol has already been published. Even with the vaccinations campaigns, the burden of the pandemic is yet out of sight, as it still killing thousands daily, and those who have recovered from the acute COVID-19 illness can present chronic symptoms. Therefore, we recommend health professionals to continuously up-to-date themselves, as new information is added to make better clinical decisions.

Source: RESENDE, M. D. de .; RESENDE, G. D. de .; RIQUIERI, L. N. .; SANTOS, A. F. A. dos .; CASTRO, A. C. A. de .; ROCHA, M. da C. . What we already know about the Post-COVID-19 Syndrome: A narrative review. Research, Society and Development, [S. l.], v. 11, n. 12, p. e108111234143, 2022. DOI: 10.33448/rsd-v11i12.34143. https://rsdjournal.org/index.php/rsd/article/view/34143

The majority of severe COVID-19 patients develop anti-cardiac autoantibodies

Abstract:

Severe cases of COVID-19 are characterized by an inflammatory burst, which is accompanied by multiorgan failure. The elderly population has higher risk for severe or fatal outcome for COVID-19. Inflammatory mediators facilitate the immune system to combat viral infection by producing antibodies against viral antigens. Several studies reported that the pro-inflammatory state and tissue damage in COVID-19 also promotes autoimmunity by autoantibody generation. We hypothesized that a subset of these autoantibodies targets cardiac antigens.

Here we aimed to detect anti-cardiac autoantibodies in severe COVID-19 patients during hospitalization. For this purpose, 104 COVID-19 patients were recruited, while 40 heart failure patients with dilated cardiomyopathy and 20 patients with severe aortic stenosis served as controls. Patients were tested for anti-cardiac autoantibodies, using human heart homogenate as a bait. Follow-up samples were available in 29 COVID-19 patients. Anti-cardiac autoantibodies were detected in 68% (71 out of 104) of severe COVID-19 patients.

Overall, 39% of COVID-19 patients had anti-cardiac IgG autoantibodies, while 51% had anti-cardiac autoantibodies of IgM isotype. Both IgG and IgM anti-cardiac autoantibodies were observed in 22% of cases, and multiple cardiac antigens were targeted in 38% of COVID-19 patients. These anti-cardiac autoantibodies targeted a diverse set of myocardial proteins, without apparent selectivity. As controls, heart failure patients (with dilated cardiomyopathy) had similar occurrence of IgG (45%, p = 0.57) autoantibodies, while significantly lower occurrence of IgM autoantibodies (30%, p = 0.03). Patients with advanced aortic stenosis had significantly lower number of both IgG (11%, p = 0.03) and IgM (10%, p < 0.01) type anti-cardiac autoantibodies than that in COVID-19 patients. Furthermore, we detected changes in the anti-cardiac autoantibody profile in 7 COVID-19 patients during hospital treatment.

Surprisingly, the presence of these anti-cardiac autoantibodies did not affect the clinical outcome and the prevalence of the autoantibodies did not differ between the elderly (over 65 years) and the patients younger than 65 years of age. Our results demonstrate that the majority of hospitalized COVID-19 patients produce novel anti-cardiac IgM autoantibodies. COVID-19 also reactivates resident IgG autoantibodies. These autoantibodies may promote autoimmune reactions, which can complicate post-COVID recuperation, contributing to post-acute sequelae of COVID-19 (long COVID).

Source: Fagyas M, Nagy B Jr, Ráduly AP, Mányiné IS, Mártha L, Erdősi G, Sipka S Jr, Enyedi E, Szabó AÁ, Pólik Z, Kappelmayer J, Papp Z, Borbély A, Szabó T, Balla J, Balla G, Bai P, Bácsi A, Tóth A. The majority of severe COVID-19 patients develop anti-cardiac autoantibodies. Geroscience. 2022 Sep 16:1–14. doi: 10.1007/s11357-022-00649-6. Epub ahead of print. PMID: 36112333; PMCID: PMC9483490. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9483490/ (Full text)

Prevalence and clinical presentation of long COVID in children: a systematic review

Abstract:

A systematic literature review was conducted up to 15th February 2022 to summarize long COVID evidence and to assess prevalence and clinical presentation in children and adolescents. Articles reporting long COVID prevalence and symptoms based on original data in the paediatric population were included. Case series quality was assessed through the JBI Critical Appraisal Checklist. For observational studies, adherence to STROBE checklist was evaluated. Twenty-two articles were included: 19 observational studies (12 cohort/7 cross-sectional) and 3 case series. Nine studies provided a control group. We found a high variability in terms of prevalence (1.6-70%). The most frequently reported symptoms were fatigue (2-87%), headache (3.5-80%), arthro-myalgias (5.4-66%), chest tightness or pain (1.4-51%), and dyspnoea (2-57.1%). Five studies reported limitations in daily function due to long COVID. Alterations at brain imaging were described in one study, transient electrocardiographic abnormalities were described in a minority of children, while most authors did not evidence long-term pulmonary sequelae. Older age, female sex, and previous long-term pathological conditions were more frequently associated with persistent symptoms.

Conclusion: Long COVID evidence in children is limited, heterogeneous, and based on low-quality studies. The lockdown consequences are difficult to distinguish from long COVID symptoms. High-quality studies are required: WHO definition of long COVID should be used, controlled clinical studies should be encouraged, and the impact of new variants on long COVID prevalence should be investigated to ensure an objective analysis of long COVID characteristics in children and a proper allocation of healthcare system resources.

What is known: • Children rarely develop a severe respiratory disease in the acute phase of COVID-19. • A limited number of patients develop a multisystem inflammatory condition that can lead to multiorgan failure and shock.

What is new: • Persistent symptoms after SARS-CoV-2 infection are reported in children and limitations in daily function due to long COVID symptoms affect school attendance. • Functional complaints of post-acute COVID are difficult to be distinguished from those due to social restrictions.

Source: Pellegrino R, Chiappini E, Licari A, Galli L, Marseglia GL. Prevalence and clinical presentation of long COVID in children: a systematic review. Eur J Pediatr. 2022 Sep 15:1–15. doi: 10.1007/s00431-022-04600-x. Epub ahead of print. PMID: 36107254; PMCID: PMC9476461.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9476461/ (Full text)

Bioinformatics and systems biology approach to identify the pathogenetic link of Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Background: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global crisis. Although many people recover from COVID-19 infection, they are likely to develop persistent symptoms similar to those of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) after discharge. Those constellations of symptoms persist for months after infection, called Long COVID, which may lead to considerable financial burden and healthcare challenges. However, the mechanisms underlying Long COVID and ME/CFS remain unclear.

Methods: We collected the genes associated with Long COVID and ME/CFS in databases by restricted screening conditions and clinical sample datasets with limited filters. The common genes for Long COVID and ME/CFS were finally obtained by taking the intersection. We performed several advanced bioinformatics analyses based on common genes, including gene ontology and pathway enrichment analyses, protein–protein interaction (PPI) analysis, transcription factor (TF)–gene interaction network analysis, transcription factor–miRNA co-regulatory network analysis, and candidate drug analysis prediction.

Results: We found nine common genes between Long COVID and ME/CFS and gained a piece of detailed information on their biological functions and signaling pathways through enrichment analysis. Five hub proteins (IL-6, IL-1B, CD8A, TP53, and CXCL8) were collected by the PPI network. The TF–gene and TF–miRNA coregulatory networks were demonstrated by NetworkAnalyst. In the end, 10 potential chemical compounds were predicted.

Conclusion: This study revealed common gene interaction networks of Long COVID and ME/CFS and predicted potential therapeutic drugs for clinical practice. Our findings help to identify the potential biological mechanism between Long COVID and ME/CFS. However, more laboratory and multicenter evidence is required to explore greater mechanistic insight before clinical application in the future.

Source: Lv Y, Zhang T, Cai J, Huang C, Zhan S and Liu J. Bioinformatics and systems biology approach to identify the pathogenetic link of Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front. Immunol. 13:952987  https://www.frontiersin.org/articles/10.3389/fimmu.2022.952987/full (Full text)

Long-term neuromuscular consequences of SARS-Cov-2 and their similarities with myalgic encephalomyelitis/chronic fatigue syndrome: results of the retrospective CoLGEM study

Abstract:

Background: Patients with long-COVID often complain of continuous fatigue, myalgia, sleep problems, cognitive dysfunction, and post-exertional malaise. No data are available on EMG recording of evoked myopotentials (M-waves) or exercise-induced alterations in long-COVID patients, providing evidence of muscle membrane fatigue. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) develops in more than half of patients after an infectious disease, particularly viral diseases. A large proportion (around 70%) of these patients have neuromuscular disorders with M-wave alterations during and after exercise. Our hypothesis was that M-wave alterations would be also found in long-COVID patients, in association with neuromuscular symptoms, similar to ME/CFS.

Methods: This retrospective observational ColGEM (Covid LonG Encéphalomyelite Myalgique) study compared 59 patients with long-COVID and 55 ME/CFS patients with a history of severe infection who presented before the COVID pandemic. All of these patients underwent the same protocol consisting of a questionnaire focusing on neural and neuromuscular disorders and M-wave recording in the rectus femoris muscle before, during, and 10 min after a progressive cycling exercise. Maximal handgrip strength (MHGS) and maximal exercise power were also measured. The frequency of symptoms and magnitude of M-wave changes in the two groups were compared using non-parametric and parametric tests.

Results: The frequency of fatigue, myalgia, sleep problems, cognitive dysfunction, and post-exertional malaise as well as the magnitude of exercise-induced M-wave alterations were the same in the two groups. By contrast, digestive problems were less present in long-COVID. M-wave alterations were greater in ME/CFS patients as in those with long-COVID when the highest muscle strength and highest exercise performance were measured.

Conclusions: These high clinical and biological similarities between long-COVID and ME/CFS support the hypothesis that SARS-Cov-2 infection can cause ME/CFS symptoms. Trial registration Registered retrospectively.

Source: Retornaz F, Rebaudet S, Stavris C, Jammes Y. Long-term neuromuscular consequences of SARS-Cov-2 and their similarities with myalgic encephalomyelitis/chronic fatigue syndrome: results of the retrospective CoLGEM study. J Transl Med. 2022 Sep 24;20(1):429. doi: 10.1186/s12967-022-03638-7. PMID: 36153556. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-022-03638-7 (Full text)