Tag: long covid review

Multisystem inflammatory syndrome in children (MIS-C): Implications for long COVID

Abstract:

The COVID-19 pandemic caused by the coronavirus 2 of the severe acute respiratory syndrome (SARS-CoV-2) has significantly affected people around the world, leading to substantial morbidity and mortality. Although the pandemic has affected people of all ages, there is increasing evidence that children are less susceptible to SARS-CoV-2 infection and are more likely to experience milder symptoms than adults. However, children with COVID-19 can still develop serious complications, such as multisystem inflammatory syndrome in children (MIS-C).

This narrative review of the literature provides an overview of the epidemiology and immune pathology of SARS-CoV-2 infection and MIS-C in children. The review also examines the genetics of COVID-19 and MIS-C in children, including the genetic factors that can influence the susceptibility and severity of the diseases and their implications for personalized medicine and vaccination strategies.

By examining current evidence and insights from the literature, this review aims to contribute to the development of effective prevention and treatment strategies for COVID-19, MIS-C, and long COVID syndromes in children.

Source: Constantin T, Pék T, Horváth Z, Garan D, Szabó AJ. Multisystem inflammatory syndrome in children (MIS-C): Implications for long COVID. Inflammopharmacology. 2023 Jul 17. doi: 10.1007/s10787-023-01272-3. Epub ahead of print. PMID: 37460909. https://link.springer.com/article/10.1007/s10787-023-01272-3 (Full text)

Understanding the neurological implications of acute and long COVID using brain organoids

Abstract:

As early as in the acute phase of the coronavirus disease 2019 (COVID-19) pandemic, the research community voiced concerns about the long-term implications of infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), like many other viruses, can trigger chronic disorders that last months or even years.

Long COVID, the chronic and persistent disorder lasting more than 12 weeks after the primary infection with SARS-CoV-2, involves a variable number of neurological manifestations, ranging from mild to severe and even fatal. In vitro and in vivo modeling suggest that SARS-CoV-2 infection drives changes within neurons, glia and the brain vasculature.

In this Review, we summarize the current understanding of the neuropathology of acute and long COVID, with particular emphasis on the knowledge derived from brain organoid models. We highlight the advantages and main limitations of brain organoids, leveraging their human-derived origin, their similarity in cellular and tissue architecture to human tissues, and their potential to decipher the pathophysiology of long COVID.

Source: García-González L, Martí-Sarrias A, Puertas MC, Bayón-Gil Á, Resa-Infante P, Martinez-Picado J, Navarro A, Acosta S. Understanding the neurological implications of acute and long COVID using brain organoids. Dis Model Mech. 2023 Jul 1;16(7):dmm050049. doi: 10.1242/dmm.050049. Epub 2023 Jul 17. PMID: 37458167. https://journals.biologists.com/dmm/article/16/7/dmm050049/323961/Understanding-the-neurological-implications-of  (Full text)

Hematological alterations associated with long COVID-19

Abstract:

Long COVID-19 is a condition characterized by persistent symptoms lasting beyond the acute phase of COVID-19. Long COVID-19 produces diverse symptomatology and can impact organs and systems, including the hematological system. Several studies have reported, in COVID-19 patients, hematological abnormalities. Most of these alterations are associated with a higher risk of severe disease and poor outcomes.

This literature review identified studies reporting hematological parameters in individuals with Long COVID-19. Findings suggest that Long COVID-19 is associated with a range of sustained hematological alterations, including alterations in red blood cells, anemia, lymphopenia, and elevated levels of inflammatory markers such as ferritin, D-dimer, and IL-6.

These alterations may contribute to a better understanding of the pathophysiology of Long COVID-19 and its associated symptoms. However, further research is needed to elucidate the underlying mechanisms and potential treatments for these hematological changes in individuals with Long COVID-19.

Source: Lechuga Guilherme C., Giovanni De-Simone Salvatore, Morel Carlos M. Hematological alterations associated with long COVID-19. Frontiers in Physiology, Vol 14, 2023. DOI: 10.3389/fphys.2023.1203472  ISSN: 1664-042X https://www.frontiersin.org/articles/10.3389/fphys.2023.1203472 https://www.frontiersin.org/articles/10.3389/fphys.2023.1203472/full (Full text)

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)

Correlation between Hepatocyte Growth Factor (HGF) with D-Dimer and Interleukin-6 as Prognostic Markers of Coagulation and Inflammation in Long COVID-19 Survivors

Abstract:

In general, an individual who experiences the symptoms of Severe Acute Respiratory Syndrome Coronavirus 2 or SARS-CoV-2 infection is declared as recovered after 2 weeks. However, approximately 10–20% of these survivors have been reported to encounter long-term health problems, defined as ‘long COVID-19’, e.g., blood coagulation which leads to stroke with an estimated incidence of 3%, and pulmonary embolism with 5% incidence.
At the time of infection, the immune response produces pro-inflammatory cytokines that stimulate stromal cells to produce pro-hepatocyte growth factor (pro-HGF) and eventually is activated into hepatocyte growth factor (HGF), which helps the coagulation process in endothelial and epithelial cells. HGF is a marker that appears as an inflammatory response that leads to coagulation.
Currently, there is no information on the effect of SARS-CoV-2 infection on serum HGF concentrations as a marker of the prognosis of coagulation in long COVID-19 survivors. This review discusses the pathophysiology between COVID-19 and HGF, IL-6, and D-dimer.
Source: Zaira B, Yulianti T, Levita J. Correlation between Hepatocyte Growth Factor (HGF) with D-Dimer and Interleukin-6 as Prognostic Markers of Coagulation and Inflammation in Long COVID-19 Survivors. Current Issues in Molecular Biology. 2023; 45(7):5725-5740. https://doi.org/10.3390/cimb45070361 https://www.mdpi.com/1467-3045/45/7/361 (Full text)

Long COVID, the Brain, Nerves, and Cognitive Function

Abstract:

SARS-CoV-2, a single-stranded RNA coronavirus, causes an illness known as coronavirus disease 2019 (COVID-19). Long-term complications are an increasing issue in patients who have been infected with COVID-19 and may be a result of viral-associated systemic and central nervous system inflammation or may arise from a virus-induced hypercoagulable state. COVID-19 may incite changes in brain function with a wide range of lingering symptoms.
Patients often experience fatigue and may note brain fog, sensorimotor symptoms, and sleep disturbances. Prolonged neurological and neuropsychiatric symptoms are prevalent and can interfere substantially in everyday life, leading to a massive public health concern. The mechanistic pathways by which SARS-CoV-2 infection causes neurological sequelae are an important subject of ongoing research. Inflammation- induced blood-brain barrier permeability or viral neuro-invasion and direct nerve damage may be involved. Though the mechanisms are uncertain, the resulting symptoms have been documented from numerous patient reports and studies.
This review examines the constellation and spectrum of nervous system symptoms seen in long COVID and incorporates information on the prevalence of these symptoms, contributing factors, and typical course. Although treatment options are generally lacking, potential therapeutic approaches for alleviating symptoms and improving quality of life are explored.
Source: Reiss AB, Greene C, Dayaramani C, Rauchman SH, Stecker MM, De Leon J, Pinkhasov A. Long COVID, the Brain, Nerves, and Cognitive Function. Neurology International. 2023; 15(3):821-841. https://doi.org/10.3390/neurolint15030052 https://www.mdpi.com/2035-8377/15/3/52 (Full text)

The immunology of long COVID

Abstract:

Long COVID is the patient-coined term for the disease entity whereby persistent symptoms ensue in a significant proportion of those who have had COVID-19, whether asymptomatic, mild or severe. Estimated numbers vary but the assumption is that, of all those who had COVID-19 globally, at least 10% have long COVID. The disease burden spans from mild symptoms to profound disability, the scale making this a huge, new health-care challenge.

Long COVID will likely be stratified into several more or less discrete entities with potentially distinct pathogenic pathways. The evolving symptom list is extensive, multi-organ, multisystem and relapsing–remitting, including fatigue, breathlessness, neurocognitive effects and dysautonomia. A range of radiological abnormalities in the olfactory bulb, brain, heart, lung and other sites have been observed in individuals with long COVID. Some body sites indicate the presence of microclots; these and other blood markers of hypercoagulation implicate a likely role of endothelial activation and clotting abnormalities.

Diverse auto-antibody (AAB) specificities have been found, as yet without a clear consensus or correlation with symptom clusters. There is support for a role of persistent SARS-CoV-2 reservoirs and/or an effect of Epstein–Barr virus reactivation, and evidence from immune subset changes for broad immune perturbation. Thus, the current picture is one of convergence towards a map of an immunopathogenic aetiology of long COVID, though as yet with insufficient data for a mechanistic synthesis or to fully inform therapeutic pathways.

Source: Altmann, D.M., Whettlock, E.M., Liu, S. et al. The immunology of long COVID. Nat Rev Immunol (2023). https://doi.org/10.1038/s41577-023-00904-7 https://www.nature.com/articles/s41577-023-00904-7 (Full text)

Long COVID and its cardiovascular consequences: What is known?

Abstract:

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused high morbidity and mortality and has been a source of substantial challenges for healthcare systems globally. Despite a full recovery, a significant proportion of patients demonstrate a broad spectrum of cardiovascular, pulmonary and neurological symptoms that are believed to be caused by long-term tissue damage and pathological inflammation, which play a vital role in disease development. Microvascular dysfunction also causes significant health problems.

This review aimed to critically appraise the current data on the long-term cardiovascular sequelae of coronavirus disease 2019 (COVID-19), with a primary focus on cardiovascular symptoms such as chest pain, fatigue, palpitations, and breathlessness, and more significant disease entities including myocarditis, pericarditis and postural tachycardia syndrome. Potential risk factors identified in recent studies that contribute towards the development of long COVID are also included alongside a summary of recent advances in diagnostics and putative treatment options.

Source: Składanek JA, Leśkiewicz M, Gumiężna K, Baruś P, Piasecki A, Klimczak-Tomaniak D, Sygitowicz G, Kochman J, Grabowski M, Tomaniak M. Long COVID and its cardiovascular consequences: What is known? Adv Clin Exp Med. 2023 Jun 30. doi: 10.17219/acem/167482. Epub ahead of print. PMID: 37386857. https://advances.umw.edu.pl/en/ahead-of-print/167482/ (Full text)

Advancing the Management of Long COVID by Integrating into Health Informatics Domain: Current and Future Perspectives

Abstract:

The ongoing COVID-19 pandemic has profoundly affected millions of lives globally, with some individuals experiencing persistent symptoms even after recovering. Understanding and managing the long-term sequelae of COVID-19 is crucial for research, prevention, and control. As a result, to monitor the health of individuals affected by these conditions, they must maintain up-to-date health records using digital health informatics apps for surveillance.

In this review, we provide an overview of the existing literature on identifying long COVID manifestations through hierarchical classification and the characterization of long COVID by different hierarchical groups based on the Human Phenotype Ontology (HPO). We outline the aspects of the National COVID Cohort Collaborative (N3C) and Researching COVID to Enhance Recovery (RECOVER) in artificial intelligence (AI) to identify long COVID.

Knowledge exploration, using the concept map for the clinical pathways of long COVID presented in this paper, provides an overview of the data needed to explore tackling the long-term effect of COVID-19 by integrating innovative cohesive frameworks and designing health informatics-based applications. To the best of our knowledge, this is the first paper to explore the potential incorporation of long COVID as a variable risk factor within a digital health informatics application.

Source: Ambalavanan, R.; Snead, R.S.; Marczika, J.; Kozinsky, K.; Aman, E. Advancing the Management of Long COVID by Integrating into Health Informatics Domain: Current and Future Perspectives. Preprints.org2023, 2023062111. https://doi.org/10.20944/preprints202306.2111.v1 https://www.preprints.org/manuscript/202306.2111/v1 (Full text available as PDF file)

The potential role of Rhodiola rosea L. extract WS® 1375 for patients with post-COVID-19 fatigue

Abstract:

Fatigue and physical exhaustion are the dominant symptoms of post-coronavirus (COVID-19) conditions that might even develop after only mild acute disease. Post-acute infection syndromes have been observed after various infections, e.g., Coxiella burnetii, Ebola, Dengue, Polio, severe acute respiratory syndrome (SARS), Chikungunya, West Nile Virus, Borrelia, or Giardina lamblia. The similarities in symptoms and courses suggest a high likelihood of common pathogenetic pathways, including persistent infection, autoimmune reactions, dysregulation of the microbiome, inability to repair tissue damage, or endothelial dysfunction.

Some herbal drugs, so-called adaptogens, exert effects resulting in an increase in the resistance or regulatory potential of organisms against biological, chemical and physical burden or stress. Therefore, it seems possible that adaptogens can be helpful in cases of post-COVID-19 symptoms. One of these adaptogens is Rhodiola rosea L. The proprietary ethanolic extract made from roots and rhizomes of Rhodiola rosea WS® 1375 has been reported to modulate neuroinflammation in response to stress stimuli in preclinical models. Moreover, it activated the synthesis or resynthesis of adenosine triphosphate (ATP) in skeletal muscle mitochondria and counteracted muscle fatigue.

In three clinical trials with subjects suffering from burnout symptoms, prolonged or chronic fatigue symptoms or life-stress symptoms, clinically relevant improvements of fatigue and exhaustion were reported over 4 to 12 weeks of treatment at a very favorable tolerability and safety profile in heterogeneous patient populations. In conclusion, Rhodiola rosea extract WS® 1375 has a promising pharmacological and therapeutic profile for the treatment of fatigue and physical exhaustion associated with post-COVID-19 conditions.

Source: Wegener T, Edwards D, Kasper S. The potential role of Rhodiola rosea L. extract WS® 1375 for patients with post-COVID-19 fatigue. hb TIMES Schw Aerztej. 2023;8(1):56-61. doi:10.36000/hbT.2023.09.001 https://schw-aerztej.healthbooktimes.org/article/74319-the-potential-role-of-rhodiola-rosea-l-extract-ws-1375-for-patients-with-post-covid-19-fatigue (Full text)