Comprehensive genomic analysis, including whole-genome sequencing (WGS), enables iterative data reanalysis, potentially improving diagnostic yield as new gene–disease associations and analytical methods emerge. Although reanalysis has been shown to increase diagnostic yield across disease groups, uncertainty remains regarding its optimal timing and overall impact. We systematically reprocessed and reanalyzed WGS data from a heterogeneous clinical cohort collected over five years to evaluate the effect of reanalysis on diagnostic yield. Clinical WGS cases (~3000) analyzed at the Department of Genomic Medicine, Copenhagen University Hospital, were reviewed. Cases without a causative variant underwent reanalysis. The cohort included singletons and families across major disease groups, including cancer, neurodevelopmental, hematological, immunological, and endocrine disorders. Samples were reprocessed using the latest in-house germline WGS pipeline, including structural variant analysis, and reinterpreted using updated gene panels and latest disease knowledge. Baseline diagnostic yield was 15% in singletons (n = 2209) and 30% in family probands (n = 245). Reanalysis increased yield to 19% and 36%, respectively. Of 1551 curated variants, 79 were clinically reportable, predominantly identified through expanded in silico gene panels. Reanalysis increased overall diagnostic yield from 17% to 21% (22–26% excluding sporadic cancers), with greatest benefit from broad gene panels and semi-automated workflows.

A novel heterozygous missense variant in STAT3 (NM_139276.3: c.1250G > C, NP_644805.1: p.(Arg417Thr) was identified in a Danish family spanning five generations with diverse phenotypes consistent with autosomal dominant STAT3-Hyper-IgE-Syndrome (STAT3-HIES). Genetic analysis confirmed the absence of the variant in population databases, and computational predictions of pathogenicity were conflicting. Functional assessment revealed that the variant STAT3 Arg417Thr maintained normal DNA binding but exhibited reduced IL-6–induced transcriptional activity and no negative-dominance. Further, significantly impaired STAT3-dependent, IL-10–mediated suppression of TNF-α production were found in patient-derived monocytes, consistent with a partial loss-of-function effect. Clinically, affected individuals presented with recurrent staphylococcal skin abscesses, eczema, atopic or infectious complications, and characteristic facial features. There was a marked variability in extra-hematopoietic manifestations such as retained primary teeth, vascular anomalies, and psychiatric disorders. Laboratory findings included elevated serum IgE levels, but only slightly reduced or normal Th17 cell counts. NIH-HIES scores varied within the family (range: 12–34), highlighting the variability of clinical expression. Based on ACMG guidelines, the variant was classified as likely pathogenic due to absence from controls, co-segregation with disease, and supportive functional evidence. This report highlights the challenges in interpreting novel STAT3 variants and the critical need for functional validation in uncertain cases. The findings emphasize the importance of molecular diagnosis irrespective of clinical scoring and address the ethical complexities of genetic testing in familial disease.

OBJECTIVES:Syphilis has re-emerged globally recently. However, valid data on stroke risk after syphilis infection are limited. We aimed to assess the risk of stroke among patients with syphilis and to account for family-related factors as well as confounding by test indication. METHODS:We conducted a nationwide, population-based matched cohort study in Denmark using linked registry and laboratory data from 2000 to 2022. Individuals aged 16-80 years with a positive syphilis serology test were matched 1:9 on sex and date of birth to individuals from the general population. To address confounding by test indication, a syphilis test-negative cohort was matched 1:1 to the syphilis-positive cohort. To assess familial and shared environmental factors, sibling cohorts corresponding to each primary cohort were included. Stroke incidence was ascertained through hospital registries. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox regression, and cumulative incidence functions were used to estimate absolute risk. RESULTS:The study included 3593 syphilis test-positive individuals, 3590 syphilis test-negative individuals, and 32 629 individuals from the general population contributing over 300 000 person-years of follow-up. The median age was 36 years, and 81% were male. The 10-year cumulative risk of stroke among syphilis-positive individuals was 1.8% (95% CI: 1.3-2.4). Stroke risk was markedly higher among syphilis-positive individuals compared with the general population (HR: 5.4 [95% CI: 3.7-7.7]) but not compared with syphilis-negative individuals (HR: 1.5 [95% CI: 0.9-2.4]). Siblings of syphilis-positive individuals also had an increased risk of stroke compared with siblings from the general population (HR 2.2 [95% CI: 1.4-3.6]) but not compared with siblings of syphilis-negative individuals. CONCLUSIONS:Individuals tested for syphilis-regardless of test result-have a higher risk of stroke than the general population. These findings suggest that confounding by test indication and shared familial factors, rather than syphilis infection itself, contribute substantially to the observed association.

HIV-related stigma remains a major barrier to improving the lives of people with HIV (PWH) and curbing the epidemic globally. This cross-sectional study assessed HIV-related stigma, based on The HIV Stigma Framework, among PWH in Denmark, and examined its potential associations with sociodemographic characteristics, as well as with HIV-related, psychosocial and sexual health measures. Data from 630 participants (486 men and 144 women) in the SHARE study-a nationwide survey on psychosocial and sexual health among PWH in Denmark conducted from 2021 to 2022-were analysed using sex-stratified linear and logistic regression models adjusted for relevant confounders. Results showed that anticipated stigma was the most commonly reported stigma mechanism, with 68% of men and 77% of women expressing high levels of concern about HIV status sharing. In contrast, enacted stigma was reported by 9% of men and 22% of women. The multivariate regression analyses revealed that higher stigma levels were associated with originating from low- or middle-income countries and with a history of mental health problems, whereas non-heterosexual identity and a longer time since HIV diagnosis were linked to lower stigma. In both men and women, stigma was significantly associated with fewer close friends, loneliness, anxiety and reduced sexual desire. Among men, stigma was also significantly associated with sharing one's HIV status with fewer people, depression, suicidal tendencies and erectile dysfunction. In conclusion, HIV-related stigma, notably stigma related to anticipated stigma, remains prevalent among PWH in Denmark and it is significantly associated with a range of psychosocial and sexual challenges.

Several patients exhibit a severity-dependent reduced pulmonary diffusing capacity (DLCOc) following coronavirus disease 2019 (COVID-19) infection. This has been attributed to fibrosis-like restrictive lung disease, as shown by chest high-resolution computed tomography (HRCT), and concurrent ventilatory disturbances observed by ventilation-perfusion single-photon emission computed tomography (V/Q SPECT) imaging. The aim of this study was to investigate whether reductions in DL,COc at short- and intermediate-term follow-up were associated with initial severity of COVID-19, and to which extend this was linked to the presence of fibrosis-like abnormalities on HRCT and ventilatory disturbances on V/Q SPECT. A total of 153 patients diagnosed with COVID-19 between March 2020 and March 2021 were included in the study. The patients underwent lung function testing, chest HRCT, and V/Q SPECT at short-term (5.6 months) follow-up. Individuals exhibiting any evidence of post-COVID-19 sequelae (n = 121) were also referred to intermediate follow-up (12.5 months). At short-term follow-up, a severity dependent reduction in DL,COc was observed, which was not evident at intermediate follow-up. At both short-term and intermediate follow-up, HRCT showed ground-glass opacity (GGO) and fibrosis-like abnormalities related to disease severity. Most patients had V/Q defects mainly with ventilatory abnormalities, including both matched and inversely matched defects at both follow-up times. The severity-dependent reduction in DL,COc at short-term follow-up, associated with restrictive lung function pattern, GGO and fibrosis on HRCT, and ventilatory disturbances on V/Q SPECT, showed spontaneous recovery by intermediate follow-up. However, the restrictive ventilatory disturbances and associated morphological changes persisted.

BACKGROUND:Elexacaftor/Tezacaftor/Ivacaftor (ETI) has raised concerns about liver-related side effects. This study evaluated changes in liver function tests (LFTs) and the prevalence of hepatotoxicity over two years of ETI treatment in a nationwide cohort of Danish people with cystic fibrosis (pwCF) METHODS: Changes in LFTs were assessed in pwCF aged ≥12 years, including those with pre-existing hepatic impairment, using data from the Danish CF Registry (2016-2025). Statistical analyses included piecewise linear mixed models for long-term changes and descriptive analysis of abnormal LFTs to assess hepatotoxicity. RESULTS:A total of 331 pwCF were included. Compared to pre-ETI levels, alanine aminotransferase (ALT) levels were significantly elevated at six months post-ETI but stabilized and approached pre-ETI levels by 24 months. Alkaline phosphatase (ALP) levels were lower at all timepoints, with a statistically significant decrease at 24 months. Gamma-glutamyl transferase (GGT) levels were consistently lower post-ETI. The prevalence of abnormal ALT, ALP, and GGT was initially higher post-ETI, peaking at one month, then steadily declining to pre-treatment values within two years. Three individuals (0.9 %) had signs of severe hepatotoxicity with ALT >5x upper limit of normal (ULN) and bilirubin >2xULN post-ETI. Among those with pre-existing hepatic impairment and those with unexpected liver complications post-ETI 5/7 and 5/8, respectively, reached the full ETI dose. CONCLUSION:ALT levels almost normalized, while GGT and ALP levels declined within two years of ETI treatment. Reassuringly, severe hepatotoxicity was rare, suggesting that close monitoring may suffice for managing mild to moderate hepatotoxicity in pwCF.

OBJECTIVE:To investigate retention in care, viral suppression, and virological failure in pregnant and postpartum women with HIV compared to nonpregnant/nonpostpartum women with HIV in Denmark, and to explore factors associated with adverse HIV care outcomes. DESIGN:A nationwide registry-based cohort study. METHODS:All women with HIV, who delivered in Denmark from 2000 to 2019, alongside a comparison group of nonpregnant/nonpostpartum women with HIV were included from the Danish HIV Birth Cohort and the Danish HIV Cohort Study and linked to national health registries. We assessed outcomes: retention in care (two HIV RNA or CD4+ measurements ≥90 days apart within a year), viral suppression (HIV RNA <200 copies/ml at the latest measurement), and virological failure (two consecutive HIV RNA measurements >200 copies/ml or one >1000 copies/ml). Incidence rate ratios evaluated group differences, and logistic regression analyzed factors linked to adverse outcomes. RESULTS:We included 564 pregnant and 1705 nonpregnant/nonpostpartum women with HIV. Retention in care was significantly lower during pregnancy, especially for deliveries before 2014, and in the second postpartum year. No significant differences in viral suppression were found between groups after stratification by delivery year or in women with more than 1 year since HIV diagnosis. Pregnant women had higher rates of virological failure, while postpartum women had lower rates, significant only in the second postpartum year for women delivering before 2010. CONCLUSION:Based on CD4+/HIV RNA measurements, retention in care was lower in pregnant and postpartum women, particularly in the second year. Reassuringly, viral suppression and virological failure rates were comparable.

Goals: We aimed to evaluate the Danish CRC screening program, estimate colonic neoplasia's prevalence, and assess the utilized BP regimens. Background: People with cystic fibrosis (pwCF) have an increased risk of precancerous polyps and colorectal cancer (CRC), with occurrence at an earlier age compared with the general population. Consequently, colonoscopy screening is recommended. PwCF requires specific bowel preparation (BP) regimens to ensure an adequate colonoscopy. Study: We conducted a national retrospective cohort study, which included all pwCF eligible for colonoscopy according to international recommendations in 26 months. Results: Among 119 eligible pwCF, 58 completed colonoscopies during the screening period. The screening was omitted in 25% of pwCF. Among the pwCF undergoing colonoscopy screening, precancerous polyps were found in 24% and none with CRC. One patient developed CRC before being offered screening. Risk factors for neoplasia were old age and male sex. The quality of BP was high, even though most pwCF received standard BP. The best quality was found in nonorgan transplanted, pwCF who received modulator treatment and those with no laxatives use. Conclusions: We detected a high adherence to CRC screening, but also a substantial proportion of pwCF who were not informed about screening recommendations, calling for greater awareness among clinicians. Although lower than previously described, our study revealed high numbers of precancerous polyps and CRC compared with the general population, underlining the need for screening. BP quality remained high, despite frequent use of standard regimens, implicating the need for more individualized regimens before undergoing colonoscopy.

Objective:To investigate physical, psychosocial and sexual health outcomes in >= 50 years-old people with and without HIV.Design:Cross-sectional study in Denmark comparing health outcomes by HIV status.Methods:Data were drawn from the SHARE study, a nationwide survey conducted between 2021 and 2022, examining psychosocial, sexual and reproductive health in people with HIV (PWH), and compared to data from people without HIV (PWOH) in the nationally representative Project SEXUS cohort study. Health outcomes were assessed using validated patient-reported outcome measures, with sex-stratified logistic regression models adjusting for sociodemographic and other confounding factors.Results:The study included 322 men and 67 women with HIV and 15 548 men and 13 926 women without HIV. PWH were more likely to report being single and having non-Danish parentage. HIV was associated with higher odds of liver disease in both men and women, cardiovascular and lung diseases in men, and osteoporosis and hypertension in women. Compared with PWOH, men with HIV more often reported depressive symptoms or a history of treatment for anxiety, while women with HIV more often reported loneliness, suicidal thoughts and domestic abuse. Sexually, PWH more often reported reduced sexual desire and activity, men with HIV more often reported erectile dysfunction or orgasmic dysfunction and women with HIV more often reported lubrication dysfunction or genital pain dysfunction.Conclusions:PWH aged >= 50 years in Denmark face significantly more physical, psychosocial and sexual health challenges than PWOH. Clinical attention to these disparities is crucial for improving the overall health of ageing PWH.

PURPOSE: Genetics of Common Variable Immunodeficiency (CVID) is complex and not fully elucidated. This study presents the clinical and genetic findings of a Danish CVID cohort and investigate whether initial genetic findings can be re-classified upon re-evaluation years later in time. METHODS: From 2016 to 2021, individuals with CVID or a CVID-like-phenotype were examined using whole exome or whole genome sequencing in combination with comprehensive gene-panels. The results were re-evaluated to ensure up-to-date American College of Medical Genetics and Genomics (ACMG) classification after a median of 3.9 years. Further, a clinical-interpretation-algorithm is proposed. RESULTS: Of 69 enrolled individuals, 57 met the current ESID-CVID-criteria of whom 29 (51%) had a genetic find. In total 67 ACMG class 3 to 5 variants were detected in 39 different genes. Class 3 variants (variants of uncertain significance (VUS)) accounted for 81% in the initial analysis. Upon re-evaluation 17 of 54 (31%) of the originally reported VUS were re-classified to a different ACMG-class or excluded. The developed clinical-interpretation-algorithm demonstrated high interobserver-agreement. A “definite/probable” disease causing (or contributing) genetic variant was found in 19% of the CVID-cohort and a “possible” in 18%. CONCLUSION: A genetic cause of CVID could be identified in a minority of CVID-individuals, whereas the majority had no or uncertain genetic findings. Re-evaluation of genetic results over time is recommended, though VUS remain a significant challenge in CVID-genetics. Therefore, continued research in both CVID-genetics and in non-genetic causes of CVID is needed.

Abstract Background Recent changes in the infant feeding guidelines for women living with HIV from high-income countries recommend a more supportive approach focusing on shared decision-making. Limited information is available on the infant feeding knowledge of women living with HIV and how healthcare providers engage with them in this context. This multicenter, longitudinal, mixed methods study aims to get a comprehensive and nuanced understanding of infant feeding knowledge among women living with HIV of Nordic and non-Nordic origin living in Nordic countries, and their interaction with healthcare providers regarding infant feeding planning. Methods Pregnant women living with HIV in Denmark, Finland, and Sweden were recruited in 2019–2020. The Positive Attitudes Concerning Infant Feeding (PACIFY) questionnaire was completed in the 3rd trimester (T1), three (T2), and six (T3) months postpartum. Women who completed the quantitative survey were also invited to participate in qualitative semi-structured interviews at T1 and T3. Results from the survey and interviews were brought together through merging to assess for concordance, complementarity, expansion, or discordance between the datasets and to draw meta-inferences. Results In total, 44 women living with HIV completed the survey, of whom 31 also participated in the interviews. The merged analyses identified two overarching domains: Knowledge about breastfeeding in the U = U era and Communications with healthcare providers. The women expressed confusion about breastfeeding in the context of undetectable equals untransmittable (U = U). Women of Nordic origin were more unsure about whether breastfeeding was possible in the context of U = U than women of non-Nordic origin. Increased postpartum monitoring with monthly testing of the mother was not seen as a barrier to breastfeeding, but concerns were found regarding infant testing and infant ART exposure. Infant feeding discussions with healthcare providers were welcome but could also question whether breastfeeding was feasible, and many participants highlighted a need for more information. Conclusions Healthcare providers caring for women living with HIV must have up-to-date knowledge of HIV transmission risks during breastfeeding and engage in shared decision-making to optimally support infant feeding choices.

Infections in pregnancy are common, and although often not harmful to the woman or her unborn child, some infections may be associated with severe adverse outcomes. Pregnancy causes physiological and immunological adaptations which may make pregnant women more susceptible to infections and at increased risk of more severe illness. Infections in pregnancy represent a challenging area of concern for many specialists and general practitioners. Center for Pregnancy and Infection was developed to enhance knowledge, diagnosis, treatment, and care for pregnant women with infection in Denmark, as pointed out in this review.

Background The extent of cardiac involvement in cystic fibrosis (CF) remains to be determined. The remarkable therapeutic advancements with new highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulator treatment and subsequent increase in life expectancy substantiates further research. We aimed to explore the prevalence of cardiac alterations in people with CF (pwCF) compared to matched controls and investigate potential cardiovascular risk factors. Methods In this cross-sectional study, 104 pwCF underwent clinical and echocardiographic assessment. All participants were matched 1:1 with controls from the general population. Results Of 104 pwCF, 44 % were female, mean age was 34 years, and 93 % received CFTR modulator treatment. The prevalence of abnormal cardiac function in pwCF was 44 %, more than double the prevalence in controls. PwCF were found to have smaller left ventricular (LV) dimensions, worse LV diastolic function, and reduced right ventricle (RV) as well as LV systolic function. After multivariable adjustment, LV diastolic function as well as LV and RV systolic function remained poorer in pwCF as compared to controls. Male sex and decreasing FEV1/FVC ratio remained independently associated with abnormal cardiac function in pwCF (male sex: OR 3.94 (1.56; 9.95), p = 0.004 and FEV1/FVC ratio: OR 2.05 per 0.1 unit decrease (1.21; 3.52), p = 0.008, respectively). Conclusions Both left- and right-sided cardiac alterations were found in pwCF. After adjustments for risk factors, both RV and LV systolic measures remained altered in pwCF, compared to controls. Male sex and decreasing pulmonary function evaluated by FEV1/FVC-ratio were associated with abnormal cardiac function in pwCF.

Abstract Background Cystic fibrosis (CF) is an autosomal recessive disease affecting multiple organs. Emerging evidence indicates an elevated risk of cardiovascular complications in people with CF (pwCF), with some studies implicating CF-related cardiomyopathy as an underlying mechanism. Whether screening for cardiac symptoms and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels may aid in identifying cardiac impairment in pwCF remains unknown. Purpose To assess prevalence of dyspnea and chest pain in pwCF and investigate whether symptoms and NT-pro-BNP are predictive of cardiac impairment. Methods We interviewed 104 adult pwCF and 104 age- and sex-matched controls from the general population about symptoms of dyspnea and chest pain. All participants were examined with transthoracic echocardiography and NT-proBNP. Cardiac impairment was defined as left ventricular (LV) ejection fraction (LVEF) <50%, LV global longitudinal strain (GLS) < 16% or presence of diastolic dysfunction. Results Chest pain was more frequent in pwCF than in controls: (29% vs. 1%, p<0.001), although primarily characterized as atypical and non-exertional chest pain (27%). PwCF also suffered more from dyspnea than controls (89% vs. 18%, p<0.001) (Figure 1) and more pwCF had abnormal cardiac function compared to controls (44% versus 22%, p<0.001). Median NT-proBNP in pwCF was 50.0 pg/ml (40.7; 100.8) and increasing NT-proBNP level was associated with decreasing FEV1 (L) (estimate: -0.008, p<0.001). NT-proBNP level was not associated with neither dyspnea nor chest pain (p=0.60 and p=0.15, respectively). PwCF with dyspnea did not differ from those without on clinical or echocardiographic parameters. However, pwCF with chest pain had lower absolute GLS compared to pwCF without (17.4% vs.18.5%, p=0.026). Neither dyspnea nor chest pain was more frequent in pwCF with cardiac impairment versus normal cardiac function (54% vs. 39%, p=0.17 and 29% vs. 28%, p=0.91, respectively). Decreasing absolute GLS was associated with increased odds of chest pain (OR 1.25, 95% CI 1.02; 1.53, p=0.030) (Figure 2). Neither dyspnea or chest pain alone, nor in combination with NT-proBNP were able to predict abnormal cardiac function. While dyspnea and chest pain combined showed a slight improvement in sensitivity and positive predictive value for diagnosing cardiac impairment, the combination of symptoms and increased NT-proBNP did not enhance diagnostic accuracy. Conclusions In this cross-sectional study, dyspnea and atypical, non-exertional chest pain were common symptoms in adult pwCF. While abnormal cardiac function was prevalent in pwCF, neither symptoms, NT-proBNP nor a combination of these were associated with increased odds of cardiac impairment. Dyspnea and chest pain, though prevalent, are multifactorial in pwCF and do not seem to serve as sensitive markers of cardiac impairment, even when combined with NT-proBNP level.

ObjectivesThe HIV/AIDS epidemic has disproportionately affected men who have sex with men (MSM) since its onset. Despite important medical advancements in treatment, the enduring effects of living with HIV continue to adversely impact the health and well-being of this population. This cross-sectional nationwide study examined psychosocial and sexual health among MSM in Denmark, comparing those living with and without HIV.MethodsData from MSM living with HIV were collected from the SHARE study, a Danish nationwide survey that investigated psychosocial, sexual and reproductive health among people with HIV, and compared with data from MSM without HIV, retrieved from the nationally representative cohort study, Project SEXUS. Associations between HIV status and psychosocial and sexual health outcomes were examined using logistic regression models while controlling for potentially confounding variables.ResultsAmong 369 MSM with HIV and 1002 MSM without HIV, logistic regression analyses revealed that living with HIV was significantly associated with having current symptoms of anxiety and depression and greater dissatisfaction with one's body. Additionally, MSM with HIV significantly more often than MSM without HIV reported low sexual desire, sexual inactivity, a lack of sexual needs in the last year and erectile dysfunction. Having received payment for sex was more frequently reported by MSM with HIV, as was sexualised drug use, including chemsex drugs.ConclusionCompared with MSM without HIV, MSM with HIV in Denmark report a higher burden of mental health and sex life challenges.

BackgroundPast and ongoing advancements in cystic fibrosis (CF) care warrant long-term analysis of the societal impact of the condition. This study aims to evaluate changes in key socioeconomic factors across three decades among people living with CF (pwCF), compared with both the general population and an early-onset chronic disease population.MethodsThis nationwide, registry-based, matched cohort study included all pwCF ≥ 18 years in Denmark in the years 1990, 2000, 2010, and 2018. Each person living with CF was matched to five individuals in the general population and five individuals living with type 1 diabetes or juvenile arthritis based on age, sex, and municipality.ResultsThe Danish adult CF population increased nearly fourfold from 88 in 1990 to 331 in 2018, and mean age increased by ten years. The educational level of pwCF was similar to the two comparator cohorts, while pwCF were less often in employment and more often permanently outside the labor force. Personal and household income levels of the CF cohort were higher than those of the comparator cohorts.ConclusionsThe disadvantage in employment for pwCF remained, but, over time, the societal profiles of the one-year CF cohorts increasingly converged with those of the comparator cohorts, indicative of improved clinical management, extended life expectancy, and the supportive role of the Danish welfare system in reducing health inequalities. Further research should be done to evaluate the effects of the newly introduced modulator therapies on employment, considering the broader societal impact and impact on quality of life.

The aim of this study was to investigate insulin secretion, insulin sensitivity, disposition index and insulin clearance by glucose tolerance status in individuals with cystic fibrosis (CF) and exocrine pancreatic insufficiency. In a cross-sectional study, we conducted an extended (ten samples) OGTT in individuals with pancreatic-insufficient CF (PI-CF). Participants were divided into normal glucose tolerance (NGT), early glucose intolerance (EGI), impaired glucose tolerance (IGT) and CF-related diabetes (CFRD) groups. We used three different oral minimal models to assess insulin secretion, insulin sensitivity and insulin clearance during the OGTT. We evaluated insulin secretion using total secretion (Φ total), first-phase secretion (Φ dynamic) and second-phase secretion (Φ static) from the model, and we estimated the disposition index by multiplying Φ total and insulin sensitivity. Among 61 participants (NGT 21

AbstractMany patients exhibit persistently reduced pulmonary diffusing capacity after coronavirus disease 2019 (COVID‐19). In this study, dual test gas diffusing capacity for carbon monoxide and nitric oxide (DL,CO,NO) metrics and their relationship to disease severity and physical performance were examined in patients who previously had COVID‐19. An initial cohort of 148 patients diagnosed with COVID‐19 of all severities between March 2020 and March 2021 had a DL,CO,NO measurement performed using the single‐breath method at 5.7 months follow‐up. All patients with at least one abnormal DL,CO,NO metric (n = 87) were revaluated at 12.5 months follow‐up. The DL,CO,NO was used to provide the pulmonary diffusing capacity for nitric oxide (DL,NO), the pulmonary diffusing capacity for carbon monoxide (DL,CO,5s), the alveolar–capillary membrane diffusing capacity and the pulmonary capillary blood volume. At both 5.7 and 12.5 months, physical performance was assessed using a 30 s sit‐to‐stand test and the 6 min walk test. Approximately 60% of patients exhibited a severity‐dependent decline in at least one DL,CO,NO metric at 5.7 months follow‐up. At 12.5 months, both DL,NO and DL,CO,5s had returned towards normal but still remained abnormal in two‐thirds of the patients. Concurrently, improvements in physical performance were observed, but with no apparent relationship to any DL,CO,NO metric. The severity‐dependent decline in DL,NO and DL,CO observed at 5.7 months after COVID‐19 appears to be reduced consistently at 12.5 months follow‐up in the majority of patients, despite marked improvements in physical performance.