Tag: long covid symptoms

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and COVID-19: is there a connection?

Abstract:

Objectives: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic systemic disease that leads to neurological, immunological, autonomic, and energy metabolism dysfunction. COVID-19 has been reported to cause similar symptoms to ME/CFS. The study aims to investigate the prevalence of myalgic encephalomyelitis in patients post-COVID-19 infection by assessing acute and long-term COVID-19 symptoms.

Methods: A cross-sectional questionnaire was developed based on the ME/CFS diagnostic criteria, as specified by the IOM clinical diagnostic criteria, and administered to participants with confirmed COVID-19 who are more than 18 years old and have BMI below 40 Kg/m2. Data from 437 participants were completed.

Results: The current study results revealed that 8.1% of the study participants met the ME/CFS diagnostic criteria. Interestingly, 2.8 of the study participants were classified to have COVID-19 related to ME/CFS. While 4.6% of participants were determined to have disease-related fatigue, 0.7% of participants showed ME/CFS that was not related to COVID-19, and 3.7% of participants were considered to have long COVID-19. Almost one-fourth of the study participants had a family history of ME/CFS. The current study demonstrated that the prevalence of ME/CFS is similar to slightly higher than reported in the literature.

Conclusion: The presence of a relationship between ME/CFS and COVID-19 has been supported by the results of our study. Follow-up of COVID-19 patients is strongly recommended to ensure proper management of ME/CFS symptoms.

Source: Muhaissen SA, Abu Libdeh A, ElKhatib Y, Alshayeb R, Jaara A, Bardaweel SK. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and COVID-19: is there a connection? Curr Med Res Opin. 2023 Jul 28:1-24. doi: 10.1080/03007995.2023.2242244. Epub ahead of print. PMID: 37501626. https://pubmed.ncbi.nlm.nih.gov/37501626/

Clinical phenotypes and quality of life to define post-COVID-19 syndrome: a cluster analysis of the multinational, prospective ORCHESTRA cohort

Summary:

Background: Lack of specific definitions of clinical characteristics, disease severity, and risk and preventive factors of post-COVID-19 syndrome (PCS) severely impacts research and discovery of new preventive and therapeutics drugs.

Methods: This prospective multicenter cohort study was conducted from February 2020 to June 2022 in 5 countries, enrolling SARS-CoV-2 out- and in-patients followed at 3-, 6-, and 12-month from diagnosis, with assessment of clinical and biochemical features, antibody (Ab) response, Variant of Concern (VoC), and physical and mental quality of life (QoL). Outcome of interest was identification of risk and protective factors of PCS by clinical phenotype, setting, severity of disease, treatment, and vaccination status. We used SF-36 questionnaire to assess evolution in QoL index during follow-up and unsupervised machine learning algorithms (principal component analysis, PCA) to explore symptom clusters. Severity of PCS was defined by clinical phenotype and QoL. We also used generalized linear models to analyse the impact of PCS on QoL and associated risk and preventive factors. CT registration number: NCT05097677.

Findings: Among 1796 patients enrolled, 1030 (57%) suffered from at least one symptom at 12-month. PCA identified 4 clinical phenotypes: chronic fatigue-like syndrome (CFs: fatigue, headache and memory loss, 757 patients, 42%), respiratory syndrome (REs: cough and dyspnoea, 502, 23%); chronic pain syndrome (CPs: arthralgia and myalgia, 399, 22%); and neurosensorial syndrome (NSs: alteration in taste and smell, 197, 11%). Determinants of clinical phenotypes were different (all comparisons p < 0.05): being female increased risk of CPs, NSs, and CFs; chronic pulmonary diseases of REs; neurological symptoms at SARS-CoV-2 diagnosis of REs, NSs, and CFs; oxygen therapy of CFs and REs; and gastrointestinal symptoms at SARS-CoV-2 diagnosis of CFs. Early treatment of SARS-CoV-2 infection with monoclonal Ab (all clinical phenotypes), corticosteroids therapy for mild/severe cases (NSs), and SARS-CoV-2 vaccination (CPs) were less likely to be associated to PCS (all comparisons p < 0.05). Highest reduction in QoL was detected in REs and CPs (43.57 and 43.86 vs 57.32 in PCS-negative controls, p < 0.001). Female sex (p < 0.001), gastrointestinal symptoms (p = 0.034) and renal complications (p = 0.002) during the acute infection were likely to increase risk of severe PCS (QoL <50). Vaccination and early treatment with monoclonal Ab reduced the risk of severe PCS (p = 0.01 and p = 0.03, respectively).

Interpretation: Our study provides new evidence suggesting that PCS can be classified by clinical phenotypes with different impact on QoL, underlying possible different pathogenic mechanisms. We identified factors associated to each clinical phenotype and to severe PCS. These results might help in designing pathogenesis studies and in selecting high-risk patients for inclusion in therapeutic and management clinical trials.

Funding: The study received funding from the Horizon 2020 ORCHESTRA project, grant 101016167; from the Netherlands Organisation for Health Research and Development (ZonMw), grant 10430012010023; from Inserm, REACTing (REsearch & ACtion emergING infectious diseases) consortium and the French Ministry of Health, grant PHRC 20-0424.

Source: Elisa Gentilotti, Anna Górska, Adriana Tami, Roy Gusinow, Massimo Mirandola, Jesús Rodríguez Baño, et al. Clinical phenotypes and quality of life to define post-COVID-19 syndrome: a cluster analysis of the multinational, prospective ORCHESTRA cohort. Lancet,  “eClinicalMedicine” https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00284-5/fulltext (Full text)

Post-acute sequelae of COVID-19: understanding and addressing the burden of multisystem manifestations

Abstract:

Individuals with SARS-CoV-2 infection can develop symptoms that persist well beyond the acute phase of COVID-19 or emerge after the acute phase, lasting for weeks or months after the initial acute illness. The post-acute sequelae of COVID-19, which include physical, cognitive, and mental health impairments, are known collectively as long COVID or post-COVID-19 condition.

The substantial burden of this multisystem condition is felt at individual, health-care system, and socioeconomic levels, on an unprecedented scale. Survivors of COVID-19-related critical illness are at risk of the well known sequelae of acute respiratory distress syndrome, sepsis, and chronic critical illness, and these multidimensional morbidities might be difficult to differentiate from the specific effects of SARS-CoV-2 and COVID-19.

We provide an overview of the manifestations of post-COVID-19 condition after critical illness in adults. We explore the effects on various organ systems, describe potential pathophysiological mechanisms, and consider the challenges of providing clinical care and support for survivors of critical illness with multisystem manifestations.

Research is needed to reduce the incidence of post-acute sequelae of COVID-19-related critical illness and to optimise therapeutic and rehabilitative care and support for patients.

Source: Parotto M, Gyöngyösi M, Howe K, Myatra SN, Ranzani O, Shankar-Hari M, Herridge MS. Post-acute sequelae of COVID-19: understanding and addressing the burden of multisystem manifestations. Lancet Respir Med. 2023 Jul 17:S2213-2600(23)00239-4. doi: 10.1016/S2213-2600(23)00239-4. Epub ahead of print. PMID: 37475125. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(23)00239-4/fulltext (Full text)

Mitigating neurological, cognitive, and psychiatric sequelae of COVID-19-related critical illness

Abstract:

Despite advances in the treatment and mitigation of critical illness caused by infection with SARS-CoV-2, millions of survivors have a devastating, post-acute infection syndrome known as long COVID. A large proportion of patients with long COVID have nervous system dysfunction, which is also seen in the distinct but overlapping condition of post-intensive care syndrome (PICS), putting survivors of COVID-19-related critical illness at high risk of long-lasting morbidity affecting multiple organ systems and, as a result, engendering measurable deficits in quality of life and productivity.

In this Series paper, we discuss neurological, cognitive, and psychiatric sequelae in patients who have survived critical illness due to COVID-19. We review current knowledge of the epidemiology and pathophysiology of persistent neuropsychological impairments, and outline potential preventive strategies based on safe, evidence-based approaches to the management of pain, agitation, delirium, anticoagulation, and ventilator weaning during critical illness. We highlight priorities for current and future research, including possible therapeutic approaches, and offer considerations for health services to address the escalating health burden of long COVID.

Source: Pandharipande P, Williams Roberson S, Harrison FE, Wilson JE, Bastarache JA, Ely EW. Mitigating neurological, cognitive, and psychiatric sequelae of COVID-19-related critical illness. Lancet Respir Med. 2023 Jul 17:S2213-2600(23)00238-2. doi: 10.1016/S2213-2600(23)00238-2. Epub ahead of print. PMID: 37475124. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(23)00238-2/fulltext (Full text)

Using Data Science and a Health Equity Lens to Identify Long-COVID Sequelae Among Medically Underserved Populations

Abstract:

Understanding how post-acute COVID-19 syndrome (PACS or long COVID) manifests among underserved populations, who experienced a disproportionate burden of acute COVID-19, can help providers and policymakers better address this ongoing crisis. To identify clinical sequelae of long COVID among underserved populations treated in the primary care safety net, we conducted a causal impact analysis with electronic health records (EHR) to compare symptoms among community health center patients who tested positive (n=4,091) and negative (n=7,118) for acute COVID-19.

We found 18 sequelae with statistical significance and causal dependence among patients who had a visit after 60 days or more following acute COVID-19. These sequelae encompass most organ systems and include breathing abnormalities, malaise and fatigue, and headache. This study adds to current knowledge about how long COVID manifests in a large, underserved population.

Source: Nasir M, Cook N, Parras D, Mukherjee S, Miller G, Ferres JL, Chung-Bridges K. Using Data Science and a Health Equity Lens to Identify Long-COVID Sequelae Among Medically Underserved Populations. J Health Care Poor Underserved. 2023;34(2):521-534. doi: 10.1353/hpu.2023.0047. PMID: 37464515. https://pubmed.ncbi.nlm.nih.gov/37464515/

Post-COVID cognitive dysfunction: current status and research recommendations for high risk population

Abstract:

Post-COVID cognitive dysfunction (PCCD) is a condition in which patients with a history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, usually three months from the onset, exhibit subsequent cognitive impairment in various cognitive domains, and cannot be explained by an alternative diagnosis.

While our knowledge of the risk factors and management strategy of PCCD is still incomplete, it is necessary to integrate current epidemiology, diagnosis and treatment evidence, and form consensus criteria to better understand this disease to improve disease management. Identifying the risk factors and vulnerable population of PCCD and providing reliable strategies for effective prevention and management is urgently needed.

In this paper, we reviewed epidemiology, diagnostic markers, risk factors and available treatments on the disease, formed research recommendation framework for vulnerable population, under the background of post-COVID period.

Source: Quan M, Wang X, Gong M, Wang Q, Li Y, Jia J. Post-COVID cognitive dysfunction: current status and research recommendations for high risk population. Lancet Reg Health West Pac. 2023 Jul 5;38:100836. doi: 10.1016/j.lanwpc.2023.100836. PMID: 37457901; PMCID: PMC10344681. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10344681/ (Full text)

Cognitive impairment after Long COVID-19: Current Evidence and Perspectives

Abstract:

COVID-19 is a respiratory infectious disease caused by the SARS-CoV-2 virus. Most patients recover after treatment, but COVID-19 treatment may lead to cognitive impairment. Recent studies have found that some recoverers experience cognitive impairments such as decreased memory and attention, and sleep disorder, indicating that COVID-19 may have longerterm effects on cognitive function.

Studies have found that COVID-19 may cause cognitive decline by damaging key brain regions such as the hippocampus and anterior cingulate cortex. Studies have also found that COVID-19 patients have active neuroinflammation, mitochondrial dysfunction, and microglial activation, suggesting that neuroinflammation, mitochondrial stress, and neurodegenerative changes may be potential mechanisms leading to cognitive impairment.

In summary, the possibility of cognitive impairment after COVID-19 treatment deserves close attention. Large-scale follow-up studies will help further explore the impact of COVID-19 on cognitive function and provide evidence to support clinical treatment and rehabilitation practices. Neuropathological and biological studies can explore precise mechanisms in-depth and provide a theoretical basis for prevention, treatment, and intervention research.

Given the risks of long-term COVID-19 and reinfection, it is necessary to integrate basic and clinical research data to maximize the maintenance of patient’s cognitive function and life quality. This also provides important experience in responding to similar public health events. This article integrates clinical and basic evidence of cognitive impairment after COVID-19 and discusses potential mechanisms and future research directions.

Source: Zhi-Tao Li, ZHANG ZHEN, Zhuoya Zhang, Zhi-Yong Wang, Hao Li. Cognitive impairment after Long COVID-19: Current Evidence and Perspectives. Front. Neurol. Sec. Neuroinfectious Diseases. Volume 14 – 2023 | doi: 10.3389/fneur.2023.1239182 https://www.frontiersin.org/articles/10.3389/fneur.2023.1239182/abstract

Evaluation of Outpatients in the Post-COVID-19 Period in Terms of Autonomic Dysfunction and Silent Ischemia

Abstract:

Introduction and objective: In this context, the objective of this study is to evaluate the 24-hour ambulatory electrocardiography (ECG) recordings, autonomous function with heart rate variability (HRV), and silent ischemia (SI) attacks with ST depression burden (SDB) and ST depression time (SDT) of post-COVID-19 patients. Materials and methods: The 24-hour ambulatory ECG recordings obtained >12 weeks after the diagnosis of COVID-19 were compared between 55 consecutive asymptomatic and 73 symptomatic post-COVID-19 patients who applied to the cardiology outpatient clinic with complaints of palpitation and chest pain in comparison with asymptomatic post-COVID-19 patients in Kars Harakani state hospital. SDB, SDT, and HRV parameters were analyzed. Patients who had been on medication that might affect HRV, had comorbidities that might have caused coronary ischemia, and were hospitalized with severe COVID-19 were excluded from the study.

Results: There was no significant difference between symptomatic and asymptomatic post-COVID-19 patients in autonomic function. On the other hand, SDB and SDT parameters were significantly higher in symptomatic post-COVID-19 patients than in asymptomatic post-COVID-19 patients. Multivariate analysis indicated that creatine kinase-myoglobin binding (CK-MB) (OR:1.382, 95% CI:1.043-1.831; p=0.024) and HRV index (OR: 1.033, 95% CI:1.005-1.061; p=0.019) were found as independent predictors of palpitation and chest pain symptoms in post-COVID-19 patients.

Conclusion: The findings of this study revealed that parasympathetic overtone and increased HRV were significantly higher in symptomatic patients with a history of COVID-19 compared to asymptomatic patients with a history of COVID-19 in the post-COVID-19 period. Additionally, 24-hour ambulatory ECG recordings and ST depression analysis data indicated that patients who experienced chest pain in the post-COVID-19 period experienced silent ischemia (SI) attacks.

Source: Karakayalı M, Artac I, Ilis D, Omar T, Rencuzogullari I, Karabag Y, Altunova M, Arslan A, Guzel E. Evaluation of Outpatients in the Post-COVID-19 Period in Terms of Autonomic Dysfunction and Silent Ischemia. Cureus. 2023 Jun 11;15(6):e40256. doi: 10.7759/cureus.40256. PMID: 37440812; PMCID: PMC10335598. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10335598/ (Full text)

The effect of nirmatrelvir-ritonavir on the long-term risk of neuropsychiatric sequelae following COVID-19

Abstract:

The retrospective cohort was conducted to assess the effect of nirmatrelvir-ritonavir (NMV-r) on the long-term risk of neuropsychiatric sequela following COVID-19. TriNetX research network was used to identify nonhospitalized adult patients who tested positive for severe acute respiratory syndrome coronavirus 2 infection or were diagnosed with COVID-19 between March 1, 2020 and July 1, 2022. Further propensity score matching method was used to create two matched cohorts with and without receiving NMV-r.

The primary outcome was the incidence of neuropsychiatric sequela within a 90-day to 1-year period following a diagnosis of COVID-19. After screening 119 494 527 electronic health records, two matched cohorts of each 27 194 patients were identified. During the follow-up period, the NMV-r group demonstrated a reduced risk of any neuropsychiatric sequelae compared to the control group (odds ratio [OR], 0.634; 95% confidence interval [CI], 0.604-0.667).

In comparison with the control group, the patient treated with NMV-r exhibited a markedly diminished risk of developing neurocognitive sequela (OR, 0.377; 95% CI, 0.325-0.439) and psychiatric sequela (OR, 0.629; 95% CI, 0.593-0.666). In addition, patients treated with NMV-r had a significantly reduced risk of developing dementia (OR, 0.365; 95% CI, 0.255-0.522), depression (OR, 0.555; 95% CI, 0.503-0.612), insomnia (OR, 0.582; 95% CI, 0.508-0.668) and anxiety disorder (OR, 0.645 95% CI, 0.600-0.692). Moreover, the beneficial effect of NMV-r on the neuropsychiatric sequelae was observed across further subgroup analyses.

Among nonhospitalized COVID-19 patients, who at risk of disease progression, the use of NMV-r is associated with a reduction in the long-term risk of neuropsychiatric sequela, including dementia, depression, insomnia and anxiety disorder. It may be necessary to re-evaluate the use of NMV-r, as a preventive measure to reduce the risk of severe acute disease and post-acute adverse mental health outcomes.

Source: Liu TH, Wu JY, Huang PY, Tsai YW, Lai CC. The effect of nirmatrelvir-ritonavir on the long-term risk of neuropsychiatric sequelae following COVID-19. J Med Virol. 2023 Jul;95(7):e28951. doi: 10.1002/jmv.28951. PMID: 37436873. https://pubmed.ncbi.nlm.nih.gov/37436873/

SARS-CoV-2 post-acute sequelae in previously hospitalised patients: systematic literature review and meta-analysis

Abstract:

Background: Many individuals hospitalised with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection experience post-acute sequelae of SARS-CoV-2 infection (PASC), sometimes referred to as “long COVID”. Our objective was to conduct a systematic literature review and meta-analysis to identify PASC-associated symptoms in previously hospitalised patients and determine the frequency and temporal nature of PASC.

Methods: Searches of MEDLINE, Embase, Cochrane Library (2019-2021), World Health Organization International Clinical Trials Registry Platform and reference lists were performed from November to December 2021. Articles were assessed by two reviewers against eligibility criteria and a risk of bias tool. Symptom data were synthesised by random effects meta-analyses.

Results: Of 6942 records, 52 studies with at least 100 patients were analysed; ∼70% were Europe-based studies. Most data were from the first wave of the pandemic. PASC symptoms were analysed from 28 days after hospital discharge. At 1-4 months post-acute SARS-CoV-2 infection, the most frequent individual symptoms were fatigue (29.3% (95% CI 20.1-40.6%)) and dyspnoea (19.6% (95% CI 12.8-28.7%)). Many patients experienced at least one symptom at 4-8 months (73.1% (95% CI 44.2-90.3%)) and 8-12 months (75.0% (95% CI 56.4-87.4%)).

Conclusions: A wide spectrum of persistent PASC-associated symptoms were reported over the 1-year follow-up period in a significant proportion of participants. Further research is needed to better define PASC duration and determine whether factors such as disease severity, vaccination and treatments have an impact on PASC.

Source: Kelly JD, Curteis T, Rawal A, Murton M, Clark LJ, Jafry Z, Shah-Gupta R, Berry M, Espinueva A, Chen L, Abdelghany M, Sweeney DA, Quint JK. SARS-CoV-2 post-acute sequelae in previously hospitalised patients: systematic literature review and meta-analysis. Eur Respir Rev. 2023 Jul 12;32(169):220254. doi: 10.1183/16000617.0254-2022. PMID: 37437914; PMCID: PMC10336551. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10336551/ (Full text)