Patients' evaluation of aftercare following hospitalization for COVID-19: satisfaction and unmet needs.

BACKGROUND: Patient experiences with COVID-19 aftercare remain largely unknown. We evaluated COVID-19 aftercare from a patient perspective one year after hospitalization, assessing satisfaction and its associated factors, and unmet needs. METHODS: The Satisfaction with COVID-19 Aftercare Questionnaire (SCAQ) was developed as part of a multicenter prospective cohort study and administered one year after hospital discharge. The SCAQ assesses (1) patient satisfaction, comprising information provision, rehabilitation, follow-up by hospitals and general practitioners (GPs), the most important aftercare topics, and overall satisfaction, and (2) unmet needs. RESULTS: 487/561 (87%) COVID-19 patients completed the SCAQ, all had been discharged from the hospital between March 2020 and May 2021. Among responders, the median age of patients was 60 (IQR 54-67) years, 338 (69%) were male, and the median length of stay in the hospital was 13 (6-27) days. Patients were least satisfied with information on who could be contacted with questions when health problems arise (59% satisfied or very satisfied). Many patients (75%) received rehabilitation, most frequently community-based (70%). Across the different community-based therapies, ≥ 60% of patients were satisfied with shared-decision making and ≥ 70% with the received therapy; a majority (≥ 79%) indicated a preference for receiving the same therapy again if needed. Regarding follow-up by hospitals, 86% of patients received this follow-up, most frequently visiting a pulmonologist (96%), being generally satisfied with the received aftercare. Aftercare from GPs was received by 39% of patients, with 88% being satisfied with the GP's availability and 79% with referral to appropriate aftercare providers. Patients (> 50%) considered information-related items most important in aftercare. Overall, patients rated their satisfaction with aftercare 8/10 (7-9) points. Those who received medical rehabilitation (versus no rehabilitation, adjusted beta 0.61 [95%CI 0.11 to 1.11], p = 0.02) or aftercare by a hospital medical specialist (1.1 [0.46 to 1.64], p < 0.001) or GP (0.39 [0.053 to 0.72], p = 0.023) reported significantly higher satisfaction than those without such aftercare. Unmet needs were reported by 35% of patients, with lack of information (20%) and lack of additional aftercare and/or involvement of their GP (19%) being the most frequently reported. CONCLUSION: Despite the forced quick development of COVID-19 aftercare, patients were generally satisfied. Follow-up by healthcare professionals and information provision is important to meet patients' aftercare needs.

Lung transplant airway complications treated with biodegradable airway stents: The Dutch multi-center experience.

INTRODUCTION: Treatment of post lung-transplant airway complications is challenging, and treatment with conventional airway stents is associated with adverse events. More recently, biodegradable airway stents (BDS) have been introduced and may be used to reduce these adverse events. In this study we explore the feasibility of treatment with BDS post lung transplant. METHODS: All patients treated with BDS in The Netherlands were included in this retrospective multicenter study. Feasibility, life span of the stent, occurrence of adverse events, and evolution of lung function were evaluated. RESULTS: Twelve patients (six malacia and six stenosis) received a total of 57 BDS, ranging from 1 to 10 BDS per patient. Six patients had been pretreated with conventional airway stents. Median stent life span was 112 days (range 66-202). No adverse events occurred during stent placement. In 5 out of 57 stent placements, a single additional bronchoscopy was necessary because of mucus accumulation (n = 4) or excessive granulation tissue (n = 1). All stent naïve patients became airway stent independent after treatment; all patients pretreated with conventional airway stents were still airway stent dependent at the end of follow up. CONCLUSION: Treatment with BDS is safe and feasible. Adverse events were mild and easily treatable. All patients with initial treatment with BDS were airway stent independent at the end of follow up with a median treatment of 4 BDS.

Clinical Characteristics and Outcomes of Immunocompromised Patients With Coronavirus Disease 2019 Caused by the Omicron Variant: A Prospective, Observational Study.

BACKGROUND: Illness after infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is less severe compared with previous variants. Data on the disease burden in immunocompromised patients are lacking. We investigated the clinical characteristics and outcomes of immunocompromised patients with coronavirus disease 2019 (COVID-19) caused by Omicron. METHODS: Organ transplant recipients, patients on anti-CD20 therapy, and allogenic hematopoietic stem cell transplantation recipients infected with the Omicron variant were included. Characteristics of consenting patients were collected and patients were contacted regularly until symptom resolution. To identify possible risk factors for hospitalization, a univariate logistic analysis was performed. RESULTS: 114 consecutive immunocompromised patients were enrolled. Eighty-nine percent had previously received 3 mRNA vaccinations. While only 1 patient died, 23 (20%) were hospitalized for a median of 11 days. A low SARS-CoV-2 immunoglobulin G (IgG) antibody response (<300 BAU [binding antibody units]/mL) at diagnosis, being older, being a lung transplant recipient, having more comorbidities, and having a higher frailty score were associated with hospital admission (all P < .01). At the end of follow-up, 25% had still not fully recovered. Of the 23 hospitalized patients, 70% had a negative and 92% had a low IgG (<300 BAU/mL) antibody response at admission. Sotrovimab was administered to 17 of these patients, and 1 died. CONCLUSIONS: While the mortality in immunocompromised patients infected with Omicron was low, hospital admission was frequent and the duration of symptoms often prolonged. In addition to vaccination, other interventions are needed to limit the morbidity from COVID-19 in immunocompromised patients.

Home monitoring of lung function, symptoms and quality of life after admission with COVID-19 infection: The HOMECOMIN' study.

BACKGROUND AND OBJECTIVE: To develop targeted and efficient follow-up programmes for patients hospitalized with coronavirus disease 2019 (COVID-19), structured and detailed insights in recovery trajectory are required. We aimed to gain detailed insights in long-term recovery after COVID-19 infection, using an online home monitoring programme including home spirometry. Moreover, we evaluated patient experiences with the home monitoring programme. METHODS: In this prospective multicentre study, we included adults hospitalized due to COVID-19 with radiological abnormalities. For 6 months after discharge, patients collected weekly home spirometry and pulse oximetry measurements, and reported visual analogue scales on cough, dyspnoea and fatigue. Patients completed the fatigue assessment scale (FAS), global rating of change (GRC), EuroQol-5D-5L (EQ-5D-5L) and online tool for the assessment of burden of COVID-19 (ABCoV tool). Mixed models were used to analyse the results. RESULTS: A total of 133 patients were included in this study (70.1% male, mean age 60 years [SD 10.54]). Patients had a mean baseline forced vital capacity of 3.25 L (95% CI: 2.99-3.44 L), which increased linearly in 6 months with 19.1% (Δ0.62 L, p < 0.005). Patients reported substantial fatigue with no improvement over time. Nevertheless, health status improved significantly. After 6 months, patients scored their general well-being almost similar as before COVID-19. Overall, patients considered home spirometry useful and not burdensome. CONCLUSION: Six months after hospital admission for COVID-19, patients' lung function and quality of life were still improving, although fatigue persisted. Home monitoring enables detailed follow-up for patients with COVID-19 at low burden for patients and for the healthcare system.

Intensive Care Unit-Specific Virtual Reality for Critically Ill Patients With COVID-19: Multicenter Randomized Controlled Trial.

BACKGROUND: Although psychological sequelae after intensive care unit (ICU) treatment are considered quite intrusive, robustly effective interventions to treat or prevent these long-term sequelae are lacking. Recently, it was demonstrated that ICU-specific virtual reality (ICU-VR) is a feasible and acceptable intervention with potential mental health benefits. However, its effect on mental health and ICU aftercare in COVID-19 ICU survivors is unknown. OBJECTIVE: This study aimed to explore the effects of ICU-VR on mental health and on patients' perceived quality of, satisfaction with, and rating of ICU aftercare among COVID-19 ICU survivors. METHODS: This was a multicenter randomized controlled trial. Patients were randomized to either the ICU-VR (intervention) or the control group. All patients were invited to an COVID-19 post-ICU follow-up clinic 3 months after hospital discharge, during which patients in the intervention group received ICU-VR. One month and 3 months later (4 and 6 months after hospital discharge), mental health, quality of life, perceived quality, satisfaction with, and rating of ICU aftercare were scored using questionnaires. RESULTS: Eighty-nine patients (median age 58 years; 63 males, 70%) were included. The prevalence and severity of psychological distress were limited throughout follow-up, and no differences in psychological distress or quality of life were observed between the groups. ICU-VR improved satisfaction with (mean score 8.7, SD 1.6 vs 7.6, SD 1.6 [ICU-VR vs control]; t64=-2.82, P=.006) and overall rating of ICU aftercare (mean overall rating of aftercare 8.9, SD 0.9 vs 7.8, SD 1.7 [ICU-VR vs control]; t64=-3.25; P=.002) compared to controls. ICU-VR added to the quality of ICU aftercare according to 81% of the patients, and all patients would recommend ICU-VR to other ICU survivors. CONCLUSIONS: ICU-VR is a feasible and acceptable innovative method to improve satisfaction with and rating of ICU aftercare and adds to its perceived quality. We observed a low prevalence of psychological distress after ICU treatment for COVID-19, and ICU-VR did not improve psychological recovery or quality of life. Future research is needed to confirm our results in other critical illness survivors to potentially facilitate ICU-VR's widespread availability and application during follow-up. TRIAL REGISTRATION: Netherlands Trial Register NL8835; https://www.trialregister.nl/trial/8835. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-021-05271-z.

Estimated Global Proportions of Individuals With Persistent Fatigue, Cognitive, and Respiratory Symptom Clusters Following Symptomatic COVID-19 in 2020 and 2021.

Importance: Some individuals experience persistent symptoms after initial symptomatic SARS-CoV-2 infection (often referred to as Long COVID). Objective: To estimate the proportion of males and females with COVID-19, younger or older than 20 years of age, who had Long COVID symptoms in 2020 and 2021 and their Long COVID symptom duration. Design, Setting, and Participants: Bayesian meta-regression and pooling of 54 studies and 2 medical record databases with data for 1.2 million individuals (from 22 countries) who had symptomatic SARS-CoV-2 infection. Of the 54 studies, 44 were published and 10 were collaborating cohorts (conducted in Austria, the Faroe Islands, Germany, Iran, Italy, the Netherlands, Russia, Sweden, Switzerland, and the US). The participant data were derived from the 44 published studies (10 501 hospitalized individuals and 42 891 nonhospitalized individuals), the 10 collaborating cohort studies (10 526 and 1906), and the 2 US electronic medical record databases (250 928 and 846 046). Data collection spanned March 2020 to January 2022. Exposures: Symptomatic SARS-CoV-2 infection. Main Outcomes and Measures: Proportion of individuals with at least 1 of the 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after SARS-CoV-2 infection in 2020 and 2021, estimated separately for hospitalized and nonhospitalized individuals aged 20 years or older by sex and for both sexes of nonhospitalized individuals younger than 20 years of age. Results: A total of 1.2 million individuals who had symptomatic SARS-CoV-2 infection were included (mean age, 4-66 years; males, 26%-88%). In the modeled estimates, 6.2% (95% uncertainty interval [UI], 2.4%-13.3%) of individuals who had symptomatic SARS-CoV-2 infection experienced at least 1 of the 3 Long COVID symptom clusters in 2020 and 2021, including 3.2% (95% UI, 0.6%-10.0%) for persistent fatigue with bodily pain or mood swings, 3.7% (95% UI, 0.9%-9.6%) for ongoing respiratory problems, and 2.2% (95% UI, 0.3%-7.6%) for cognitive problems after adjusting for health status before COVID-19, comprising an estimated 51.0% (95% UI, 16.9%-92.4%), 60.4% (95% UI, 18.9%-89.1%), and 35.4% (95% UI, 9.4%-75.1%), respectively, of Long COVID cases. The Long COVID symptom clusters were more common in women aged 20 years or older (10.6% [95% UI, 4.3%-22.2%]) 3 months after symptomatic SARS-CoV-2 infection than in men aged 20 years or older (5.4% [95% UI, 2.2%-11.7%]). Both sexes younger than 20 years of age were estimated to be affected in 2.8% (95% UI, 0.9%-7.0%) of symptomatic SARS-CoV-2 infections. The estimated mean Long COVID symptom cluster duration was 9.0 months (95% UI, 7.0-12.0 months) among hospitalized individuals and 4.0 months (95% UI, 3.6-4.6 months) among nonhospitalized individuals. Among individuals with Long COVID symptoms 3 months after symptomatic SARS-CoV-2 infection, an estimated 15.1% (95% UI, 10.3%-21.1%) continued to experience symptoms at 12 months. Conclusions and Relevance: This study presents modeled estimates of the proportion of individuals with at least 1 of 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after symptomatic SARS-CoV-2 infection.

CO-FLOW: COvid-19 Follow-up care paths and Long-term Outcomes Within the Dutch health care system: study protocol of a multicenter prospective cohort study following patients 2 years after hospital discharge.

BACKGROUND: First studies indicate that up to 6 months after hospital discharge, coronavirus disease 2019 (COVID-19) causes severe physical, cognitive, and psychological impairments, which may affect participation and health-related quality of life (HRQoL). After hospitalization for COVID-19, a number of patients are referred to medical rehabilitation centers or skilled nursing facilities for further treatment, while others go home with or without aftercare. The aftercare paths include 1] community-based rehabilitation; 2] in- and outpatient medical rehabilitation; 3] inpatient rehabilitation in skilled nursing facilities; and 4] sheltered care (inpatient). These aftercare paths and the trajectories of recovery after COVID-19 urgently need long-term in-depth evaluation to optimize and personalize treatment. CO-FLOW aims, by following the outcomes and aftercare paths of all COVID-19 patients after hospital discharge, to systematically study over a 2-year period: 1] trajectories of physical, cognitive, and psychological recovery; 2] patient flows, healthcare utilization, patient satisfaction with aftercare, and barriers/facilitators regarding aftercare as experienced by healthcare professionals; 3] effects of physical, cognitive, and psychological outcomes on participation and HRQoL; and 4] predictors for long-term recovery, health care utilization, and patient satisfaction with aftercare. METHODS: CO-FLOW is a multicenter prospective cohort study in the mid-west of the Netherlands with a 2-year follow-up period. Measurements comprise non-invasive clinical tests and patient reported outcome measures from a combined rehabilitation, pulmonary, and intensive care perspective. Measurements are performed at 3, 6, 12, and 24 months after hospital discharge and, if applicable, at rehabilitation discharge. CO-FLOW aims to include at least 500 patients who survived hospitalization for COVID-19, aged ≥18 years. DISCUSSION: CO-FLOW will provide in-depth knowledge on the long-term sequelae of COVID-19 and the quality of current aftercare paths for patients who survived hospitalization. This knowledge is a prerequisite to facilitate the right care in the right place for COVID-19 and comparable future infectious diseases. TRIAL REGISTRATION: The Netherlands Trial Register (NTR), https://www.trialregister.nl . Registered: 12-06-2020, CO-FLOW trialregister no. NL8710.

COVID-19 in solid organ transplant recipients: a single-center experience.

Solid organ transplant (SOT) recipients may be at risk for severe COVID-19. Data on the clinical course of COVID-19 in immunosuppressed patients are limited, and the effective treatment strategy for these patients is unknown. We describe our institutional experience with COVID-19 in SOT. Demographic, clinical, and treatment data were extracted from the electronic patient files. A total of 23 SOT transplant recipients suffering from COVID-19 were identified (n = 3 heart; n = 15 kidney; n = 1 kidney-after-heart; n = 3 lung, and n = 1 liver transplant recipient). The presenting symptoms were similar to nonimmunocompromised patients. Eighty-three percent (19/23) of the patients required hospitalization, but only two of these were transferred to the intensive care unit. Five patients died from COVID-19; all had high Clinical Frailty Scores. In four of these patients, mechanical ventilation was deemed futile. In 57% of patients, the immunosuppressive therapy was not changed and only three patients were treated with chloroquine. Most patients recovered without experimental antiviral therapy. Modification of the immunosuppressive regimen alone could be a therapeutic option for SOT recipients suffering from moderate to severe COVID-19. Pre-existent frailty is associated with death from COVID-19.

Acute COVID-19 treatment is not associated with health problems 2 years after hospitalization.

OBJECTIVES: Various mechanisms, such as immune dysregulation, viral reservoir, and auto-immunity, are hypothesized to underlie the pathogenesis of long-term health problems after hospitalization for COVID-19. We aimed to assess the effect of in-hospital COVID-19 treatments on prominent long-term health problems. METHODS: In this prospective multicenter cohort study, we enrolled patients (age ≥18 years) who had been hospitalized for COVID-19 in the Netherlands between July 2020 and October 2021. We retrospectively collected data on in-hospital COVID-19 treatments, including steroid, anti-inflammatory, and antiviral treatments. Patients completed questionnaires on self-reported recovery, dyspnea, fatigue, cognitive failures, and health-related quality of life and performed the 6-minute walk test at the 2-year follow-up visit. RESULTS: Five hundred two patients with COVID-19 were included, all were discharged from the hospital between March 2020 and June 2021. The median age at admission was 60.0 (IQR 53.0-68.0) years and 350 (69.7%) patients were male. At hospital admission, 5/405 (1.2%) of the patients had been vaccinated against SARS-CoV-2. Among all 502 patients, the majority (248 [49.4%]) received steroids only, 57 (11.4%) anti-inflammatory treatment, 78 (15.5%) antiviral treatment, and 119 (23.7%) none during hospitalization. Long-term health problems were common in all groups. We found that in-hospital treatments were not significantly associated with health problems at 2 years after hospital discharge, nor after adjusting for confounders. CONCLUSION: Many patients with COVID-19 suffer from long-term health problems 2 years after hospital discharge. Acute treatment for COVID-19 is not associated with long-term health problems.

Is albuminuria screening and treatment optimal in patients with type 2 diabetes in primary care? Observational data of the GIANTT cohort.

BACKGROUND: Failure of diagnosing and treatment of albuminuria play a role in morbidity and mortality in type 2 diabetes (T2DM). We evaluated guideline adherence and factors associated with albuminuria screening and treatment in T2DM patients in primary care. METHODS: Guidelines recommend annual measurement of albuminuria and, if increased, treatment with renin-angiotensin-aldosterone system (RAAS) blockers. We performed a cohort study of T2DM patients managed by 182 Dutch general practitioners (GPs; Groningen Initiative to Analyse Type 2 diabetes Treatment database), and evaluated guideline adherence in the years 2007-2009. We assessed whether demographic, clinical, organizational or provider factors determined guideline adherence with multilevel analyses. RESULTS: Data were available for 14 120 T2DM patients [47.6% male, mean age 67.3 ± 11.7 years, median diabetes duration 6 (IQR: 3-10) years]. The albumin-creatinine ratio (ACR) was measured in 45.2% in 2007, 57.4% in 2008 and 56.8% in 2009. Only 23.7% of all patients were measured every year and 21.4% were never measured. The ACR was more often measured in patients <75 years, with a previous ACR measurement, using anti-diabetic medication, and receiving additional care by a diabetes support facility. RAAS treatment was prescribed to 78.4% of patients with prevalent micro/macroalbuminuria, 66.5% with incident micro/macroalbuminuria, 59.3% with normoalbuminuria and 52.1% of those without ACR measurements. In those not treated with RAAS blockers, it was initiated in 14.3, 12.3, 3.0 and 2.3%, respectively. The presence of micro/macroalbuminuria, higher blood pressure, incidence of cardiovascular events and treatment with antihypertensive medication were the determinants of RAAS-treatment initiation. CONCLUSIONS: Guideline implementation regarding the management of albuminuria in T2DM patients in primary care should be further improved.

Antibodies against angiotensin II receptor type 1 and endothelin A receptor are increased in COVID-19 patients.

Background: Increased titers of autoantibodies targeting the G-protein-coupled receptors angiotensin II type 1 receptor (AT1R) and endotelin-1 type A receptor (ETAR) are associated with severe coronavirus disease 2019 (COVID-19) infection. The aim of this study was to determine whether 1) these antibodies are specifically related to COVID-19 disease pathogenesis or increased during any severe respiratory illness, 2) if they are formed during illness, and 3) if they correlate with inflammatory markers or long-term symptoms. Methods: Antibodies against AT1R, ETAR, and antinuclear antibodies (ANAs) were measured in n=40 prospectively enrolled COVID-19 patients and n=207 COVID-19 patients included in a biobank. Clinical and laboratory findings were prospectively and retrospectively assessed in both cohorts, and results were combined for analysis. The presence of auto-antibodies against AT1R or ETAR in peripheral blood was compared between hospitalized patients with COVID-19 and controls (n=39). Additionally, AT1R and ETAR titers were compared between patients with an unfavorable disease course, defined as intensive care admission and/or death during hospital admission (n=121), to those with a favorable disease course (n=126). A subset of intubated patients with severe COVID-19 were compared to intubated patients with acute respiratory distress syndrome (ARDS) due to any other cause. Results: Significantly increased AT1R and ETAR antibody titers were found in COVID-19 patients compared to controls, while titers were equal between favorable and unfavorable COVID-19 disease course groups. On ICU, intubated patients with COVID-19 had significantly increased AT1R and ETAR titers compared to patients with ARDS due to any other cause. The titers did not correlate with baseline inflammatory markers during admission or with diffusion capacity, cognitive impairment, or fatigue measured at 3 months follow-up. Conclusions: In patients hospitalized for COVID-19, antibodies against AT1R and ETAR are increased compared to controls and patients with ARDS due to other causes than COVID-19. The baseline antibody titers do not correlate with inflammatory markers or long-term symptoms in this study.

Diagnostic accuracy of eNose 'breathprints' for therapeutic drug monitoring of Tacrolimus trough levels in lung transplantation.

In order to prevent long-term immunity-related complications after lung transplantation, close monitoring of immunosuppressant levels using therapeutic drug monitoring (TDM) is paramount. Novel electronic nose (eNose) technology may be a non-invasive alternative to the current invasive procedures for TDM. We investigated the diagnostic and categorization capacity of eNose breathprints for Tacrolimus trough blood plasma levels (TACtrough) in lung transplant recipients (LTRs). We performed eNose measurements in stable LTR attending the outpatient clinic. We evaluated (1) the correlation between eNose measurements and TACtrough, (2) the diagnostic capacity of eNose technology for TACtrough, and (3) the accuracy of eNose technology for categorization of TACtroughinto three clinically relevant categories (low: <7µg ml-1, medium: 7-10µg ml-1, and high: >10µg ml-1). A total of 186 measurements from 86 LTR were included. There was a weak but statistically significant correlation (r= 0.21,p= 0.004) between the eNose measurements and TACtrough. The root mean squared error of prediction for the diagnostic capacity was 3.186 in the training and 3.131 in the validation set. The accuracy of categorization ranged between 45%-63% for the training set and 52%-69% in the validation set. There is a weak correlation between eNose breathprints and TACtroughin LTR. However, the diagnostic as well as categorization capacity for TACtroughusing eNose breathprints is too inaccurate to be applicable in TDM.

Diagnostic performance of electronic nose technology in chronic lung allograft dysfunction.

BACKGROUND: There is a need for reliable biomarkers for the diagnosis of chronic lung allograft dysfunction (CLAD). In this light, we investigated the diagnostic value of exhaled breath analysis using an electronic nose (eNose) for CLAD, CLAD phenotype, and CLAD stage in lung transplant recipients (LTR). METHODS: We performed eNose measurements in LTR with and without CLAD, visiting the outpatient clinic. Through supervised machine learning, the diagnostic value of eNose for CLAD was assessed in a random training and validation set. Next, we investigated the diagnostic value of the eNose measurements combined with known risk factors for CLAD. Model performance was evaluated using ROC-analysis. RESULTS: We included 152 LTR (median age 60 years, 49% females), of whom 38 with CLAD. eNose-based classification of patients with and without CLAD provided an AUC of 0.86 in the training set, and 0.82 in the validation set. After adding established risk factors for CLAD (age, gender, type of transplantation, time after transplantation and prior occurrence of acute cellular rejection) to a model with the eNose data, the discriminative ability of the model improved to an AUC of 0.94 (p = 0.02) in the training set and 0.94 (p = 0.04) in the validation set. Discrimination between BOS and RAS was good (AUC 0.95). Discriminative ability for other phenotypes (AUCs ranging 0.50-0.92) or CLAD stages (AUC 0.56) was limited. CONCLUSION: Exhaled breath analysis using eNose is a promising novel biomarker for enabling diagnosis and phenotyping CLAD. eNose technology could be a valuable addition to the diagnostic armamentarium for suspected graft failure in LTR.

Detection of Bacterial Colonization in Lung Transplant Recipients Using an Electronic Nose.

Background: Bacterial colonization (BC) of the lower airways is common in lung transplant recipients (LTRs) and increases the risk of chronic lung allograft dysfunction. Diagnosis often requires bronchoscopy. Exhaled breath analysis using electronic nose (eNose) technology may noninvasively detect BC in LTRs. Therefore, we aimed to assess the diagnostic accuracy of an eNose to detect BC in LTRs. Methods: We performed a cross-sectional analysis within a prospective, single-center cohort study assessing the diagnostic accuracy of detecting BC using eNose technology in LTRs. In the outpatient clinic, consecutive LTR eNose measurements were collected. We assessed and classified the eNose measurements for the presence of BC. Using supervised machine learning, the diagnostic accuracy of eNose for BC was assessed in a random training and validation set. Model performance was evaluated using receiver operating characteristic analysis. Results: In total, 161 LTRs were included with 80 exclusions because of various reasons. Of the remaining 81 patients, 16 (20%) were classified as BC and 65 (80%) as non-BC. eNose-based classification of patients with and without BC provided an area under the curve of 0.82 in the training set and 0.97 in the validation set. Conclusions: Exhaled breath analysis using eNose technology has the potential to noninvasively detect BC.

Cognitive and psychological recovery patterns across different care pathways 12 months after hospitalization for COVID-19: A multicenter cohort study (CO-FLOW).

BACKGROUND: The comparison of recovery patterns for different care pathways following COVID-19 is necessary for optimizing rehabilitation strategies. OBJECTIVES: To evaluate cognitive and psychological outcomes across different care pathways up to 12 months after hospitalization for COVID-19. METHODS: CO-FLOW is an ongoing multicenter prospective cohort study with assessments at 3, 6, and 12 months after hospitalization for COVID-19. The main outcomes are cognitive deficits (Montreal Cognitive Assessment, score <26), cognitive failure (Cognitive Failure Questionnaire, score >43), posttraumatic stress disorder (PTSD; Impact of Event Scale-Revised, score ≥33), and anxiety and depression (Hospital Anxiety and Depression Scale, subscale score ≥11). RESULTS: In total, data from 617 participants were analyzed. Mean age was 59.7 (SD 11.4) years and 188 (31%) were female. Significant recovery occurred within the first 6 months post-discharge (p ≤ 0.001). Cognitive deficits persisted in 21% (101/474), and psychological problems in 15% (74/482) of people at 12 months. Significantly improved cognition scores were reported for people who did not receive rehabilitation ('No-rehab'; 124/617, 20%; mean difference, MD 2.32, 95% CI 1.47 to 3.17; p<0.001), those who received community-based rehabilitation ('Com-rehab'; 327/617, 53%; MD 1.27, 95% CI 0.77 to 1.78; p<0.001), and those who received medical rehabilitation ('Med-rehab'; 86/617, 14%; MD 1.63, 95% CI 0.17 to 3.10; p = 0.029). Med-rehab participants experienced more cognitive failure from 3 to 6 months (MD 4.24, 95% 1.63 to 6.84; p = 0.001). Com-rehab showed recovery for PTSD (MD -2.43, 95% -3.50 to -1.37; p<0.001), anxiety (MD -0.67, 95% -1.02 to -0.32; p<0.001), and depression (MD -0.60, 95% -0.96 to -0.25; p<0.001), but symptoms persisted at 12 months. CONCLUSIONS: Survivors of COVID-19 showed cognitive and psychological recovery, especially within the first 6 months after hospitalization. Most persistent problems were related to cognitive functioning at 12 months. Recovery differed rehabilitation settings. Additional cognitive or psychological support might be warranted in people who medical or community-based rehabilitation.

Immunological profiling in long COVID: overall low grade inflammation and T-lymphocyte senescence and increased monocyte activation correlating with increasing fatigue severity.

Background: Many patients with SARS-CoV-2 infection develop long COVID with fatigue as one of the most disabling symptoms. We performed clinical and immune profiling of fatigued and non-fatigued long COVID patients and age- and sex-matched healthy controls (HCs). Methods: Long COVID symptoms were assessed using patient-reported outcome measures, including the fatigue assessment scale (FAS, scores ≥22 denote fatigue), and followed up to one year after hospital discharge. We assessed inflammation-related genes in circulating monocytes, serum levels of inflammation-regulating cytokines, and leukocyte and lymphocyte subsets, including major monocyte subsets and senescent T-lymphocytes, at 3-6 months post-discharge. Results: We included 37 fatigued and 36 non-fatigued long COVID patients and 42 HCs. Fatigued long COVID patients represented a more severe clinical profile than non-fatigued patients, with many concurrent symptoms (median 9 [IQR 5.0-10.0] vs 3 [1.0-5.0] symptoms, p<0.001), and signs of cognitive failure (41%) and depression (>24%). Immune abnormalities that were found in the entire group of long COVID patients were low grade inflammation (increased inflammatory gene expression in monocytes, increased serum pro-inflammatory cytokines) and signs of T-lymphocyte senescence (increased exhausted CD8+ TEMRA-lymphocytes). Immune profiles did not significantly differ between fatigued and non-fatigued long COVID groups. However, the severity of fatigue (total FAS score) significantly correlated with increases of intermediate and non-classical monocytes, upregulated gene levels of CCL2, CCL7, and SERPINB2 in monocytes, increases in serum Galectin-9, and higher CD8+ T-lymphocyte counts. Conclusion: Long COVID with fatigue is associated with many concurrent and persistent symptoms lasting up to one year after hospitalization. Increased fatigue severity associated with stronger signs of monocyte activation in long COVID patients and potentially point in the direction of monocyte-endothelial interaction. These abnormalities were present against a background of immune abnormalities common to the entire group of long COVID patients.

Humoral and cellular immune responses after COVID-19 vaccination of lung transplant recipients and patients on the waiting list: a 6-month follow-up.

Background: Data on cellular response and the decay of antibodies and T cells in time are scarce in lung transplant recipients (LTRs). Additionally, the development and durability of humoral and cellular immune responses have not been investigated in patients on the waitlist for lung transplantation (WLs). Here, we report our 6-month follow-up of humoral and cellular immune responses of LTRs and WLs, compared with controls. Methods: Humoral responses to two doses of the mRNA-1273 vaccination were assessed by determining spike (S)-specific IgG antibodies and neutralizing antibodies. Cellular responses were investigated by interferon gamma (IFN-γ) release assay (IGRA) and IFN-γ ELISpot assay at 28 days and 6 months after the second vaccination. Results: In LTRs, the level of antibodies and T-cell responses was significantly lower at 28 days after the second vaccination. Also, WLs had lower antibody titers and lower T-cell responses compared with controls. Six months after the second vaccination, all groups showed a decrease in antibody titers and T-cell responses. In WLs, the rate of decline of neutralizing antibodies and T-cell responses was significantly higher than in controls. Conclusion: Our results show that humoral and cellular responses in LTRs, if they develop, decrease at rates comparable with controls. In contrast, the inferior cellular responses and the rapid decay of both humoral and cellular responses in the WL groups imply that WLs may not be protected adequately by two vaccinations and repeat boostering may be necessary to induce protection that lasts beyond the months immediately post-transplantation.

Puzzling persisting symptoms after COVID-19.

There is an increasingly evident discrepancy between experienced symptoms and underlying pulmonary injury, thus motivating further research to identify the underlying mechanisms of persistent pulmonary symptoms after #COVID19 https://bit.ly/33nyUxl.