Systems on Top of Nasal Cannula Improve Oxygen Delivery in Patients with COVID-19: a Randomized Controlled Trial.

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.

Non-specific symptoms and post-treatment Lyme disease syndrome in patients with Lyme borreliosis: a prospective cohort study in Belgium (2016-2020).

BACKGROUND: Patients with Lyme borreliosis (LB) may report persisting non-specific symptoms such as fatigue, widespread musculoskeletal pain or cognitive difficulties. When present for more than 6 months and causing a reduction in daily activities, this is often referred to as post-treatment Lyme disease syndrome (PTLDS). This study aimed to compare the occurrence of symptoms between LB patients and controls, to estimate the proportion of LB patients developing PTLDS and to identify risk factors. METHODS: A prospective cohort study was set up including three subpopulations: patients with an erythema migrans (EM) (i) or disseminated/late LB (ii) and a non-LB control group (iii). At 6- and 12-months follow-up, the occurrence of several symptoms, including six symptoms used to define PTLDS, i.e. muscle pain, joint pain, fatigue, memory problems, difficulties concentrating and problems finding words, and impact on daily activities, was compared between LB patients and controls. Finally, the proportion of LB patients developing PTLDS as defined by the Infectious Disease Society of America was estimated, including a time frame for symptoms to be present. RESULTS: Although the risk of presenting PTLDS-related symptoms was significantly higher in EM patients (n = 120) compared to controls (n = 128) at 6 months follow-up, the risk of presenting at least one of these symptoms combined with impact on daily activities was not significantly higher in EM patients, at either 6- or 12-months follow-up. A significant association was found between disseminated/late LB (n = 15) and the occurrence of any PTLDS-symptom with an impact on daily activities at both time points. The proportion of patients with PTLDS was estimated at 5.9% (95% CI 2.7-12.9) in EM patients and 20.9% (95% CI 6.8-64.4) in patients with disseminated/late LB (RR = 3.53, 95% CI 0.98-12.68, p = 0.053). No significant risk factors were identified, which may be explained by small sample sizes. CONCLUSIONS: In our study, PTLDS was present in both LB cohorts, yet with a higher percentage in disseminated/late LB patients. Additional research is needed into risk factors for and causes of this syndrome. In addition, development and validation of standardized methods to assess the PTLDS case definition, easily applicable in practice, is of great importance.

A comparative analysis of the outcomes of patients with influenza or COVID-19 in a tertiary hospital in Belgium.

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.

Relapsing-remitting Optic Neuropathy in an HIV-infected Patient: Secondary Auto-immune Optic Neuropathy or Infectious Optic Neuropathy? A Case Report and Review of the Literature.

It can be challenging to disentangle human immunodeficiency virus (HIV)-related infectious optic neuropathy and secondary triggered auto-immune disease when an HIV positive patient presents with vision loss. We report a 44-year-old untreated HIV positive Congolese woman who presented with two episodes of vision loss associated with pain in first her left eye and then her right eye and was diagnosed with a relapsing optic neuropathy. A correlation was observed between the clinical activity and cerebrospinal fluid viral load, CD4-count in the blood and magnetic resonance imaging signs of blood - optic nerve barrier breakdown. CD4 cell counts and viral loads are great clinical features to identify the type of acute optic neuropathy since differential diagnosis between an infectious optic neuropathy or an auto-immune induced optic neuropathy such as neuromyelitis optica spectrum disorder or immune reconstitution inflammatory syndrome can be puzzling.

Clinical usefulness of fully automated chemiluminescent immunoassay for quantitative antibody measurements in COVID-19 patients.

Since December 2019, we have been in the battlefield with a new threat to the humanity, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), characterized by viral pneumonia. It may be asymptomatic or cause various symptoms, ranging from flu-like symptoms to acute respiratory distress syndrome and eventually death. At present, the only reliable test for COVID-19 diagnosis is quantitative reverse transcriptase-polymerase chain reaction. Assessing the immune response against SARS-CoV-2 could increase the detection sensitivity of infected population. Hereby, we report the performances of a fully automated chemiluminescent immunoassay (CLIA) on 276 serum samples. One hundred samples obtained from COVID-19 negative subjects (COVID-19 free) were analyzed to evaluate the diagnostic specificity of antibody (Ab) detection. Thereafter, 176 samples obtained from 125 patients with confirmed COVID-19 (COVID-19 patients) were selected to assess the diagnostic sensitivity of the CLIA. All samples were analyzed on MAGLUMI 800 platform. All COVID-19 free samples had Ab levels below the cutoff values. Hence, the diagnostic specificity was estimated at 100% (95% confidence interval [CI] = 96.3-100.0; positive predictive value = 100%). By the 18th day from the onset of symptoms, we reached an optimal diagnostic sensitivity (more than 95.0%) In fact, the diagnostic sensitivity increased over time and between 15 and 25 days after symptoms onset, reached 95.5% (95% CI = 84.9-99.2). The new automated CLIA analyzer appeared to be a robust and reliable method to measure specific Ab against COVID-19 at high throughput. Our data suggest that combining Ab and nucleic acid detection could increase diagnostic sensitivity.

Determinants of IgG antibodies kinetics after severe and critical COVID-19.

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.

Serum uric acid, disease severity and outcomes in COVID-19.

BACKGROUND: The severity of coronavirus disease 2019 (COVID-19) is highly variable between individuals, ranging from asymptomatic infection to critical disease with acute respiratory distress syndrome requiring mechanical ventilation. Such variability stresses the need for novel biomarkers associated with disease outcome. As SARS-CoV-2 infection causes a kidney proximal tubule dysfunction with urinary loss of uric acid, we hypothesized that low serum levels of uric acid (hypouricemia) may be associated with severity and outcome of COVID-19. METHODS: In a retrospective study using two independent cohorts, we investigated and validated the prevalence, kinetics and clinical correlates of hypouricemia among patients hospitalized with COVID-19 to a large academic hospital in Brussels, Belgium. Survival analyses using Cox regression and a competing risk approach assessed the time to mechanical ventilation and/or death. Confocal microscopy assessed the expression of urate transporter URAT1 in kidney proximal tubule cells from patients who died from COVID-19. RESULTS: The discovery and validation cohorts included 192 and 325 patients hospitalized with COVID-19, respectively. Out of the 517 patients, 274 (53%) had severe and 92 (18%) critical COVID-19. In both cohorts, the prevalence of hypouricemia increased from 6% upon admission to 20% within the first days of hospitalization for COVID-19, contrasting with a very rare occurrence (< 1%) before hospitalization for COVID-19. During a median (interquartile range) follow-up of 148 days (50-168), 61 (12%) patients required mechanical ventilation and 93 (18%) died. In both cohorts considered separately and in pooled analyses, low serum levels of uric acid were strongly associated with disease severity (linear trend, P < 0.001) and with progression to death and respiratory failure requiring mechanical ventilation in Cox (adjusted hazard ratio 5.3, 95% confidence interval 3.6-7.8, P < 0.001) or competing risks (adjusted hazard ratio 20.8, 95% confidence interval 10.4-41.4, P < 0.001) models. At the structural level, kidneys from patients with COVID-19 showed a major reduction in urate transporter URAT1 expression in the brush border of proximal tubules. CONCLUSIONS: Among patients with COVID-19 requiring hospitalization, low serum levels of uric acid are common and associate with disease severity and with progression to respiratory failure requiring invasive mechanical ventilation.

Optimal sampling strategies for darunavir and external validation of the underlying population pharmacokinetic model.

PURPOSE: A variety of diagnostic methods are available to validate the performance of population pharmacokinetic models. Internal validation, which applies these methods to the model building dataset and to additional data generated through Monte Carlo simulations, is often sufficient, but external validation, which requires a new dataset, is considered a more rigorous approach, especially if the model is to be used for predictive purposes. Our first objective was to validate a previously published population pharmacokinetic model of darunavir, an HIV protease inhibitor boosted with ritonavir or cobicistat. Our second objective was to use this model to derive optimal sampling strategies that maximize the amount of information collected with as few pharmacokinetic samples as possible. METHODS: A validation dataset comprising 164 sparsely sampled individuals using ritonavir-boosted darunavir was used for validation. Standard plots of predictions and residuals, NPDE, visual predictive check, and bootstrapping were applied to both the validation set and the combined learning/validation set in NONMEM to assess model performance. D-optimal designs for darunavir were then calculated in PopED and further evaluated in NONMEM through simulations. RESULTS: External validation confirmed model robustness and accuracy in most scenarios but also highlighted several limitations. The best one-, two-, and three-point sampling strategies were determined to be pre-dose (0 h); 0 and 4 h; and 1, 4, and 19 h, respectively. A combination of samples at 0, 1, and 4 h was comparable to the optimal three-point strategy. These could be used to reliably estimate individual pharmacokinetic parameters, although with fewer samples, precision decreased and the number of outliers increased significantly. CONCLUSIONS: Optimal sampling strategies derived from this model could be used in clinical practice to enhance therapeutic drug monitoring or to conduct additional pharmacokinetic studies.

SARS-CoV-2 causes a specific dysfunction of the kidney proximal tubule.

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.

In-hospital management of persons with haemophilia and COVID-19: Practical guidance.

A new disease (COVID-19) caused by a coronavirus (SARS-CoV-2) that appeared in China at the end of 2019 is currently spreading globally. This emerging virus is mainly responsible for respiratory tract infections and potentially fatal pneumonia, mainly in more frail patients. Persons with haemophilia of variable severity and from all parts of the world will likely be infected and develop COVID-19. We here propose practical guidance for the in-hospital specific management of haemophilia persons with COVID-19 including their possible transfer to the intensive care unit. Rapid identification of the haemophilia status, undelayed and regular liaison with the haemophilia team, proper therapy with factor concentrates or alternative treatments appear instrumental to prevent haemophilia-related complications in this setting. Information of patients and their families about COVID-19, psychological support and good appreciation of the impact of haemophilia on therapeutic decisions including end-of-life directives are also addressed.

A biological profile for diagnosis and outcome of COVID-19 patients.

Objectives As severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) pandemic is increasing its victims on a global scale with recurring outbreaks, it remains of outmost importance to rapidly identify people requiring an intensive care unit (ICU) hospitalization. The aim of this study was to identify Coronavirus Disease 2019 (COVID-19) biomarkers, to investigate their correlation with disease severity and to evaluate their usefulness for follow-up. Methods Fifty patients diagnosed with SARS-Cov-2 were included in March 2020. Clinical and biological data were collected at admission, during hospitalization and one month after discharge. Patients were divided into two severity groups: non-ICU (28) and ICU and/or death (22) to stratify the risk. Results Blood parameters in COVID-19 patients at admission showed increased C-reactive protein (CRP) (100%), ferritin (92%), lactate dehydrogenase (LDH) (80%), white blood cell (WBC) count (26%) with lymphopenia (52%) and eosinopenia (98%). There were significant differences in levels of CRP, ferritin, D-dimers, fibrinogen, lymphocyte count, neutrophil count and neutrophil-to-lymphocyte ratio (NLR) among the two severity groups. Mapping of biomarker's kinetics distinguished early and late parameters. CRP, ferritin, LDH, lymphopenia and eosinopenia were present upon admission with a peak at the first week. Late biomarkers such as anemia, neutrophilia and elevated liver biomarkers appeared after one week with a peak at three weeks of hospitalization. Conclusions We confirmed that high-values of CRP, NLR, D-dimers, ferritin as well as lymphopenia and eosinopenia were consistently found and are good markers for risk stratification. Kinetics of these biomarkers correlate well with COVID-19 severity. Close monitoring of early and late biomarkers is crucial in the management of critical patients to avoid preventable deaths.

Coinfection of Mycobacterium malmoense and Mycobacterium chimaera in a kidney transplant recipient: A case report and review of the literature.

Nontuberculous mycobacteria (NTM) are ubiquitous organisms found in soil and water. Solid organ recipients are at increased risk of NTM infections due to impaired immunity. Although the NTM infections rate is low, it increases morbidity and the risk of mortality. Diagnosis is often delayed because of the lack of specific clinical symptoms and requires a high index of suspicion. Management may be challenging: long-term treatment with risks of side effects and interactions with immunosuppressive regimen; reduction of immunosuppression; and risk of allograft rejection. Prognosis is widely variable. We report the first case of Mycobacterium malmoense chest infection with concomitant Mycobacterium chimaera urinary tract infection in a kidney transplant recipient. The evolution was marked by poor tolerance of the treatment with severe adverse events and disabled functional status.

Time trend of clinical cases of Lyme disease in two hospitals in Belgium, 2000-2013.

BACKGROUND: As several studies indicated an increase in Lyme disease (LD), notably in neighbouring countries, concerns have arisen regarding the evolution of Lyme disease in Belgium. In order to confirm or infirm the increase of LD in Belgium, we focused on hospital admissions of patients diagnosed with LD between 2000 and 2013 based on hospital admission databases from two hospitals in Belgium. METHODS: Hospital databases are a stable recording system. We did a retrospective analysis of the medical files of patients hospitalized with Lyme disease in two Belgian hospitals between 2000 and 2013. RESULTS: The annual number of cases of LD for the two studied Belgian hospitals remained stable between 2000 and 2013, ranging from 1 for the Cliniques universitaires Saint-Luc to 15 for the the Clinique Saint-Pierre. No increasing trend were noted in the estimated annual incidence rate but the average estimated annual incidence rate was higher for the hospital Saint-Pierre (8.1 ± 3.7 per 100,000 inhabitants) than Saint-Luc (2.2 ± 1.5 per 100,000 inhabitants). The number of hospital cases of LD peaked between June and November. CONCLUSIONS: Based on hospital admissions with LD, no increasing trend was observed for the period 2000-2013 in the two studied Belgian hospitals. This is in line with other studies carried out in Belgium.

Surgical management of liver hydatid disease: subadventitial cystectomy versus resection of the protruding dome.

BACKGROUND: The aim of this study was to compare postoperative outcome and long-term results after management of liver hydatid cysts (LHC) by subadventitial cystectomy (SC) and resection of the protruding dome (RPD) in two tertiary liver surgery centers. METHODS: Medical records of 52 patients who underwent SC in one center, and 27 patients who underwent RPD in another center between 1991 and 2011 were reviewed. Patients underwent long-term follow-up, including serology tests and morphological examinations. RESULTS: Postoperative mortality was nil. The rate of severe morbidity was 7.7 and 22% (p = 0.082), while the rate of serological clearing-up was 20 and 13.3% after SC and RPD, respectively (p = 1.000). After a mean follow-up of 41 months (1-197), four patients developed a long-term cavity-related complication (LTCRC) after RPD (including one recurrence) and none after SC (p = 0.012). All LTCRCs occurred in patients with hydatid cysts located at the liver dome; three required an invasive procedure by either puncture aspiration injection re-aspiration (N = 1) or repeat surgery (N = 2). CONCLUSIONS: RPD exposes to specific LTCRC, especially when hydatid cysts are located at the liver dome, while SC allows ad integrum restoration of the operated liver. Therefore, SC should be considered as the standard surgical treatment for LHC in experienced hepato-pancreato-biliary centers.