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1.
Front Immunol ; 12: 749774, 2021.
Article in English | MEDLINE | ID: covidwho-1789370

ABSTRACT

The immune system is an efficiently toned machinery that discriminates between friends and foes for achieving both host defense and homeostasis. Deviation of immune recognition from foreign to self and/or long-lasting inflammatory responses results in the breakdown of tolerance. Meanwhile, educating the immune system and developing immunological memory are crucial for mounting defensive immune responses while protecting against autoimmunity. Still to elucidate is how diverse environmental factors could shape autoimmunity. The emergence of a world pandemic such as SARS-CoV-2 (COVID-19) not only threatens the more vulnerable individuals including those with autoimmune conditions but also promotes an unprecedented shift in people's dietary approaches while urging for extraordinary hygiene measures that likely contribute to the development or exacerbation of autoimmunity. Thus, there is an urgent need to understand how environmental factors modulate systemic autoimmunity to better mitigate the incidence and or severity of COVID-19 among the more vulnerable populations. Here, we discuss the effects of diet (macronutrients and micronutrients) and hygiene (the use of disinfectants) on autoimmunity with a focus on systemic lupus erythematosus.


Subject(s)
Autoimmune Diseases/epidemiology , Autoimmunity , COVID-19/epidemiology , COVID-19/immunology , Diet/methods , Hygiene , Immune Tolerance , Pandemics , SARS-CoV-2 , Animals , COVID-19/prevention & control , COVID-19/virology , Humans , Incidence , Severity of Illness Index
2.
Rev Med Suisse ; 18(776): 631-632, 2022 Apr 06.
Article in French | MEDLINE | ID: covidwho-1780509
3.
Science ; 375(6585): 1080, 2022 Mar 11.
Article in English | MEDLINE | ID: covidwho-1779303

ABSTRACT

Study finds human version of mouse immune regulators.


Subject(s)
Autoimmune Diseases/immunology , T-Lymphocyte Subsets/immunology , T-Lymphocytes, Cytotoxic/immunology , Animals , Humans , Mice , Receptors, KIR/analysis
4.
Front Immunol ; 13: 841126, 2022.
Article in English | MEDLINE | ID: covidwho-1775675

ABSTRACT

The antibody profile against autoantigens previously associated with autoimmune diseases and other human proteins in patients with COVID-19 or multisystem inflammatory syndrome in children (MIS-C) remains poorly defined. Here we show that 30% of adults with COVID-19 had autoantibodies against the lung antigen KCNRG, and 34% had antibodies to the SLE-associated Smith-D3 protein. Children with COVID-19 rarely had autoantibodies; one of 59 children had GAD65 autoantibodies associated with acute onset of insulin-dependent diabetes. While autoantibodies associated with SLE/Sjögren's syndrome (Ro52, Ro60, and La) and/or autoimmune gastritis (gastric ATPase) were detected in 74% (40/54) of MIS-C patients, further analysis of these patients and of children with Kawasaki disease (KD), showed that the administration of intravenous immunoglobulin (IVIG) was largely responsible for detection of these autoantibodies in both groups of patients. Monitoring in vivo decay of the autoantibodies in MIS-C children showed that the IVIG-derived Ro52, Ro60, and La autoantibodies declined to undetectable levels by 45-60 days, but gastric ATPase autoantibodies declined more slowly requiring >100 days until undetectable. Further testing of IgG and/or IgA antibodies against a subset of potential targets identified by published autoantigen array studies of MIS-C failed to detect autoantibodies against most (16/18) of these proteins in patients with MIS-C who had not received IVIG. However, Troponin C2 and KLHL12 autoantibodies were detected in 2 of 20 and 1 of 20 patients with MIS-C, respectively. Overall, these results suggest that IVIG therapy may be a confounding factor in autoantibody measurements in MIS-C and that antibodies against antigens associated with autoimmune diseases or other human proteins are uncommon in MIS-C.


Subject(s)
Autoimmune Diseases , COVID-19 , Lupus Erythematosus, Systemic , Adaptor Proteins, Signal Transducing , Adenosine Triphosphatases , Adult , Autoantibodies , Autoantigens , Autoimmunity , COVID-19/complications , Child , Humans , Immunoglobulins, Intravenous , Ribonucleoproteins , Systemic Inflammatory Response Syndrome
5.
Int J Mol Sci ; 23(6)2022 Mar 21.
Article in English | MEDLINE | ID: covidwho-1753507

ABSTRACT

CD8+ T lymphocytes are a heterogeneous class of cells that play a crucial role in the adaptive immune response against pathogens and cancer. During their lifetime, they acquire cytotoxic functions to ensure the clearance of infected or transformed cells and, in addition, they turn into memory lymphocytes, thus providing a long-term protection. During ageing, the thymic involution causes a reduction of circulating T cells and an enrichment of memory cells, partially explaining the lowering of the response towards novel antigens with implications in vaccine efficacy. Moreover, the persistent stimulation by several antigens throughout life favors the switching of CD8+ T cells towards a senescent phenotype contributing to a low-grade inflammation that is a major component of several ageing-related diseases. In genetically predisposed young people, an immunological stress caused by viral infections (e.g., HIV, CMV, SARS-CoV-2), autoimmune disorders or tumor microenvironment (TME) could mimic the ageing status with the consequent acceleration of T cell senescence. This, in turn, exacerbates the inflamed conditions with dramatic effects on the clinical progression of the disease. A better characterization of the phenotype as well as the functions of senescent CD8+ T cells can be pivotal to prevent age-related diseases, to improve vaccine strategies and, possibly, immunotherapies in autoimmune diseases and cancer.


Subject(s)
Autoimmune Diseases , COVID-19 , HIV Infections , Neoplasms , Virus Diseases , CD28 Antigens , CD8-Positive T-Lymphocytes , Cellular Senescence , HIV Infections/drug therapy , Humans , SARS-CoV-2 , Tumor Microenvironment
6.
Orv Hetil ; 163(11): 414-423, 2022 03 13.
Article in Hungarian | MEDLINE | ID: covidwho-1742064

ABSTRACT

Összefoglaló. A krónikus autoimmun betegségben szenvedokben a súlyos COVID-19 kialakulásának kockázata magasabb, a SARS-CoV-2-fertozés pedig a krónikus alapbetegség progressziójához, fellángolásához vezethet. A COVID-19 elkerülésének legbiztonságosabb, legköltséghatékonyabb módszere a vakcináció, illetve az emellett alkalmazott higiénés szabályok betartása, a megfelelo maszk viselése. A hiedelemmel ellentétben önmagában az autoimmun megbetegedés nem jelent oltási ellenjavallatot, sot a rizikóállapot miatt ezek a betegek az elsok között oltandók. A COVID-19 elleni vakcina alkalmazásának egyetlen egyértelmu kontraindikációja az anamnézisben szereplo súlyos allergiás reakció (anafilaxia) a vakcina valamelyik alkotórészével szemben. A betegek olthatóságát többek között befolyásolja az aktuális betegségaktivitás és az alkalmazott kezelés. Az immunizáció idejét a legbiztonságosabban a gondozó orvos tervezheti meg. Az autoimmun betegek immunizációja során észlelheto oltási reakciók és szövodmények incidenciája megegyezik az egészséges populációban is tapasztalt elofordulási gyakorisággal. Orv Hetil. 2022; 163(11): 414-423. Summary. The risk of developing severe COVID-19 is higher in patients with autoimmune diseases, and SARS-CoV-2 infection can lead to progression and exacerbation of the underlying chronic disease. The safest and most cost-effective way to avoid COVID-19 is to be vaccinated, to follow the hygiene rules and to wear an appropriate mask. Contrary to belief, autoimmune disease alone is not a contraindication to vaccination and, in fact, patients should be among the first to be vaccinated because of the risk. The only clear contraindication to the use of COVID-19 vaccine is a history of severe allergic reaction (anaphylaxis) to any of the components of the vaccine. Indication of vaccination migh be influenced by, among other things, the current disease activity and the treatment applied. The timing of immunization can be the most safely planned by the attending physician. The incidence of vaccination reactions and complications during immunization in autoimmune patients is similar to that seen in the healthy population. Orv Hetil. 2022; 163(11): 414-423.


Subject(s)
Autoimmune Diseases , COVID-19 , Viral Vaccines , Autoimmune Diseases/epidemiology , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Child , Humans , SARS-CoV-2
9.
Pathol Res Pract ; 232: 153834, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1720753

ABSTRACT

BACKGROUND: Cases of severe autoimmune blistering diseases (AIBDs) have recently been reported in association with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. AIMS: To describe a report of oropharyngeal Pemphigus Vulgaris (OPV) triggered by the mRNABNT162b2 vaccine (Comirnaty®/ Pfizer/ BioNTech) and to analyze the clinical and immunological characteristics of the AIBDs cases reported following the SARS-CoV-2 vaccination. METHODS: The clinical and immunological features of our case of OPV were documented. A review of the literature was conducted and only cases of AIBDs arising after the SARS-CoV-2 vaccination were included. CASE REPORT: A 60-year old female patients developed oropharyngeal and nasal bullous lesions seven days after the administration of a second dose of the mRNABNT162b2 vaccine (Comirnaty®/ Pfizer/BioNtech). According to the histology and direct immunofluorescence findings showing the presence of supra-basal blister and intercellular staining of IgG antibodies and the presence of a high level of anti-Dsg-3 antibodies (80 U/ml; normal < 7 U/ml) in the serum of the patients, a diagnosis of oropharyngeal Pemphigus Vulgaris was made. REVIEW: A total of 35 AIBDs cases triggered by the SARS-CoV-2 vaccination were found (including our report). 26 (74.3%) were diagnosed as Bullous Pemphigoid, 2 (5.7%) as Linear IgA Bullous Dermatosis, 6 (17.1%) as Pemphigus Vulgaris and 1 (2.9%) as Pemphigus Foliaceus. The mean age of the sample was 72.8 years and there was a predominance of males over females (F:M=1:1.7). In 22 (62.9%) cases, the disease developed after Pfizer vaccine administration, 6 (17.1%) after Moderna, 3 (8.6%) after AstraZeneca, 3 (8.6%) after CoronaVac (one was not specified). All patients were treated with topical and/or systemic corticosteroids, with or without the addition of immunosuppressive drugs, with a good clinical response in every case. CONCLUSION: Clinicians should be aware of the potential, though rare, occurrence of AIBDs as a possible adverse event after the SARS-CoV-2 vaccination. However, notwithstanding, they should encourage their patients to obtain the vaccination in order to assist the public health systems to overcome the COVID-19 pandemic.


Subject(s)
Autoimmune Diseases , COVID-19 , Pemphigus , Aged , Blister/complications , Blister/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Female , Humans , Male , Middle Aged , Pandemics , Pemphigus/drug therapy , Pemphigus/epidemiology , SARS-CoV-2 , Vaccination
12.
Front Immunol ; 13: 832533, 2022.
Article in English | MEDLINE | ID: covidwho-1705491

ABSTRACT

Immunoproteomics has emerged as a versatile tool for analyzing the antibody repertoire in various disease contexts. Until recently, characterization of antibody molecules in biological fluids was limited to bulk serology, which identifies clinically relevant features of polyclonal antibody responses. The past decade, however, has seen the rise of mass-spectrometry-enabled proteomics methods that have allowed profiling of the antibody response at the molecular level, with the disease-specific serological repertoire elucidated in unprecedented detail. In this review, we present an up-to-date survey of insights into the disease-specific immunological repertoire by examining how quantitative proteomics-based approaches have shed light on the humoral immune response to infection and vaccination in pathogenic illnesses, the molecular basis of autoimmune disease, and the tumor-specific repertoire in cancer. We address limitations of this technology with a focus on emerging potential solutions and discuss the promise of high-resolution immunoproteomics in therapeutic discovery and novel vaccine design.


Subject(s)
Antibodies/analysis , Immunoproteins/analysis , Proteomics/methods , Animals , Autoimmune Diseases/immunology , Humans , Mass Spectrometry , Neoplasms/immunology , Vaccines/immunology
13.
Eur J Med Res ; 27(1): 23, 2022 Feb 12.
Article in English | MEDLINE | ID: covidwho-1703609

ABSTRACT

BACKGROUND: Immunocompromised (IC) patients are at higher risk of severe SARS-CoV-2 infection, morbidity, and mortality compared to the general population. They should be prioritized for primary prevention through vaccination. This study aimed to evaluate the efficacy of COVID-19 mRNA vaccines in IC patients through a systematic review and meta-analysis approach. METHOD: PubMed-MEDLINE, Scopus, and Web of Science were searched for original articles reporting the immunogenicity of two doses of mRNA COVID-19 vaccines in adult patients with IC condition between June 1, 2020 and September 1, 2021. Meta-analysis was performed using either random or fixed effect according to the heterogeneity of the studies. Subgroup analysis was performed to identify potential sources of heterogeneity. RESULTS: A total of 26 studies on 3207 IC patients and 1726 healthy individuals were included. The risk of seroconversion in IC patients was 48% lower than those in controls (RR = 0.52 [0.42, 0.65]). IC patients with autoimmune conditions were 54%, and patients with malignancy were 42% more likely to have positive seroconversion than transplant recipients (P < 0.01). Subgroup meta-analysis based on the type of malignancy, revealed significantly higher proportion of positive seroconversion in solid organ compared to hematologic malignancies (RR = 0.88 [0.85, 0.92] vs. 0.61 [0.44, 0.86], P = 0.03). Subgroup meta-analysis based on type of transplantation (kidney vs. others) showed no statistically significant between-group difference of seroconversion (P = 0.55). CONCLUSIONS: IC patients, especially transplant recipients, developed lower immunogenicity with two-dose of COVID-19 mRNA vaccines. Among patients with IC, those with autoimmune conditions and solid organ malignancies are mostly benefited from COVID-19 vaccination. Findings from this meta-analysis could aid healthcare policymakers in making decisions regarding the importance of the booster dose or more strict personal protections in the IC patients.


Subject(s)
COVID-19 Vaccines/immunology , Immunocompromised Host , Vaccines, Synthetic/immunology , /immunology , Autoimmune Diseases/immunology , COVID-19 Vaccines/therapeutic use , Case-Control Studies , Humans , Neoplasms/immunology , Organ Transplantation , Vaccines, Synthetic/therapeutic use , /therapeutic use
14.
J Immunol Res ; 2022: 1433323, 2022.
Article in English | MEDLINE | ID: covidwho-1697599

ABSTRACT

We performed a database mining on 102 transcriptomic datasets for the expressions of 29 m6A-RNA methylation (epitranscriptomic) regulators (m6A-RMRs) in 41 diseases and cancers and made significant findings: (1) a few m6A-RMRs were upregulated; and most m6A-RMRs were downregulated in sepsis, acute respiratory distress syndrome, shock, and trauma; (2) half of 29 m6A-RMRs were downregulated in atherosclerosis; (3) inflammatory bowel disease and rheumatoid arthritis modulated m6A-RMRs more than lupus and psoriasis; (4) some organ failures shared eight upregulated m6A-RMRs; end-stage renal failure (ESRF) downregulated 85% of m6A-RMRs; (5) Middle-East respiratory syndrome coronavirus infections modulated m6A-RMRs the most among viral infections; (6) proinflammatory oxPAPC modulated m6A-RMRs more than DAMP stimulation including LPS and oxLDL; (7) upregulated m6A-RMRs were more than downregulated m6A-RMRs in cancer types; five types of cancers upregulated ≥10 m6A-RMRs; (8) proinflammatory M1 macrophages upregulated seven m6A-RMRs; (9) 86% of m6A-RMRs were differentially expressed in the six clusters of CD4+Foxp3+ immunosuppressive Treg, and 8 out of 12 Treg signatures regulated m6A-RMRs; (10) immune checkpoint receptors TIM3, TIGIT, PD-L2, and CTLA4 modulated m6A-RMRs, and inhibition of CD40 upregulated m6A-RMRs; (11) cytokines and interferons modulated m6A-RMRs; (12) NF-κB and JAK/STAT pathways upregulated more than downregulated m6A-RMRs whereas TP53, PTEN, and APC did the opposite; (13) methionine-homocysteine-methyl cycle enzyme Mthfd1 downregulated more than upregulated m6A-RMRs; (14) m6A writer RBM15 and one m6A eraser FTO, H3K4 methyltransferase MLL1, and DNA methyltransferase, DNMT1, regulated m6A-RMRs; and (15) 40 out of 165 ROS regulators were modulated by m6A eraser FTO and two m6A writers METTL3 and WTAP. Our findings shed new light on the functions of upregulated m6A-RMRs in 41 diseases and cancers, nine cellular and molecular mechanisms, novel therapeutic targets for inflammatory disorders, metabolic cardiovascular diseases, autoimmune diseases, organ failures, and cancers.


Subject(s)
Atherosclerosis/genetics , Epigenesis, Genetic , Neoplasms/genetics , RNA, Messenger/metabolism , Reactive Oxygen Species/metabolism , Adenosine/analogs & derivatives , Adenosine/metabolism , Autoimmune Diseases/genetics , Datasets as Topic , Gene Expression Profiling , Humans , Inflammation/genetics , Metabolic Diseases/genetics , Methylation
15.
BMJ Case Rep ; 15(2)2022 Feb 09.
Article in English | MEDLINE | ID: covidwho-1685520

ABSTRACT

Neurological manifestations are common in SARS-CoV-2 infection, including life-threatening acute muscle weakness, due to neuromuscular disorders such as acute transverse myelitis (TM) and Guillain-Barré syndrome (GBS). These syndromes can rarely coexist and present as an overlap syndrome. Here, we report a patient who developed acute symmetrical proximal lower limb weakness 5 days after diagnosis of COVID-19. GBS was diagnosed due to the presence of motor signs, albumin-cytological dissociation in cerebrospinal fluid examination and axonal damage according to nerve condition tests. However, abnormal areas on MRI of the thoracic spine and lack of improvement with intravenous immunoglobulin supported a diagnosis of TM. Therefore, a possible overlap between GBS and TM was established. To our knowledge, this is the third case report of GBS/TM overlap syndrome after COVID-19. The patient's full and rapid recovery with intravenous corticosteroids and plasmapheresis supports our diagnosis.


Subject(s)
Autoimmune Diseases , COVID-19 , Guillain-Barre Syndrome , Myelitis, Transverse , Guillain-Barre Syndrome/diagnosis , Guillain-Barre Syndrome/drug therapy , Humans , Myelitis, Transverse/diagnosis , Myelitis, Transverse/drug therapy , Myelitis, Transverse/etiology , SARS-CoV-2
16.
Front Immunol ; 12: 734279, 2021.
Article in English | MEDLINE | ID: covidwho-1686469

ABSTRACT

Newly emerging variants of coronavirus 2 (SARS-CoV-2) raise concerns about the spread of the disease, and with the rising case numbers, the Coronavirus disease 2019 (COVID-19) remains a challenging medical emergency towards the end of the year 2021. Swiftly developed novel vaccines aid in the prevention of the spread, and it seems that a specific cure will not be at hand soon. The prognosis of COVID-19 in patients with autoimmune/autoinflammatory rheumatic diseases (AIIRD) is more severe when compared to the otherwise healthy population, and vaccination is essential. Evidence for both the efficacy and safety of COVID-19 vaccination in AIIRD under immunosuppression is accumulating, but the effect of Interleukin-1 on vaccination in general and in AIIRD patients is rarely addressed in the current literature. In light of the current literature, it seems that the level of agreement on the timing of COVID-19 vaccination is moderate in patients using IL-1 blockers, and expert opinions may vary. Generally, it may be recommended that patients under IL-1 blockade can be vaccinated without interrupting the anti-cytokine therapy, especially in patients with ongoing high disease activity to avoid disease relapses. However, in selected cases, after balancing for disease activity and risk of relapses, vaccination may be given seven days after the drug levels have returned to baseline, especially for IL-1 blocking agents with long half-lives such as canakinumab and rilonacept. This may help to ensure an ideal vaccine response in the face of the possibility that AIIRD patients may develop a more pronounced and severe COVID-19 disease course.


Subject(s)
Antirheumatic Agents/adverse effects , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Interleukin-1beta/antagonists & inhibitors , Rheumatic Diseases/drug therapy , SARS-CoV-2/immunology , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Antirheumatic Agents/therapeutic use , Autoimmune Diseases/drug therapy , Autoimmune Diseases/immunology , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Recombinant Fusion Proteins/adverse effects , Recombinant Fusion Proteins/therapeutic use , Rheumatic Diseases/immunology , Vaccination
17.
Rheumatol Int ; 42(5): 759-770, 2022 May.
Article in English | MEDLINE | ID: covidwho-1680770

ABSTRACT

Vasculitides, a form of inflammatory autoimmune disease targeting the vessels, constitute an entity with significant morbidity and mortality. Infections have long been associated with vasculitides as a result of the incident immunosuppression following treatment induction and maintenance. Several microbial pathogens have been described as etiologic factors of infections in this patient population according to the type of vessels affected. Intense research has also been recently conducted in the interplay between vasculitides and certain viral infections, namely human immunodeficiency virus and severe acute respiratory syndrome coronavirus 2. Of note, a plethora of scientific evidence is available regarding the role of infections as triggering factors for vasculitides. Among the main mechanisms implicated in this direction are the activation of B and T cells, the direct endothelial insult, the immune complex-mediated vascular injury, and the cell-mediated, type IV hypersensitivity vessel damage. Therefore, this review aims to summarize all the available evidence concerning this bidirectional interplay between infections and vasculitides.


Subject(s)
Autoimmune Diseases , COVID-19 , HIV Infections , Vasculitis , Antigen-Antibody Complex , Autoimmune Diseases/complications , COVID-19/complications , HIV Infections/complications , Humans , Vasculitis/etiology
18.
Clin Infect Dis ; 74(3): 427-436, 2022 02 11.
Article in English | MEDLINE | ID: covidwho-1684536

ABSTRACT

BACKGROUND: People with autoimmune or inflammatory conditions taking immunomodulatory/suppressive medications may have higher risk of novel coronavirus disease 2019 (COVID-19). Chronic disease care has also changed for many patients, with uncertain downstream consequences. METHODS: We included participants with autoimmune or inflammatory conditions followed by specialists at Johns Hopkins. Participants completed periodic surveys querying comorbidities, disease-modifying medications, exposures, COVID-19 testing and outcomes, social behaviors, and disruptions to healthcare. We assessed whether COVID-19 risk is higher among those on immunomodulating or suppressive agents and characterized pandemic-associated changes to care and mental health. RESULTS: In total, 265 (5.6%) developed COVID-19 over 9 months of follow-up (April-December 2020). Patient characteristics (age, race, comorbidity, medications) were associated with differences in social distancing behaviors during the pandemic. Glucocorticoid exposure was associated with higher odds of COVID-19 in models incorporating behavior and other potential confounders (odds ratio [OR]: 1.43; 95% confidence interval [CI]: 1.08, 1.89). Other medication classes were not associated with COVID-19 risk. Diabetes (OR: 1.72; 95% CI: 1.08, 2.73), cardiovascular disease (OR: 1.68; 95% CI: 1.24, 2.28), and kidney disease (OR: 1.76; 95% CI: 1.04, 2.97) were associated with higher odds of COVID-19. Of the 2156 reporting pre-pandemic utilization of infusion, mental health or rehabilitative services, 975 (45.2%) reported disruptions therein, which disproportionately affected individuals experiencing changes to employment or income. CONCLUSIONS: Glucocorticoid exposure may increase risk of COVID-19 in people with autoimmune or inflammatory conditions. Disruption to healthcare and related services was common. Those with pandemic-related reduced income may be most vulnerable to care disruptions.


Subject(s)
Autoimmune Diseases , COVID-19 , Autoimmune Diseases/epidemiology , COVID-19 Testing , Humans , Pandemics , Risk Factors , SARS-CoV-2
19.
JMIR Public Health Surveill ; 8(1): e29872, 2022 01 05.
Article in English | MEDLINE | ID: covidwho-1677621

ABSTRACT

BACKGROUND: Individuals with comorbid conditions have been disproportionately affected by COVID-19. Since regulatory trials of COVID-19 vaccines excluded those with immunocompromising conditions, few patients with cancer and autoimmune diseases were enrolled. With limited vaccine safety data available, vulnerable populations may have conflicted vaccine attitudes. OBJECTIVE: We assessed the prevalence and independent predictors of COVID-19 vaccine hesitancy and acceptance among individuals with serious comorbidities and assessed self-reported side effects among those who had been vaccinated. METHODS: We conducted a cross-sectional, 55-item, online survey, fielded January 15, 2021 through February 22, 2021, among a random sample of members of Inspire, an online health community of over 2.2 million individuals with comorbid conditions. Multivariable regression analysis was utilized to determine factors independently associated with vaccine hesitancy and acceptance. RESULTS: Of the 996,500 members of the Inspire health community invited to participate, responses were received from 21,943 individuals (2.2%). Respondents resided in 123 countries (United States: 16,277/21,943, 74.2%), had a median age range of 56-65 years, were highly educated (college or postgraduate degree: 10,198/17,298, 58.9%), and had diverse political leanings. All respondents self-reported at least one comorbidity: cancer, 27.3% (5459/19,980); autoimmune diseases, 23.2% (4946/21,294); chronic lung diseases: 35.4% (7544/21,294). COVID-19 vaccine hesitancy was identified in 18.6% (3960/21,294), with 10.3% (2190/21,294) declaring that they would not, 3.5% (742/21,294) stating that they probably would not, and 4.8% (1028/21,294) not sure whether they would agree to be vaccinated. Hesitancy was expressed by the following patients: cancer, 13.4% (731/5459); autoimmune diseases, 19.4% (962/4947); chronic lung diseases: 17.8% (1344/7544). Positive predictors of vaccine acceptance included routine influenza vaccination (odds ratio [OR] 1.53), trust in responsible vaccine development (OR 14.04), residing in the United States (OR 1.31), and never smoked (OR 1.06). Hesitancy increased with a history of prior COVID-19 (OR 0.86), conservative political leaning (OR 0.93), younger age (OR 0.83), and lower education level (OR 0.90). One-quarter (5501/21,294, 25.8%) had received at least one COVID-19 vaccine injection, and 6.5% (1390/21,294) completed a 2-dose series. Following the first injection, 69.0% (3796/5501) self-reported local reactions, and 40.0% (2200/5501) self-reported systemic reactions, which increased following the second injection to 77.0% (1070/1390) and 67.0% (931/1390), respectively. CONCLUSIONS: In this survey of individuals with serious comorbid conditions, significant vaccine hesitancy remained. Assumptions that the most vulnerable would automatically accept COVID-19 vaccination are erroneous and thus call for health care team members to initiate discussions focusing on the impact of the vaccine on an individual's underlying condition. Early self-reported side effect experiences among those who had already been vaccinated, as expressed by our population, should be reassuring and might be utilized to alleviate vaccine fears. Health care-related social media forums that rapidly disseminate accurate information about the COVID-19 vaccine may play an important role.


Subject(s)
Autoimmune Diseases , COVID-19 , Neoplasms , Aged , Autoimmune Diseases/epidemiology , COVID-19 Vaccines , Comorbidity , Cross-Sectional Studies , Humans , Internet , Middle Aged , Neoplasms/epidemiology , SARS-CoV-2 , United States
20.
Front Immunol ; 12: 838082, 2021.
Article in English | MEDLINE | ID: covidwho-1674340

ABSTRACT

Recombinant antibodies such as nanobodies are progressively demonstrating to be a valid alternative to conventional monoclonal antibodies also for clinical applications. Furthermore, they do not solely represent a substitute for monoclonal antibodies but their unique features allow expanding the applications of biotherapeutics and changes the pattern of disease treatment. Nanobodies possess the double advantage of being small and simple to engineer. This combination has promoted extremely diversified approaches to design nanobody-based constructs suitable for particular applications. Both the format geometry possibilities and the functionalization strategies have been widely explored to provide macromolecules with better efficacy with respect to single nanobodies or their combination. Nanobody multimers and nanobody-derived reagents were developed to image and contrast several cancer diseases and have shown their effectiveness in animal models. Their capacity to block more independent signaling pathways simultaneously is considered a critical advantage to avoid tumor resistance, whereas the mass of these multimeric compounds still remains significantly smaller than that of an IgG, enabling deeper penetration in solid tumors. When applied to CAR-T cell therapy, nanobodies can effectively improve the specificity by targeting multiple epitopes and consequently reduce the side effects. This represents a great potential in treating malignant lymphomas, acute myeloid leukemia, acute lymphoblastic leukemia, multiple myeloma and solid tumors. Apart from cancer treatment, multispecific drugs and imaging reagents built with nanobody blocks have demonstrated their value also for detecting and tackling neurodegenerative, autoimmune, metabolic, and infectious diseases and as antidotes for toxins. In particular, multi-paratopic nanobody-based constructs have been developed recently as drugs for passive immunization against SARS-CoV-2 with the goal of impairing variant survival due to resistance to antibodies targeting single epitopes. Given the enormous research activity in the field, it can be expected that more and more multimeric nanobody molecules will undergo late clinical trials in the next future. Systematic Review Registration.


Subject(s)
Single-Domain Antibodies/chemistry , Single-Domain Antibodies/therapeutic use , Animals , Autoimmune Diseases/immunology , Autoimmune Diseases/therapy , Communicable Diseases/immunology , Communicable Diseases/therapy , Humans , Immunomodulation , Molecular Imaging , Molecular Targeted Therapy , Neoplasms/diagnostic imaging , Neoplasms/immunology , Neoplasms/therapy , Recombinant Proteins/chemistry , Recombinant Proteins/immunology , Recombinant Proteins/therapeutic use , Single-Domain Antibodies/immunology
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