Anti-CCL2 therapy reduces oxygen toxicity to the immature lung.

Oxygen toxicity constitutes a key contributor to bronchopulmonary dysplasia (BPD). Critical step in the pathogenesis of BPD is the inflammatory response in the immature lung with the release of pro-inflammatory cytokines and the influx of innate immune cells. Identification of efficient therapies to alleviate the inflammatory response remains an unmet research priority. First, we studied macrophage and neutrophil profiles in tracheal aspirates of n = 103 preterm infants <29 weeks´ gestation requiring mechanical ventilation. While no differences were present at birth, a higher fraction of macrophages, the predominance of the CD14+CD16+ subtype on day 5 of life was associated with moderate/severe BPD. Newborn CCL-2-/- mice insufficient in pulmonary macrophage recruitment had a reduced influx of neutrophils, lower apoptosis induction in the pulmonary tissue and better-preserved lung morphometry with higher counts of type II cells, mesenchymal stem cells and vascular endothelial cells when exposed to hyperoxia for 7 days. To study the benefit of a targeted approach to prevent the pulmonary influx of macrophages, wildtype mice were repeatedly treated with CCL-2 blocking antibodies while exposed to hyperoxia for 7 days. Congruent with the results in CCL-2-/- animals, the therapeutic intervention reduced the pulmonary inflammatory response, attenuated cell death in the lung tissue and better-preserved lung morphometry. Overall, our preclinical and clinical datasets document the predominant role of macrophage recruitment to the pathogenesis of BPD and establish the abrogation of CCL-2 function as novel approach to protect the immature lung from hyperoxic injury.

Association between potentially traumatic birthing experience and worsening postpartum depression or anxiety trajectories among participants in perinatal collaborative care model.

BACKGROUND: Having a potentially traumatic birth experience (PTBE) is a known risk factor for postpartum depression (PPD) and postpartum anxiety (PPA). PTBE-related PPA or PPD can peak long after six weeks postpartum, when typical screening for PPD and PPA typically occurs, leaving many of these individuals disconnected from care. Collaborative care models (CCMs) have been shown to reduce PPD and PPA via collaboration between care managers, obstetric clinicians, and mental health professionals. Whether participating in a CCM mitigates the risk of worsening PPD or PPA after PTBE is unknown. OBJECTIVE: To examine trajectories of PPD and PPA among those who experienced a PTBE and participated in a CCM. STUDY DESIGN: This secondary analysis of a prospective cohort study included people enrolled in COMPASS, a CCM program embedded within all Northwestern Medicine prenatal clinics. All pregnant or postpartum people with a history of a mental health conditions or current mental health symptoms during pregnancy or within a year postpartum are eligible for COMPASS referral. Those who enroll in COMPASS are screened every two to four weeks for depression and anxiety symptoms using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), respectively. For this secondary analysis, COMPASS participants were stratified into two groups based on whether they had a PTBE, defined as postpartum hemorrhage, maternal intensive care unit (ICU) admission, or preterm birth <35 weeks (the gestational age cut-off for required Neonatal Intensive Care Unit (NICU) admission at this medical center). PTBE was evaluated as a composite and as its individual subcomponents. The primary outcomes were worsening trajectories for PPD or PPA, defined by a score increase of ≥1 standard deviation on the PHQ-9 or GAD-7, respectively, on at least two assessments for up to one year postpartum. A propensity score was used in multivariable models to control for covariates that significantly differed in bivariable analysis. RESULTS: Among 2,312 COMPASS participants, 413 (17.9%) had PTBE. Compared to those without a PTBE, those with PTBE were more likely to have a pregnancy conceived via IVF, public insurance, or be diagnosed with preexisting diabetes, preexisting hypertension, or obesity. Among 736 and 282 participants with at least two PPD and PPA assessments, 65 (2.8%) and 27 (1.2%) had worsening PPD or PPA trajectories, respectively. After using propensity scores to control for differences identified between groups, PTBE was not associated with worsening trajectories for PPD [aOR 0.92 (95% CI 0.36, 2.38)] or PPA [(aOR 0.64 (95% CI 0.12, 3.26)]. There was no association between individual conditions within the PTBE composite and worsening PPD or PPA trajectories. CONCLUSIONS: Among those enrolled in COMPASS, worsening PPD or PPA trajectories were uncommon, and PTBE were not associated with worsening trajectories. Given the abundance of literature suggesting that PTBE are associated with worse PPD and PPA symptoms, these findings suggest that enrollment in a CCM may be associated with mitigation of the negative impact of PTBE.

Proactive Coping in Early Pregnancy and Adverse Pregnancy Outcomes.

Objective: Outside of pregnancy, proactive coping has been associated with both mental and physical well-being and with improved quality of life in chronic disease, but its effects in pregnancy are understudied. Our objective was to evaluate whether early pregnancy proactive coping was associated with adverse perinatal outcomes. Study Design: This was a planned secondary analysis of nulliparous pregnant people recruited from a tertiary care center. Participants completed a validated assessment of proactive coping (Proactive Coping Scale) at 8-20 weeks and were followed longitudinally through delivery. Detailed pregnancy and delivery data were collected by trained research personnel. The primary outcome was a composite of adverse perinatal outcomes including unplanned cesarean delivery, gestational diabetes, and hypertensive disorders of pregnancy. Secondary analyses included individual perinatal composite components and a neonatal morbidity composite measure. Multivariate regression compared adverse perinatal outcomes by Proactive Coping Scale quartile, controlling for a priori confounders. Results: Of the 281 parturients, the median Proactive Coping Scale score was 45.0 (range 25-55), and 47% experienced an adverse perinatal outcome. After adjusting for confounders, those in the lowest Proactive Coping Scale quartile had 2.2 times higher odds of experiencing an adverse perinatal outcome compared to those in the highest Proactive Coping Scale quartile. There were no differences in odds of the individual composite components or the adverse neonatal outcome. Conclusion: Lower early pregnancy proactive coping scores are associated with significant increase in adverse perinatal outcomes. Interventions that target improving proactive coping may be a novel mechanism for reducing perinatal morbidity.

Proactive coping is the process of preparing for a stressor or goal, which has been studied in the context of chronic disease. We sought to understand how proactive coping relates to pregnancy outcomes. Our results indicated that higher proactive coping scores were associated with lower risk of adverse pregnancy outcomes. Therefore, interventions to increase proactive coping may have a role in reducing adverse pregnancy outcomes.

Association Between Hispanic Ethnicity and Engagement in a Remote Postpartum Blood Pressure Monitoring Programs: Secondary Analysis of a Pilot Randomized Trial.

OBJECTIVE: Remote self-measured blood pressure (SMBP) programs improve racial health equity among postpartum people with hypertensive disorders of pregnancy (HDP) who receive recommended blood pressure ascertainment after hospital discharge.1-3 However, as prior studies have been conducted within racially diverse but ethnically homogeneous populations,1-3 the effect of SMBP programs on ethnicity-based inequities is less understood.4 We examined whether SMBP rates differed among Hispanic versus non-Hispanic participants in remote SMBP programs. STUDY DESIGN: This is a planned secondary analysis of a RCT conducted among postpartum patients with HDP who were enrolled into our remote SMBP program, in which they obtain SMBP and then manually enter the SMBP value into a patient portal for individual provider response. In the parent trial, consenting patients were randomized to continued manual blood pressure entry of SMBP or use of a Bluetooth-enabled blood pressure cuff synched to a smartphone application utilizing artificial intelligence to respond to each obtained blood pressure or symptom for six weeks and to flag abnormalities for providers. Both SMBP programs were available in Spanish and English. For this study, women who self-reported their ethnicity were stratified into two ethnic groups - Hispanic and non-Hispanic - regardless of randomization group. Those who did not self-report ethnicity but completed all study procedures in Spanish were also categorized as Hispanic. Outcomes were the same in the parent study and this secondary analysis. The primary outcome was ≥1 SMBP assessment within 10 days postpartum. Secondary outcomes included number of blood pressure assessments and healthcare utilization outcomes (remote antihypertensive medication initiation or dose-increase and presentation to the Emergency Department or readmission for hypertension within 30 days of discharge). Participants rated their experience with SMBP via a scale from 0 (worst possible) to 10 (best possible) and the Decision Regret Scale, which assessed their regret in SMBP program participation (0=no regret; 100=high regret)).5 Outcomes were compared between groups. Risk differences (RD) were calculated for categorical and regression coefficients for continuous outcomes. The parent RCT was IRB-approved and published on clinicaltrials.gov (NCT05595629) before enrollment. RESULTS: Among 119 women in the parent study, 83 (70%) self-reported ethnicity and the proportion of Hispanic people was similar in both treatment groups. This study compared 23 Hispanic (19% monolingual in Spanish) to 62 non-Hispanic women. Rates of SMBP assessment within 10 days postpartum was similar (Hispanic 64% vs non-Hispanic 79%; RD -0.1 (95% Confidence Interval (CI) -0.4, 0.1). There were no differences in mean number of remote SMBP assessments or rates of remote antihypertensive medication initiation or dose titration. The rates of hypertension-related presentations to the Emergency Department or hospital readmission were also similar between groups. Lastly, regardless of ethnicity, participants had low scores on the Decision Regret Scale and rated their experience with their remote SMBP program highly favorably. (See Table 1.) Conclusion: Hispanic and non-Hispanic postpartum patients with HDP had similar outcomes and favorable patient perceptions. The small sample size in this study may have produced inadequate power to detect a difference between study groups, thereby leading to Type II error. Thus, more research on Hispanic participants in remote SMBP programs is needed. However, the effect of remote SMBP programs on perinatal equity may not be limited to race-based disparities.

Rapid elucidation of agonist-driven regulation of the neurokinin 1 receptor using a GPCR phosphorylation immunoassay.

Agonist-induced phosphorylation is a crucial step in the activation/deactivation cycle of G protein-coupled receptors (GPCRs), but direct determination of individual phosphorylation events has remained a major challenge. We have recently developed a bead-based immunoassay for the quantitative assessment of agonist-induced GPCR phosphorylation that can be performed entirely in 96-well plates, thus eliminating the need for western blot analysis. In the present study, we adapted this assay to three novel phosphosite-specific antibodies directed against the neurokinin 1 (NK1) receptor, namely pS338/pT339-NK1, pT344/pS347-NK1, and pT356/pT357-NK1. We found that substance P (SP) stimulated concentration-dependent phosphorylation of all three sites, which could be completely blocked in the presence of the NK1 receptor antagonist aprepitant. The other two endogenous ligands of the tachykinin family, neurokinin A (NKA) and neurokinin B (NKB), were also able to induce NK1 receptor phosphorylation, but to a much lesser extent than substance P. Interestingly, substance P promoted phosphorylation of the two distal sites more efficiently than that of the proximal site. The proximal site was identified as a substrate for phosphorylation by protein kinase C. Analysis of GPCR kinase (GRK)-knockout cells revealed that phosphorylation was mediated by all four GRK isoforms to similar extents at the T344/S347 and the T356/T357 cluster. Knockout of all GRKs resulted in abolition of all phosphorylation signals highlighting the importance of these kinases in agonist-mediated receptor phosphorylation. Thus, the 7TM phosphorylation assay technology allows for rapid and detailed analyses of GPCR phosphorylation.

The scaling of metabolic traits differs among larvae and juvenile colonies of scleractinian corals.

Body size profoundly affects organism fitness and ecosystem dynamics through the scaling of physiological traits. This study tested for variation in metabolic scaling and its potential drivers among corals differing in life history strategies and taxonomic identity. Data were compiled from published sources and augmented with empirical measurements of corals in Moorea, French Polynesia. The data compilation revealed metabolic isometry in broadcasted larvae, but size-independent metabolism in brooded larvae; empirical measurements of Pocillopora acuta larvae also supported size-independent metabolism in brooded coral larvae. In contrast, for juvenile colonies (i.e. 1-4 cm diameter), metabolic scaling was isometric for Pocillopora spp., and negatively allometric for Porites spp. The scaling of biomass with surface area was isometric for Pocillopora spp., but positively allometric for Porites spp., suggesting the surface area to biomass ratio mediates metabolic scaling in these corals. The scaling of tissue biomass and metabolism were not affected by light treatment (i.e. either natural photoperiods or constant darkness) in either juvenile taxa. However, biomass was reduced by 9-15% in the juvenile corals from the light treatments and this coincided with higher metabolic scaling exponents, thus supporting the causal role of biomass in driving variation in scaling. This study shows that metabolic scaling is plastic in early life stages of corals, with intrinsic differences between life history strategy (i.e. brooded and broadcasted larvae) and taxa (i.e. Pocillopora spp. and Porites spp.), and acquired differences attributed to changes in area-normalized biomass.

The CHD Protein Kismet Restricts the Synaptic Localization of Cell Adhesion Molecules at the Drosophila Neuromuscular Junction.

The appropriate expression and localization of cell surface cell adhesion molecules must be tightly regulated for optimal synaptic growth and function. How neuronal plasma membrane proteins, including cell adhesion molecules, cycle between early endosomes and the plasma membrane is poorly understood. Here we show that the Drosophila homolog of the chromatin remodeling enzymes CHD7 and CHD8, Kismet, represses the synaptic levels of several cell adhesion molecules. Neuroligins 1 and 3 and the integrins αPS2 and ßPS are increased at kismet mutant synapses but Kismet only directly regulates transcription of neuroligin 2. Kismet may therefore regulate synaptic CAMs indirectly by activating transcription of gene products that promote intracellular vesicle trafficking including endophilin B (endoB) and/or rab11. Knock down of EndoB in all tissues or neurons increases synaptic FasII while knock down of EndoB in kis mutants does not produce an additive increase in FasII. In contrast, neuronal expression of Rab11, which is deficient in kis mutants, leads to a further increase in synaptic FasII in kis mutants. These data support the hypothesis that Kis influences the synaptic localization of FasII by promoting intracellular vesicle trafficking through the early endosome.

Changes in Stress Urinary Incontinence Symptoms after Pelvic Organ Prolapse Surgery: a Nationwide Cohort Study (FINPOP).

INTRODUCTION AND HYPOTHESIS: Various strategies are employed to manage stress urinary incontinence (SUI) during pelvic organ prolapse (POP) surgery. This study was aimed at facilitating shared decision-making by evaluating SUI symptom changes, staged SUI procedures, and their prognostic factors following POP surgery without concomitant SUI intervention. METHODS: We analyzed 2,677 POP surgeries from a population-based observational cohort, excluding patients with prior SUI surgery. The outcome measures were subjective SUI utilizing the Pelvic Floor Distress Inventory-20 questionnaire and number of subsequent SUI procedures. Multivariable linear models were applied to identify predictors of persistent SUI, procedures for persistent SUI, and de novo SUI. The primary assessment occurred at the 2-year follow-up. RESULTS: At baseline, 50% (1,329 out of 2,677) experienced SUI; 35% (354 out of 1,005) resolved, an additional 14% (140 out 1,005) improved, and 5.1% (67 out of 1,308) underwent a procedure for persistent SUI. De novo SUI symptoms developed in 20% (218 out of 1,087), with 3.2% (35 out of 1,087) reporting bothersome symptoms; 0.8% (11 out of 1,347) underwent a procedure for de novo SUI. High baseline symptom severity increased the risk of persistent SUI (adjusted odds ratio [aOR] 2.04, 95% confidence interval [CI] 1.65-2.53), whereas advanced preoperative apical prolapse decreased the risk (aOR 0.89, 95% CI 0.85-0.93). De novo SUI was more common with advancing age (aOR 1.03, 95% CI 1.01-1.05), baseline urgency urinary incontinence (aOR 1.21, 95% CI 1.06-1.38), and after transvaginal mesh surgery (aOR 1.93, 95% CI 1.24-3.00). It was not dependent on the compartment or preoperative degree of prolapse. CONCLUSIONS: In a pragmatic setting, POP surgery results in a low rate of subsequent SUI procedures.

Comprehensive mutagenesis maps the effect of all single-codon mutations in the AAV2 rep gene on AAV production.

Recombinant adeno-associated viruses (rAAVs) are the predominant gene therapy vector. Several rAAV vectored therapies have achieved regulatory approval, but production of sufficient rAAV quantities remains difficult. The AAV Rep proteins, which are essential for genome replication and packaging, represent a promising engineering target for improvement of rAAV production but remain underexplored. To gain a comprehensive understanding of the Rep proteins and their mutational landscape, we assayed the effects of all 39,297 possible single-codon mutations to the AAV2 rep gene on AAV2 production. Most beneficial variants are not observed in nature, indicating that improved production may require synthetic mutations. Additionally, the effects of AAV2 rep mutations were largely consistent across capsid serotypes, suggesting that production benefits are capsid independent. Our results provide a detailed sequence-to-function map that enhances our understanding of Rep protein function and lays the groundwork for Rep engineering and enhancement of large-scale gene therapy production.

Gastrointestinal colonization by Diutina (Candida) rugosa in a 6-year-old Siberian Husky.

A 6-year-old 21.5 kg castrated male Siberian Husky was presented for acute onset of lethargy, vomiting, hemorrhagic diarrhea, and inappetence. Physical examination revealed marked discomfort upon abdominal palpation and 5%-7% dehydration. The CBC and biochemical profile revealed changes consistent with mild to moderate inflammation, dehydration, and gastrointestinal (GI) disease. Despite aggressive gastrointestinal support, anorexia persisted, and an upper GI endoscopy was performed in conjunction with esophagostomy tube placement. Endoscopy revealed abnormal gastric mucosa characterized by moderately well-demarcated areas of blue-black discoloration. Impression smears of a gastric biopsy revealed abundant extracellular yeasts with morphology most consistent with Candida spp. and frequent extracellular cocci. Similar yeast and bacteria, in lower numbers, were observed on cytologic analysis of a direct smear of the rectal mucosa. A rectal swab submitted for fungal culture yielded pure growth of fungal yeasts identified as Diutina (formerly Candida) rugosa by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry. The dog's clinical signs improved with fluconazole, and he was discharged. Follow-up fungal culture of a rectal swab showed no growth of D. rugosa. To the authors' knowledge, this is the first case report that describes the clinical, hematologic, cytologic, and gross findings of enteric colonization by D. rugosa in a dog.

Cost-effectiveness of a mindful yoga intervention added to treatment as usual for young women with major depressive disorder versus treatment as usual only: Cost-effectiveness of yoga for young women with depression.

In a randomized controlled trial in the Netherlands, we studied the (cost)effectiveness of adding a mindful yoga intervention (MYI+TAU) to treatment as usual (TAU) for young women with major depressive disorder (MDD). In this paper, we present the results of the economic analyses. Societal costs and health outcomes were prospectively assessed during 15 months for all randomized participants (n = 171). Symptoms of depression (Depression Anxiety and Stress Scales; DASS) and quality adjusted life years (QALYs) were used as health outcomes in the economic analyses. Mean total societal costs during the 15 months of the study were €11.966 for the MYI+TAU group and €13.818 for the TAU group, differences in mean total societal costs were not statistically significant. Health outcomes (DASS and QALY) were slightly in favour of MYI+TAU, but differences between groups were not statistically significant. Combining costs and health outcomes in cost-effectiveness analyses indicated that MYI+TAU is likely to be cost-effective compared to TAU which was confirmed by sensitivity analyses. Although there were limitations in the cost-effectiveness analysis, findings from this study suggest that MYI+TAU warrants future attention for the potential to be cost-effective compared to TAU for young women with MDD.

Optimization, characterization, and cytotoxicity studies of novel anti-tubercular agent-loaded liposomal vesicles.

The treatment of tuberculosis is still a challenging process due to the widespread of pathogen strains resistant to antibacterial drugs, as well as the undesirable effects of anti-tuberculosis therapy. Hence, the development of safe and effective new anti-antitubercular agents, in addition to suitable nanocarrier systems, has become of utmost importance and necessity. Our research aims to develop liposomal vesicles that contain newly synthesized compounds with antimycobacterial action. The compound being studied is a derivative of imidazo-tetrazine named 3-(3,5-dimethylpyrazole-1-yl)-6-(isopropylthio) imidazo [1,2-b] [1,2,4,5] tetrazine compound. Several factors that affect liposomal characteristics were studied. The maximum encapsulation efficiency was 53.62 ± 0.09. The selected liposomal formulation T8* possessed a mean particle size of about 205.3 ± 3.94 nm with PDI 0.282, and zeta potential was + 36.37 ± 0.49 mv. The results of the in vitro release study indicated that the solubility of compound I was increased by its incorporation in liposomes. The free compound and liposomal preparation showed antimycobacterial activity against Mycobacterium tuberculosis H37Rv (ATCC 27294) at MIC value 0.94-1.88 µg/ml. We predict that the liposomes may be a good candidate for delivering new antitubercular drugs.

Psyche: The 5th 'P' and its Associated Impact on the Second Stage of Labor.

OBJECTIVE: Patients with depression during labor display dysregulated patterns of oxytocin release and this may impact second stage of labor. The objective of this study was to evaluate the association between maternal preconception and antenatal depressive disorders on the duration of second stage of labor and perinatal outcomes. STUDY DESIGN: Secondary analysis of patients enrolled in the Behavioral and Mood in Mothers, Behavior in Infants study who reached the second stage of labor. Participants were assigned to: pre-conception only major depressive disorder (MDD), prenatal major depressive disorder, and non-depressed controls. Primary outcome was prolonged second stage of labor. Secondary outcomes included perinatal morbidities. RESULTS: 172 patients were included. 24.4% (42/172) participants had preconception-only MDD, 42.4% (73/172) patients had prenatal MDD, and 33.1% (57/172) patients had as non-depressed controls. The adjusted pair-wise analysis between groups showed no significant difference in the duration of second stage. No statistically significant differences were noted between groups for adverse neonatal outcomes. CONCLUSION: Maternal depressive disorders did not impact length of second stage of labor or immediate perinatal outcomes.

Concise approach to γ-(het)aryl- and γ-alkenyl-γ-aminobutyric acids. Synthesis of vigabatrin.

γ-Aminobutyric acid (GABA) and GABA derivatives have attracted increased attention over the years in the fields of medicinal chemistry and chemical biology due to their interesting biological properties and synthetic relevance. Here, we report a short synthetic route to γ-(het)aryl- and γ-alkenyl-γ-aminobutyric acids, including the antiepileptic drug vigabatrin, from readily available donor-acceptor cyclopropanes and ammonia or methylamine. This protocol includes a facile synthesis of 2-oxopyrrolidine-3-carboxamides and their acid hydrolysis to γ-aryl- or γ-alkenyl-substituted GABAs, which can serve as perspective building blocks for the synthesis of various GABA-based N-heterocycles and bioactive compounds.

Pelvic girdle pain in pregnancy and early postpartum - prevalence and risk factors in a multi-ethnic cohort.

BACKGROUND: Pelvic girdle pain (PGP) is common during and after pregnancy. It has been assumed that Scandinavian women report more PGP than women of other ethnicities. However, there are few population-based studies on ethnic differences and few with ethnicity as risk factor for PGP. The purposes of the present study were: To examine the prevalence of self-reported PGP through pregnancy and early postpartum in a multi-ethnic cohort. To investigate how ethnicity and patient characteristics were associated with risk of PGP during pregnancy and early postpartum. To investigate if clinical and personal factors obtained in gestation week (GW) 15 were associated with PGP in GW28 and postpartum week (PPW) 14. METHODS: This study analyzed questionnaire data from 823 women from the Stork - Groruddalen mult-iethnic cohort study in Norway. Chi-square tests were used to investigate ethnic differences in prevalence of self-reported PGP, and logistic regression analyses to identify factors associated with self-reported PGP. RESULTS: Women from South-Asia and Middle East reported 10-20% higher prevalence of self-reported PGP at all time points compared with Western women. Ethnicity was associated with PGP in GW15 and PPW14, adjusted for parity. Pain locations in pelvic area (PGP locations) in GW15, especially combined symphysis and posterior PGP, gave the highest risk (OR=7.4) for PGP in GW28 and in PPW14 (OR = 3.9). Being multiparous was a risk for PGP in PPW14 (OR=1.9). CONCLUSIONS: Women of South Asian and Middle Eastern background had higher risk of self-reported PGP than Western women. Ethnicity was associated with PGP in GW15 and PPW14, after adjustments for parity. PGP locations in GW15 was the most prominent risk factor for PGP in GW28 and PPW14, whilst ethnicity was not significant in multivariable analyses.

Absence of Type I Interferon Autoantibodies or Significant Interferon Signature Alterations in Adults With Post-COVID-19 Syndrome.

Genetic defects in the interferon (IFN) system or neutralizing autoantibodies against type I IFNs contribute to severe COVID-19. Such autoantibodies were proposed to affect post-COVID-19 syndrome (PCS), possibly causing persistent fatigue for >12 weeks after confirmed SARS-CoV-2 infection. In the current study, we investigated 128 patients with PCS, 21 survivors of severe COVID-19, and 38 individuals who were asymptomatic. We checked for autoantibodies against IFN-α, IFN-ß, and IFN-ω. Few patients with PCS had autoantibodies against IFNs but with no neutralizing activity, indicating a limited role of type I IFNs in PCS pathogenesis. In a subset consisting of 28 patients with PCS, we evaluated IFN-stimulated gene activity and showed that it did not correlate with fatigue. In conclusion, impairment of the type I IFN system is unlikely responsible for adult PCS.