Tag: covid-19

Thromboembolism in the Complications of Long COVID-19

Abstract:

SARS-CoV-2 is a +ssRNA helical coronavirus responsible for the global pandemic caused by coronavirus disease 19 (COVID-19). Classical clinical symptoms from primary COVID-19 when symptomatic include cough, fever, pneumonia or even ARDS; however, they are limited primarily to the respiratory system. Long-COVID-19 sequalae is responsible for many pathologies in almost every organ system and may be present in up to 30% of patients who have developed COVID-19.

Our review focuses on how long-COVID-19 (3 -24 weeks after primary symptoms) may lead to an increased risk for stroke and thromboembolism. Patients who were found to be primarily at risk for thrombotic events included critically ill and immunocompromised patients. Additional risk factors for thromboembolism and stroke included diabetes, hypertension, respiratory and cardiovascular disease, and obesity.

The etiology of how long-COVID-19 leads to a hypercoagulable state are yet to be definitively elucidated. However, anti-phospholipid antibodies and elevated D-dimer are present in many patients who develop thromboembolism. In addition, chronic upregulation and exhaustion of the immune system may lead to a pro-inflammatory and hypercoagulable state, increasing the likelihood for induction of thromboembolism or stroke. ‘

This article provides an up-to-date review on the proposed etiologies for thromboembolism and stroke in patients with long-COVID-19 and to assist health care providers in examining patients who may be at a higher risk for developing these pathologies.

Source: Leilani A Lopes, Devendra K Agrawal. Thromboembolism in the Complications of Long COVID-19. Cardiology and Cardiovascular
Medicine. 7 (2023): 123-128. https://fortunepublish.com/articles/10.26502.fccm.92920317.pdf (Full text)

Socioeconomic inequalities of Long COVID: a retrospective population-based cohort study in the United Kingdom

Abstract:

Objectives: To estimate the risk of Long COVID by socioeconomic deprivation and to further examine the inequality by sex and occupation.

Design: We conducted a retrospective population-based cohort study using data from the ONS COVID-19 Infection Survey between 26 April 2020 and 31 January 2022. This is the largest nationally representative survey of COVID-19 in the UK with longitudinal data on occupation, COVID-19 exposure and Long COVID.

Setting: Community-based survey in the UK.

Participants: A total of 201,799 participants aged 16 to 64 years and with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Main outcome measures: The risk of Long COVID at least 4 weeks after SARS-CoV-2 infection by index of multiple deprivation (IMD) and the modifying effects of socioeconomic deprivation by sex and occupation.

Results: Nearly 10% (n = 19,315) of participants reported having Long COVID. Multivariable logistic regression models, adjusted for a range of variables (demographic, co-morbidity and time), showed that participants in the most deprived decile had a higher risk of Long COVID (11.4% vs. 8.2%; adjusted odds ratio (aOR): 1.46; 95% confidence interval (CI): 1.34, 1.59) compared to the least deprived decile. Significantly higher inequalities (most vs. least deprived decile) in Long COVID existed in healthcare and patient-facing roles (aOR: 1.76; 95% CI: 1.27, 2.44), in the education sector (aOR: 1.68; 95% CI: 1.31, 2.16) and in women (aOR: 1.56; 95% CI: 1.40, 1.73) than men (aOR: 1.32; 95% CI: 1.15, 1.51).

Conclusions: This study provides insights into the heterogeneous degree of inequality in Long COVID by deprivation, sex and occupation. These findings will help inform public health policies and interventions in incorporating a social justice and health inequality lens.

Source: Shabnam S, Razieh C, Dambha-Miller H, Yates T, Gillies C, Chudasama YV, Pareek M, Banerjee A, Kawachi I, Lacey B, Morris EJ, White M, Zaccardi F, Khunti K, Islam N. Socioeconomic inequalities of Long COVID: a retrospective population-based cohort study in the United Kingdom. J R Soc Med. 2023 May 10:1410768231168377. doi: 10.1177/01410768231168377. Epub ahead of print. PMID: 37164035. https://journals.sagepub.com/doi/10.1177/01410768231168377 (Full text)

Factors associated with psychiatric outcomes and coping in Long COVID

Abstract:

The relationship between Long COVID (LC) and psychiatric outcomes, as well as factors associated with presence and absence of these, has so far been insufficiently studied. Here we evaluated psychiatric symptoms and coping among patients with LC and patients recovered from COVID-19 who participated in a large international survey. Given increased rates of psychiatric illness with chronic medical conditions and known immune-inflammatory contributors to psychiatric disease, we hypothesized that a subset, but not the entirety, of LC respondents may have comorbid psychopathology.

A substantial minority of both groups experienced suicidality, depression and anxiety symptoms, with these symptoms being more common in the LC group. LC respondents used more adaptive coping styles. Psychiatric outcomes in LC were associated with younger age, greater reductions in overall health, higher symptom severity, limitations to physical capability, lower income, financial hardship, psychiatric history, employment impact, male sex, men and non-binary gender, and negative experiences with medical professionals, family, friends, partners and employers.

Source: Re’em, Y., Stelson, E.A., Davis, H.E. et al. Factors associated with psychiatric outcomes and coping in Long COVID. Nat. Mental Health 1, 361–372 (2023). https://doi.org/10.1038/s44220-023-00064-6 https://www.nature.com/articles/s44220-023-00064-6 (Full text)

Long-Term Effects of SARS-CoV-2 in the Brain: Clinical Consequences and Molecular Mechanisms

Abstract:

Numerous investigations have demonstrated significant and long-lasting neurological manifestations of COVID-19. It has been suggested that as many as four out of five patients who sustained COVID-19 will show one or several neurological symptoms that can last months after the infection has run its course. Neurological symptoms are most common in people who are less than 60 years of age, while encephalopathy is more common in those over 60. Biological mechanisms for these neurological symptoms need to be investigated and may include both direct and indirect effects of the virus on the brain and spinal cord. Individuals with Alzheimer’s disease (AD) and related dementia, as well as persons with Down syndrome (DS), are especially vulnerable to COVID-19, but the biological reasons for this are not clear.
Investigating the neurological consequences of COVID-19 is an urgent emerging medical need, since close to 700 million people worldwide have now had COVID-19 at least once. It is likely that there will be a new burden on healthcare and the economy dealing with the long-term neurological consequences of severe SARS-CoV-2 infections and long COVID, even in younger generations. Interestingly, neurological symptoms after an acute infection are strikingly similar to the symptoms observed after a mild traumatic brain injury (mTBI) or concussion, including dizziness, balance issues, anosmia, and headaches. The possible convergence of biological pathways involved in both will be discussed. The current review is focused on the most commonly described neurological symptoms, as well as the possible molecular mechanisms involved.
Source: Granholm A-C. Long-Term Effects of SARS-CoV-2 in the Brain: Clinical Consequences and Molecular Mechanisms. Journal of Clinical Medicine. 2023; 12(9):3190. https://doi.org/10.3390/jcm12093190 https://www.mdpi.com/2077-0383/12/9/3190 (Full text)

From Cell to Symptoms: The Role of SARS-CoV-2 Cytopathic Effects in the Pathogenesis of COVID-19 and Long COVID

Abstract:

Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection triggers various events from molecular to tissue level, which in turn is given by the intrinsic characteristics of each patient. Given the molecular diversity characteristic of each cellular phenotype, the possible cytopathic, tissue and clinical effects are difficult to predict, which determines the heterogeneity of COVID-19 symptoms.
The purpose of this article is to provide a comprehensive review of the cytopathic effects of SARS-CoV-2 on various cell types, focusing on the development of COVID-19, which in turn may lead, in some patients, to a persistence of symptoms after recovery from the disease, a condition known as long COVID. We describe the molecular mechanisms underlying virus-host interactions, including alterations in protein expression, intracellular signaling pathways, and immune responses.
In particular, the article highlights the potential impact of these cytopathies on cellular function and clinical outcomes, such as immune dysregulation, neuropsychiatric disorders, and organ damage. The article concludes by discussing future directions for research and implications for the management and treatment of COVID-19 and long COVID.
Source: Gonzalez-Garcia P, Fiorillo Moreno O, Zarate Peñata E, Calderon-Villalba A, Pacheco Lugo L, Acosta Hoyos A, Villarreal Camacho JL, Navarro Quiroz R, Pacheco Londoño L, Aroca Martinez G, Moares N, Gabucio A, Fernandez-Ponce C, Garcia-Cozar F, Navarro Quiroz E. From Cell to Symptoms: The Role of SARS-CoV-2 Cytopathic Effects in the Pathogenesis of COVID-19 and Long COVID. International Journal of Molecular Sciences. 2023; 24(9):8290. https://doi.org/10.3390/ijms24098290 https://www.mdpi.com/1422-0067/24/9/8290 (Full text)

Possible Pathogenesis and Prevention of Long COVID: SARS-CoV-2-Induced Mitochondrial Disorder

Abstract:

Patients who have recovered from coronavirus disease 2019 (COVID-19) infection may experience chronic fatigue when exercising, despite no obvious heart or lung abnormalities. The present lack of effective treatments makes managing long COVID a major challenge.
One of the underlying mechanisms of long COVID may be mitochondrial dysfunction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can alter the mitochondria responsible for energy production in cells. This alteration leads to mitochondrial dysfunction which, in turn, increases oxidative stress. Ultimately, this results in a loss of mitochondrial integrity and cell death. Moreover, viral proteins can bind to mitochondrial complexes, disrupting mitochondrial function and causing the immune cells to over-react. This over-reaction leads to inflammation and potentially long COVID symptoms.
It is important to note that the roles of mitochondrial damage and inflammatory responses caused by SARS-CoV-2 in the development of long COVID are still being elucidated. Targeting mitochondrial function may provide promising new clinical approaches for long-COVID patients; however, further studies are needed to evaluate the safety and efficacy of such approaches.
Source: Chen T-H, Chang C-J, Hung P-H. Possible Pathogenesis and Prevention of Long COVID: SARS-CoV-2-Induced Mitochondrial Disorder. International Journal of Molecular Sciences. 2023; 24(9):8034. https://doi.org/10.3390/ijms24098034 https://www.mdpi.com/1422-0067/24/9/8034 (Full text)

Brain imaging and neuropsychological assessment of individuals recovered from a mild to moderate SARS-CoV-2 infection

Abstract:

As severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infections have been shown to affect the central nervous system, the investigation of associated alterations of brain structure and neuropsychological sequelae is crucial to help address future health care needs. Therefore, we performed a comprehensive neuroimaging and neuropsychological assessment of 223 nonvaccinated individuals recovered from a mild to moderate SARS-CoV-2 infection (100 female/123 male, age [years], mean ± SD, 55.54 ± 7.07; median 9.7 mo after infection) in comparison with 223 matched controls (93 female/130 male, 55.74 ± 6.60) within the framework of the Hamburg City Health Study.
Primary study outcomes were advanced diffusion MRI measures of white matter microstructure, cortical thickness, white matter hyperintensity load, and neuropsychological test scores. Among all 11 MRI markers tested, significant differences were found in global measures of mean diffusivity (MD) and extracellular free water which were elevated in the white matter of post-SARS-CoV-2 individuals compared to matched controls (free water: 0.148 ± 0.018 vs. 0.142 ± 0.017, P < 0.001; MD [10−3 mm2/s]: 0.747 ± 0.021 vs. 0.740 ± 0.020, P < 0.001). Group classification accuracy based on diffusion imaging markers was up to 80%. Neuropsychological test scores did not significantly differ between groups.
Collectively, our findings suggest that subtle changes in white matter extracellular water content last beyond the acute infection with SARS-CoV-2. However, in our sample, a mild to moderate SARS-CoV-2 infection was not associated with neuropsychological deficits, significant changes in cortical structure, or vascular lesions several months after recovery. External validation of our findings and longitudinal follow-up investigations are needed.

Significance:

In this case–control study, we demonstrate that non-vaccinated individuals recovered from a mild to moderate severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection show significant alterations of the cerebral white matter identified by diffusion-weighted imaging, such as global increases in extracellular free water and mean diffusivity. Despite the observed brain white matter alterations in this sample, a mild to moderate SARS-CoV-2 infection was not associated with worse cognitive functions within the first year after recovery. Collectively, our findings indicate the presence of a prolonged neuroinflammatory response to the initial viral infection. Further longitudinal research is necessary to elucidate the link between brain alterations and clinical features of post-SARS-CoV-2 individuals.
Source: Marvin Petersen, Felix Leonard Nägele, Carola Mayer, and Bastian Cheng. Brain imaging and neuropsychological assessment of individuals recovered from a mild to moderate SARS-CoV-2 infection. Neuroscience, May 23, 2023, 120 (22) e2217232120 https://doi.org/10.1073/pnas.2217232120 (Full text)

Trajectories of the evolution of post COVID-19 condition, up to two years after symptoms onset

Abstract:

Background: We aimed to identify trajectories of the evolution of post COVID-19 condition, up to two years after symptom onset.

Methods: The ComPaRe long COVID e-cohort is a prospective cohort of patients with symptoms lasting at least two months after SARS-CoV2 infection. We used trajectory modelling to identify different trajectories in the evolution of post COVID-19 condition, based on symptoms collected every 60 days using the long COVID Symptom Tool.

Findings: A total of 2,197 patients were enrolled in the cohort between December 2020 and July 2022 when the Omicron variant was not dominant. Three trajectories of the evolution of post COVID-19 condition were identified: “high persistent symptoms” (4%), “rapidly decreasing symptoms” (5%), and “slowly decreasing symptoms” (91%). Participants with high persistent symptoms were older and more likely to report a history of systemic diseases. They often reported tachycardia, bradycardia, palpitations, and arrhythmia. Participants with rapidly decreasing symptoms were younger and more likely to report a confirmed infection. They often reported diarrhoea and back pain. Participants with slowly decreasing symptoms were more likely to have functional diseases.

Interpretation: Most of patients with post COVID-19 condition improve slowly over time, while 5% have rapid improvement in the two years after symptom onset and 4% have a persistent condition.

Source: Servier C, Porcher R, Pane I, Ravaud P, Tran VT. Trajectories of the evolution of post COVID-19 condition, up to two years after symptoms onset. Int J Infect Dis. 2023 May 12:S1201-9712(23)00558-1. doi: 10.1016/j.ijid.2023.05.007. Epub ahead of print. PMID: 37182548; PMCID: PMC10176960. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10176960/ (Full text)

Prevalence and risk factors for long COVID after mild disease: A cohort study with a symptomatic control group

Abstract:

Background: There is limited data on the prevalence and risk factors for long COVID and few prospective studies with appropriate control groups and adequate sample sizes. We performed a prospective study to determine the prevalence and risk factors for long COVID.

Methods: We recruited individuals aged ≥15 years who were clinically suspected of having an acute SARS-CoV-2 infection from September 2020 to April 2021. We collected nasopharyngeal swabs three to five days following symptom onset for analysing using reverse transcriptase polymerase chain reaction (RT-PCR). We also collected clinical and sociodemographic characteristics from both SARS-CoV-2 positive and negative participants using structured questionnaires. We followed-up the participants via telephone interview to assess early outcomes and persistent symptoms. For COVID-19 cases, 5D-3L EuroQol questionnaire was used to assess the impact of symptoms on quality of life.

Results: We followed 814 participants (412 COVID-19 positive and 402 COVID-19 negative persons). Most (n = 741/814) had mild symptoms. Both groups had similar sociodemographic and clinical characteristics, except for the hospitalization rate (15.8% in the COVID-19 positive vs 1.5% in the COVID-19 negative group). One month after disease onset, 122/412 (29.6%) individuals in the COVID-19 positive (long COVID) and 24 (6%) in the COVID-19 negative group reported residual symptoms. In the long COVID group, fatigue, olfactory disorder, and myalgia were the most frequent symptoms in the acute phase. Compared to recovered individuals, older age and having more than five symptoms during the acute phase were risk factors for long COVID. Quality of life was evaluated in 102 out of 122 cases of long COVID, with 57 (55.9%) reporting an impact in at least one dimension of the European Quality of Life 5 Dimensions 3 Level (EQ-5D-3L) questionnaire.

Conclusions: In this prospective study consisting predominantly of individuals with mild disease, the persistence of symptoms after an acute respiratory illness was associated with a diagnosis of COVID-19. Polysymptomatic acute disease and older age were risk factors for long COVID.

Source: Cazé AB, Cerqueira-Silva T, Bomfim AP, de Souza GL, Azevedo AC, Brasil MQ, Santos NR, Khouri R, Dan J, Bandeira AC, Cavalcanti LP, Barral-Netto M, Barral A, Barbosa CG, Boaventura VS. Prevalence and risk factors for long COVID after mild disease: A cohort study with a symptomatic control group. J Glob Health. 2023 May 12;13:06015. doi: 10.7189/jogh.13.06015. PMID: 37166260; PMCID: PMC10173895. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10173895/ (Full text)

Identification and diagnosis of long COVID-19: A scoping review

Abstract:

Long COVID-19 (LC-19) is a condition that has affected a high percentage of the population that recovered from the initial disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). LC-19 diagnosis is currently poorly defined because of its variable, multisystem, episodic symptoms, and lack of uniformity in the critical time points associated with the disease. Considering the number of cases, workers’ compromised efficiency or inability to return to their duties can affect organizations and impact economies. LC-19 represents a significant burden on multiple levels and effectively reduces quality of life. These factors necessitate the establishment of firm parameters of diagnoses to provide a foundation for ongoing and future studies of clinical characteristics, epidemiology, risk factors, and therapy.

In this scoping review, we conducted a literature search across multiple publication sites to identify papers of interest regarding the diagnosis of LC-19. We identified 225 records of interest and categorized them into seven categories. Based on our findings, there are only 11 original papers that outline the diagnostic process in detail with little overlap. This scoping review highlights the lack of consensus regarding the definition and, thereby, the LC-19 diagnosis processes. Due to no clear directive and considering the many unknowns surrounding the natural history of the disease and further recovery/sequelae from COVID-19, continued discussion and agreement on a definition/diagnosis will help future research and management of these patients.

Source: Srikanth S, Boulos JR, Dover T, Boccuto L, Dean D. Identification and diagnosis of long COVID-19: A scoping review. Prog Biophys Mol Biol. 2023 May 12;182:1-7. doi: 10.1016/j.pbiomolbio.2023.04.008. Epub ahead of print. PMID: 37182545; PMCID: PMC10176974. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10176974/ (Full text)