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1.
Arch Dermatol Res ; 314(9): 897-902, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2277566

ABSTRACT

Little is known about the relationship of COVID-19 outcomes with onychomycosis. We investigated the relationship of onychomycosis with COVID-19 outcomes. A retrospective cohort study was performed on SARS-CoV-2 positive adult outpatients or inpatients who had onychomycosis and other skin diseases. Overall, 430 adults were identified with SARS-CoV-2 and a skin disease, including 98 with diagnosed onychomycosis. In bivariable logistic regression models, onychomycosis was associated with increased hospitalization {odds ratio(OR) [95% confidence interval (CI)]: 3.56 [2.18-5.80]}, initial inpatient vs. outpatient visits (OR [95% CI]: 2.24 [1.35-3.74]), use of oxygen therapy (OR [95% CI]: 2.77 [1.60-4.79]), severe-critical vs. asymptomatic-mild severity (OR [95% CI]: 2.28 [1.32-3.94]), and death (OR [95% CI]: 7.48 [1.83-30.47]) from COVID-19, but not prolonged hospitalization (OR [95% CI]: 1.03 [0.47-2.25]). In multivariable models adjusting for socio-demographics, comorbidities, and immunosuppressant medication use, the associations with onychomycosis remained significant for hospitalization, inpatient visits, oxygen therapy, severe-critical COVID-19. Onychomycosis was a significant independent risk factor for COVID-19 severity, hospitalization, and receiving supplemental oxygen therapy.


Subject(s)
COVID-19 , Onychomycosis , Adult , COVID-19/epidemiology , COVID-19/therapy , Humans , Immunosuppressive Agents , Onychomycosis/epidemiology , Onychomycosis/therapy , Oxygen/therapeutic use , Retrospective Studies , SARS-CoV-2
2.
Diagnostics (Basel) ; 13(4)2023 Feb 12.
Article in English | MEDLINE | ID: covidwho-2232293

ABSTRACT

BACKGROUND: COVID-19 is a heterogenous disease resulting in long-term sequela in predisposed individuals. It is not uncommon that recovering patients endure non-respiratory ill-defined manifestations, including anosmia, and neurological and cognitive deficit persisting beyond recovery-a constellation of conditions that are grouped under the umbrella of long-term COVID-19 syndrome. Association between COVID-19 and autoimmune responses in predisposed individuals was shown in several studies. AIM AND METHODS: To investigate autoimmune responses against neuronal and CNS autoantigens in SARS-CoV-2-infected patients, we performed a cross-sectional study with 246 participants, including 169 COVID-19 patients and 77 controls. Levels of antibodies against the acetylcholine receptor, glutamate receptor, amyloid ß peptide, alpha-synucleins, dopamine 1 receptor, dopamine 2 receptor, tau protein, GAD-65, N-methyl D-aspartate (NMDA) receptor, BDNF, cerebellar, ganglioside, myelin basic protein, myelin oligodendrocyte glycoprotein, S100-B, glial fibrillary acidic protein, and enteric nerve were measured using an Enzyme-Linked Immunosorbent Assay (ELISA). Circulating levels of autoantibodies were compared between healthy controls and COVID-19 patients and then classified by disease severity (mild [n = 74], severe [n = 65], and requiring supplemental oxygen [n = 32]). RESULTS: COVID-19 patients were found to have dysregulated autoantibody levels correlating with the disease severity, e.g., IgG to dopamine 1 receptor, NMDA receptors, brain-derived neurotrophic factor, and myelin oligodendrocyte glycoprotein. Elevated levels of IgA autoantibodies against amyloid ß peptide, acetylcholine receptor, dopamine 2 receptor, myelin basic protein, and α-synuclein were detected in COVID-19 patients compared with healthy controls. Lower IgA autoantibody levels against NMDA receptors, and IgG autoantibodies against glutamic acid decarboxylase 65, amyloid ß peptide, tau protein, enteric nerve, and S100-B were detected in COVID-19 patients versus healthy controls. Some of these antibodies have known clinical correlations with symptoms commonly reported in the long COVID-19 syndrome. CONCLUSIONS: Overall, our study shows a widespread dysregulation in the titer of various autoantibodies against neuronal and CNS-related autoantigens in convalescent COVID-19 patients. Further research is needed to provide insight into the association between these neuronal autoantibodies and the enigmatic neurological and psychological symptoms reported in COVID-19 patients.

3.
J Med Virol ; 95(2): e28538, 2023 02.
Article in English | MEDLINE | ID: covidwho-2219761

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with increased levels of autoantibodies targeting immunological proteins such as cytokines and chemokines. Reports further indicate that COVID-19 patients may develop a broad spectrum of autoimmune diseases due to reasons not fully understood. Even so, the landscape of autoantibodies induced by SARS-CoV-2 infection remains uncharted territory. To gain more insight, we carried out a comprehensive assessment of autoantibodies known to be linked to diverse autoimmune diseases observed in COVID-19 patients in a cohort of 231 individuals, of which 161 were COVID-19 patients (72 with mild, 61 moderate, and 28 with severe disease) and 70 were healthy controls. Dysregulated IgG and IgA autoantibody signatures, characterized mainly by elevated concentrations, occurred predominantly in patients with moderate or severe COVID-19 infection. Autoantibody levels often accompanied anti-SARS-CoV-2 antibody concentrations while stratifying COVID-19 severity as indicated by random forest and principal component analyses. Furthermore, while young versus elderly COVID-19 patients showed only slight differences in autoantibody levels, elderly patients with severe disease presented higher IgG autoantibody concentrations than young individuals with severe COVID-19. This work maps the intersection of COVID-19 and autoimmunity by demonstrating the dysregulation of multiple autoantibodies triggered during SARS-CoV-2 infection. Thus, this cross-sectional study suggests that SARS-CoV-2 infection induces autoantibody signatures associated with COVID-19 severity and several autoantibodies that can be used as biomarkers of COVID-19 severity, indicating autoantibodies as potential therapeutical targets for these patients.


Subject(s)
Autoimmune Diseases , COVID-19 , Aged , Humans , Autoantibodies , Cross-Sectional Studies , SARS-CoV-2 , Immunoglobulin G
5.
Nat Biomed Eng ; 6(8): 992-1003, 2022 08.
Article in English | MEDLINE | ID: covidwho-2000897

ABSTRACT

Pathogenic autoreactive antibodies that may be associated with life-threatening coronavirus disease 2019 (COVID-19) remain to be identified. Here, we show that self-assembled genome-scale libraries of full-length proteins covalently coupled to unique DNA barcodes for analysis by sequencing can be used for the unbiased identification of autoreactive antibodies in plasma samples. By screening 11,076 DNA-barcoded proteins expressed from a sequence-verified human ORFeome library, the method, which we named MIPSA (for Molecular Indexing of Proteins by Self-Assembly), allowed us to detect circulating neutralizing type-I and type-III interferon (IFN) autoantibodies in five plasma samples from 55 patients with life-threatening COVID-19. In addition to identifying neutralizing type-I IFN-α and IFN-ω autoantibodies and other previously known autoreactive antibodies in patient plasma, MIPSA enabled the detection of as yet unidentified neutralizing type-III anti-IFN-λ3 autoantibodies that were not seen in healthy plasma samples or in convalescent plasma from ten non-hospitalized individuals with COVID-19. The low cost and simple workflow of MIPSA will facilitate unbiased high-throughput analyses of protein-antibody, protein-protein and protein-small-molecule interactions.


Subject(s)
Autoantibodies , COVID-19 , COVID-19/therapy , Gene Library , Humans , Immunization, Passive , Interferon-alpha , COVID-19 Serotherapy
6.
PLoS One ; 17(8): e0271310, 2022.
Article in English | MEDLINE | ID: covidwho-1974317

ABSTRACT

BACKGROUND: COVID-19 can cause some individuals to experience chronic symptoms. Rates and predictors of chronic COVID-19 symptoms are not fully elucidated. OBJECTIVE: To examine occurrence and patterns of post-acute sequelae of SARS-CoV2 infection (PASC) symptomatology and their relationship with demographics, acute COVID-19 symptoms and anti-SARS-CoV-2 IgG antibody responses. METHODS: A multi-stage observational study was performed of adults (≥18 years) from 5 US states. Participants completed two rounds of electronic surveys (May-July 2020; April-May 2021) and underwent testing to anti-SARS-CoV-2 nucleocapsid protein IgG antibody testing. Latent Class Analysis was used to identify clusters of chronic COVID-19 symptoms. RESULTS: Overall, 390 adults (median [25%ile, 75%ile] age: 42 [31, 54] years) with positive SARS-CoV-2 antibodies completed the follow-up survey; 92 (24.7%) had ≥1 chronic COVID-19 symptom, with 11-month median duration of persistent symptoms (range: 1-12 months). The most common chronic COVID-19 symptoms were fatigue (11.3%), change in smell (9.5%) or taste (5.6%), muscle or joint aches (5.4%) and weakness (4.6%). There were significantly higher proportions of ≥1 persistent COVID-19 symptom (31.5% vs. 18.6%; Chi-square, P = 0.004), and particularly fatigue (15.8% vs. 7.3%, P = 0.008) and headaches (5.4% vs. 1.0%, P = 0.011) in females compared to males. Chronic COVID-19 symptoms were also increased in individuals with ≥6 acute COVID-19 symptoms, Latent class analysis revealed 4 classes of symptoms. Latent class-1 (change of smell and taste) was associated with lower anti-SARS-CoV-2 antibody levels; class-2 and 3 (multiple chronic symptoms) were associated with higher anti-SARS-CoV-2 antibody levels and more severe acute COVID-19 infection. LIMITATIONS: Ambulatory cohort with less severe acute disease. CONCLUSION: Individuals with SARS-CoV-2 infection commonly experience chronic symptoms, most commonly fatigue, changes in smell or taste and muscle/joint aches. Female sex, severity of acute COVID-19 infection, and higher anti-SARS-CoV-2 IgG levels were associated with the highest risk of having chronic COVID-19 symptoms.


Subject(s)
COVID-19 , Adult , Antibodies, Viral , Fatigue , Female , Humans , Immunoglobulin G , Male , Pain , RNA, Viral , SARS-CoV-2
7.
Nat Commun ; 13(1): 1220, 2022 03 09.
Article in English | MEDLINE | ID: covidwho-1735246

ABSTRACT

COVID-19 shares the feature of autoantibody production with systemic autoimmune diseases. In order to understand the role of these immune globulins in the pathogenesis of the disease, it is important to explore the autoantibody spectra. Here we show, by a cross-sectional study of 246 individuals, that autoantibodies targeting G protein-coupled receptors (GPCR) and RAS-related molecules associate with the clinical severity of COVID-19. Patients with moderate and severe disease are characterized by higher autoantibody levels than healthy controls and those with mild COVID-19 disease. Among the anti-GPCR autoantibodies, machine learning classification identifies the chemokine receptor CXCR3 and the RAS-related molecule AGTR1 as targets for antibodies with the strongest association to disease severity. Besides antibody levels, autoantibody network signatures are also changing in patients with intermediate or high disease severity. Although our current and previous studies identify anti-GPCR antibodies as natural components of human biology, their production is deregulated in COVID-19 and their level and pattern alterations might predict COVID-19 disease severity.


Subject(s)
Autoantibodies/immunology , COVID-19/immunology , Receptors, G-Protein-Coupled/immunology , Renin-Angiotensin System/immunology , Autoantibodies/blood , Autoimmunity , Biomarkers/blood , COVID-19/blood , COVID-19/classification , Cross-Sectional Studies , Female , Humans , Machine Learning , Male , Multivariate Analysis , Receptor, Angiotensin, Type 1/immunology , Receptors, CXCR3/immunology , SARS-CoV-2 , Severity of Illness Index
8.
J Allergy Clin Immunol Pract ; 9(9): 3331-3338.e2, 2021 09.
Article in English | MEDLINE | ID: covidwho-1693328

ABSTRACT

BACKGROUND: The complex relationship between clinical manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and individual immune responses is not fully elucidated. OBJECTIVE: To examine phenotypes of symptomatology and their relationship with positive anti-SARS-CoV-2 IgG antibody responses. METHODS: An observational study was performed of adults (≥18 years) from 5 US states. Participants completed an electronic survey and underwent testing to anti-SARS-CoV-2 nucleocapsid protein IgG antibody between May and July 2020. Latent class analysis was used to identify characteristic symptom clusters. RESULTS: Overall, 9507 adults (mean age, 39.6 ± 15.0 years) completed the survey; 6665 (70.1%) underwent antibody testing for anti-SARS-CoV-2 IgG. Positive SARS-CoV-2 antibodies were associated with self-reported positive SARS-CoV-2 nasal swab result (bivariable logistic regression; odds ratio [95% CI], 5.98 [4.83-7.41]), household with 6 or more members (1.27 [1.14-1.41]) and sick contact (3.65 [3.19-4.17]), and older age (50-69 years: 1.55 [1.37-1.76]; ≥70 years: 1.52 [1.16-1.99]), but inversely associated with female sex (0.61 [0.55-0.68]). Latent class analysis revealed 8 latent classes of symptoms. Latent classes 1 (all symptoms) and 4 (fever, cough, muscle ache, anosmia, dysgeusia, and headache) were associated with the highest proportion (62.0% and 57.4%) of positive antibodies, whereas classes 6 (fever, cough, muscle ache, headache) and 8 (anosmia, dysgeusia) had intermediate proportions (48.2% and 40.5%), and classes 3 (headache, diarrhea, stomach pain) and 7 (no symptoms) had the lowest proportion (7.8% and 8.5%) of positive antibodies. CONCLUSIONS: SARS-CoV-2 infections manifest with substantial diversity of symptoms, which are associated with variable anti-SARS-CoV-2 IgG antibody responses. Prolonged fever, anosmia, and receiving supplemental oxygen therapy had strongest associations with positive SARS-CoV-2 IgG.


Subject(s)
COVID-19 , Adult , Aged , Antibodies, Viral , Cross-Sectional Studies , Female , Humans , Immunoglobulin G , Middle Aged , SARS-CoV-2
10.
Arch Dermatol Res ; 314(10): 999-1002, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1415028

ABSTRACT

Atopic dermatitis is characterized by immune dysregulation, which may predispose toward worse COVID-19 outcomes. We conducted a retrospective cohort study to investigate the relationship of atopic dermatitis with COVID-19 symptom severity, hospitalization, length of hospital stay, requirement for oxygen therapy, long-term morbidity and mortality. Multivariable logistic regression models were constructed to examine the impact of atopic dermatitis (independent variable) on COVID-19 symptom severity, hospitalization, length of hospital stay, requirement for oxygen therapy, long-term morbidity and mortality (dependent variables). SARS-CoV-2 positive adult patients with diagnosed AD had similar odds of hospitalization (adjusted odds ratio [95% confidence interval]: 0.51 [0.20-1.35]), acute level of care at initial medical care (0.67 [0.35-1.30]), severe-critical SARS-CoV-2 (0.82 [0.29-2.30]), requirement of supplemental non-mechanical oxygen therapy (1.33 [0.50-3.58]), extended hospital stay (2.24 [0.36-13.85]), lingering COVID-19 symptoms (0.58 [0.06-5.31]) and COVID-19 death (0.002 [< 0.001- > 999]) compared to patients without AD. Our findings suggest AD is not an independent risk factor for COVID-19 severity or complications.


Subject(s)
COVID-19 , Dermatitis, Atopic , Adult , COVID-19/epidemiology , COVID-19/therapy , Dermatitis, Atopic/epidemiology , Dermatitis, Atopic/therapy , Humans , Oxygen , Retrospective Studies , SARS-CoV-2
11.
Am J Clin Dermatol ; 22(5): 693-707, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1361347

ABSTRACT

BACKGROUND: Pivotal phase III studies demonstrated that abrocitinib, an oral, once-daily, JAK1-selective inhibitor, is effective treatment for moderate-to-severe atopic dermatitis (AD) as monotherapy and in combination with topical therapy. OBJECTIVE: The aim of this study was to evaluate the long-term safety of abrocitinib 200 mg and 100 mg in an integrated analysis of a phase IIb study, four phase III studies, and one long-term extension study. METHODS: Two cohorts were analyzed: a placebo-controlled cohort from 12- to 16-week studies and an all-abrocitinib cohort including patients who received one or more abrocitinib doses. Adverse events (AEs) of interest and laboratory data are reported. RESULTS: Total exposure in the all-abrocitinib cohort (n = 2856) was 1614 patient-years (PY); exposure was ≥ 24 weeks in 1248 patients and ≥ 48 weeks in 606 (maximum 108 weeks). In the placebo-controlled cohort (n = 1540), dose-related AEs (200 mg, 100 mg, placebo) were nausea (14.6%, 6.1%, 2.0%), headache (7.8%, 5.9%, 3.5%), and acne (4.7%, 1.6%, 0%). Platelet count was reduced transiently in a dose-dependent manner; 2/2718 patients (200-mg group) had confirmed platelet counts of < 50 × 103/mm3 at week 4. Incidence rates (IRs) were 2.33/100PY and 2.65/100 PY for serious infection, 4.34/100PY and 2.04/100PY for herpes zoster, and 11.83/100PY and 8.73/100PY for herpes simplex in the 200-mg and 100-mg groups, respectively. IRs for nonmelanoma skin cancer, other malignancies, and major adverse cardiovascular events were < 0.5/100PY for both doses. Five venous thromboembolism events occurred (IR 0.30/100PY), all in the 200-mg group. There were three deaths due to gastric carcinoma (diagnosed at day 43), sudden death, and COVID-19. CONCLUSION: Abrocitinib, with proper patient and dose selection, has a manageable tolerability and longer-term safety profile appropriate for long-term use in patients with moderate-to-severe AD. TRIAL REGISTRIES: ClinicalTrials.gov: NCT02780167, NCT03349060, NCT03575871, NCT03720470, NCT03627767, NCT03422822.


Subject(s)
Dermatitis, Atopic/drug therapy , Infections/epidemiology , Protein Kinase Inhibitors/adverse effects , Pyrimidines/adverse effects , Skin Neoplasms/epidemiology , Sulfonamides/adverse effects , Acne Vulgaris/chemically induced , Adolescent , Adult , Aged , Cardiovascular Diseases/epidemiology , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Female , Headache/chemically induced , Herpes Simplex/epidemiology , Herpes Zoster/epidemiology , Humans , Incidence , Lymphocyte Count , Male , Middle Aged , Nausea/chemically induced , Platelet Count , Protein Kinase Inhibitors/administration & dosage , Pyrimidines/administration & dosage , Risk Factors , Sulfonamides/administration & dosage , Time Factors , Venous Thromboembolism/epidemiology , Young Adult
12.
J Allergy Clin Immunol ; 149(3): 977-987.e14, 2022 03.
Article in English | MEDLINE | ID: covidwho-1356276

ABSTRACT

BACKGROUND: Primary (week 16) results from the ongoing phase 3, double-blind AD Up study (NCT03568318) demonstrate a positive benefit-risk profile for upadacitinib + topical corticosteroid (TCS) in patients with moderate-to-severe atopic dermatitis. OBJECTIVE: We evaluated the efficacy and safety of upadacitinib + TCS through 52 weeks. METHODS: Patients aged 12 to 75 years with chronic moderate-to-severe atopic dermatitis (≥10% of body surface area affected, Eczema Area and Severity Index [EASI] ≥16, Validated Investigator's Global Assessment for atopic dermatitis [vIGA-AD] ≥3, and Worst Pruritus Numerical Rating Scale [WP-NRS] score ≥4) were randomized 1:1:1 to once-daily upadacitinib 15 mg + TCS, upadacitinib 30 mg + TCS, or placebo (PBO) + TCS (rerandomized at week 16 to upadacitinib + TCS). Safety and efficacy, including proportion of patients experiencing ≥75% improvement in EASI (EASI-75), vIGA-AD of clear/almost clear with improvement ≥2 grades (vIGA-AD 0/1), and WP-NRS improvement ≥4, were assessed through week 52. Missing data were primarily handled by nonresponse imputation incorporating multiple imputation for missing values due to coronavirus disease 2019 (COVID-19). RESULTS: Of 901 patients, 300 were randomized to upadacitinib 15 mg + TCS, 297 to upadacitinib 30 mg + TCS, and 304 to PBO + TCS. For all end points, efficacy for upadacitinib 15 mg + TCS and upadacitinib 30 mg + TCS at week 16 was maintained through week 52. At week 52, the proportions of patients treated with upadacitinib 15 mg + TCS and upadacitinib 30 mg + TCS who experienced EASI-75 were 50.8% and 69.0%, respectively; 33.5% and 45.2%, respectively, experienced vIGA-AD 0/1; and 45.3% and 57.5%, respectively, experienced WP-NRS improvement ≥4. Upadacitinib + TCS was well tolerated through 52 weeks; no new important safety risks beyond the current label were observed. No deaths were reported; major adverse cardiovascular events and venous thromboembolic events were infrequent (≤0.2/100 patient-years). CONCLUSIONS: Results through 52 weeks demonstrate long-term maintenance of efficacy and a favorable safety profile of upadacitinib + TCS in patients with moderate-to-severe AD.


Subject(s)
Adrenal Cortex Hormones/administration & dosage , Dermatitis, Atopic/drug therapy , Dermatologic Agents/administration & dosage , Heterocyclic Compounds, 3-Ring/administration & dosage , Administration, Topical , Adolescent , Adrenal Cortex Hormones/adverse effects , Adult , Aged , Child , Dermatitis, Atopic/pathology , Dermatologic Agents/adverse effects , Double-Blind Method , Drug Therapy, Combination , Female , Heterocyclic Compounds, 3-Ring/adverse effects , Humans , Male , Middle Aged , Severity of Illness Index , Treatment Outcome , Young Adult
13.
Hum Vaccin Immunother ; 17(11): 4013-4014, 2021 Nov 02.
Article in English | MEDLINE | ID: covidwho-1303869

ABSTRACT

The Coronavirus disease-2019 (COVID-19) pandemic led to the development of several candidate vaccines. However, current research suggests that the potential of successful vaccines is tempered by vaccine skepticism or hesitancy. If vaccine efficacy is 80%, then the herd immunity required from vaccination is about 75-90%. The aim of the current study was to study factors impacting COVID-19 vaccine hesitancy in a representative sample of adults (age≥18 years) in a COVID-19 hotspotAbbreviations: COVID-19: coronavirus disease-19.


Subject(s)
COVID-19 , Adolescent , Adult , COVID-19 Vaccines , Cross-Sectional Studies , Humans , New York , SARS-CoV-2 , Vaccination , Vaccination Hesitancy , Vaccine Efficacy
14.
JAMA Netw Open ; 4(3): e212816, 2021 03 01.
Article in English | MEDLINE | ID: covidwho-1125118

ABSTRACT

Importance: Data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in the United States are still emerging. Objective: To elucidate SARS-CoV-2 seroprevalence and symptom onset in a culturally linked community across 5 states in the United States. Design, Setting, and Participants: This cross-sectional study included adults (aged ≥18 years) recruited from the orthodox Jewish community across 5 states (California, Connecticut, Michigan, New Jersey, and New York) in 3 geographically distinct areas of the United States between May 13 and July 6, 2020. Participants completed an online survey and underwent SARS-CoV-2 antibody testing. Main Outcomes and Measures: Seroprevalence and date of symptom onset of SARS-CoV-2. Results: Overall, 9507 adults (mean [SD] age, 39.6 [15.0] years; 3777 [39.7%] women) completed the SARS-CoV-2 survey, of whom 6665 (70.1%) had immunoglobin G anti-SARS-CoV-2 antibody levels assessed. A high seroprevalence of SARS-CoV-2 antibodies was observed across all communities, with the highest proportion of positive testing observed in New Jersey (1080 of 3323 [32.5%]) and New York (671 of 2196 [30.6%]). Most individuals with a positive SARS-CoV-2 immunoglobin G antibody test reported a date of symptom-onset between March 9 and March 31, 2020 (California: 135 of 154 [87.7%]; Connecticut: 32 of 34 [94.1%]; Michigan: 44 of 50 [88.0%]; New Jersey: 964 of 1168 [82.5%]; New York: 571 of 677 [84.3%]). This start date was coincident with the Jewish festival of Purim, celebrated March 9 to 10, 2020, with extensive intracommunity spread in the weeks following (mean and mode of peak symptom onset, March 20, 2020), occurring in the absence of strong general and culture-specific public health directives. Conclusions and Relevance: This cross-sectional study of orthodox Jewish adults across the US found that socioculturally bound communities experienced early parallel outbreaks in discrete locations, notably prior to substantive medical and governmental directives. Further research should clarify optimal national, local, community-based, and government policies to prevent outbreaks in social and cultural communities that traditionally gather for holidays, assemblies, and festivals.


Subject(s)
COVID-19/epidemiology , Culturally Competent Care , Disease Transmission, Infectious , Holidays , Jews/statistics & numerical data , Minority Groups , Public Health , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/transmission , COVID-19 Serological Testing , California/epidemiology , Connecticut/epidemiology , Cross-Sectional Studies , Disease Outbreaks , Female , Humans , Judaism , Male , Michigan/epidemiology , Middle Aged , New Jersey/epidemiology , New York/epidemiology , Residence Characteristics , SARS-CoV-2 , Seroepidemiologic Studies , United States/epidemiology , Young Adult
15.
JAMA Dermatol ; 156(12): 1333-1343, 2020 12 01.
Article in English | MEDLINE | ID: covidwho-1008230

ABSTRACT

Importance: Baricitinib, an oral selective Janus kinase 1 and 2 inhibitor, effectively reduced disease severity in moderate to severe atopic dermatitis (AD) in 2 phase 3 monotherapy studies. Objective: To assess the efficacy and safety of 4 mg and 2 mg of baricitinib in combination with background topical corticosteroid (TCS) therapy in adults with moderate to severe AD who previously had an inadequate response to TCS therapy. Design, Setting, and Participants: This double-blind, placebo-controlled, phase 3 randomized clinical trial, BREEZE-AD7 (Study of Baricitinib [LY3009104] in Combination With Topical Corticosteroids in Adults With Moderate to Severe Atopic Dermatitis) was conducted from November 16, 2018, to August 22, 2019, at 68 centers across 10 countries in Asia, Australia, Europe, and South America. Patients 18 years or older with moderate to severe AD and an inadequate response to TCSs were included. After completing the study, patients were followed up for up to 4 weeks or enrolled in a long-term extension study. Interventions: Patients were randomly assigned (1:1:1) to receive 2 mg of baricitinib once daily (n = 109), 4 mg of baricitinib once daily (n = 111), or placebo (n = 109) for 16 weeks. The use of low-to-moderate potency TCSs was allowed. Main Outcomes and Measures: The primary end point was the proportion of patients achieving a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0 (clear) or 1 (almost clear), with a 2-point or greater improvement from baseline at week 16. Results: Among 329 patients (mean [SD] age, 33.8 [12.4] years; 216 [66%] male), at week 16, a vIGA-AD score of 0 (clear) or 1 (almost clear) was achieved by 34 patients (31%) receiving 4 mg of baricitinib and 26 (24%) receiving 2 mg of baricitinib compared with 16 (15%) receiving placebo (odds ratio vs placebo, 2.8 [95% CI, 1.4-5.6]; P = .004 for the 4-mg group; 1.9 [95% CI, 0.9-3.9]; P = .08 for the 2-mg group). Treatment-emergent adverse events were reported in 64 of 111 patients (58%) in the 4-mg group, 61 of 109 patients (56%) in the 2-mg group, and 41 of 108 patients (38%) in the placebo group. Serious adverse events were reported in 4 patients (4%) in the 4-mg group, 2 (2%) in the 2-mg group, and 4 (4%) in the placebo group. The most common adverse events were nasopharyngitis, upper respiratory tract infections, and folliculitis. Conclusions and Relevance: A dose of 4 mg of baricitinib in combination with background TCS therapy significantly improved the signs and symptoms of moderate to severe AD, with a safety profile consistent with previous studies of baricitinib in AD. Trial Registration: ClinicalTrials.gov Identifier: NCT03733301.


Subject(s)
Azetidines/administration & dosage , Dermatitis, Atopic/drug therapy , Glucocorticoids/administration & dosage , Purines/administration & dosage , Pyrazoles/administration & dosage , Sulfonamides/administration & dosage , Administration, Cutaneous , Administration, Oral , Adult , Azetidines/adverse effects , Dermatitis, Atopic/diagnosis , Dermatitis, Atopic/immunology , Dose-Response Relationship, Drug , Double-Blind Method , Drug Administration Schedule , Drug Therapy, Combination/adverse effects , Drug Therapy, Combination/methods , Female , Folliculitis/chemically induced , Folliculitis/epidemiology , Folliculitis/immunology , Glucocorticoids/adverse effects , Humans , Janus Kinase 1/antagonists & inhibitors , Janus Kinase 1/metabolism , Janus Kinase 2/antagonists & inhibitors , Janus Kinase 2/metabolism , Male , Middle Aged , Nasopharyngitis/chemically induced , Nasopharyngitis/epidemiology , Nasopharyngitis/immunology , Purines/adverse effects , Pyrazoles/adverse effects , Respiratory Tract Infections/chemically induced , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/immunology , Severity of Illness Index , Signal Transduction/drug effects , Signal Transduction/immunology , Sulfonamides/adverse effects , Young Adult
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