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Mycobacterial infections, both tuberculosis and nontuberculous, are more common in patients with haematological malignancies and haematopoietic stem cell transplant recipients than in the general population-although these infections remain rare. Mycobacterial infections pose both diagnostic and therapeutic challenges. The management of mycobacterial infections is particularly complicated for patients in haematology because of the many drug-drug interactions between antimycobacterial drugs and haematological and immunosuppressive treatments. The management of mycobacterial infections must also consider the effect of delaying haematological management. We surveyed the management practices for latent tuberculosis infection (LTBI) in haematology centres in Europe. We then conducted a meticulous review of the literature on the epidemiology, diagnosis, and management of LTBI, tuberculosis, and nontuberculous mycobacterial infections among patients in haematology, and we formulated clinical guidelines according to standardised European Conference on Infections in Leukaemia (ECIL) methods. In this Review, we summarise the available literature and the recommendations of ECIL 8 for managing mycobacterial infections in patients with haematological malignancies.

In-center maintenance hemodialysis (HD) patients are at high risk of acquiring coronavirus disease 2019 (COVID-19) by cross-contamination inside the unit. The aim of this study was to assess retrospectively the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission during the very first pandemic phase (March-July 2020) in a cohort of in-center maintenance HD patients and in nurses the same HD facility, using a phylogenetic approach. All SARS-CoV-2 quantitative reverse-transcription polymerase chain reaction positive patients and nurses from our HD unit-respectively 10 out of 98, and 8 out of 58- and two other positive patients dialyzed in our self-care unit were included. Whole-genome viral sequencing and phylogenetic analysis supported the cluster investigation. Five positive patients were usually dialyzed in the same room and same shift before their COVID-19 diagnosis was made. Viral sequencing performed on 4/5 patients' swabs showed no phylogenetic link between their viruses. The fifth patient (whose virus could not be sequenced) was dialyzed at the end of the dialysis room and was treated by a different nurse than the one in charge of the other patients. Three nurses shared the same virus detected in both self-care patients (one of them had been transferred to our in-center facility). The epidemiologically strongly suspected intra-unit cluster could be ruled out by viral genome sequencing. The infection control policy did not allow inter-patient contamination within the HD facility, in contrast to evidence of moderate dissemination within the nursing staff and in the satellite unit. Epidemiologic data without phylogenetic confirmation might mislead the interpretation of the dynamics of viral spreading within congregate settings.

BACKGROUND: The delivery of a high and consistent [Formula: see text] is imperative to treat acute hypoxemia. The objective of this study was to analyze the effective inspired oxygen concentration delivered by different low-flow oxygen therapy systems challenged with different oxygen flows and respiratory patterns in an experimental lung model. METHODS: An adult lung model ventilated in volume control mode simulated different respiratory patterns to obtain mean inspiratory flow of 22.5, 30.0, 37.5, or 45.0 L/min. The oxygen concentration sampled inside the lung model by nasal cannula, simple face mask, non-rebreather mask, and double-trunk mask above nasal cannula tested at oxygen flows of 10, 12.5, and 15 L/min was quantified. The 3 masks were sealed tight onto the model’s airway opening. They were also tested with standardized leaks to determine their clinical performance. RESULTS: All oxygen delivery systems delivered higher oxygen concentration with increasing oxygen flows, regardless of the respiratory pattern. Within each device, the increase in inspiratory flow decreased oxygen concentration when using nasal cannula (P = .03), the simple face mask (P = .03), but not the non-rebreather mask (P = .051) nor the double-trunk mask (P = .13). In sealed condition, the double-trunk mask outperformed the non-rebreather mask and simple face mask (P < .001); mean oxygen concentration was 84.2%, 68.5%, and 60.8%, respectively. Leaks amplified oxygen concentration differences between the double-trunk mask and the other masks as the oxygen delivery decreased by 4.6% with simple face mask (95% CI 3.1–6.1%, P < .001), 7.8% with non-rebreather mask (95% CI 6.3–9.3%, P < .001), and 2.5% with double-trunk mask (95% CI 1–4%, P = .002). With leaks, the oxygen concentration provided by the simple face mask and the non-rebreather mask was similar (P = .15). CONCLUSIONS: Lung oxygen concentration values delivered by the double-trunk mask were higher than those obtained with other oxygen delivery systems, especially when leaks were present.

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The kinetics of IgG antibodies after coronavirus disease 2019 (COVID‐19) remain poorly understood. We investigated factors influencing severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) IgG antibody levels and time to seronegativation during the follow‐up of severe and critically ill patients. We retrospectively reviewed serological evaluations drawn during the follow‐up of severe or critical laboratory‐proven COVID‐19 patients hospitalized at a large academic hospital. Specific IgG titers were measured using a chemiluminescent assay targeting anti‐spike and anti‐nucleocapsid protein IgG. The influence of time, demographic factors, clinical and paraclinical characteristics, and COVID‐19 therapeutics on IgG levels were assessed through linear regression using a mixed‐effect model, and delay until IgG negativation through a Weibull regression model. The cohort included 116 patients with a total of 154 IgG measurements drawn at a median of 79 days after diagnosis. IgG antibodies were increased with age (p = 0.005) and decreased significantly over time (p = 0.0002). Using elapsed time and age as covariates, we demonstrated higher IgG levels in patients with a higher body mass index (BMI) (p = 0.0026) and lower IgG levels in immunocompromised patients (p = 0.032). A high BMI was further found to delay and immunodeficiency to hasten significantly seronegativation, whereas no significant effect was observed with corticosteroids. These data highlight the waning over time of IgG antibodies after severe or critical COVID‐19. Age, BMI, and immunosuppression also appear to influence the IgG kinetics, while short‐term corticotherapy does not. Those data improve the understanding of SARS‐CoV‐2 serology while further research should determine the determinants of long‐term seroprotection., Highlights Anti‐SARS‐CoV‐2 IgG antibody levels measured during follow‐up of severe and critical COVID‐19 were studied. We analyzed the influence of time, demographics, clinical and paraclinical characteristics and COVID‐19 treatments on specific IgG levels and time to seronegativation. Time and immunodepression were associated to reduced IgG levels at follow‐up, while age and BMI were associated to increased levels. Corticosteroids given as short‐term treatment for COVID‐19 did not show influence. BMI and immunodepression were respectively associated with decreased and increased rates of seronegativation.

Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent hereditary kidney disorder. Liver cysts are the most common extrarenal manifestation of the disease and usually remain asymptomatic. Liver cyst infection is rare, and its treatment is challenging. Liver transplantation (LT) is the only curative therapeutic option in symptomatic polycystic liver disease associated with ADPKD. Only a few cases of LT for recurrent liver cyst infection have been published. To our knowledge, we report the first case of sequential liver-kidney transplantation for recurrent liver cysts infection in a patient with ADPKD. A 55-year-old woman with ADPKD who had a kidney transplantation (KT) presented with multiple liver cysts infection 9 months after her KT. These episodes started after biliary tract complications due to an ampullary adenoma necessitating multiple endoscopic interventions. Her general status gradually degraded because antibiotic treatment was not effective, and she underwent LT for recurrent liver cysts infection 1 year and 9 months after her KT. LT in this setting turned out to be challenging but was possible. We think that better biliary tract workup before KT may prompt better care in these patients.

Background and Objective: In the absence of characterization on pharmacokinetics and reference concentrations for hydroxychloroquine in COVID-19 patients, the dose and treatment duration for hydrochloroquine are currently empirical, mainly based on in vitro data, and may vary across national guidelines and clinical study protocols. The aim of this paper is to describe the pharmacokinetics of hydroxychloroquine in COVID-19 patients, considered to be a key step toward its dosing optimization. Methods: We have developed a population pharmacokinetic model for hydroxychloroquine in COVID-19 patients using prospectively collected pharmacokinetic data from patients either enrolled in a clinical trial or treated with hydroxychloroquine as part of standard of care in two tertiary Belgian hospitals. Results: The final population pharmacokinetic model was a one-compartment model with first-order absorption and elimination. The estimated parameter values were 9.3/h, 860.8 L, and 15.7 L/h for the absorption rate constant, the central compartment volume, and the clearance, respectively. The bioavailability factor was fixed to 0.74 based on previously published models. Model validations by bootstraps, prediction corrected visual predictive checks, and normalized prediction distribution errors gave satisfactory results. Simulations were performed to compare the exposure obtained with alternative dosing regimens. Conclusion: The developed models provide useful insight for the dosing optimization of hydroxychloroquine in COVID-19 patients. The present results should be used in conjunction with exposure-efficacy and exposure-safety data to inform optimal dosing of hydroxychloroquine in COVID-19., SCOPUS: ar.j, info:eu-repo/semantics/published

Neutralizing monoclonal antibody treatments have shown promising preliminary results in kidney transplant recipients infected with severe acute respiratory syndrome coronavirus 2. However, their efficacy in kidney transplant recipients infected with the Omicron variant has not been reported yet.Single-center retrospective study.We included all consecutive kidney transplant recipients treated with monoclonal antibodies for severe acute respiratory syndrome coronavirus 2 infections (positive polymerase chain reaction on nasopharyngeal swab) between June 10, 2021, and January 14, 2022. Forty-seven kidney transplant recipients were included. All patients had symptoms evolving for ≤7 days and no oxygen therapy need at monoclonal antibody infusion.Symptoms at diagnosis were mainly cough (n = 25; 53%) and fever (n = 15; 32%). Eighty-three percent of the cohort (n = 39) had been vaccinated with at least 2 doses before infection, of whom 30 (77%) had demonstrated a vaccine-induced humoral response. They were treated with either casirivimab-imdevimab (n = 16; 34%) or sotrovimab (n = 31; 66%) a median of 2 days (range, 0-6 days) after the onset of symptoms. Except for 1 mild allergic reaction during casirivimab-imdevimab infusion, no side effects were reported. The median viral loads at admission (day 0) and 7 days after monoclonal antibody infusion were 2,110,027 copies/mL (range, 1,000-153,798,962 copies/mL) and 1,000 copies/mL (range, 0-10,000,000 copies/mL), respectively. Genotypes were available for 22 kidney transplant recipients (47%). Omicron, Delta, and Gamma variants were identified in 13 (59%), 8 (36%), and 1 (5%) patients, respectively. In kidney transplant recipients infected with the Omicron variant, the median viral loads at day 0 and day 7 were 752,789 copies/mL (range, 4,000-12,859,300 copies/mL) and 1,353 copies/mL (range, 0-1,211,163 copies/mL), respectively. 2 kidney transplant recipients required hospitalization immediately after sotrovimab perfusion for oxygen therapy that was weaned in 3 days, allowing patients' discharge. None were admitted to the intensive care unit or died.Small sample size, no control group.Neutralizing monoclonal antibody therapy is associated with positive outcomes in kidney transplant recipients with mild coronavirus disease 2019, including those infected with the Omicron variant.

SARS-CoV-2 vaccines offered great hope in controlling the worldwide COVID-19 pandemic. At present, SARS-CoV-2 vaccines have shown excellent efficacy to prevent COVID-19 but immunocompromised patients were left-off most vaccine clinical trials albeit their extreme vulnerability. Indeed, immunosuppression is associated with a higher risk of developing severe COVID-19 with mortality rates over 30% reported in patients with hematologic malignancies (HM). [...]

We thank Mungmunpuntipantip and Wiwanitkit1 for their constructive comments. Among the 47 kidney transplant recipients included in this study, 17 had antihuman leukocyte antigen antibodies detected within 2 years prior to infection, but none had donor-specific antibodies.2 Antihuman leukocyte antigen antibody status was not available for 6 patients. No patient was treated for acute rejection in the 2 years prior to infection. ^...]

INTRODUCTION: The COVID-19 pandemic has emerged as a global health problem, associated with high morbidity and mortality rates. The aim of this study was to compare the outcomes of hospitalized patients with COVID-19 or with seasonal influenza in a teaching hospital in Belgium. METHODS: In this retrospective, single-center cohort study, 1384 patients with COVID-19 and 226 patients with influenza were matched using a propensity score with a ratio of 3:1. Primary outcomes included admission to intensive care unit (ICU), intubation rates, hospital length of stay, readmissions within 30 days and in-hospital mortality. Secondary outcomes included pulmonary bacterial superinfection, cardiovascular complications and ECMO. RESULTS: Based on the analysis of the matched sample, patients with influenza had an increased risk of readmission within 30 days (Risk Difference (RD): 0.07, 95% CI: 0.03 to 0.11) and admission to intensive care unit (RD: 0.09, 95% CI: 0.03 to 0.15) compared with those with COVID-19. Patients with influenza had also more pulmonary bacterial superinfections (46.2% vs 7.4%) and more cardiovascular complications (32% vs 3.9%) than patients with COVID-19.However, a two-fold increased risk of mortality (RD: -0.10, 95% CI: 0.15 to -0.05) was observed in COVID-19 compared to influenza. ECMO was also more required among the COVID-19 patients who died than among influenza patients (5% vs 0%). CONCLUSIONS: COVID-19 is associated with a higher in-hospital mortality compared to influenza infection, despite a high rate of ICU admission in the influenza group. These findings highlighted that the severity of hospitalized patients with influenza should not be underestimated.

BACKGROUND: The management of surgical site infection (SSI) after craniotomy remains challenging with few existing recommendations. PATIENTS AND METHODS: We reviewed the medical files of patients who underwent surgery between 2009 and 2018 to manage infection after craniotomy at our tertiary hospital. The Cox proportional hazards model and the Renyi test were used to investigate the association between relapse or all-cause mortality and selected variables. We compared infections with and without intra-cranial involvement using the Fisher test and the Wilcoxon rank sum test. RESULTS: Seventy-seven episodes of infection were identified in 58 patients. The proportion of relapse was estimated to be 32.2% (± standard deviation [SD] 6.9) at five years. Intra-cranial infection was present in 15.6% of the cases (n = 12). Bone flap was removed in the majority of cases (93.5%) and the overall median duration of antibiotic therapy was six weeks (interquartile range [IQR] 6-12 weeks). Staphylococcus aureus was associated with a higher risk of relapse (p = 0.037). The administration of parenteral antibiotic agents (p = 0.012) and bone flap removal (p = 0.0051) were correlated with less relapse. In contrast, immunosuppressive drug use and radiotherapy were correlated with a higher risk of relapse (p = 0.014 and p = 0.031, respectively) and a higher all-cause mortality (p = 0.0093 and p < 0.0001, respectively). We found no difference between infections with and without intra-cranial involvement. CONCLUSIONS: Bone flap removal and parenteral antibiotic agents remain important in the management of SSI after craniotomy and were associated with less relapse in our study. More studies are needed to better determine the optimal treatment of this infection.

BACKGROUND: Treating hypoxemia while meeting the soaring demands of oxygen can be a challenge during the COVID-19 pandemic. OBJECTIVE: To determine the efficacy of the surgical facemask and the double-trunk mask on top of the low-flow oxygen nasal cannula on arterial partial pressure of oxygen (PaO2) in hypoxemic COVID-19 patients. DESIGN: Randomized controlled trial. PARTICIPANTS: Hospitalized adults with COVID-19 and hypoxemia treated with the low-flow nasal cannula were enrolled between November 13, 2020, and March 05, 2021. INTERVENTIONS: Patients were randomized in a 1:1:1 ratio to receive either the nasal cannula alone (control) or the nasal cannula covered by the surgical facemask or the double-trunk mask. Arterial blood gases were collected at baseline and 30 min after the use of each system. The oxygen output was adapted afterwards to retrieve the baseline pulse oxygen saturation. The final oxygen output value was recorded after another 30-min period. MAIN MEASURES: The primary outcome was the absolute change in PaO2. Secondary outcomes included changes in oxygen output, arterial partial pressure of carbon dioxide (PaCO2), vital parameters, and breathlessness. KEY RESULTS: Arterial blood samples were successfully collected in 24/27 (8 per group) randomized patients. Compared to the nasal cannula alone, PaO2 increased with the surgical facemask (mean change: 20 mmHg, 95% CI: 0.7-38.8; P = .04) and with the double-trunk mask (mean change: 40 mmHg; 95% CI: 21-59; P < .001). Oxygen output was reduced when adding the surgical facemask (median reduction: 1.5 L/min [95% CI: 0.5-4.5], P < .001) or the double-trunk mask (median reduction: 3.3 L/min [95% CI: 2-5], P < .001). The double-trunk mask was associated with a PaCO2 increase of 2.4 mmHg ([95% CI: 0-4.7], P = .049). Neither mask influenced vital parameters or breathlessness. CONCLUSIONS: The addition of the surgical facemask or the double-trunk mask above the nasal cannula improves arterial oxygenation and reduces oxygen consumption.

BACKGROUND Little is known regarding the optimal management of nocardiosis among solid organ transplant (SOT) recipients. It is often suggested to avoid trimethoprim/sulfamethoxazole (TMP-SMX) monotherapy in heavily immunocompromised patients (such as SOT recipients) and/or in case of severe or disseminated nocardiosis. Our aim was to report our experience with TMP-SMX monotherapy in SOT recipients with nocardiosis. METHODS Using data from a previously published European study, we assessed the incidence of adverse events in SOT recipients receiving TMP-SMX monotherapy and assessed its effectiveness. RESULTS Thirty-one SOT recipients with nocardiosis were included, mostly kidney transplant recipients (20/31, 65%). Eleven (36%) had disseminated infection, and four (13%) had brain nocardiosis. Most patients had lung and/or pleural involvement (26/31, 84%). Daily dose of trimethoprim at initiation was 10 [6.4-14.8]��mg/kg. The median estimated glomerular filtration rate at time of diagnosis of nocardiosis was 44 [30-62] ml/min/1.73��m��. TMP-SMX was discontinued prematurely in one third of the patients (10/31, 32%, mostly for hematological toxicity [n��=��3] or increased serum creatinine [n��=��3]). Focusing on the 24 (77%) patients who completed at least 30��days of TMP-SMX monotherapy, 4 had late (>30��days) drug discontinuation, 1 experienced treatment failure, and 19 completed planned TMP-SMX monotherapy. Clinical outcome was favorable in these 19 patients, despite the fact that 8 (42%) had disseminated infection and 2 (11%) brain nocardiosis. Overall, all-cause 1-year mortality was 10% (3/31). CONCLUSIONS TMP-SMX monotherapy appears to be effective for the treatment of most nocardiosis among SOT recipients. Interventional studies are needed to compare its safety and effectiveness with those of other regimens used to treat posttransplant nocardiosis.

Dear Editors, Nocardiosis is a rare but potentially severe bacterial opportunistic infection that may occur after solid organ transplantation (SOT), typically among thoracic transplant recipients and/or in recipients with a high degree of immunosuppression due to anti-rejection therapy [1]. However, nocardiosis may also occur late after transplantation among minimally immunosuppressed patients, suggesting that additional risk factors exist [1]. Recently, autoantibodies against granulocyte macrophage colony-stimulating factor (GM-CSF) have been identified among five previously healthy patients with disseminated nocardiosis [2]. These autoantibodies likely promote nocardiosis by reducing neutrophil and macrophage activation, phagocytosis, and bactericidal activity [2]. We hypothesized that anti-GM-CSF autoantibodies might be involved in post-SOT nocardiosis, especially in patients who apparently have a relatively low degree of immunosuppression. [...]

This study aims to evaluate SARS-CoV-2 seroprevalence among health care workers (HCWs) and to assess self-reported risk factors for seropositivity. A total of 3255 HCWs were included and the overall seroprevalence was 7.8%. The likelihood of seropositivity was higher in participants reporting any COVID-19 symptoms within the last 4 months (OR 8.32, 95% CI 5.83-11.88, P < 0.001). Being a female HCW (OR 1.32, 95% CI 1.11-2.32, P < 0.01), having a cohabitant who was infected with SARS-CoV-2 (OR 2.55, 95% CI 1.78-3.66 P < 0.001) or a cohabitant who was a nursing home caregiver (OR 3.71, 95% CI 1.59-8.65, P = 0.002) were independently associated with an increased risk of seropositivity. Working in a COVID-19 unit (OR 1.64, 95% CI 1.21-2.23, P < 0.001) and being exposed to a SARS-CoV-2 infected co-worker (OR 1.30,95% CI 0.97-1.74, P = 0.016) resulted in higher seropositivity rate. Even if in-hospital exposure may play a significant role, increased infection risk is most likely attributable to household contact.

BACKGROUND: The impact of the COVID-19 pandemic on functional exercise capacity seemed quickly clinically evident. The objective of this study was to assess the functional exercise capacity of patients with severe COVID-19 and to evaluate the effect of a telerehabilitation program in the specific context of the COVID-19 pandemic. METHOD: Patients hospitalized for severe or critical COVID-19 were recruited. The functional exercise capacity (1-min sit-to-stand test (STST)) was prospectively quantified at discharge. A telerehabilitation program was then proposed. A control group was composed with the patients refusing the program. RESULTS: At discharge, none of the 48 recruited patients had a STST higher than the 50th percentile and 77% of them were below the 2.5th percentile. SpO2 was 92.6 ± 3.0% after STST and 15 patients had oxygen desaturation. After 3-months of follow-up, the number of repetitions during STST significantly increased either in telerehabilitation (n = 14) (p < 0.001) or in control groups (n = 13) (p = 0.002) but only one patient had a result higher than the 50th percentile (in Telerehabilitation group) and 37% of them were still under the 2.5th percentile for this result. The improvement was significantly and clinically greater after the telerehabilitation program (p = 0.005). No adverse events were reported by the patients during the program. CONCLUSIONS: Patients hospitalized for COVID-19 have a low functional exercise capacity at discharge and the recovery after three months is poor. The feasibility and the effect of a simple telerehabilitation program were verified, this program being able to substantially improve the functional recovery after three months.

The first wave of coronavirus disease 2019 (COVID-19) was particularly dramatic for kidney transplant recipients (KTRs) around the world.1 A recent European registry study showed 28-day mortality and intensive care unit (ICU) admission rates at 22% and 21%, respectively.2 In the United States, a multicenter cohort study revealed a 28-day mortality rate at 18%.3 Fortunately, patients from our tertiary KT center were less impacted with mortality and ICU admission rates at 11% and 11%, respectively. [...]

Dear Editor, Hypoxaemia is a typical feature of the coronavirus disease 2019 (COVID-19). The rapid rise in the number of patients requiring oxygen therapy during the pandemic may cause a sharp increase in oxygen demands and potential threats of supply disruption, particularly in developing countries1 or nursing homes. Moreover, the use of elevated oxygen flows via nasal cannula raises concerns about exhaled air dispersion distance and the potential risk of generating aerosols [...]

Coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is particularly life threatening in patients with kidney failure under dialysis, with mortality rate at 28 days of 21.2% in the ERA-EDTA registry and 25% in the ERACODA (European Renal Association COVID-19 Database) database. [...]

Patients on in-center maintenance hemodialysis (HD) are at potentially high risk of acquiring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease 2019 [COVID-19]) inside the HD unit, due to social contacts during the frequent HD sessions. Data concerning the dynamics of anti–SARS-CoV-2 antibodies in patients on HD are scarce. [...]

Background Evidence of immune-mediated neurological syndromes associated with the severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is limited. We therefore investigated clinical, serological and CSF features of coronavirus disease 2019 (COVID-19) patients with neurological manifestations. Methods Consecutive COVID-19 patients with neurological manifestations other than isolated anosmia and/or non-severe headache, and with no previous neurological or psychiatric disorders were prospectively included. Neurological examination was performed in all patients and lumbar puncture with CSF examination was performed when not contraindicated. Serum anti-gangliosides antibodies were tested when clinically indicated. Results Of the 349 COVID-19 admitted to our center between March 23rd and April 24th 2020, 15 patients (4.3%) had neurological manifestations and fulfilled the study inclusion/exclusion criteria. CSF examination was available in 13 patients and showed lymphocytic pleocytosis in 2 patients: 1 with anti-contactin-associated protein 2 (anti-Caspr2) antibody encephalitis and 1 with meningo-polyradiculitis. Increased serum titer of anti-GD1b antibodies was found in three patients and was associated with variable clinical presentations, including cranial neuropathy with meningo-polyradiculitis, brainstem encephalitis and delirium. CSF PCR for SARS-CoV-2 was negative in all patients. Conclusions In SARS-Cov-2 infected patients with neurological manifestations, CSF pleocytosis is associated with para- or post-infectious encephalitis and polyradiculitis. Anti-GD1b and anti-Caspr2 autoantibodies can be identified in certain cases, raising the question of SARS-CoV-2-induced secondary autoimmunity.

Halil Yildiz,1,&ast; Diego Castanares-Zapatero,2,&ast; Guillaume Pierman,1 Lucie Pothen,1 Julien De Greef,1 Frank Aboubakar Nana,3 Hector Rodriguez-Villalobos,4 Leila Belkhir,1 Jean Cyr Yombi1 1Department of Internal Medicine and Infectious Diseases, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain (UCLouvain), Brussels, Belgium; 2Department of Intensive Care Unit, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, Belgium; 3Department of Pneumology, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, Belgium; 4Department of Microbiology, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, Belgium&ast;These authors contributed equally to this workCorrespondence: Halil YildizDepartment of Internal Medicine and Infectious Diseases, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, 10 avenue hippocrate, Brussels, BelgiumTel +3227641902Fax +3227641046Email halil.yildiz@uclouvain.beIntroduction: The neutrophil-to-lymphocyte ratio (NLR) could be a predictive factor of severe COVID-19. However, most relevant studies are retrospective, and the optimal NLR cut-off point has not been determined. The objective of our research was identification and validation of the best NLR cut-off value on admission that could predict high in-hospital mortality in COVID-19 patients.Methods: Medical files of all patients admitted for COVID-19 pneumonia in our dedicated COVID-units between March and April 2020 (derivation cohort) and between October and December 2020 (validation cohort) were reviewed.Results: Two hundred ninety-nine patients were included in the study (198 in the derivation and 101 in the validation cohort, respectively). Youden’s J statistic in the derivation cohort determined the optimal cut-off value for the performance of NLR at admission to predict mortality in hospitalized patients with COVID-19. The NLR cut-off value of 5.94 had a sensitivity of 62% and specificity of 64%. In ROC curve analysis, the AUC was 0.665 [95% CI 0.530– 0.801, p= 0.025]. In the validation cohort, the best predictive cut-off value of NLR was 6.4, which corresponded to a sensitivity of 63% and a specificity of 64% with AUC 0.766 [95% CI 0.651– 0.881, p < 0.001]. When the NLR cut-off value of 5.94 was applied in the validation cohort, there was no significant difference in death and survival in comparison with the derivation NLR cut-off. Net reclassification improvement (NRI) analysis showed no significant classification change in outcome between both NLR cut-off values (NRI:0.012, p=0.31).Conclusion: In prospective analysis, an NLR value of 5.94 predicted high in-hospital mortality upon admission in patients hospitalized for COVID-19 pneumonia.Keywords: neutrophil-to-lymphocyte ratio, coronavirus disease, SARS-CoV-2 infection, COVID-19, risk factors, laboratory markers

Background: Patients with coronavirus disease (COVID-19) can develop severe hypoxemia. Meeting the soaring demands of oxygen may be a challenge. Objective: To test the efficacy of an easily handmade system, the double-trunk mask (DTM), in reducing oxygen consumption while maintaining patient’s oxygenation level. Methods: Hospitalized adults with COVID-19 and hypoxemia treated with low-flow oxygen therapy we recruited. The standard oxygen delivery system was replaced by the DTM with nasal cannula for 30 minutes with an oxygen output adapted to maintain an identical oxygen saturation by pulse oximetry. The standard oxygen delivery system was then reinstated for 30 minutes. Primary outcome was the absolute change in oxygen flow between the standard delivery systems and the DTM. Secondary outcomes were changes in blood gases, vital parameters and patient comfort. Results: Eleven patients were analyzed (mean age 61 years; 27% male). Compared with standard delivery systems, the oxygen output was significantly reduced with the DTM (median, 5 vs 1.5 L/min (95% CI -4 to -1.5, p=0.003)) when oxygen saturation and arterial oxygen tension remained stable. The DTM was also associated with a significant but slight increase in arterial carbon dioxide tension (median, 36 mmHg vs 37 mmHg, p=0.006), and respiratory rate (median, 26 vs 30 breaths/min, p=0.05). Other parameters were unaltered. The DTM was generally judged less comfortable than the baseline oxygen delivery system, especially in patients requiring low oxygen flow at baseline. Conclusions: The DTM is a simple and efficient system to reduce oxygen consumption. This may have clinical implications in places where oxygen supplies are limited.

Coronavirus disease 2019 (COVID-19) is commonly associated with kidney damage, and the angiotensin converting enzyme 2 (ACE2) receptor for SARS-CoV-2 is highly expressed in the proximal tubule cells. Whether patients with COVID-19 present specific manifestations of proximal tubule dysfunction remains unknown. To test this, we examined a cohort of 49 patients requiring hospitalization in a large academic hospital in Brussels, Belgium. There was evidence of proximal tubule dysfunction in a subset of patients with COVID-19, as attested by low-molecular-weight proteinuria (70-80%), neutral aminoaciduria (46%), and defective handling of uric acid (46%) or phosphate (19%). None of the patients had normoglycemic glucosuria. Proximal tubule dysfunction was independent of pre-existing comorbidities, glomerular proteinuria, nephrotoxic medications or viral load. At the structural level, kidneys from patients with COVID-19 showed prominent tubular injury, including in the initial part of the proximal tubule, with brush border loss, acute tubular necrosis, intraluminal debris, and a marked decrease in the expression of megalin in the brush border. Transmission electron microscopy identified particles resembling coronaviruses in vacuoles or cisternae of the endoplasmic reticulum in proximal tubule cells. Among features of proximal tubule dysfunction, hypouricemia with inappropriate uricosuria was independently associated with disease severity and with a significant increase in the risk of respiratory failure requiring invasive mechanical ventilation using Cox (adjusted hazard ratio 6.2, 95% CI 1.9-20.1) or competing risks (adjusted sub-distribution hazard ratio 12.1, 95% CI 2.7-55.4) survival models. Thus, our data establish that SARS-CoV-2 causes specific manifestations of proximal tubule dysfunction and provide novel insights into COVID-19 severity and outcome., Graphical abstract

In December, 2019, a new acute respiratory syndrome appeared in Wuhan, China. The disease, later named COVID19, is caused by a new coronavirus (SARS-CoV-2) [1e3]. Clinical presentation is mild in about 80%, moderate to severe in 15% and critical in 5% of cases. [...]

To the Editor, Recently Herraiz et al. [1] found that the percentage of positive tests in asymptomatic women admitted to delivery was only 0.5% during the post-peak period in Madrid(1). Their results was Concordant with those of Gagliardi et al. [2] but discordant with those found in others cities such as New York [3], [4], [5]. Bianco et al. showed that more than 15% of asymptomatic maternity patients tested positive for Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection despite having screened negative with the use of a telephone screening tool. [...]

Numerous cases of e-cigarette, or vaping, associated lung injury (EVALI) have recently prompted an investigation of the outbreak in the US [1]. Only two non-fatal cases have been reported so far in Europe: one case of hypersensitivity pneumonia in the UK after the use of flavoured e-cigarette liquid by a young adolescent [2], and one US imported case recently described in Spain [3]. To our knowledge, this is the first report of a fatal EVALI case in Europe. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Marliere has nothing to disclose. Conflict of interest: Dr. Hoton has nothing to disclose. Conflict of interest: Dr. De Greef has nothing to disclose. Conflict of interest: Dr. Belkhir has nothing to disclose. Conflict of interest: Dr. Jacquet has nothing to disclose. Conflict of interest: Dr. Wallemacq has nothing to disclose. Conflict of interest: Dr. Gohy has nothing to disclose.

Rationale & Objective The world is facing a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although kidney transplant recipients are at increased risk for viral infections, the impact of their chronic immunosuppressed status on the risk for acquiring coronavirus disease 2019 (COVID-19) and disease severity is unknown. Study Design All cases of COVID-19 infection in our cohort of kidney transplant recipients were prospectively monitored. Clinical features, management, and outcomes were recorded. A standard strategy of immunosuppression minimization was applied: discontinue the antimetabolite drug and reduce trough levels of calcineurin or mammalian target of rapamycin inhibitors. Unless contraindicated, hydroxychloroquine was administered only to hospitalized patients. Setting & Participants 22 COVID-19 infections were diagnosed in our cohort of 1,200 kidney transplant recipients. Results Most common initial symptoms included fever, cough, or dyspnea. 18 (82%) patients required hospitalization. Of those patients, 3 had everolimus-based immunosuppression. Computed tomography of the chest at admission (performed in 15 patients) showed mild (n=3), moderate (n=8), extensive (n=1), severe (n=2), and critical (n=1) involvement. Immunosuppression reduction was initiated in all patients. Hydroxychloroquine was administered to 15 patients. 11 patients required supplemental oxygen; 2 of them were admitted to an intensive care unit (ICU) with mechanical ventilation. After a median of 10 days, 13 kidney transplant recipients were discharged, 2 were hospitalized in non-ICU units, 1 was in the ICU, and 2 patients had died. Limitations Small sample size and short follow-up. Conclusions The clinical presentation of COVID-19 infection was similar to that reported in the general population. A standard strategy of immunosuppression minimization and treatment was applied, with 11% mortality among kidney transplant recipients hospitalized with COVID-19 infection.