Persistent Autoimmune Activation and Proinflammatory State in Post-Coronavirus Disease 2019 Syndrome.

BACKGROUND: The immunopathological pathways enabling post-coronavirus disease 2019 (COVID-19) syndrome (PCS) development are not entirely known. We underwent a longitudinal analysis of patients with COVID-19 who developed PCS aiming to evaluate the autoimmune and immunological status associated with this condition. METHODS: Thirty-three patients were included for longitudinal clinical and autoantibody analyses, 12 of whom were assessed for cytokines and lymphocyte populations. Patients were followed for 7-11 months after acute COVID-19. Autoimmune profile and immunological statuses were evaluated mainly by enzyme-linked-immunosorbent assays and flow cytometry. RESULTS: Latent autoimmunity and overt autoimmunity persisted over time. A proinflammatory state was observed in patients with PCS characterized by up-regulated interferon-α, tumor necrosis factor-α, granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-17A, IL-6, IL-1ß, and IL-13, whereas interferon-γ-induced protein 10 (IP-10) was decreased. In addition, PCS was characterized by increased levels of Th9, CD8+ effector T cells, naive B cells, and CD4+ effector memory T cells. Total levels of immunoglobulin G S1-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies remained elevated over time. CONCLUSIONS: The clinical manifestations of PCS are associated with the persistence of a proinflammatory and effector phenotype induced by SARS-CoV-2 infection. This long-term persistent immune activation may contribute to the development of latent and overt autoimmunity. Results suggest the need to evaluate the role of immunomodulation in the treatment of PCS.

Autoimmunity is a hallmark of post-COVID syndrome.

Autoimmunity has emerged as a characteristic of the post-COVID syndrome (PCS), which may be related to sex. In order to further investigate the relationship between SARS-CoV-2 and autoimmunity in PCS, a clinical and serological assessment on 100 patients was done. Serum antibody profiles against self-antigens and infectious agents were evaluated by an antigen array chip for 116 IgG and 104 IgM antibodies. Thirty pre-pandemic healthy individuals were included as a control group. The median age of patients was 49 years (IQR: 37.8 to 55.3). There were 47 males. The median post-COVID time was 219 (IQR: 143 to 258) days. Latent autoimmunity and polyautoimmunity were found in 83% and 62% of patients, respectively. Three patients developed an overt autoimmune disease. IgG antibodies against IL-2, CD8B, and thyroglobulin were found in more than 10% of the patients. Other IgG autoantibodies, such as anti-interferons, were positive in 5-10% of patients. Anti-SARS-CoV-2 IgG antibodies were found in > 85% of patients and were positively correlated with autoantibodies, age, and body mass index (BMI). Few autoantibodies were influenced by age and BMI. There was no effect of gender on the over- or under-expression of autoantibodies. IgG anti-IFN-λ antibodies were associated with the persistence of respiratory symptoms. In summary, autoimmunity is characteristic of PCS, and latent autoimmunity correlates with humoral response to SARS-CoV-2.

Autoimmune and autoinflammatory conditions after COVID-19 vaccination. New case reports and updated literature review.

Autoimmunity linked to COVID-19 immunization has been recorded throughout the pandemic. Herein we present six new patients who experienced relapses of previous autoimmune disease (AD) or developed a new autoimmune or autoinflammatory condition following vaccination. In addition, we documented additional cases through a systematic review of the literature up to August 1st, 2022, in which 464 studies (928 cases) were included. The majority of patients (53.6%) were women, with a median age of 48 years (IQR: 34 to 66). The median period between immunization and the start of symptoms was eight days (IQR: 3 to 14). New-onset conditions were observed in 81.5% (n: 756) of the cases. The most common diseases associated with new-onset events following vaccination were immune thrombocytopenia, myocarditis, and Guillain-Barré syndrome. In contrast, immune thrombocytopenia, psoriasis, IgA nephropathy, and systemic lupus erythematosus were the most common illnesses associated with relapsing episodes (18.5%, n: 172). The first dosage was linked with new-onset events (69.8% vs. 59.3%, P = 0.0100), whereas the second dose was related to relapsing disease (29.5% vs. 59.3%, P = 0.0159). New-onset conditions and relapsing diseases were more common in women (51.5% and 62.9%, respectively; P = 0.0081). The groups were evenly balanced in age. No deaths were recorded after the disease relapsed, while 4.7% of patients with new-onset conditions died (P = 0.0013). In conclusion, there may be an association between COVID-19 vaccination and autoimmune and inflammatory diseases. Some ADs seem to be more common than others. Vaccines and SARS-CoV-2 may induce autoimmunity through similar mechanisms. Large, well-controlled studies are warranted to validate this relationship and assess additional variables such as genetic and other environmental factors.

New insights into the taxonomy of autoimmune diseases based on polyautoimmunity.

OBJECTIVE: The clinical coexistence of two or more autoimmune diseases (ADs) fulfilling classification criteria is termed "overt polyautoimmunity" (PolyA), whereas the presence of autoantibodies unrelated to an index AD, without clinical criteria fulfillment, is known as "latent PolyA". We aimed to explore a new taxonomy of ADs based on PolyA. METHODS: In a cross-sectional study of 292 subjects, we evaluated the presence of PolyA in 146, 45, 29, 17, and 17 patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), autoimmune thyroid disease (AITD) and systemic sclerosis (SSc), respectively, and 38 healthy controls. Clinical assessment, autoantibody profile (by autoantigen array chip), lymphocytes immunophenotype and cytokine profile (by flow cytometry) were evaluated simultaneously. A mixed cluster methodology was used to classify ADs. RESULTS: Latent PolyA was more frequent than overt PolyA, ranging from 69.9% in RA to 100% in SSc. Nevertheless, both latent and overt PolyA clustered together. Over-expressed IgG autoantibodies were found to be hallmarks for the identification of index ADs. The combination of autoantibodies allowed high accuracy in the classification of ADs. Three well-defined clusters based on PolyA were observed with distinctive clinical and immunological phenotypes. CONCLUSIONS: This proof-of-concept study indicates that ADs can be classified according to PolyA. PolyA should be considered in all studies dealing with ADs, including epidemiological, genetic, and clinical trials.

Safety and efficacy of convalescent plasma for severe COVID-19: a randomized, single blinded, parallel, controlled clinical study.

BACKGROUND: Convalescent plasma (CP) has been widely used to treat COVID-19 and is under study. However, the variability in the current clinical trials has averted its wide use in the current pandemic. We aimed to evaluate the safety and efficacy of CP in severe coronavirus disease 2019 (COVID-19) in the early stages of the disease. METHODS: A randomized controlled clinical study was conducted on 101 patients admitted to the hospital with confirmed severe COVID-19. Most participants had less than 14 days from symptoms onset and less than seven days from hospitalization. Fifty patients were assigned to receive CP plus standard therapy (ST), and 51 were assigned to receive ST alone. Participants in the CP arm received two doses of 250 mL each, transfused 24 h apart. All transfused plasma was obtained from "super donors" that fulfilled the following criteria: titers of anti-SARS-CoV-2 S1 IgG ≥ 1:3200 and IgA ≥ 1:800 antibodies. The effect of transfused anti-IFN antibodies and the SARS-CoV-2 variants at the entry of the study on the overall CP efficacy was evaluated. The primary outcomes were the reduction in viral load and the increase in IgG and IgA antibodies at 28 days of follow-up. The per-protocol analysis included 91 patients. RESULTS: An early but transient increase in IgG anti-S1-SARS-CoV-2 antibody levels at day 4 post-transfusion was observed (Estimated difference [ED], - 1.36; 95% CI, - 2.33 to - 0.39; P = 0.04). However, CP was not associated with viral load reduction in any of the points evaluated. Analysis of secondary outcomes revealed that those patients in the CP arm disclosed a shorter time to discharge (ED adjusted for mortality, 3.1 days; 95% CI, 0.20 to 5.94; P = 0.0361) or a reduction of 2 points on the WHO scale when compared with the ST group (HR adjusted for mortality, 1.6; 95% CI, 1.03 to 2.5; P = 0.0376). There were no benefits from CP on the rates of intensive care unit admission (HR, 0.82; 95% CI, 0.35 to 1.9; P = 0.6399), mechanical ventilation (HR, 0.66; 95% CI, 0.25 to 1.7; P = 0.4039), or mortality (HR, 3.2; 95% CI, 0.64 to 16; P = 0.1584). Anti-IFN antibodies and SARS-CoV-2 variants did not influence these results. CONCLUSION: CP was not associated with viral load reduction, despite the early increase in IgG anti-SARS-CoV-2 antibodies. However, CP is safe and could be a therapeutic option to reduce the hospital length of stay. Trial registration NCT04332835.

COVID-19 convalescent plasma composition and immunological effects in severe patients.

Convalescent plasma (CP) has emerged as a treatment for COVID-19. However, the composition and mechanism of action are not fully known. Therefore, we undertook a two-phase controlled study in which, first the immunological and metabolomic status of recovered and severe patients were evaluated. Secondly, the 28-day effect of CP on the immune response in severe patients was assessed. Nineteen recovered COVID-19 patients, 18 hospitalized patients with severe disease, and 16 pre-pandemic controls were included. Patients with severe disease were treated with CP transfusion and standard therapy (i.e., plasma recipients, n = 9) or standard therapy alone (n = 9). Clinical and biological assessments were done on day 0 and during follow-up on days 4, 7, 14, and 28. Clinical parameters, viral load, total immunoglobulin (Ig) G and IgA anti-S1-SARS-CoV-2 antibodies, neutralizing antibodies (NAbs), autoantibodies, cytokines, T and B cells, and metabolomic and lipidomic profiles were examined. Total IgG and IgA anti-S1-SARS-CoV-2 antibodies were key factors for CP selection and correlated with NAbs. In severe COVID-19 patients, mostly interleukin (IL)-6 (P = <0.0001), IL-10 (P = <0.0001), IP-10 (P = <0.0001), fatty acyls and glycerophospholipids were higher than in recovered patients. Latent autoimmunity and anti-IFN-α antibodies were observed in both recovered and severe patients. COVID-19 CP induced an early but transient cytokine profile modification and increases IgG anti-S1-SARS-CoV-2 antibodies. At day 28 post-transfusion, a decrease in activated, effector and effector memory CD4+ (P < 0.05) and activated and effector CD8+ (P < 0.01) T cells and naïve B cells (P = 0.001), and an increase in non-classical memory B cells (P=<0.0001) and central memory CD4+ T cells (P = 0.0252) were observed. Moreover, IL-6/IFN-γ (P = 0.0089) and IL-6/IL-10 (P = 0.0180) ratios decreased in plasma recipients compared to those who received standard therapy alone. These results may have therapeutic implications and justify further post-COVID-19 studies.

Autoinflammatory and autoimmune conditions at the crossroad of COVID-19.

Coronavirus disease 2019 (COVID-19) has been categorized as evolving in overlapping phases. First, there is a viral phase that may well be asymptomatic or mild in the majority, perhaps 80% of patients. The pathophysiological mechanisms resulting in minimal disease in this initial phase are not well known. In the remaining 20% of cases, the disease may become severe and/or critical. In most patients of this latter group, there is a phase characterized by the hyperresponsiveness of the immune system. A third phase corresponds to a state of hypercoagulability. Finally, in the fourth stage organ injury and failure occur. Appearance of autoinflammatory/autoimmune phenomena in patients with COVID-19 calls attention for the development of new strategies for the management of life-threatening conditions in critically ill patients. Antiphospholipid syndrome, autoimmune cytopenia, Guillain-Barré syndrome and Kawasaki disease have each been reported in patients with COVID-19. Here we present a scoping review of the relevant immunological findings in COVID-19 as well as the current reports about autoinflammatory/autoimmune conditions associated with the disease. These observations have crucial therapeutic implications since immunomodulatory drugs are at present the most likely best candidates for COVID-19 therapy. Clinicians should be aware of these conditions in patients with COVID-19, and these observations should be considered in the current development of vaccines.

Prevalence of latent and overt polyautoimmunity in autoimmune thyroid disease: A systematic review and meta-analysis.

BACKGROUND: Thyroid autoimmunity is the most frequent condition involved in polyautoimmunity (PolyA). However, the frequency of latent and overt PolyA in patients with autoimmune thyroid disease (AITD) as the index condition is unknown. Therefore, the purpose of this study was to determine the prevalence of these types of PolyA in patients with AITD as the index condition. METHODS: This study adhered to the relevant sections of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. Searches through MEDLINE, Embase and LILACS were done to find articles in Spanish and English. Relevant vocabulary terms and key terms related to AITD and other autoimmune diseases were used. Two investigators independently screened the eligible studies, extracted data and assessed the quality and risk of bias. Fixed and random effect models were used accordingly. Cluster analysis was used to determine similarities among diseases in the articles included (based on Jaccard index). RESULTS: A total of 56 articles fulfilled the inclusion criteria. Of these, 25 were case-controls, 17 were cohorts, and 14 were cross-sectional studies. These studies included a total of 47 509 patients. Female was the predominant gender and included 38 950 patients (81.23%, 95% CI: 80.85-81.60). Graves' disease (GD) was the most common type of thyroid autoimmunity (69.16%, 95% CI: 68.23-70.07). Globally, overt PolyA was found in 13.46% of the patients with AITD. This type of PolyA was represented mainly by type 1 diabetes and autoimmune gastritis. Latent PolyA was presented in 17.45% of the patients, and anti-proinsulin, anti-parietal cells and dsDNA antibodies were the most common. HT had the highest frequency of overt PolyA in Europe (15.60%, 95% CI: 14.72-16.53), whereas latent PolyA was most common in patients with GD in Asia (21.03%, 95% CI: 17.76-24.71). Overt and latent PolyA were associated with gastrointestinal and endocrinological ADs in most of cases and clustered with rheumatological, dermatological and neurological ADs. CONCLUSIONS: Latent and overt PolyA are common in patients with AITD. These results provide insightful information for early diagnosis and management of concurrent ADs in patients with AITD. Aggregation of ADs in different clusters may help to define different phenotypes associated with thyroid autoimmunity that are critically relevant in clinical settings.

Osteoarticular manifestations of Mayaro virus infection.

PURPOSE OF REVIEW: To carry out an update on the state of the art of the Mayaro virus (MAYV) infection and its osteoarticular implications. RECENT FINDINGS: There is a wide distribution of MAYV in Latin America and documented exported cases to the United States and Europe. Although osteoarticular involvement is not the most frequent, it is one the most associated with disability. The main mechanisms related to arthropathy involves cellular infiltrates (i.e. macrophages, natural killer cells, lymphocytes) together with production of cytokines, such as IL-6, IL-7, IL8, IL-12p70. SUMMARY: MAYV infection is an emerging disease, which has been reported in many and increasing number of countries of Latin America. There is a high risk of epidemic outbreaks, given the inadequate vector control (Aedes mosquitoes). Its main symptoms, like other arbovirus infections, involve the presence of headache, rash, conjunctivitis, and arthralgias. MAYV arthropathy is usually severe, can last in time, and is associated with severe disability. There is currently no treatment for MAYV. Prevention of MAYV as a public health burden will be achieved by integrating vector control with vaccines (still under development).

Chronic inflammatory demyelinating polyneuropathy as an autoimmune disease.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease characterized by neurological symptoms and signs of progressive weakness, paresthesias, and sensory dysfunction. Other symptoms include reduced or absent tendon reflexes, cranial nerve involvement, autonomic symptoms, ataxia, and neuropathic pain. Unlike other autoimmune diseases, CIDP generally affects older individuals and has a male predominance. The onset is generally insidious and can take up to 8 weeks with a relapsing-recovery pattern. Like all autoimmune diseases, the etiology is multifactorial, with both genetic and environmental factors contributing to it. Case reports of CIDP have found associations with multiple pathogenic organisms including Hepatitis B and C viruses, Bartonella henselae, Mycoplasma pneumoniae, Human immunodeficiency virus, Cytomegalovirus and Epstein-Barr virus. Possible antigenic self-targets include myelin protein 0, myelin protein 2, peripheral myelin protein 22, Connexin 32, and myelin basic protein. Antibodies targeting the Ranvier node proteins such as contactin-1, contactin-associated protein 1, and neurofascin 155 have been described. CIDP is treated with rehabilitation and pharmacological modalities. Pharmacological treatments target autoimmune dysfunction and include corticosteroids, intravenous immunoglobulin, subcutaneous immunoglobulin, plasma exchange, immunosuppressive and immunomodulatory agents such as methotrexate, cyclophosphamide, rituximab, and mycophenolate mofetil. Although there are few observational studies and randomized clinical trials with limited evidence supporting the use of immunosuppressive drugs, they are widely used in clinical practice. A comprehensive review of CIDP is presented herein in light of the autoimmune tautology.

Cluster analysis of autoimmune rheumatic diseases based on autoantibodies. New insights for polyautoimmunity.

Autoimmune diseases (ADs) are a chronic and clinically heterogeneous group of diseases characterized by share common immunopathogenic mechanisms and risk factors (i.e., the autoimmune tautology), which explain the fact that one AD may coexist with others (i.e., polyautoimmunity - PolyA). In the present exploratory study, a mixed-cluster analysis of the most common autoimmune rheumatic diseases (ARDs) was done. A total of 187 consecutive women with established systemic lupus erythematosus (n = 70), rheumatoid arthritis (n = 51), systemic sclerosis (n = 35) and Sjögren's syndrome (n = 31) were included. A comprehensive clinical, autoantibody and cytokine assessment was simultaneously done. Total PolyA was registered in 142 (75.9%) patients. Six clusters were obtained, built mainly on autoantibodies: PolyA-I to -VI. The PolyA-III cluster showed the highest frequency of overt PolyA (p = 0.01), and the PolyA-I, -III, and -IV clusters exhibited the highest positivity for IL-12/23p40 (p = 0.015). These results provide new insights into the pathophysiology of PolyA and warrant prospective validation to enable development of a more accurate taxonomy of ARDs.

Cytokine imbalance in patients with systemic sclerosis and resilience: the key role of interleukin-6.

OBJECTIVES: Resilience, the ability to respond positively to adverse events, may be influenced by long-term stressors and autoimmune/inflammatory conditions such as systemic sclerosis (SSc). Since the immune system plays a role in the development of resilience, we aimed to evaluate the relationship between a panel of cytokines and resilience in patients with SSc. METHODS: Thirty-five consecutive women with established SSc were involved in this exploratory study. Clinical characteristics, including severity of symptoms and resilience, a panel of 15 serum cytokines and 17 autoantibodies were assessed simultaneously. Multivariate methods were used to analyse the data. RESULTS: Interleukin-6 (IL-6) levels were associated with severity of symptoms (ß=1.8395, p=0.04), and low resilience scores (ß= -0.581120, p=0.02). Furthermore, resilience was not associated with clinical manifestations nor polyautoimmunity. Cytokine levels did not significantly differ between groups based on regular physical activity. CONCLUSIONS: The results highlight the importance of IL-6 as a key mediator in the altered cytokine network of SSc.

Tick-borne diseases and autoimmunity: A comprehensive review.

Tick-borne diseases (TBDs) are emerging and reemerging diseases transmitted by ticks, which portray wide heterogeneity and global distribution. TBDs may present acute clinical pictures that resemble those of autoimmune diseases (i.e., musculoskeletal symptoms, cutaneous involvement, neurologic impairment, renal failure, etc.), and in some cases infection is considered a triggering factor for autoimmunity (e.g., rheumatoid arthritis, autoimmune thyroid disease, vasculitides). The clinician should consider TBDs among the differential diagnoses when approaching autoimmune-like signs in areas of tick infestation. Epidemiological setting (e.g., endemic areas, seasons) and an accurate diagnostic approach (i.e., clinical history, physical examination and laboratory tests) are necessary to confirm TBDs. Further, control and prevention of TBDs is warranted. Research in the fields of ticks microbiome and vaccination (i.e., wildlife and humans) are ahead to control vector transmission and bacterial infection. This review offers a comprehensive update on TBDs and their relationship with autoimmunity.

Autonomic symptoms following Zika virus infection.

PURPOSE: To determine if autonomic symptoms are associated with previous Zika virus infection. METHODS: Case-control study including 35 patients with Zika virus infection without evidence of neurological disease and 105 controls. Symptoms of autonomic dysfunction were assessed with the composite autonomic symptom scale 31 (COMPASS-31). RESULTS: Patients with previous Zika virus infection had significantly higher COMPASS-31 score than controls regardless of age and sex (p = 0.007). The main drivers for the higher scores where orthostatic intolerance (p = 0.003), secretomotor (p = 0.04) and bladder symptoms (p < 0.001). CONCLUSION: Zika virus infection is associated with autonomic dysfunction. The mechanisms remain to be elucidated.

Cytokine and autoantibody clusters interaction in systemic lupus erythematosus.

BACKGROUND: Evidence supports the existence of different subphenotypes in systemic lupus erythematosus (SLE) and the pivotal role of cytokines and autoantibodies, which interact in a highly complex network. Thus, understanding how these complex nonlinear processes are connected and observed in real-life settings is a major challenge. Cluster approaches may assist in the identification of these subphenotypes, which represent such a phenomenon, and may contribute to the development of personalized medicine. Therefore, the relationship between autoantibody and cytokine clusters in SLE was analyzed. METHODS: This was an exploratory study in which 67 consecutive women with established SLE were assessed. Clinical characteristics including disease activity, a 14-autoantibody profile, and a panel of 15 serum cytokines were measured simultaneously. Mixed-cluster methodology and bivariate analyses were used to define autoantibody and cytokine clusters and to identify associations between them and related variables. RESULTS: First, three clusters of autoantibodies were defined: (1) neutral, (2) antiphospholipid antibodies (APLA)-dominant, and (3) anti-dsDNA/ENA-dominant. Second, eight cytokines showed levels above the threshold thus making possible to find 4 clusters: (1) neutral, (2) chemotactic, (3) G-CSF dominant, and (4) IFNα/Pro-inflammatory. Furthermore, the disease activity was associated with cytokine clusters, which, in turn, were associated with autoantibody clusters. Finally, when all biomarkers were included, three clusters were found: (1) neutral, (2) chemotactic/APLA, and (3) IFN/dsDNA, which were also associated with disease activity. CONCLUSION: These results support the existence of three SLE cytokine-autoantibody driven subphenotypes. They encourage the practice of personalized medicine, and support proof-of-concept studies.

A comprehensive analysis and immunobiology of autoimmune neurological syndromes during the Zika virus outbreak in Cúcuta, Colombia.

We have focused on the epidemiology and immunobiology of Zika virus (ZIKV) infection and factors associated with the development of Guillain-Barré syndrome (GBS) and other neurological syndromes in Cúcuta, the capital of North Santander department, Colombia. Data of patients with ZIKV disease reported to the national population-based surveillance system were used to calculate the basic reproduction number (R0) and the attack rates (ARs) as well as to develop epidemiological maps. Patients with neurological syndromes were contacted and their diagnoses were confirmed. A case-control study in which 29 patients with GBS associated with ZIKV compared with 74-matched control patients with ZIKV infection alone was undertaken. Antibodies against arboviruses and other infections that may trigger GBS were evaluated. The estimated value of R0 ranged between 2.68 (95% CI 2.54-2.67) to 4.57 (95% CI 4.18-5.01). The sex-specific ARs were 1306 per 100,000 females, and 552 per 100,000 males. A non-linear interaction between age and gender on the ARs was observed. The incidence of GBS in Cúcuta increased 4.41 times secondary to ZIKV infection. The lag time between ZIKV infection and neurological symptoms was 7 days (interquartile range 2-14.5). Patients with GBS appeared to represent a lower socioeconomic status and were living near to environmentally contaminated areas. All GBS patients were positive for IgG antibodies against both ZIKV and Dengue virus, and 69% were positive for Chikungunya virus. Noteworthy, GBS was associated with a previous infection with M. pneumoniae (OR: 3.95; 95% CI 1.44-13.01; p = 0.006). No differences in antibody levels against C. jejuni, Epstein-Barr virus and cytomegalovirus were observed. High rates of cranial nerves involvement and dysautonomia were present in 82% and 75.9%, respectively. Intensive care unit (ICU) admission was necessary in 69% of the GBS patients. Most of the patients disclosed a high disability condition (Hughes grade 4). Dysautonomia was the main risk factor of poor GBS prognosis (i.e., ICU admission and disability). Thirteen patients were diagnosed with other neurological syndromes different to GBS (6 with transverse myelitis, 3 with encephalitis, 3 with peripheral facial palsy and one with thoraco-lumbosacral myelopathy). Our data confirm an increased transmission of ZIKV in Cúcuta, and provide support to the view that severe neurological syndromes are related to ZIKV disease. The complex ways by which previous infections and socioeconomic status interact to increase the risk of GBS in people infected by ZIKV should be further investigated.

Predictors of mortality in hospitalised patients with COVID-19: a 1-year case-control study.

BACKGROUND: A paucity of predictive models assessing risk factors for COVID-19 mortality that extend beyond age and gender in Latino population is evident in the current academic literature. OBJECTIVES: To determine the associated factors with mortality, in addition to age and sex during the first year of the pandemic. DESIGN: A case-control study with retrospective revision of clinical and paraclinical variables by systematic revision of clinical records was conducted. Multiple imputations by chained equation were implemented to account for missing variables. Classification and regression trees (CART) were estimated to evaluate the interaction of associated factors on admission and their role in predicting mortality during hospitalisation. No intervention was performed. SETTING: High-complexity centre above 2640 m above sea level (masl) in Colombia. PARTICIPANTS: A population sample of 564 patients admitted to the hospital with confirmed COVID-19 by PCR. Deceased patients (n=282) and a control group (n=282), matched by age, sex and month of admission, were included. MAIN OUTCOME MEASURE: Mortality during hospitalisation. MAIN RESULTS: After the imputation of datasets, CART analysis estimated 11 clinical profiles based on respiratory distress, haemoglobin, lactate dehydrogenase, partial pressure of oxygen to inspired partial pressure of oxygen ratio, chronic kidney disease, ferritin, creatinine and leucocytes on admission. The accuracy model for prediction was 80.4% (95% CI 71.8% to 87.3%), with an area under the curve of 78.8% (95% CI 69.63% to 87.93%). CONCLUSIONS: This study discloses new interactions between clinical and paraclinical features beyond age and sex influencing mortality in COVID-19 patients. Furthermore, the predictive model could offer new clues for the personalised management of this condition in clinical settings.

Metabolic fingerprinting of systemic sclerosis: a systematic review.

Introduction: Systemic sclerosis (SSc) is a chronic autoimmune disease, marked by an unpredictable course, high morbidity, and increased mortality risk that occurs especially in the diffuse and rapidly progressive forms of the disease, characterized by fibrosis of the skin and internal organs and endothelial dysfunction. Recent studies suggest that the identification of altered metabolic pathways may play a key role in understanding the pathophysiology of the disease. Therefore, metabolomics might be pivotal in a better understanding of these pathogenic mechanisms. Methods: Through a systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines (PRISMA), searches were done in the PubMed, EMBASE, Web of Science, and Scopus databases from 2000 to September 2022. Three researchers independently reviewed the literature and extracted the data based on predefined inclusion and exclusion criteria. Results: Of the screened studies, 26 fulfilled the inclusion criteria. A total of 151 metabolites were differentially distributed between SSc patients and healthy controls (HC). The main deregulated metabolites were those derived from amino acids, specifically homocysteine (Hcy), proline, alpha-N-phenylacetyl-L-glutamine, glutamine, asymmetric dimethylarginine (ADMA), citrulline and ornithine, kynurenine (Kyn), and tryptophan (Trp), as well as acylcarnitines associated with long-chain fatty acids and tricarboxylic acids such as citrate and succinate. Additionally, differences in metabolic profiling between SSc subtypes were identified. The diffuse cutaneous systemic sclerosis (dcSSc) subtype showed upregulated amino acid-related pathways involved in fibrosis, endothelial dysfunction, and gut dysbiosis. Lastly, potential biomarkers were evaluated for the diagnosis of SSc, the identification of the dcSSc subtype, pulmonary arterial hypertension, and interstitial lung disease. These potential biomarkers are within amino acids, nucleotides, carboxylic acids, and carbohydrate metabolism. Discussion: The altered metabolite mechanisms identified in this study mostly point to perturbations in amino acid-related pathways, fatty acid beta-oxidation, and in the tricarboxylic acid cycle, possibly associated with inflammation, vascular damage, fibrosis, and gut dysbiosis. Further studies in targeted metabolomics are required to evaluate potential biomarkers for diagnosis, prognosis, and treatment response.

COVID-19 vaccine and autoimmunity. A new case of autoimmune hepatitis and review of the literature.

Autoimmunity following COVID-19 vaccination has been reported. Herein, a 79-year-old man with clinical and immunological features of autoimmune hepatitis type 1 after ChAdOx1 nCoV-19 vaccination is presented. Clinical manifestations rapidly remitted after the instauration of immunomodulatory management. This case, together with a comprehensive review of the literature, illustrates the association between COVID-19 vaccines and the development of autoimmune conditions.