To investigate whether lung microbial composition differs between individuals with rheumatoid arthritis and pulmonary fibrosis (RA-PF) compared to those without fibrosis (RA-no-PF). We enrolled 54 RA patients (22 RA-PF, 32 RA-no-PF) from rheumatology and pulmonary clinics. PF was defined by high-resolution computed tomography (HRCT) findings. Induced sputum was analyzed using 16 S rRNA sequencing to identify the relative abundance of sputum bacteria. Taxonomic differences between groups were evaluated using three independent analytic approaches: Mann-Whitney U, DESeq2, and EdgeR, with false discovery rate correction. Logistic regression examined associations between Lautropia abundance and clinical variables. Individuals with RA-PF were older, more often male, and had a higher history of smoking than those with RA-no-PF. Alpha diversity was lower in RA-PF, while beta diversity did not differ between groups. Across the three analytic methods, Lautropia consistently showed decreased abundance in RA-PF compared to RA-no-PF. In multivariable models adjusting for age, sex, and smoking, RA-PF remained independently associated with undetectable levels of Lautropia (OR = 0.14, p = 0.023). Within RA-PF, when Lautropia was undetectable, there was no difference in pulmonary physiology but did show a trend towards more lung fibrosis. Sputum Lautropia is significantly reduced in RA-PF, and its absence may correlate with more severe fibrosis. These findings support a potential role for the lung microbiome in the pathogenesis of pulmonary fibrosis and raise the possibility that commensal taxa such as Lautropia modulate fibrotic pathways. Longitudinal and mechanistic studies are needed to determine whether Lautropia depletion precedes fibrosis and whether microbial-directed approaches represent new therapeutic avenues in RA.

Background:Current treatments for idiopathic pulmonary fibrosis (IPF) slow but do not stop/reverse disease progression. The lysophosphatidic acid (LPA) axis is identified as a therapeutic target for IPF. Objective:This study aims to assess BI 1819479, an LPA pathway inhibitor, in patients with IPF (ClinicalTrials.gov Identifier: NCT06335303). Methods:In this placebo-controlled, phase II trial, patients will be randomised (2:1:1:1) to receive one of three oral doses of BI 1819479 or placebo, stratified by nintedanib/pirfenidone use. Patients aged ≥40 years with IPF, forced vital capacity (FVC) ≥45% of predicted normal and haemoglobin-corrected diffusing capacity for carbon monoxide ≥25% of predicted normal at screening will be included. Patients with relevant airway obstruction (pre-bronchodilator forced expiratory volume in 1 s/FVC <0.7), acute IPF exacerbation ≤12 weeks prior to screening, treatment with immunosuppressive medications (other than oral corticosteroids) or prednisone >15 mg·day-1 or equivalent, will be excluded. Treatment with approved IPF treatments (nintedanib/pirfenidone) is allowed if at a stable dose for ≥12 weeks prior to trial entry. Patients will be treated until completing 52 weeks, or 24 weeks after the last patient is randomised, whichever occurs first. The primary end-point is the annual rate of FVC decline (mL·year-1) assessed up to 52 weeks; the secondary end-point is absolute change from baseline in FVC at week 24. Safety will be assessed throughout. Conclusion:This trial evaluates the efficacy, safety and dose range of BI 1819479 in patients with IPF, offering a potential additional treatment option, and will establish appropriate dosing for phase III trials.

Interstitial lung disease (ILD) is a common and morbid complication of rheumatoid arthritis. Despite its prevalence and impact on patients, there is no agreement on how to screen for rheumatoid arthritis-associated ILD, when to initiate treatment, and the optimal treatment regimen. Due to a scarcity of high-quality studies to guide strict evidence-based guidelines, a multidisciplinary group of rheumatoid arthritis-associated ILD experts was convened to discuss the current body of evidence, synthesise the evidence qualitatively, and provide clinically useful consensus statements pertaining to the risk factors for rheumatoid arthritis-associated ILD, screening for ILD in rheumatoid arthritis, and the treatment of rheumatoid arthritis-associated ILD. These statements are meant to guide clinicians caring for patients with rheumatoid arthritis at risk for ILD and those with established rheumatoid arthritis-associated ILD to facilitate a timely diagnosis, ongoing monitoring of disease progression, and initiation of treatment when appropriate.

RATIONALE:Common and rare variants that are associated with the risk of developing idiopathic pulmonary fibrosis (IPF) have been identified predominantly in European ancestry populations. OBJECTIVES:To better understand the genetic variants that contribute to IPF in individuals with Asian ancestry, we conducted a genome-wide association study of IPF in East Asian populations. METHODS:We included 1026 patients with IPF and compared them to 1723 unaffected controls of Japanese and Korean ancestry. Genome-wide association analysis was conducted in the Japanese and Korean ancestry cohorts separately and combined using meta-analysis. Restricted maximum likelihood was used to estimate the SNP-based heritability and local ancestry of chromosome 11 was inferred for each subject. MEASUREMENTS AND MAIN RESULTS:We identified loci on chromosomes 4 (FAM13A; rs7690839), 5 (TERT; rs7734992), 6 (DSP; rs2076295), and 11 (MUC5B; rs35705950) that were significantly associated with risk of IPF. Importantly, the sentinel variants in each of these loci are the same as, or in strong linkage disequilibrium with, the risk variants that have been observed in studies of European ancestry populations. In aggregate, common variants (not including the MUC5B promoter variant) account for approximately 25% of the risk of developing IPF in these East Asian ancestry cohorts. Moreover, local ancestry analysis indicates that the presence of MUC5B promoter variant in the East Asian population is not a result of admixture with European ancestry populations. CONCLUSIONS:We conclude that the IPF risk loci in East Asian populations are shared with those of European ancestry populations, although their risk allele frequencies and effect sizes differ. These findings indicate shared genetic risk factors of IPF across ancestries.

RATIONALE:Whole genome sequencing-estimated telomere length (WGS-TL) correlates with directly measured peripheral blood telomere length. However, raw WGS-TL does not account for normal age-related telomere attrition to identify patients with idiopathic pulmonary fibrosis (IPF) with pathologically short telomeres. OBJECTIVES:Determine utility of age-adjusted WGS-TL to identify adults with telomere-related qualifying variants (TRQV) and whether it associates with survival. METHODS:WGS-TL from two samples of community-dwelling adults (MESA) and cigarette smokers (COPDGene) were used to construct an age-adjusted WGS-TL nomogram (n = 9,940) using linear regression models that regressed on raw WGS-TL and adjusted for chronologic age. Using this nomogram, age-adjusted WGS-TL were generated in IPF cases from the Pulmonary Fibrosis Foundation Patient Registry (PFF-PR) (n = 825) to determine diagnostic performance characteristics for identifying TRQV and survival discrimination. MEASUREMENTS AND MAIN RESULTS:There was a higher proportion of IPF patients from the PFF-PR with abnormally short age-adjusted WGS-TL < 10th percentile (28%) compared to MESA (5%) or COPDGene (10%). Among IPF patients, age-adjusted WGS-TL < 10th percentile outperformed raw WGS-TL < 10th percentile at discriminating TRQV (area under the receiver operating curve 0.66 [95% CI 0.60-0.73] vs. 0.62 [95% CI 0.56-0.69]). At both the shorter age-adjusted and raw WGS-TL thresholds, specificity (0.74-0.99) was higher than sensitivity (0.10-0.58). Age-adjusted WGS-TL below 10th percentile was associated with shorter three-year transplant-free survival (HR 1.35, 95% CI 1.05,1.74) but did not improve survival discrimination over clinical variables alone. CONCLUSION:Age-adjusting WGS-TL enables identification of IPF patients with pathologically short telomeres, modestly improves detection of TRQV, and associates with survival.

Despite the availability of effective vaccines and a recent decrease in annual deaths, COVID-19 remains a leading cause of death. Serological studies provide insights into host immunobiology of adaptive immune response to infection, which holds promise for identifying high-risk individuals for adverse COVID-19 outcomes. We investigated correlates of anti-nucleocapsid antibody responses following SARS-CoV-2 infection in a US population-based meta-cohort of adults participating in longstanding National Institutes of Health-funded cohort studies. Anti-nucleocapsid antibodies were measured from dried blood spots collected between February 2021 and February 2023. Among 1419 Collaborative Cohort of Cohorts for COVID-19 Research participants with prior SARS-CoV-2 infection, the mean age (standard deviation) was 65.8 (12.1), 61% were women, and 42.8% self-reported membership in a race/ethnicity minority group. The proportion of participants reactive to nucleocapsid peaked at 69% by 4 months after infection and waned to only 44% ≥12 months after infection. Higher anti-nucleocapsid antibody response was associated with older age, Hispanic or American Indian Alaskan Native (vs White) race/ethnicity, lower income, lower education, former smoking, and higher anti-spike antibody levels. Asian race (vs White) and vaccination (even after infection) were associated with lower nucleocapsid reactivity. Neither vaccine manufacturer nor common cardiometabolic comorbidities were not associated with anti-nucleocapsid response. These findings inform the underlying immunobiology of adaptive immune response to infection, as well as the potential utility of anti-nucleocapsid antibody response for clinical practice and COVID-19 serosurveillance.

Importance Identifying factors associated with resilience during the COVID-19 pandemic can inform targeted interventions and resource allocation for groups disproportionately affected by systemic inequities. Objective To examine factors associated with self-reported resilience during the COVID-19 pandemic in racially and ethnically diverse, community-dwelling US adults. Design, Setting, and Participants This cross-sectional study was conducted as part of the Collaborative Cohort of Cohorts for COVID-19 Research (C4R) study, which assessed the associations of the pandemic with self-reported resilience of participants from 14 established US prospective cohorts since January 2021. This report includes participants who responded to the self-reported resilience question on C4R questionnaires. Data was initially analyzed from October 2023 to May 2024, with updated analyses performed from August 2024 to April 2025. Exposure Race and ethnicity, behavior factors, health conditions, and social determinants of health measurements accessed before and during the COVID-19 pandemic through cohort visits and C4R questionnaires. Main Outcomes and Measures Self-reported resilience was collected via 1 question (from the Brief Resilience Scale) in C4R questionnaires, “I tend to bounce back quickly after hard times.” Participants who answered agree or strongly agree were classified as resilient, and those who reported neutral, disagree, or strongly disagree were classified as not resilient. Modified Poisson regression was performed to estimate prevalence ratios (PRs) and access multivariable-adjusted associations with resilience. Results Of 31 045 participants (18 672 [60%] women; 10 746 [34.6%] aged <65 years), 1185 (3.8%) identified as American Indian, 6728 (21.7%) as Black, 293 (0.9%) as East Asian, 6311 (20.3%) as Hispanic, 565 (1.8%) as South Asian, and 15 961 (51.3%) as White; a total of 23 103 participants (74.4%) self-identified as resilient. Compared with White participants, Black and Hispanic participants had higher prevalence of self-reported resilience (adjusted PR [aPR], 1.04; 95% CI, 1.02-1.06; aPR, 1.08; 95% CI, 1.06-1.11; respectively) and American Indian and East Asian participants had lower prevalence (aPR, 0.90; 95% CI, 0.86-0.94; aPR, 0.76; 95% CI, 0.68-0.84; respectively). Higher education, being married or living as married, higher income, and overweight were also associated with higher prevalence of resilience. Being female, having diabetes, and being unemployed were associated with lower prevalence of self-reported resilience. Compared with participants with public insurance only, participants with private insurance had higher prevalence of resilience (aPR, 1.07; 95% CI, 1.03-1.10). COVID-19 vaccination and infection statuses were not significantly associated with resilience. Modification analyses showed important racial and ethnic differences in how factors such as hypertension, marital status, and insurance status were associated with resilience. Conclusions and Relevance In this cross-sectional study of 31 045 adults, self-reported resilience varied by race, ethnicity, and sociodemographic factors. These findings highlight the complex interplay of individual and social factors in shaping the perception of resilience.

BACKGROUND:Shorter leukocyte telomere length (LTL) has been reported in patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) and linked to increased disease severity and mortality in idiopathic pulmonary fibrosis, which shares similarities with RA-ILD. We aimed to evaluate the impact of short LTL on baseline respiratory disease severity, disease progression and survival in patients with RA-ILD. METHODS:Patients diagnosed with RA-ILD following multidisciplinary assessment were enrolled in a prospective French observational study. LTL was measured at enrolment using qPCR. Short LTL was defined as age-adjusted LTL <10th percentile. Lung disease progression was defined as death, lung transplantation or functional respiratory decline (absolute decrease in forced vital capacity (FVC) ≥5% predicted or diffusing capacity of the lung for carbon monoxide (D LCO) ≥10% predicted). RESULTS:Among 101 patients with RA-ILD, 46% were male, mean±sd age at enrolment was 66±10 years and 43 (43%) had short LTL. Patients with short LTL had lower FVC % predicted (82% versus 93%) and D LCO % predicted (49% versus 63%) at enrolment, and greater 12-month decline in FVC % predicted and D LCO % predicted in mixed effects models (-7.7% (95% CI -11.6- -3.8%); p<0.001 and -4.5 (95% CI -7.2- -1.8%); p=0.001, respectively), although transplant-free survival was similar over a median (interquartile range) follow-up of 3.6 (1.8-7.0) years. Lung disease progression was observed within 12 months of enrolment in 33 (33%) patients, more frequently in patients with short LTL (47% versus 22%; univariate p=0.011) and lower FVC at enrolment. Multivariate logistic regression identified lower FVC and short LTL as predictors of 12-month progression (OR 0.97 (95% CI 0.94-1.00); p=0.031 and OR 2.80 (95% CI 0.99-8.29); p=0.056, respectively). CONCLUSION:Short LTL is associated with baseline severity and 12-month progression in RA-ILD.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a complex and heterogeneous disease. Given this, we reasoned that differences in genetic profiles may be associated with unique clinical and radiologic features. Computational image analysis, sometimes referred to as radiomics, provides objective, quantitative assessments of radiologic features in subjects with pulmonary fibrosis. Objectives: To determine if the genetic risk profile of patients with IPF identifies unique computational imaging phenotypes. Methods: Participants with IPF were included in this study if they had genotype data and computed tomography (CT) scans of the chest available for computational image analysis. The extent of lung fibrosis and the likelihood of a usual interstitial pneumonia (UIP) pattern were scored automatically using two separate, previously validated deep learning techniques for CT analysis. UIP pattern was also classified visually by radiologists according to established criteria. Results: Among 329 participants with IPF, MUC5B and ZKSCAN1 were independently associated with the deep learning-based UIP score. None of the common variants were associated with fibrosis extent by computational imaging. We did not find an association between MUC5B or ZKSCAN1 and visually assessed UIP pattern. Conclusions: Select genetic variants are associated with computer-based classification of UIP on CT in this IPF cohort. Analysis of radiologic features using deep learning may enhance our ability to identify important genotype-phenotype associations in fibrotic lung diseases.

BACKGROUND:Interstitial lung disease (ILD) develops in 5-10% of patients with RA and contributes significantly to morbidity and mortality, particularly in those with a fibrotic phenotype. Yet, biomarkers to reliably identify RA patients with underlying pulmonary fibrosis are inadequate. Herein, we used sputum to identify lung-based biomarkers that distinguish RA patients with underlying pulmonary fibrosis and may better inform underlying pathogenesis in RA-ILD. METHODS:We included 37 RA patients with pulmonary fibrosis (RA-PF) and 30 RA patients without ILD (RA-no-ILD). Induced sputum and serum were tested for TGF-β levels by immunoassay. DNA was extracted to determine presence of the MUC5B ILD-risk allele ('T'). High-resolution CT (HRCT) and pulmonary function tests (PFTs) were completed within 3 months of sputum collection and quantified to determine lung disease severity. RESULTS:Sputum TGF-β was significantly elevated in individuals with RA-PF compared with RA-no-ILD (P < 0.001) and correlated with more fibrosis on HRCT (P = 0.005) and lower forced vital capacity (P = 0.006) and diffusion capacity of carbon monoxide (P = 0.044) on PFTs. Within RA-PF patients, sputum TGF-β was higher in those with the MUC5B ILD-risk genotype (GT/TT) (P = 0.038). There were no differences in serum levels of TGF-β between groups. CONCLUSION:We demonstrate that sputum levels of TGF-β are significantly elevated in individuals with RA-PF, correlate with lung disease severity, and are elevated in those with the MUC5B ILD-risk polymorphism. These findings could identify novel approaches to ILD screening in RA and potential targeted therapeutic strategies for RA-ILD.

Background: There is growing interest in identifying early stages of interstitial lung disease (ILD) to improve patient outcomes. This document reviews updated evidence on interstitial lung abnormalities (ILAs); provides suggestions for screening, evaluation, and management; proposes criteria for distinguishing ILAs from ILD; and identifies research priorities. Methods: A committee of clinical and methodology experts met by video conference to define ILAs and ILD by consensus and voted on 11 prespecified questions after reviewing synthesized evidence from a systematic literature search. Agreement of >= 70% was required to approve each suggestion. Results: ILA is defined as nondependent bilateral parenchymal abnormalities on computed tomography, including ground-glass opacities or reticulations, lung distortion, traction bronchiectasis, and/or honeycombing involving >= 5% of a lung zone. The updated definition removes the prior exclusion of high-risk populations. ILD is distinguished from ILAs by symptoms (dyspnea/cough) attributable to an interstitial process, abnormal or declining lung function, fibrotic (honeycombing and/or reticulation with traction bronchiectasis involving >= 5% of total lung volume) or progressive imaging abnormalities, and/or specific fibrotic ILD patterns on imaging or pathology. Suggestions include ILA/ILD assessment on imaging acquired for lung cancer screening, screening adults with connective tissue disease and first-degree relatives of patients with familial pulmonary fibrosis, assessing baseline symptoms and pulmonary function among those with ILAs, and monitoring ILAs with chest computed tomography every 2-3 years. Conclusions: This document presents a comprehensive literature review of ILAs with updates to the Fleischner Society ILA definition, establishes a working ILD definition, and provides evidence-based suggestions for ILA evaluation and management.

Background: Rheumatoid arthritis (RA) affects roughly 1% of the population and commonly involves the lungs. Of lung involvement in RA, interstitial lung disease (ILD) is well known; however, airways disease in RA is relatively understudied. Research Question: What are the baseline airways abnormalities in a prospective cohort of patients with RA based on pulmonary function testing (PFT) results, high-resolution CT (HRCT) scans, and computational imaging analysis and are there associations between these abnormalities and respiratory symptoms? Study Design and Methods In this single-center study, 188 patients with RA without a clinical diagnosis of ILD underwent HRCT imaging and PFT. Radiologists assessed HRCT scans for airway abnormalities. Computational imaging via VIDA Vision software and in-house quantitative CT imaging analysis was applied to 147 HRCT scans to quantify airway abnormalities. Results: Airways obstruction (FEV1 to FVC ratio < 0.7) was present in 20.7% of patients and was associated with older age, male sex, and higher smoking rate. Radiologists identified airway abnormalities in 61% of patients: 55% had bronchial wall thickening, 12% had bronchiectasis, and 5% had mosaic attenuation. These airways findings were associated with older age; male sex; lower FEV1, FVC, and FEV1 to FVC ratio; and higher rates of rheumatoid factor positivity. Prespecified quantitative CT scan metrics (wall thickening percentage and emphysema percentage) correlated with obstruction in PFT results and more severe respiratory symptoms, including shortness of breath and cough. Interpretation: High rates of airways abnormalities were found in this prospective RA cohort based on three methods of detection. Significant associations were identified between quantitative CT scan measures and respiratory symptoms. Airways disease may be an underrecognized extra-articular manifestation of RA and quantitative CT imaging may be a sensitive method to detect the clinical impact on respiratory symptoms.

BACKGROUND:Advances in the field of genetics of interstitial lung diseases (ILDs) have led to the recent consensus statements made by expert groups. International standards for genetic testing in ILD have not yet been established. We aimed to examine current real-world strategies employed by pulmonologists working with familial ILD. METHODS:A panel of pulmonologists with expertise in ILD developed an international survey aimed at clinicians working with ILD. The survey consisted of 74 questions divided into eight topics: characteristics of respondents, diagnosis, screening of first-degree relatives, screening tools, genetic testing methods, lung transplantation, ethical concerns, and future needs. RESULTS:Overall, 237 pulmonologists from 50 countries participated. A family history of ILD was asked for by 91% of respondents while fewer asked for symptoms related to telomere disorders. Respondents stated that 59% had access to genetic testing, and 30% to a genetic multidisciplinary team (MDT). Many respondents were unaware of specific genetic testing methods. Pathogenic genetic variants were seen as a potential contraindication for lung transplantation in 6-8% of respondents. Genetic screening of relatives was supported by 80% of respondents who indicated insufficient evidence and a lack of formal guidelines for genetics and ILD. Only 16% had a standardized program. CONCLUSION:Most pulmonologists ask for a family history of ILD and recommend genetic testing for ILD and screening in relatives but have limited knowledge of specific tests and access to genetic MDT. Evidence-based guidelines to inform patients, relatives, and physicians are still warranted.

BACKGROUND:Prior work suggests different interstitial lung diseases (ILDs) that share the radiological usual interstitial pneumonia (UIP) pattern have an overall worse prognosis. However, epidemiological data with longitudinal sampling and replication remains lacking. METHODS:Data was used from the Pulmonary Fibrosis Foundation Patient Registry (PFF-PR) (n=932) and a meta-cohort of ILD research studies (n=1579). Linear mixed-effects models and Cox proportional hazard models were used to determine forced vital capacity (FVC) slopes and 5-year transplant-free survival, respectively, by ILD diagnosis and UIP radiological pattern. Secondarily, we examined FVC and survival by diagnosis and radiological fibrosis quantified by data-driven texture analysis (DTA) in the PFF-PR. Models were adjusted for age, sex, smoking and antifibrotic and immunosuppression medication use. RESULTS:The proportions of idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis (FHP) and connective tissue disease (CTD)-ILD were the following for PFF-PR (70%, 11%, 19%) and meta-cohort (21%, 32%, 47%). In the PFF-PR, CTD-ILD with UIP CT pattern was associated with slower FVC decline (-34.4 mL/year) compared with IPF (-158.4 mL/year) and longer transplant-free survival (HR 0.50, 95% CI 0.29 to 0.85). This was replicated in the meta cohort for FVC (-53.1 vs -185.9 mL/year, p<0.0001) and survival (HR 0.38, 95% CI 0.27 to 0.53). A similar pattern was seen using DTA to objectively categorise patients into higher and lower radiological fibrosis. Between IPF and FHP-UIP, FVC decline was not significantly different in the PFF-PR (-203.4 vs -158.4 mL/year, p=0.58) and meta-cohort (-124.0 vs -185.9 mL/year, p=0.25). CONCLUSIONS:Even in the presence of a UIP CT pattern, there may still be differences in lung function over time and survival, particularly for CTD-ILD.

OBJECTIVES:This randomized, placebo-controlled pilot trial evaluated the efficacy and safety of abatacept in patients with anti-synthetase syndrome-associated interstitial lung disease (ASyS-ILD). METHODS:Participants with active ASyS-ILD were randomized to receive abatacept (n = 9) or placebo (n = 11) for 24 weeks, followed by a 24-week open-label extension with abatacept for all participants. The primary endpoint was a change in % predicted forced vital capacity (%FVC) from baseline to week 24. Secondary endpoints included changes in the FVC (ml), % predicted diffusing capacity of the lung for carbon monoxide (%DLCO), shortness of breath questionnaire (SOBQ) and pulmonary disease activity on a visual analogue scale (VAS) at weeks 24 and 48. Pre-post baseline analysis of FVC and quantitative image analysis (QIA) of high-resolution computed tomographic scans were performed. Data were analysed using a generalized linear mixed model. The study was not powered for primary or secondary endpoints. RESULTS:At week 24, there was no significant difference in the primary endpoint of %FVC change between abatacept and placebo (between treatment difference of -0.35, 95%CI -6.91 to 6.21, P = 0.914) and in all secondary endpoints. However, by week 48, trends favouring abatacept in %FVC, FVC (ml), %DLCO and SOBQ were observed without statistical significance. There was a significant improvement in pulmonary disease activity VAS and pre-post baseline slopes of %FVC and QIA scores in the abatacept arm. Abatacept was generally well tolerated. CONCLUSION:Abatacept did not significantly improve %FVC at 24 weeks. However, trends at 48 weeks suggest potential benefits, supporting the need for a larger, long-term randomized controlled trial. CLINICAL TRIAL REGISTRATION:clinicaltrials.gov; NCT03215927.

Background: Despite the availability of effective vaccines and a recent decrease in annual deaths, coronavirus disease-2019 (COVID-19) remains a leading cause of death. Serological studies of anti-nucleocapsid (N) antibody response to infection provide insights into host immunobiology of adaptive immune response, which holds promise for identifying high-risk individuals for adverse acute and chronic COVID-19 outcomes. Hypothesis: Among participants previously infected with SARS-CoV-2, traditional vascular disease risk factors are associated with higher anti-N antibodies while vaccination is associated with lower anti-N antibodies. Methods: Among previously infected participants, anti-N antibodies were measured from dried blood spots collected between February 2021-February 2023 among 1,419 Collaborative Cohort of Cohorts for COVID-19 Research (C4R) participants with prior SARS-CoV-2 infection. We measured anti-N IgG antibodies reported as median fluorescence intensity (MFI) units; reactivity (i.e., seropositivity) was defined based on MFI above a validated threshold. Vascular disease risk factors were assessed via pre-pandemic in-person examination, questionnaires, and medical record review. Multivariable generalized linear models regressed anti-N reactivity (modified Poisson) or LN transformed MFI (linear). Results: Among 1,419 participants with prior infection, mean age (standard deviation) was 65.8(12.1) years, 61% were women, and 42.8% were self-reported from a race/ethnicity minority group. Participant reactivity to nucleocapsid peaked at 69% by 4 months post-infection and waned to only 44% ≥12 months after infection. After multivariable adjustment, higher anti-N antibody response was associated with older age, Hispanic (vs. White) or American Indian (vs. White) race/ethnicity, lower income and education, former smoking, and higher anti-spike antibody levels. Asian race (vs. White) and vaccination ( even after infection ) were associated with lower nucleocapsid reactivity; common cardiometabolic co-morbidities were not associated with anti-N reactivity or levels (Figures 1 and 2). Conclusions: Among participants previously infected with SARS-CoV-2, select sociodemographic and behavioral risk factors were associated with higher anti-N antibody levels while vaccination was associated with lower anti-N antibody levels. The observation that vaccination, even after infection, is related to lower anti-N antibody levels merits further investigation.

Abstract:Cryptogenic organizing pneumonia (COP), formerly called bronchiolitis obliterans organizing pneumonia (BOOP), was first described in the 1980s and is classified as a rare idiopathic interstitial pneumonia (IIP). COP classically presents in a subacute fashion following a flu-like illness with fever, non-productive cough, and fatigue. Imaging often reveals diffuse, bilateral, peribronchovascular and peripheral, consolidative and ground-glass opacities although various imaging subtypes also exist. Physical examination may be normal or reveal inspiratory crackles. Hypoxemia, when present, is commonly identified with exertion but can also occur at rest. Diagnostic evaluation relies on excluding secondary causes of organizing pneumonia and includes a thorough history including medications, exposures, and signs or symptoms of underlying rheumatologic disease. Invasive diagnostic testing including tissue sampling allows for histopathologic confirmation of COP while excluding secondary causes including infection and malignancy. Although video-assisted thoracoscopic surgery (VATS) lung biopsy is often the preferred method of obtaining sufficient tissue, less invasive means may be employed based on patient-specific factors. A defining feature of COP is steroid-responsiveness, and most experts recommend prolonged corticosteroid courses (6-12 months). Response to corticosteroids and prognosis are typically excellent. Relapse rates range from 25 to 50% and occur most often during steroid taper or complete withdrawal necessitating additional therapy. Steroid-sparing immunosuppression may be used in select circumstances. Further study is needed to define optimal corticosteroid dose and duration.