Impact of the COVID-19 pandemic on Clostridioides difficile infection in a tertiary healthcare institution in Belgium.

OBJECTIVES: Clostridioides difficile infection (CDI) causes the greatest number of healthcare-associated infectious diarrhoea. CDIs are transmitted by direct and indirect patient-to-patient contact and risk increases with the use of antibiotics. Since early 2020, the COVID-19 pandemic has affected healthcare systems in many ways including substantial changes in hygiene behaviour. The aim of this study was to assess whether CDI incidence differed during the COVID-19 pandemic compared to a year before. METHODS: All tests for suspected CDI cases were recorded for a hospital in Brussels, Belgium. The percentage of CDI-positive results and incidences (total and healthcare-associated (HA)-CDI)) for years 2019, 2020, 2021, and 2022 were calculated. Antibiotic consumption was analysed for years 2019 and 2020. RESULTS: Since the COVID-19 pandemic struck, a significant reduction of up to 39% was observed in the number of Clostridioides difficile stool tests in our hospital. A significant decrease in the percentage of positive tests and a 50% decrease in the incidence of CDI (total and HA-CDI) was found for 2020 compared with 2019 and confirmed for years 2021 and 2022. The decrease in CDI incidence was mostly marked in haematology, nephrology, and gastroenterology units. No significant change in the use of antibiotics was found. CONCLUSION: The global decrease in CDI incidence observed in our hospital was not associated with a change in the use of antibiotics. The control measures implemented to prevent COVID-19 transmission may explain a reduction in CDI incidence. An underdiagnosis of CDI cannot be excluded.

There Is a Risk of Spread During a Nebulization Session in a Patient with COVID-19.

Introduction: A hypothetical risk of SARS-CoV-2 airborne transmission through nebulization was suggested based on a potential environmental contamination by the fugitive aerosol emitted in the environment during the procedure. The aim of this study was to verify this risk from the fugitive aerosol emitted by COVID-19 patients during one nebulization session. Methods: In this cohort study, COVID-19 patients treated with nebulization were recruited at their admission to the hospital. Patients had to perform a nebulization session while a BioSampler® and a pump were used to vacuum the fugitive aerosol and collect it for SARS-CoV-2 RNA detection. Results: Ten consecutive patients hospitalized with COVID-19 were recruited. The median viral load was 6.5 × 106 copies/mL. Two out of the 10 samples from the fugitive aerosol collected were positive to SARS-CoV-2. Conclusion: The risk of fugitive aerosol contamination with SARS-CoV-2 during nebulization has now been verified.

Evaluation of a commercial interferon-γ release assay for the detection of SARS-CoV-2 T-cell response after vaccination.

Objective: Evidence regarding the role of cellular immunity in protecting against COVID-19 is emerging. To better assess immune status, simple and robust assays measuring specific T-cell responses associated with humoral responses are needed. We aimed to evaluate the Quan-T-Cell SARS-CoV-2 test for measuring cellular immune responses in vaccinated healthy and immunosuppressed subjects. Methods: T-cell responses were assessed in healthy vaccinated and unvaccinated and unexposed healthcare workers to determine the sensitivity and specificity of the EUROIMMUN SARS-CoV-2 Quan-T-Cell IGRA test performed on vaccinated kidney transplant recipients (KTRs). Results: The EUROIMMUN SARS-CoV-2 Quan-T-Cell IGRA test showed good sensitivity (87.2%) and specificity (92.3%) at the calculated 147 mIU/mL cutoff, with an 88.33% accuracy. In KTRs, specific cellular immunity was lower than the antibody response; however, those with a positive IGRA result produced as much IFN-γ as healthy individuals. Conclusions: The EUROIMMUN SARS-CoV-2 Quan-T-Cell IGRA test showed good sensitivity and specificity for the detection of specific T-cell responses against the SARS-CoV-2 spike protein. These results present an additional tool for better management of COVID-19, especially in vulnerable populations.

Streptococcus Pneumoniae Bacteremia with Acute Kidney Injury and Transient ADAMTS13 Deficiency.

A 43-year-old woman with a medical history of splenectomy for immune thrombocytopenic purpura was diagnosed with Streptococcus pneumoniae bacteremia. Her initial complaints were fever and more importantly painful extremities that appeared cyanotic. During her hospitalisation, she never developed cardiocirculatory failure but presented acute kidney injury (AKI) with oliguria. Laboratory investigations confirmed AKI with serum creatinine 2.55 mg/dL which peaked at 6.49 mg/dL. There was also evidence for disseminated intravascular coagulation (DIC) with decreased platelet count, low fibrinogen levels, and high D-dimer levels. There were no signs of haemolytic anaemia. The initial ADAMTS13 activity was low (17%) but slowly recovered. Renal function progressively improved with supportive therapy, as opposed to the progressing skin necrosis. The association of DIC and low ADAMTS13 activity may have contributed to the severity of microthrombotic complications, even in the absence of thrombotic microangiopathy as thrombotic thrombocytopenic purpura (TTP) or pneumococcal-associated haemolytic uremic syndrome (pa-HUS).

Safety, Efficacy, and Relapse of Nirmatrelvir-Ritonavir in Kidney Transplant Recipients Infected With SARS-CoV-2.

Introduction: The efficacy of nirmatrelvir-ritonavir (NR; Paxlovid, Pfizer, New York, NY) to decrease the risk of progression to severe COVID-19 in high-risk patients has been demonstrated. However, evidence in infected kidney transplant recipients (KTRs) is lacking. Moreover, NR has significant and potentially harmful interactions with calcineurin inhibitors (CNIs). Methods: In this single-center retrospective study, we included all KTRs treated with NR from April 28 to June 3, 2022. A standard management strategy of CNI dose adaptation (discontinuation of tacrolimus 12 hours before the start of NR and administration of 20% of the cyclosporine dose) and laboratory follow-up was applied. Results: A total of 14 patients were included. Compared with day-0 (day before NR initiation), day-7 plasma creatinine concentrations and SARS-CoV-2 viral loads were similar (P = 0.866) and decreased (P = 0.002), respectively. CNI trough concentrations at the end of the treatment were satisfactory, nonetheless, with high individual variability. After a median follow-up time of 34 days, no death or viral pneumonia were observed. Nevertheless, 2 patients experienced early SARS-CoV-2 infection relapses (at day-10 and day-21) associated with an increase in SARS-CoV-2 viral loads. Conclusion: NR can be used in KTRs but requires a strict protocol of drug adaptation. We observed 2 cases of early relapse after NR treatment that need further investigations.

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.

HYGIEIA: HYpothesizing the Genesis of Infectious Diseases and Epidemics through an Integrated Systems Biology Approach.

More than two years on, the COVID-19 pandemic continues to wreak havoc around the world and has battle-tested the pandemic-situation responses of all major global governments. Two key areas of investigation that are still unclear are: the molecular mechanisms that lead to heterogenic patient outcomes, and the causes of Post COVID condition (AKA Long-COVID). In this paper, we introduce the HYGIEIA project, designed to respond to the enormous challenges of the COVID-19 pandemic through a multi-omic approach supported by network medicine. It is hoped that in addition to investigating COVID-19, the logistics deployed within this project will be applicable to other infectious agents, pandemic-type situations, and also other complex, non-infectious diseases. Here, we first look at previous research into COVID-19 in the context of the proteome, metabolome, transcriptome, microbiome, host genome, and viral genome. We then discuss a proposed methodology for a large-scale multi-omic longitudinal study to investigate the aforementioned biological strata through high-throughput sequencing (HTS) and mass-spectrometry (MS) technologies. Lastly, we discuss how a network medicine approach can be used to analyze the data and make meaningful discoveries, with the final aim being the translation of these discoveries into the clinics to improve patient care.

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.

Urine metabolomics links dysregulation of the tryptophan-kynurenine pathway to inflammation and severity of COVID-19.

SARS-CoV-2 causes major disturbances in serum metabolite levels, associated with severity of the immune response. Despite the numerous advantages of urine for biomarker discovery, the potential association between urine metabolites and disease severity has not been investigated in coronavirus disease 2019 (COVID-19). In a proof-of-concept study, we performed quantitative urine metabolomics in patients hospitalized with COVID-19 and controls using LC-MS/MS. We assessed whether metabolites alterations were associated with COVID-19, disease severity, and inflammation. The study included 56 patients hospitalized with COVID-19 (26 non-critical and 30 critical disease); 16 healthy controls; and 3 controls with proximal tubule dysfunction unrelated to SARS-CoV-2. Metabolomic profiling revealed a major urinary increase of tryptophan metabolites kynurenine (P < 0.001), 3-hydroxykynurenine (P < 0.001) and 3-hydroxyanthranilate (P < 0.001) in SARS-CoV-2 infected patients. Urine levels of kynurenines were associated with disease severity and systemic inflammation (kynurenine, r 0.43, P = 0.001; 3-hydroxykynurenine, r 0.44, P < 0.001). Increased urinary levels of neutral amino acids and imino acid proline were also common in COVID-19, suggesting specific transport defects. Urine metabolomics identified major alterations in the tryptophan-kynurenine pathway, consistent with changes in host metabolism during SARS-CoV-2 infection. The association between increased urinary levels of kynurenines, inflammation and COVID-19 severity supports further evaluation of these easily available biomarkers.

Monoclonal Antibody Therapy in Kidney Transplant Recipients With Delta and Omicron Variants of SARS-CoV-2: A Single-Center Case Series.

Rationale & Objective: 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. Study Design: Single-center retrospective study. Setting & Participants: 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. Results: 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. Limitations: Small sample size, no control group. Conclusions: 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.

Psychological distress among hospital caregivers during and after the first wave of COVID-19: Individual factors involved in the severity of symptoms expression.

Coronavirus disease 2019 has spread rapidly over the globe and has put an unprecedent psychological pressure on health care workers (HCWs). The present study aimed at quantifying the psychological consequences of the COVID-19 pandemic on HCWs during and after the first wave and identify sociodemographic, situational, and psychological risk/protective factors for symptoms severity. An online survey was sent by e-mail to all nurses and physicians employed by a teaching hospital in Brussels, Belgium. 542 (20,62%) completed the survey. 47%, 55%, 32% and 52% of participants reported posttraumatic stress, anxiety, depression and insomnia symptoms, respectively, during the peak. Two to three months later, posttraumatic symptoms emerged de novo in 54% of HCWs. It persisted in 89% of those presenting severe symptoms initially. Neuroticism was the strongest predictor of posttraumatic stress, anxiety, and insomnia. Work overload was the strongest predictor of depression and second predictor of posttraumatic stress, anxiety, and insomnia. Other significant predictors included being a nurse, the number of past traumatic experiences, avoidant coping style, and expressive suppression of emotions.

Sino-Orbital Aspergillosis in a Kidney Transplant Recipient.

Sino-orbital aspergillosis is a rare and severe infection mostly seen in immunocompromised individuals in which diagnosis may be challenging with potentially life-threatening consequences. Infection usually starts in the paranasal sinuses with secondary spreading to the adjacent orbits. Here, we report the case of a kidney transplant recipient who presented with proven invasive sino-orbital aspergillosis resulting in irreversible loss of vision despite surgical management and antifungal therapy. We review the literature with a focus on clinical presentation, diagnostic tools, and recommended treatment in the context of kidney transplantation.

Outcome of Patients with Surgical Site Infection after Craniotomy.

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.

Immunosuppression and SARS-CoV-2 Infection in Kidney Transplant Recipients.

Kidney transplant recipients (KTRs) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may have an increased risk of mortality compared with the general population and hemodialysis patients. As these patients are immunosuppressed, it might seem obvious to attribute this excess mortality to the impaired immunity induced by immunosuppression. In line with this reasoning is the low immune response, both cellular and humoral, that KTRs mount in response to the anti-SARS-CoV-2 vaccine; however, acute respiratory distress syndrome associated with coronavirus disease 2019 is triggered by a state of inflammation and cytokine release syndrome that lead to pulmonary damage and increased mortality. In that context, immunosuppressive treatment dampening the immune response could, in theory, be potentially beneficial. This review aims at analyzing the current knowledge on the impact of immunosuppressive treatment on mortality in SARS-CoV-2-infected KTRs, the optimal management of immunosuppression in the coronavirus disease 2019 era, and the vaccine response and management in immunosuppressed KTRs.

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.