Tag: long covid review

Psychiatric and neurological complications of long COVID

Abstract:

COVID-19 was primarily considered a pulmonary disease with extrapulmonary manifestations. As the pandemic spread, there has been growing evidence that the disease affects various organs/systems, including the central and peripheral nervous systems. Accumulation of clinical data demonstrates that in a large population of survivors impairments in the function of one or more organs may persist for a long time, a phenomenon commonly known as post COVID or long COVID.

Fatigue and cognitive dysfunction, such as concentration problems, short-term memory deficits, general memory loss, a specific decline in attention, language and praxis abilities, encoding and verbal fluency, impairment of executive functions, and psychomotor coordination, are amongst the most common and debilitating features of neuropsychatric symptoms of post COVID syndrome. Several patients also suffer from compromised sleep, depression, anxiety and post-traumatic stress disorder. Patients with long COVID may demonstrate brain hypometabolism, hypoperfusion of the cerebral cortex and changes in the brain structure and functional connectivity.

Children and adolescents represent a minority of COVID-19 cases, so not surprisingly data on the long-term sequelae after SARS-CoV-2 infections in these age groups are scarce. Although the pathogenesis, clinical characteristics, epidemiology, and risk factors of the acute phase of COVID-19 have been largely explained, these areas are yet to be explored in long COVID. This review aims to provide an update on what is currently known about long COVID effects on mental health.

Source: Zawilska JB, Kuczyńska K. Psychiatric and neurological complications of long COVID. J Psychiatr Res. 2022 Oct 20;156:349-360. doi: 10.1016/j.jpsychires.2022.10.045. Epub ahead of print. PMID: 36326545; PMCID: PMC9582925. https://www.sciencedirect.com/science/article/pii/S0022395622005982 (Full text)

Global prevalence of chronic fatigue syndrome among long COVID-19 patients: A systematic review and meta-analysis

Abstract:

Background: Chronic fatigue syndrome is a persistent and debilitating disorder. According to several studies, chronic fatigue syndrome has been identified among recovered COVID-19 patients as the most common symptom of long COVID. The aim of this systematic review and meta-analysis study was to obtain the prevalence of chronic fatigue syndrome in long COVID cases.

Methods: In this systematic review and meta-analysis, we analysed reported results of studies that assessed the occurrence of chronic fatigue syndrome among COVID-19 patients four weeks after the onset of symptoms. The study selection was commenced by searching PubMed, Web of Science, Science Direct, Scopus, Embase, and Google scholar using the keywords of Chronic fatigue syndrome, COVID-19, and post-COVID-19 syndrome. The searches were without a lower time limit and until April 2022. Heterogeneity of studies was assessed using the I2 index, and a random effects model was used for analysis. Data analysis was performed within the Comprehensive Meta-Analysis software (version 2).

Results: The pooled prevalence of chronic fatigue syndrome four weeks after the onset of COVID-19 symptoms, in 52 studies with a sample size of 127,117, was 45.2% (95% CI: 34.1-56.9%). Meta-regression analysis in examining the effects of the two factors of sample size, and year of study on the changes in the overall prevalence, showed that with increasing sample size, and year of study, the prevalence of chronic fatigue syndrome among long COVID patients (p < 0.05).

Conclusion: Our results show that the overall prevalence of chronic fatigue syndrome as a long COVID symptom is 45.2%. Chronic fatigue after infection with COVID-19 can negatively affect personal and social lives. Given such significant negative consequences caused by the syndrome, it is recommended that health policymakers allocate funds to reduce the adverse effects of this syndrome, by creating programs to support long COVID patients.

Source: Salari N, Khodayari Y, Hosseinian-Far A, Zarei H, Rasoulpoor S, Akbari H, Mohammadi M. Global prevalence of chronic fatigue syndrome among long COVID-19 patients: A systematic review and meta-analysis. Biopsychosoc Med. 2022 Oct 23;16(1):21. doi: 10.1186/s13030-022-00250-5. PMID: 36274177; PMCID: PMC9589726. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9589726/ (Full text)

Use of Cardiopulmonary Exercise Testing to Evaluate Long COVID-19 Symptoms in Adults: A Systematic Review and Meta-analysis

Abstract

Importance: Reduced exercise capacity is commonly reported among individuals with COVID-19 symptoms more than 3 months after SARS-CoV-2 infection (long COVID-19 [LC]). Cardiopulmonary exercise testing (CPET) is the criterion standard to measure exercise capacity and identify patterns of exertional intolerance.

Objectives: To estimate the difference in exercise capacity among individuals with and without LC symptoms and characterize physiological patterns of limitations to elucidate possible mechanisms of LC.

Data sources: A search of PubMed, EMBASE, Web of Science, preprint servers, conference abstracts, and cited references was performed on December 20, 2021, and again on May 24, 2022. A preprint search of medrxiv.org, biorxiv.org, and researchsquare.com was performed on June 9, 2022.

Study selection: Studies of adults with SARS-CoV-2 infection more than 3 months earlier that included CPET-measured peak oxygen consumption (V̇o2) were screened independently by 2 blinded reviewers; 72 (2%) were selected for full-text review, and 35 (1%) met the inclusion criteria. An additional 3 studies were identified from preprint servers.

Data extraction and synthesis: Data extraction was performed by 2 independent reviewers according to the PRISMA reporting guideline. Data were pooled using random-effects models.

Main outcomes and measures: Difference in peak V̇o2 (in mL/kg/min) among individuals with and without persistent COVID-19 symptoms more than 3 months after SARS-CoV-2 infection.

Results: A total of 38 studies were identified that performed CPET on 2160 individuals 3 to 18 months after SARS-CoV-2 infection, including 1228 with symptoms consistent with LC. Most studies were case series of individuals with LC or cross-sectional assessments within posthospitalization cohorts. Based on a meta-analysis of 9 studies including 464 individuals with LC symptoms and 359 without symptoms, the mean peak V̇o2 was -4.9 (95% CI, -6.4 to -3.4) mL/kg/min among those with symptoms with a low degree of certainty. Deconditioning and peripheral limitations (abnormal oxygen extraction) were common, but dysfunctional breathing and chronotropic incompetence were also described. The existing literature was limited by small sample sizes, selection bias, confounding, and varying symptom definitions and CPET interpretations, resulting in high risk of bias and heterogeneity.

Conclusions and relevance: The findings of this systematic review and meta-analysis study suggest that exercise capacity was reduced more than 3 months after SARS-CoV-2 infection among individuals with symptoms consistent with LC compared with individuals without LC symptoms, with low confidence. Potential mechanisms for exertional intolerance other than deconditioning include altered autonomic function (eg, chronotropic incompetence, dysfunctional breathing), endothelial dysfunction, and muscular or mitochondrial pathology.

Source: Durstenfeld MS, Sun K, Tahir P, Peluso MJ, Deeks SG, Aras MA, Grandis DJ, Long CS, Beatty A, Hsue PY. Use of Cardiopulmonary Exercise Testing to Evaluate Long COVID-19 Symptoms in Adults: A Systematic Review and Meta-analysis. JAMA Netw Open. 2022 Oct 3;5(10):e2236057. doi: 10.1001/jamanetworkopen.2022.36057. PMID: 36223120. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2797203 (Full text)

Symptomatology and microbiology of the gastrointestinal tract in post-COVID conditions

Abstract:

Post-COVID conditions, also known as post-acute sequelae of SARS-CoV-2 (PASC), refer to the persistence of symptoms in COVID-19 long-haulers. Various manifestations of post-COVID conditions are general symptoms and/or manifestations of damage in multiple organs. Besides, SARS-CoV-2 can involve the gastrointestinal tract, resulting in sequelae such as diarrhea, abdominal pain, nausea, anorexia, vomiting, constipation, abdominal distension, acid reflux, and/or gastrointestinal bleeding.
Previous investigations point to SARS-CoV-2 entry into enterocytes enhances by the angiotensin-converting enzyme 2 (ACE2) receptors. Interestingly, ACE2 receptors are abundantly expressed in the gut, implying infection with SARS-CoV-2 might occur through this route as well as in the respiratory tract. According to mounting evidence, SARS-CoV-2 RNA has been identified in fecal specimens of patients with COVID-19 during and beyond the acute phase.
In addition, studies have shown gut microbiome composition is altered in patients with PASC, hence, another putative mechanism linked to gastrointestinal symptoms is gut dysbiosis. The presence of the gut-lung axis in COVID-19 might have major implications for disease pathogenesis and treatment.
This review discussed the prevalence of gastrointestinal symptoms and pathophysiology underlying possible infection of the gut in patients with PASC. Also, SARS-COV-2 induced NLRP3 inflammasome-dependent inflammatory pathways are briefly addressed.
Source: Norouzi Masir M, Shirvaliloo M. Symptomatology and microbiology of the gastrointestinal tract in post-COVID conditions. JGH Open : an Open Access Journal of Gastroenterology and Hepatology. 2022 Aug. DOI: 10.1002/jgh3.12811. PMID: 36247234; PMCID: PMC9538198. https://europepmc.org/article/pmc/pmc9538198 (Full text)

Endothelial dysfunction in COVID-19: an overview of evidence, biomarkers, mechanisms and potential therapies

Abstract:

The fight against coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection is still raging. However, the pathophysiology of acute and post-acute manifestations of COVID-19 (long COVID-19) is understudied. Endothelial cells are sentinels lining the innermost layer of blood vessel that gatekeep micro- and macro-vascular health by sensing pathogen/danger signals and secreting vasoactive molecules. SARS-CoV-2 infection primarily affects the pulmonary system, but accumulating evidence suggests that it also affects the pan-vasculature in the extrapulmonary systems by directly (via virus infection) or indirectly (via cytokine storm), causing endothelial dysfunction (endotheliitis, endothelialitis and endotheliopathy) and multi-organ injury.

Mounting evidence suggests that SARS-CoV-2 infection leads to multiple instances of endothelial dysfunction, including reduced nitric oxide (NO) bioavailability, oxidative stress, endothelial injury, glycocalyx/barrier disruption, hyperpermeability, inflammation/leukocyte adhesion, senescence, endothelial-to-mesenchymal transition (EndoMT), hypercoagulability, thrombosis and many others. Thus, COVID-19 is deemed as a (micro)vascular and endothelial disease. Of translational relevance, several candidate drugs which are endothelial protective have been shown to improve clinical manifestations of COVID-19 patients.

The purpose of this review is to provide a latest summary of biomarkers associated with endothelial cell activation in COVID-19 and offer mechanistic insights into the molecular basis of endothelial activation/dysfunction in macro- and micro-vasculature of COVID-19 patients. We envisage further development of cellular models and suitable animal models mimicking endothelial dysfunction aspect of COVID-19 being able to accelerate the discovery of new drugs targeting endothelial dysfunction in pan-vasculature from COVID-19 patients.

Source: Xu, Sw., Ilyas, I. & Weng, Jp. Endothelial dysfunction in COVID-19: an overview of evidence, biomarkers, mechanisms and potential therapies. Acta Pharmacol Sin (2022). https://doi.org/10.1038/s41401-022-00998-0 https://www.nature.com/articles/s41401-022-00998-0 (Full text)

New‑onset neuropsychiatric sequelae and ‘long‑COVID’ syndrome (Review)

Abstract:

The ongoing coronavirus disease 2019 (COVID‑19) pandemic has had a widespread impact on individuals’ mental health through indirect psychological and social mechanisms, related to factors such as fear of infection or death, social isolation, lack of social support and financial instability.
The severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection has also been associated with the development or recurrence of neuropsychiatric symptoms, both during the acute phase, as well as during the post‑acute ‘long‑COVID’ phase. In addition to the COVID‑19 survivors with a mental health history that are at a high risk of experiencing a range of neuropsychiatric symptoms following resolution of acute COVID‑19, there is accumulating evidence that a diagnosis of COVID‑19 may also be associated with new‑onset neuropsychiatric morbidity among survivors without pre‑existing mental health disorders.
In particular, studies investigating the incidence of post‑acute neuropsychiatric sequelae, based mostly on retrospective cohort study designs and data from national health registries, have reported the development of new‑onset manifestations, including depression, anxiety, psychotic symptoms, sleep disturbances and fatigue. Nevertheless, when COVID‑19 survivors were compared with SARS‑CoV‑2‑negative controls and especially survivors of other disorders (such as influenza), the findings regarding the risk of incident neuropsychiatric manifestations varied among studies.
While there is evidence of an association between SARS‑CoV‑2 infection and the subsequent occurrence of new‑onset neuropsychiatric symptoms, especially among patients with increased disease severity, further research using methodological approaches less susceptible to confounding bias is required to establish causal relationships.
Source: Efstathiou, V., Stefanou, M., Demetriou, M., Siafakas, N., Katsantoni, E., Makris, M., Tsivgoulis, G., Zoumpourlis, V., Kympouropoulos, S. P., Tsoporis, J. N., Spandidos, D. A., Ferentinos, P., Smyrnis, N., Rizos, E.”New‑onset neuropsychiatric sequelae and ‘long‑COVID’ syndrome (Review)”. Experimental and Therapeutic Medicine 24.5 (2022): 705. https://www.spandidos-publications.com/10.3892/etm.2022.11641 (Full text available as PDF file)

Post-Viral Fatigue in COVID-19: A Review of Symptom Assessment Methods, Mental, Cognitive, and Physical Impairment

Abstract:

Coronavirus 2 is responsible for Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), and the main sequela is persistent fatigue. Post-viral fatigue is common and affects patients with mild, asymptomatic coronavirus disease-2019 (COVID-19). However, the exact mechanisms involved in developing post-COVID-19 fatigue remain unclear. Furthermore, physical and cognitive impairments in these individuals have been widely described. Therefore, this review aims to summarize and propose tools from a multifaceted perspective to assess COVID-19 infection.

Herein, we point out the instruments that can be used to assess fatigue in long-term COVID-19: fatigue in a subjective manner or fatigability in an objective manner. For physical and mental fatigue, structured questionnaires were used to assess perceived symptoms, and physical and cognitive performance assessment tests were used to measure fatigability using reduced performance.

Source: Campos MC, Nery T, Starke AC, de Bem Alves AC, Speck AE, Junior ASA. Post-Viral Fatigue in COVID-19: A Review of Symptom Assessment Methods, Mental, Cognitive, and Physical Impairment. Neurosci Biobehav Rev. 2022 Oct 3:104902. doi: 10.1016/j.neubiorev.2022.104902. Epub ahead of print. PMID: 36202253; PMCID: PMC9528075. https://www.sciencedirect.com/science/article/pii/S0149763422003918 (Full text)

Long-COVID Syndrome and the Cardiovascular System: A Review of Neurocardiologic Effects on Multiple Systems

Abstract:

Purpose of review: Long-COVID syndrome is a multi-organ disorder that persists beyond 12 weeks post-acute SARS-CoV-2 infection (COVID-19). Here, we provide a definition for this syndrome and discuss neuro-cardiology involvement due to the effects of (1) angiotensin-converting enzyme 2 receptors (the entry points for the virus), (2) inflammation, and (3) oxidative stress (the resultant effects of the virus).

Recent findings: These effects may produce a spectrum of cardio-neuro effects (e.g., myocardial injury, primary arrhythmia, and cardiac symptoms due to autonomic dysfunction) which may affect all systems of the body. We discuss the symptoms and suggest therapies that target the underlying autonomic dysfunction to relieve the symptoms rather than merely treating symptoms. In addition to treating the autonomic dysfunction, the therapy also treats chronic inflammation and oxidative stress. Together with a full noninvasive cardiac workup, a full assessment of the autonomic nervous system, specifying parasympathetic and sympathetic (P&S) activity, both at rest and in response to challenges, is recommended. Cardiac symptoms must be treated directly. Cardiac treatment is often facilitated by treating the P&S dysfunction. Cardiac symptoms of dyspnea, chest pain, and palpitations, for example, need to be assessed objectively to differentiate cardiac from neural (autonomic) etiology. Long-term myocardial injury commonly involves P&S dysfunction. P&S assessment usually connects symptoms of Long-COVID to the documented autonomic dysfunction(s).

Source: DePace NL, Colombo J. Long-COVID Syndrome and the Cardiovascular System: A Review of Neurocardiologic Effects on Multiple Systems. Curr Cardiol Rep. 2022 Sep 30:1–16. doi: 10.1007/s11886-022-01786-2. Epub ahead of print. PMID: 36178611; PMCID: PMC9524329.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9524329/ (Full text)

The Neurobiology of Long COVID

Abstract:

Persistent neurological and neuropsychiatric symptoms affect a substantial fraction of people after COVID-19 and represent a major component of the post-acute COVID syndrome, also known as long COVID. Here, we review what is understood about the pathobiology of post-acute COVID-19 impacts on the CNS and discuss possible neurobiological underpinnings of the cognitive symptoms affecting COVID-19 survivors. We propose the chief mechanisms that may contribute to this emerging neurological health crisis.
Source: Michelle Monje, Akiko Iwasaki. The Neurobiology of Long COVID. Published:October 06, 2022. DOI: https://doi.org/10.1016/j.neuron.2022.10.006 https://www.cell.com/neuron/pdf/S0896-6273(22)00910-2.pdf (Full text available as PDF file)

Gut Microbiota Dynamics in Relation to Long-COVID-19 Syndrome: Role of Probiotics to Combat Psychiatric Complications

Abstract:

Increasing numbers of patients who recover from COVID-19 report lasting symptoms, such as fatigue, muscle weakness, dementia, and insomnia, known collectively as post-acute COVID syndrome or long COVID. These lasting symptoms have been examined in different studies and found to influence multiple organs, sometimes resulting in life-threating conditions.
In this review, these symptoms are discussed in connection to the COVID-19 and long-COVID-19 immune changes, highlighting oral and psychiatric health, as this work focuses on the gut microbiota’s link to long-COVID-19 manifestations in the liver, heart, kidney, brain, and spleen. A model of this is presented to show the biological and clinical implications of gut microbiota in SARS-CoV-2 infection and how they could possibly affect the therapeutic aspects of the disease. Probiotics can support the body’s systems in fighting viral infections. This review focuses on current knowledge about the use of probiotics as adjuvant therapies for COVID-19 patients that might help to prevent long-COVID-19 complications.
Source: Alenazy MF, Aljohar HI, Alruwaili AR, Daghestani MH, Alonazi MA, Labban RS, El-Ansary AK, Balto HA. Gut Microbiota Dynamics in Relation to Long-COVID-19 Syndrome: Role of Probiotics to Combat Psychiatric Complications. Metabolites. 2022; 12(10):912. https://doi.org/10.3390/metabo12100912 (Full text)