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One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood 1 . Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials. Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Anti tumour necrosis factor (anti-TNF) drugs increase the risk of serious respiratory infection and impair protective immunity following pneumococcal and influenza vaccination. Here we report SARS-CoV-2 vaccine-induced immune responses and breakthrough infections in patients with inflammatory bowel disease, who are treated either with the anti-TNF antibody, infliximab, or with vedolizumab targeting a gut-specific anti-integrin that does not impair systemic immunity. Geometric mean [SD] anti-S RBD antibody concentrations are lower and half-lives shorter in patients treated with infliximab than vedolizumab, following two doses of BNT162b2 (566.7 U/mL [6.2] vs 4555.3 U/mL [5.4], p <0.0001; 26.8 days [95% CI 26.2 – 27.5] vs 47.6 days [45.5 – 49.8], p <0.0001); similar results are also observed with ChAdOx1 nCoV-19 vaccination (184.7 U/mL [5.0] vs 784.0 U/mL [3.5], p <0.0001; 35.9 days [34.9 – 36.8] vs 58.0 days [55.0 – 61.3], p value < 0.0001). One fifth of patients fail to mount a T cell response in both treatment groups. Breakthrough SARS-CoV-2 infections are more frequent (5.8% (201/3441) vs 3.9% (66/1682), p = 0.0039) in patients treated with infliximab than vedolizumab, and the risk of breakthrough SARS-CoV-2 infection is predicted by peak anti-S RBD antibody concentration after two vaccine doses. Irrespective of the treatments, higher, more sustained antibody levels are observed in patients with a history of SARS-CoV-2 infection prior to vaccination. Our results thus suggest that adapted vaccination schedules may be required to induce immunity in at-risk, anti-TNF-treated patients. Vaccination is effective in protecting from COVID-19. Here the authors report immune responses and breakthrough infections in twice-vaccinated patients receiving anti-TNF treatments for inflammatory bowel disease, and find dampened vaccine responses that implicate the need of adapted vaccination schedules for these patients.

Background Our goals are to quantify the impact on acute care utilization of a specialized COVID-19 clinic with an integrated remote patient monitoring program in an academic medical center and further examine these data with stakeholder perceptions of clinic effectiveness and acceptability. Methods A retrospective cohort was drawn from enrolled and unenrolled ambulatory patients who tested positive in May through September 2020 matched on age, presence of comorbidities and other factors. Qualitative semi-structured interviews with patients, frontline clinician, and administrators were analyzed in an inductive-deductive approach to identify key themes. Results Enrolled patients were more likely to be hospitalized than unenrolled patients ( N  = 11/137 in enrolled vs 2/126 unenrolled, p  = .02), reflecting a higher admittance rate following emergency department (ED) events among the enrolled vs unenrolled, though this was not a significant difference (46% vs 25%, respectively, p  = .32). Thirty-eight qualitative interviews conducted June to October 2020 revealed broad stakeholder belief in the clinic’s support of appropriate care escalation. Contrary to beliefs the clinic reduced inappropriate care utilization, no difference was seen between enrolled and unenrolled patients who presented to the ED and were not admitted ( N  = 10/137 in enrolled vs 8/126 unenrolled, p  = .76). Administrators and providers described the clinic’s integral role in allowing health services to resume in other areas of the health system following an initial lockdown. Conclusions Acute care utilization and multi-stakeholder interviews suggest heightened outpatient observation through a specialized COVID-19 clinic and remote patient monitoring program may have contributed to an increase in appropriate acute care utilization. The clinic’s role securing safe reopening of health services systemwide was endorsed as a primary, if unmeasured, benefit.

Over the last decade, precise exoplanet transmission spectroscopy has revealed the atmospheres of dozens of exoplanets, driven largely by observatories like the Hubble Space Telescope. One major discovery has been the ubiquity of atmospheric aerosols, often blocking access to exoplanet chemical inventories. Tentative trends have been identified, showing that the clarity of planetary atmospheres may depend on equilibrium temperature. Previous work has often grouped dissimilar planets together in order to increase the statistical power of any trends, but it remains unclear from observed transmission spectra whether these planets exhibit the same atmospheric physics and chemistry. We present a re-analysis of a smaller, more physically similar sample of 15 exo-Neptune transmission spectra across a wide range of temperatures (200-1000 K). Using condensation cloud and hydrocarbon haze models, we find that the exo-Neptune population is best described by low cloud sedimentation efficiency (\\(\\mathrm{f_{sed}}\\sim0.1\\)) and high metallicity (\\(100\\times\\) Solar). There is an intrinsic scatter of \\(\\sim0.5\\) scale height, perhaps evidence of stochasticity in these planets' formation processes. Observers should expect significant attenuation in transmission spectra of Neptune-size exoplanets, up to 6 scale heights for equilibrium temperatures between 500 and 800 K. With JWST's greater wavelength sensitivity, colder (<500 K) planets should be high-priority targets given their clearer atmospheres, and the need to distinguish between the \"super-puffs\" and more typical gas-dominated planets.

Recent work on the characterization of small exoplanets has allowed us to accumulate growing evidence that the sub-Neptunes with radii greater than \\(\\sim2.5\\,R_\\oplus\\) often host H\\(_2\\)/He-dominated atmospheres both from measurements of their low bulk densities and direct detections of their low mean-molecular-mass atmospheres. However, the smaller sub-Neptunes in the 1.5-2.2 R\\(_\\oplus\\) size regime are much less understood, and often have bulk densities that can be explained either by the H\\(_2\\)/He-rich scenario, or by a volatile-dominated composition known as the \"water world\" scenario. Here, we report the detection of water vapor in the transmission spectrum of the \\(1.96\\pm0.08\\) R\\(_\\oplus\\) sub-Neptune GJ9827d obtained with the Hubble Space Telescope. We observed 11 HST/WFC3 transits of GJ9827d and find an absorption feature at 1.4\\(\\mu\\)m in its transit spectrum, which is best explained (at 3.39\\(\\sigma\\)) by the presence of water in GJ9827d's atmosphere. We further show that this feature cannot be caused by unnoculted star spots during the transits by combining an analysis of the K2 photometry and transit light-source effect retrievals. We reveal that the water absorption feature can be similarly well explained by a small amount of water vapor in a cloudy H\\(_2\\)/He atmosphere, or by a water vapor envelope on GJ9827d. Given that recent studies have inferred an important mass-loss rate (\\(>0.5\\,\\)M\\(_\\oplus\\)/Gyr) for GJ9827d making it unlikely to retain a H-dominated envelope, our findings highlight GJ9827d as a promising water world candidate that could host a volatile-dominated atmosphere. This water detection also makes GJ9827d the smallest exoplanet with an atmospheric molecular detection to date.

The JWST NIRSpec integral field unit (IFU) presents a unique opportunity to observe directly imaged exoplanets from 3-5 um at moderate spectral resolution (R~2,700) and thereby better constrain the composition, disequilibrium chemistry, and cloud properties of their atmospheres. In this work, we present the first NIRSpec IFU high-contrast observations of a substellar companion that requires starlight suppression techniques. We develop specific data reduction strategies to study faint companions around bright stars, and assess the performance of NIRSpec at high contrast. First, we demonstrate an approach to forward model the companion signal and the starlight directly in the detector images, which mitigates the effects of NIRSpec's spatial undersampling. We demonstrate a sensitivity to planets that are 3e-6 fainter than their stars at 1'', or 3e-5 at 0.3''. Then, we implement a reference star point spread function (PSF) subtraction and a spectral extraction that does not require spatially and spectrally regularly sampled spectral cubes. This allows us to extract a moderate resolution (R~2,700) spectrum of the faint T-dwarf companion HD 19467 B from 2.9-5.2 um with signal-to-noise ratio (S/N)~10 per resolution element. Across this wavelength range, HD~19467~B has a flux ratio varying between 1e-5-1e-4 and a separation relative to its star of 1.6''. A companion paper by Hoch et al. more deeply analyzes the atmospheric properties of this companion based on the extracted spectrum. Using the methods developed here, NIRSpec's sensitivity may enable direct detection and spectral characterization of relatively old (~1 Gyr), cool (~250 K), and closely separated (~3-5 au) exoplanets that are less massive than Jupiter.

It is important to explore the diversity of characteristics of low-mass, low-density planets to understand the nature and evolution of this class of planets. We present a homogeneous analysis of 12 new and 9 previously published broadband photometric observations of the Uranus-sized extrasolar planet GJ 3470b, which belongs to the growing sample of sub-Jovian bodies orbiting M dwarfs. The consistency of our analysis explains some of the discrepancies between previously published results and provides updated constraints on the planetary parameters. Our data are also consistent with previous transit observations of this system. We also provide new spectroscopic measurements of GJ 3470 from 0.33 to 2.42 $\\mu$$m\\( to aid our analysis. We find \\)R_{\\star}\\( = 0.48\\)\\pm\\(0.04 \\)R_{\\odot}\\(, \\)M_{\\star}\\( = 0.51\\)\\pm\\(0.06 \\)M_{\\odot}\\(, and \\)T_{\\rm eff}\\( = 3652\\)\\pm\\(50 K for GJ 3470, along with a rotation period of \\)20.70\\pm{0.15}\\( d and an R-band amplitude of 0.01 mag, which is small enough that current transit measurements should not be strongly affected by stellar variability. We also present the most precise orbital ephemeris for this system: T\\)_{o}\\( = 2455983.70472\\)\\pm\\(0.00021 BJD\\)_{TDB}\\(, P = 3.3366487\\)^{+0.0000043}_{-0.0000033}\\( d, and we see no evidence for transit timing variations greater than 1 minute. Our reported planet to star radius ratio is 0.07642\\)\\pm\\(0.00037. The physical parameters of this planet are \\)R_{p}\\( = 3.88\\)\\pm\\(0.32 \\)R_{\\oplus}\\(, and \\)M_{p}\\( = 13.73\\)\\pm\\(1.61 \\)M_{\\oplus}\\(. Because of our revised stellar parameters, the planetary radius we present is smaller than previously reported values. We also perform a second analysis of the transmission spectrum of the entire ensemble of transit observations to date, supporting the existence of a H\\)_{2}$ dominated atmosphere exhibiting a strong Rayleigh scattering slope.