Tag: covid-19

Is post-COVID syndrome an autoimmune disease?

Abstract:

Introduction: Post-COVID syndrome (PCS) is recognized as a new entity in the context of SARS-CoV-2 infection. Though its pathogenesis is not completely understood, persistent inflammation from acute illness and the development of autoimmunity play a critical role in its development.

Areas covered: The mechanisms involved in the emergence of PCS, their similarities with post-viral and post-care syndromes, its inclusion in the spectrum of autoimmunity and possible targets for its treatment.

Expert opinion: An autoimmune phenomenon plays a major role in most causative theories explaining PCS. There is a need for both PCS definition and classification criteria (including severity scores). Longitudinal and controlled studies are necessary to better understand this new entity, and to find what additional factors participate into its development. With the high prevalence of COVID-19 cases worldwide, together with the current evidence on latent autoimmunity in PCS, we may observe an increase of autoimmune diseases (ADs) in the coming years. Vaccination’s effect on the development of PCS and ADs will also receive attention in the future. Health and social care services need to develop a new framework to deal with PCS.

Source: Anaya JM, Herrán M, Beltrán S, Rojas M. Is post-COVID syndrome an autoimmune disease? Expert Rev Clin Immunol. 2022 Jun 14:1-14. doi: 10.1080/1744666X.2022.2085561. Epub ahead of print. PMID: 35658801. https://pubmed.ncbi.nlm.nih.gov/35658801/

Comprehensive clinical assessment identifies specific neurocognitive deficits in working-age patients with long-COVID

Abstract:

Introduction: There have been more than 425 million COVID-19 infections worldwide. Post-COVID illness has become a common, disabling complication of this infection. Therefore, it presents a significant challenge to global public health and economic activity.

Methods: Comprehensive clinical assessment (symptoms, WHO performance status, cognitive testing, CPET, lung function, high-resolution CT chest, CT pulmonary angiogram and cardiac MRI) of previously well, working-age adults in full-time employment was conducted to identify physical and neurocognitive deficits in those with severe or prolonged COVID-19 illness.

Results: 205 consecutive patients, age 39 (IQR30.0-46.7) years, 84% male, were assessed 24 (IQR17.1-34.0) weeks after acute illness. 69% reported ≥3 ongoing symptoms. Shortness of breath (61%), fatigue (54%) and cognitive problems (47%) were the most frequent symptoms, 17% met criteria for anxiety and 24% depression. 67% remained below pre-COVID performance status at 24 weeks. One third of lung function tests were abnormal, (reduced lung volume and transfer factor, and obstructive spirometry). HRCT lung was clinically indicated in <50% of patients, with COVID-associated pathology found in 25% of these. In all but three HRCTs, changes were graded ‘mild’. There was an extremely low incidence of pulmonary thromboembolic disease or significant cardiac pathology. A specific, focal cognitive deficit was identified in those with ongoing symptoms of fatigue, poor concentration, poor memory, low mood, and anxiety. This was notably more common in patients managed in the community during their acute illness.

Conclusion: Despite low rates of residual cardiopulmonary pathology, in this cohort, with low rates of premorbid illness, there is a high burden of symptoms and failure to regain pre-COVID performance 6-months after acute illness. Cognitive assessment identified a specific deficit of the same magnitude as intoxication at the UK drink driving limit or the deterioration expected with 10 years ageing, which appears to contribute significantly to the symptomatology of long-COVID.

Source: Holdsworth DA, Chamley R, Barker-Davies R, O’Sullivan O, Ladlow P, Mitchell JL, Dewson D, Mills D, May SLJ, Cranley M, Xie C, Sellon E, Mulae J, Naylor J, Raman B, Talbot NP, Rider OJ, Bennett AN, Nicol ED. Comprehensive clinical assessment identifies specific neurocognitive deficits in working-age patients with long-COVID. PLoS One. 2022 Jun 10;17(6):e0267392. doi: 10.1371/journal.pone.0267392. PMID: 35687603; PMCID: PMC9187094. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9187094/ (Full text)

“Long COVID” results after hospitalization for SARS-CoV-2 infection

Abstract:

Long-term sequelae of symptomatic infection caused by SARS-CoV-2 are largely undiscovered. We performed a prospective cohort study on consecutively hospitalized Sars-CoV-2 patients (March-May 2020) for evaluating COVID-19 outcomes at 6 and 12 months. After hospital discharge, patients were addressed to two follow-up pathways based on respiratory support needed during hospitalization. Outcomes were assessed by telephone consultation or ambulatory visit.

Among 471 patients, 80.9% received no respiratory support during hospitalization; 19.1% received non-invasive ventilation (NIV) or invasive mechanical ventilation (IMV). 58 patients died during hospitalization, therefore 413 were enrolled for follow-up. At 6 months, among 355 patients, the 30.3% had any symptoms, 18.0% dyspnea, 6.2% neurological symptoms. Fifty-two out of 105 had major damages in interstitial computed tomography images. NIV/IMV patients had higher probability to suffer of symptoms (aOR = 4.00, 95%CI:1.99-8.05), dyspnea (aOR = 2.80, 95%CI:1.28-6.16), neurological symptoms (aOR = 9.72, 95%CI:2.78-34.00). At 12 months, among 344, the 25.3% suffered on any symptoms, 12.2% dyspnea, 10.1% neurological symptoms. Severe interstitial lesions were present in 37 out of 47 investigated patients.

NIV/IMV patients in respect to no respiratory support, had higher probability of experiencing symptoms (aOR = 3.66, 95%CI:1.73-7.74), neurological symptoms (aOR = 8.96, 95%CI:3.22-24.90). COVID-19 patients showed prolonged sequelae up to 12 months, highlighting the need of follow-up pathways for post-COVID-19 syndrome.

Source: Rigoni M, Torri E, Nollo G, Donne LD, Rizzardo S, Lenzi L, Falzone A, Cozzio S. “Long COVID” results after hospitalization for SARS-CoV-2 infection. Sci Rep. 2022 Jun 10;12(1):9581. doi: 10.1038/s41598-022-13077-5. PMID: 35688830; PMCID: PMC9185134. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9185134/ (Full text)

SARS-CoV-2 infection and persistence throughout the human body and brain

Abstract:

COVID-19 is known to cause multi-organ dysfunction1-3 in acute infection, with prolonged symptoms experienced by some patients, termed Post-Acute Sequelae of SARS-CoV-2 (PASC)4-5. However, the burden of infection outside the respiratory tract and time to viral clearance is not well characterized, particularly in the brain3,6-14.
We performed complete autopsies on 44 patients with COVID-19 to map and quantify SARS-CoV-2 distribution, replication, and cell-type specificity across the human body, including brain, from acute infection through over seven months following symptom onset. We show that SARS-CoV-2 is widely distributed, even among patients who died with asymptomatic to mild COVID-19, and that virus replication is present in multiple extrapulmonary tissues early in infection.
Further, we detected SARS-CoV-2 RNA in multiple anatomic sites, including regions throughout the brain, for up to 230 days following symptom onset. Despite extensive distribution of SARS-CoV-2 in the body, we observed a paucity of inflammation or direct viral cytopathology outside of the lungs. Our data prove that SARS-CoV-2 causes systemic infection and can persist in the body for months.
Source: Daniel Chertow, Sydney Stein, Sabrina Ramelli et al. SARS-CoV-2 infection and persistence throughout the human body and brain, 20 December 2021, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-1139035/v1] https://www.researchsquare.com/article/rs-1139035/v1 https://www.nature.com/articles/s41586-022-05542-y (Full text)

Post-acute COVID-19 cognitive impairment and decline uniquely associate with kynurenine pathway activation: a longitudinal observational study

Abstract:

Cognitive impairment and function post-acute mild to moderate COVID-19 are poorly understood. We report findings of 128 prospectively studied SARS-CoV-2 positive patients. Cognition and olfaction were assessed at 2-, 4- and 12-months post-diagnosis. Lung function, physical and mental health were assessed at 2-month post diagnosis. Blood cytokines, neuro-biomarkers, and kynurenine pathway (KP) metabolites were measured at 2-, 4-, 8- and 12-months. Mild to moderate cognitive impairment (demographically corrected) was present in 16%, 23%, and 26%, at 2-, 4- and 12-months post diagnosis, respectively. Overall cognitive performance mildly, but significantly (p<.001) declined. Cognitive impairment was more common in those with anosmia (p=.05), but only at 2 months. KP metabolites quinolinic acid, 3-hydroxyanthranilic acid, and kynurenine were significantly (p<.001) associated with cognitive decline. The KP as a unique biomarker offers a potential therapeutic target for COVID-19-related cognitive impairment.

Source: Lucette A. Cysique, David Jakabek, Sophia G. Bracken, Yasmin Allen-Davidian, Benjamin Heng, Sharron Chow, Mona Dehhaghi, Ananda Staats Pires, David R. Darley, Anthony Byrne, Chansavath Phetsouphanh, Anthony Kelleher, Gregory J. Dore, Gail V. Matthews, Gilles J Guillemin, Bruce J. Brew. Post-acute COVID-19 cognitive impairment and decline uniquely associate with kynurenine pathway activation: a longitudinal observational study. medRxiv 2022.06.07.22276020; doi: https://doi.org/10.1101/2022.06.07.22276020 https://www.medrxiv.org/content/10.1101/2022.06.07.22276020v1.full-text (Full text)

Persistent circulating SARS-CoV-2 spike is associated with post-acute COVID-19 sequelae

Abstract:

The diagnosis and management of post-acute sequelae of COVID-19 (PASC) poses an ongoing medical challenge. Identifying biomarkers associated with PASC would immensely improve the classification of PASC patients and provide the means to evaluate treatment strategies. We analyzed plasma samples collected from a cohort of PASC and COVID-19 patients (n = 63) to quantify circulating viral antigens and inflammatory markers. Strikingly, we detect SARS-CoV-2 spike antigen in a majority of PASC patients up to 12 months post-diagnosis, suggesting the presence of an active persistent SARS-CoV-2 viral reservoir. Furthermore, temporal antigen profiles for many patients show the presence of spike at multiple time points over several months, highlighting the potential utility of the SARS-CoV-2 full spike protein as a biomarker for PASC

Source: Zoe Swank, Yasmeen Senussi, Galit Alter, David R. Walt. Persistent circulating SARS-CoV-2 spike is associated with post-acute COVID-19 sequelae. medRxiv 2022.06.14.22276401; doi: https://doi.org/10.1101/2022.06.14.22276401 https://www.medrxiv.org/content/10.1101/2022.06.14.22276401v1 (Full text available as PDF file)

Novel genes and sex differences in COVID-19 severity

Abstract:

Here we describe the results of a genome-wide study conducted in 11 939 COVID-19 positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (p < 5×10-8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (p = 1.3×10-22 and p = 8.1×10-12, respectively), and for variants in 9q21.32 near TLE1 only among females (p = 4.4×10-8).

In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (p = 2.7×10-8) and ARHGAP33 (p = 1.3×10-8), respectively.

The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, p = 4.1×10-8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE.

We also found more SNP-heritability and larger heritability differences by age (<60 or ≥ 60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.

Source: Cruz R, Almeida SD, Heredia ML, Quintela I, Ceballos FC, Pita G, Lorenzo-Salazar JM, González-Montelongo R, Gago-Domínguez M, Porras MS, Castaño JAT, Nevado J, Aguado JM, Aguilar C, Aguilera-Albesa S, Almadana V, Almoguera B, Alvarez N, Andreu-Bernabeu Á, Arana-Arri E, Arango C, Arranz MJ, Artiga MJ, Baptista-Rosas RC, Barreda-Sánchez M, Belhassen-Garcia M, Bezerra JF, Bezerra MAC, Boix-Palop L, Brion M, Brugada R, Bustos M, Calderón EJ, Carbonell C, Castano L, Castelao JE, Conde-Vicente R, Cordero-Lorenzana ML, Cortes-Sanchez JL, Corton M, Darnaude MT, De Martino-Rodríguez A, Campo-Pérez V, Bustamante AD, Domínguez-Garrido E, Luchessi AD, Eirós R, Sanabria GME, Fariñas MC, Fernández-Robelo U, Fernández-Rodríguez A, Fernández-Villa T, Gil-Fournier B, Gómez-Arrue J, Álvarez BG, Quirós FGB, González-Peñas J, Gutiérrez-Bautista JF, Herrero MJ, Herrero-Gonzalez A, Jimenez-Sousa MA, Lattig MC, Borja AL, Lopez-Rodriguez R, Mancebo E, Martín-López C, Martín V, Martinez-Nieto O, Martinez-Lopez I, Martinez-Resendez MF, Martinez-Perez Á, Mazzeu JA, Macías EM, Minguez P, Cuerda VM, Silbiger VN, Oliveira SF, Ortega-Paino E, Parellada M, Paz-Artal E, Santos NPC, Pérez-Matute P, Perez P, Pérez-Tomás ME, Perucho T, Pinsach-Abuin ML, Pompa-Mera EN, Porras-Hurtado GL, Pujol A, León SR, Resino S, Fernandes MR, Rodríguez-Ruiz E, Rodriguez-Artalejo F, Rodriguez-Garcia JA, Ruiz-Cabello F, Ruiz-Hornillos J, Ryan P, Soria JM, Souto JC, Tamayo E, Tamayo-Velasco A, Taracido-Fernandez JC, Teper A, Torres-Tobar L, Urioste M, Valencia-Ramos J, Yáñez Z, Zarate R, Nakanishi T, Pigazzini S, Degenhardt F, Butler-Laporte G, Maya-Miles D, Bujanda L, Bouysran Y, Palom A, Ellinghaus D, Martínez-Bueno M, Rolker S, Amitrano S, Roade L, Fava F, Spinner CD, Prati D, Bernardo D, Garcia F, Darcis G, Fernández-Cadenas I, Holter JC, Banales JM, Frithiof R, Duga S, Asselta R, Pereira AC, Romero-Gómez M, Nafría-Jiménez B, Hov JR, Migeotte I, Renieri A, Planas AM, Ludwig KU, Buti M, Rahmouni S, Alarcón-Riquelme ME, Schulte EC, Franke A, Karlsen TH, Valenti L, Zeberg H, Richards B, Ganna A, Boada M, Rojas I, Ruiz A, Sánchez P, Real LM; SCOURGE Cohort Group; HOSTAGE Cohort Group; GRA@CE Cohort Group, Guillen-Navarro E, Ayuso C, González-Neira A, Riancho JA, Rojas-Martinez A, Flores C, Lapunzina P, Carracedo Á. Novel genes and sex differences in COVID-19 severity. Hum Mol Genet. 2022 Jun 16:ddac132. doi: 10.1093/hmg/ddac132. Epub ahead of print. PMID: 35708486.  https://academic.oup.com/hmg/advance-article/doi/10.1093/hmg/ddac132/6607933  (Full text available as PDF file)

Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation

Summary:

COVID survivors frequently experience lingering neurological symptoms that resemble cancer therapy-related cognitive impairment, a syndrome for which white-matter microglial reactivity and consequent neural dysregulation is central. Here, we explored the neurobiological effects of respiratory SARS-CoV-2 infection and found white-matter-selective microglial reactivity in mice and humans.
Following mild respiratory COVID in mice, persistently impaired hippocampal neurogenesis, decreased oligodendrocytes and myelin loss were evident together with elevated CSF cytokines/chemokines including CCL11. Systemic CCL11 administration specifically caused hippocampal microglial reactivity and impaired neurogenesis. Concordantly, humans with lasting cognitive symptoms post-COVID exhibit elevated CCL11 levels. Compared to SARS-CoV-2, mild respiratory influenza in mice caused similar patterns of white matter-selective microglial reactivity, oligodendrocyte loss, impaired neurogenesis and elevated CCL11 at early timepoints, but after influenza only elevated CCL11 and hippocampal pathology persisted. These findings illustrate similar neuropathophysiology after cancer therapy and respiratory SARS-CoV-2 infection which may contribute to cognitive impairment following even mild COVID.
Source: Anthony Fernández-Castañeda, Peiwen Lu, Anna C. Geraghty, Eric Song, MyoungHwa Lee, Jamie Wood, Michael R. O’Dea, Selena Dutton, Kiarash Shamardani, Kamsi Nwangwu, Rebecca Mancusi, Belgin Yalçın, Kathryn R. Taylor, Lehi AcostaAlvarez, Karen Malacon, Michael B. Keough, Lijun Ni, Pamelyn J. Woo, Daniel Contreras-Esquivel, Angus Martin Shaw Toland, Jeff R. Gehlhausen, Jon Klein, Takehiro Takahashi, Julio Silva, Benjamin Israelow, Carolina Lucas, Tianyang Mao, Mario A. Peña-Hernández, Alexandra Tabachnikova, Robert J. Homer, Laura Tabacof, Jenna Tosto-Mancuso, Erica Breyman, Amy Kontorovich, Dayna McCarthy, Martha Quezado, Hannes Vogel, Marco M. Hefti, Daniel P. Perl, Shane Liddelow, Rebecca Folkerth, David Putrino, Avindra Nath, Akiko Iwasaki, Michelle Monje. Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation.  Cell (2022). Published: June 12, 2022 DOI:https://doi.org/10.1016/j.cell.2022.06.008 https://www.sciencedirect.com/science/article/pii/S0092867422007139 (Full text available as PDF file)

Neurotoxic amyloidogenic peptides in the proteome of SARS-COV2: potential implications for neurological symptoms in COVID-19

Abstract:

COVID-19 is primarily known as a respiratory disease caused by SARS-CoV-2. However, neurological symptoms such as memory loss, sensory confusion, severe headaches, and even stroke are reported in up to 30% of cases and can persist even after the infection is over (long COVID). These neurological symptoms are thought to be produced by the virus infecting the central nervous system, however we don’t understand the molecular mechanisms triggering them. The neurological effects of COVID-19 share similarities to neurodegenerative diseases in which the presence of cytotoxic aggregated amyloid protein or peptides is a common feature. Following the hypothesis that some neurological symptoms of COVID-19 may also follow an amyloid etiology we identified two peptides from the SARS-CoV-2 proteome that self-assemble into amyloid assemblies. Furthermore, these amyloids were shown to be highly toxic to neuronal cells. We suggest that cytotoxic aggregates of SARS-CoV-2 proteins may trigger neurological symptoms in COVID-19.

Source: Charnley, M., Islam, S., Bindra, G.K. et al. Neurotoxic amyloidogenic peptides in the proteome of SARS-COV2: potential implications for neurological symptoms in COVID-19. Nat Commun 13, 3387 (2022). https://doi.org/10.1038/s41467-022-30932-1 https://www.nature.com/articles/s41467-022-30932-1 (Full text)

Long COVID-19 and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: similarities and differences of two peas in a pod

Sr. Editor,

Coronavirus disease 2019 (COVID-19) is a highly contagious respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). Prolonged recovery of COVID-19 symptoms, so-called Long COVID-19, has been described even in patients who have mild symptoms and did not required hospitalisation. Various studies showed that at least one out of ten COVID-19 symptomatic patients develop Long
COVID-19.

Although there is an absence of a evidence-based clinical practice guidelines neither a clear aetiopatogenesis, a clinical case definition of post-COVID-19 condition was proposed across the International Severe Respiratory and Emerging Infection Consortium (ISARIC) and the World Health Organization (WHO). Long COVID-19 occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis.

Read the rest of this article HERE.

Source: Qanneta R, COVID-19 persistente y Encefalomielitis Mialgica /Sındrome de Fatiga Cronica: similitudes y diferencias,  Reumatologia Clinica (2022), doi: https://doi.org/10.1016/j.reuma.2022.05.003 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9167847/pdf/main.pdf (Full text available in English as PDF file)