SARS-CoV-2 RNA and antibodies in tear fluid.

BACKGROUND/AIMS: SARS-CoV-2 is highly contagious. More evidence concerning extrapulmonary transmission routes such as the eyes is urgently needed. Although the humoral immune response is important in the viral containment, the local response in tears has not yet been studied. The aim of our study was twofold: to assess the prevalence of both SARS-CoV-2 RNA and antibodies in tear fluid. METHODS: In a first series, nasopharyngeal sampling and tear sampling by Schirmer test strips were performed in 26 acutely ill patients with COVID-19 to assess the presence of SARS-CoV-2 RNA by reverse transcription PCR. In a second series, IgG and IgA responses to SARS-CoV-2 spike protein in serum and tear fluid of convalescent individuals (n=22) were compared with control individuals (n=15) by ELISA. RESULTS: SARS-CoV-2 RNA was detected in tears of 7/26 (26.9%) patients with COVID-19. None of them had ocular symptoms. Convalescent individuals displayed a significant higher ratio of IgG (p<0.0001) and IgA (p=0.0068) in tears compared with control individuals. A sensitivity of 77.3% and specificity of 93.3% was observed for IgG, and 59.1% and 100% for IgA. CONCLUSIONS: Our results demonstrate the presence of SARS-CoV-2 RNA and a local IgG and IgA immune response in tear fluid. These data confirm the possibility of SARS-CoV-2 transmission through tear fluid and the importance of the eye as a first defence against SARS-CoV-2, indicating the potential of tears as a non-invasive surrogate for serum in monitoring the host immune response.

Beyond Guidelines and Reports on Bacterial Co-/Superinfections in the Context of COVID-19: Why Uniformity Matters.

BACKGROUND: In the period following the declaration of the COVID-19 pandemic, more evidence became available on the epidemiology of bacterial co-/superinfections (bCSs) in hospitalized COVID-19 patients. Various European therapeutic guidelines were published, including guidance on rational antibiotic use. METHODS: In this letter to the editor, we provide an overview of the largest meta-analyses or prospective studies reporting on bCS rates in COVID-19 patients and discuss why the reader should interpret the results of those reports with care. Moreover, we compare different national and international COVID-19 therapeutic guidelines from countries of the European Union. Specific attention is paid to guidance dedicated to rational antibiotic use. RESULTS: We found a significant heterogeneity in studies reporting on the epidemiology of bCSs in COVID-19 patients. Moreover, European national and international guidelines differ strongly from each other, especially with regard to the content and extent of antibiotic guidance in hospitalized COVID-19 patients. CONCLUSION: A standardized way of reporting on bCSs and uniform European guidelines on rational antibiotic use in COVID-19 patients are crucial for antimicrobial stewardship teams to halt unnecessary antibiotic use in the COVID-19 setting.

Healthcare-Associated COVID-19 across Five Pandemic Waves: Prediction Models and Genomic Analyses.

BACKGROUND: Healthcare-associated SARS-CoV-2 infections need to be explored further. Our study is an analysis of hospital-acquired infections (HAIs) and ambulatory healthcare workers (aHCWs) with SARS-CoV-2 across the pandemic in a Belgian university hospital. METHODS: We compared HAIs with community-associated infections (CAIs) to identify the factors associated with having an HAI. We then performed a genomic cluster analysis of HAIs and aHCWs. We used this alongside the European Centre for Disease Control (ECDC) case source classifications of an HAI. RESULTS: Between March 2020 and March 2022, 269 patients had an HAI. A lower BMI, a worse frailty index, lower C-reactive protein (CRP), and a higher thrombocyte count as well as death and length of stay were significantly associated with having an HAI. Using those variables to predict HAIs versus CAIs, we obtained a positive predictive value (PPV) of 83.6% and a negative predictive value (NPV) of 82.2%; the area under the ROC was 0.89. Genomic cluster analyses and representations on epicurves and minimal spanning trees delivered further insights into HAI dynamics across different pandemic waves. The genomic data were also compared with the clinical ECDC definitions for HAIs; we found that 90.0% of the 'definite', 87.8% of the 'probable', and 70.3% of the 'indeterminate' HAIs belonged to one of the twenty-two COVID-19 genomic clusters we identified. CONCLUSIONS: We propose a novel prediction model for HAIs. In addition, we show that the management of nosocomial outbreaks will benefit from genome sequencing analyses.

Healthcare-Associated SARS-CoV-2 Reinfection after 3 Months with a Phylogenetically Distinct Omicron Variant: A Case Report.

This case report describes a 60-year-old female patient suffering from systemic sclerosis, for which she received immunomodulatory drugs. Her first SARS-CoV-2-positive nasopharyngeal sample was obtained in the emergency department, on 31 January 2022. Whole genome sequencing confirmed infection with Omicron BA.1.1. Her hospital stay was long and punctuated by many complications, including admission to the intensive care unit. At the beginning of April 2022, she started complaining of increased coughing, for which another SARS-CoV-2 RT-qPCR test was performed. The latter nasopharyngeal swab showed a strongly positive result. To support the theory of healthcare-associated reinfection, whole genome sequencing was performed and confirmed reinfection with Omicron BA.2. Since this patient was one of ten positive cases in this particular ward, a hospital outbreak investigation was performed. Whole genome sequencing data were available for five of these ten patients and showed a cluster of four patients with ≤2 small nucleotide polymorphisms difference.

Fear for CoViD-19 and reluctance to work among health care workers during the epidemic, a prospective monocentric cohort study.

BACKGROUND: Health care workers (HCW) are facing the Coronavirus disease 2019 (CoViD-19) epidemic. Consequently, psychological impairments have been reported. However, literature showed controversial results on the relationship between gender, frontline HCW, and psychological impairments. This study aims to investigate CoViD-19 fear and reluctance to work in HCW. METHODS: Employees who worked between April and October 2020 at the UZ Brussel were included. Data were prospectively collected in 2 phases through a survey together with serological tests. Sampling strategy was convenience sampling. RESULTS: About 2,336 employees completed the study and response rate was 70%. The prevalence of severe CoViD-19 fear in participants increased from 9% to 15%. Employees showing way less motivation rose from 9% to 14%. The seroprevalence was 7.4% and 7.9%. Multivariable analysis found a relation between reluctance to work, study phase, female gender, shortage of personal protective equipment, and poor education on CoViD-19. Furthermore, CoViD-19 fear was related to the study phase, older age, female gender, being second-line HCW, reported exposure to CoViD-19 during work, and insufficient education on CoViD-19. DISCUSSION: Seroprevalence remained rather stable, but fear and reluctance to work significantly increased. Differences in time of data collection together with epidemiological setting might be responsible for conflicting data reported in literature. CONCLUSIONS: The evolution of the epidemiological setting might influence the results of studies investigating psychological impairments in HCW.

Undetectable viral RNA in follicular fluid, cumulus cells, and endometrial tissue samples in SARS-CoV-2-positive women.

OBJECTIVE: To study the presence of viral RNA in the follicular fluid, cumulus cells, and endometrial tissue samples in SARS-CoV-2-positive women undergoing assisted reproductive technology (ART). DESIGN: Prospective, single-center, observational study. SETTING: Tertiary hospital. PATIENT(S): A total of 16 patients undergoing transvaginal oocyte retrieval who had a positive SARS-CoV-2 RNA test <48 hours before the procedure. All patients underwent the retrieval between September 2020 and June 2021 and used in vitro fertilization or intracytoplasmic sperm injection. All embryos were vitrified to avoid conception during SARS-CoV-2 infection. INTERVENTION(S): Follicular fluid aspirated during oocyte retrieval, cumulus cells, and endometrial samples were analyzed for SARS-CoV-2 RNA using the RealStar SARS-CoV-2 RT-PCR-Kit1.0. MAIN OUTCOME MEASURE(S): The primary outcome parameter was the detection of viral RNA in the follicular fluid, cumulus cells, and endometrial cells. Fertilization rate, embryo developmental potential, and clinical outcome after frozen embryo transfer were secondary outcome parameters. RESULT(S): Samples from 16 patients were analyzed. Cycle threshold values of <40 were considered positive. All samples were negative for SARS-CoV-2 viral RNA. No inflammatory lesions of the endometrium were identified histologically. Fertilization rate, embryo development, and clinical outcomes after embryo transfer were reassuring. CONCLUSION(S): In women infected with SARS-CoV-2 who underwent ART, viral RNA was undetectable in the follicular fluid, cumulus cells, and endometrium. Caution is warranted in view of the small sample size, and the risk of SARS-CoV-2 affecting the embryo via ART cannot be ruled out. Adequate counseling of women and couples undergoing ART is crucial in parallel with further research on the effect of exposure of the early human embryo to SARS-CoV-2. CLINICAL TRIAL REGISTRATION NUMBER: NCT04425317.

Presumed Urinary Tract Infection in Patients Admitted with COVID-19: Are We Treating Too Much?

Despite the low rates of bacterial co-/superinfections in COVID-19 patients, antimicrobial drug use has been liberal since the start of the COVID-19 pandemic. Due to the low specificity of markers of bacterial co-/superinfection in the COVID-19 setting, overdiagnosis and antimicrobial overprescription have become widespread. A quantitative and qualitative evaluation of urinary tract infection (UTI) diagnoses and antimicrobial drug prescriptions for UTI diagnoses was performed in patients admitted to the COVID-19 ward of a university hospital between 17 March and 2 November 2020. A team of infectious disease specialists performed an appropriateness evaluation for every diagnosis of UTI and every antimicrobial drug prescription covering a UTI. A driver analysis was performed to identify factors increasing the odds of UTI (over)diagnosis. A total of 622 patients were included. UTI was present in 13% of included admissions, and in 12%, antimicrobials were initiated for a UTI diagnosis (0.71 daily defined doses (DDDs)/admission; 22% were scored as 'appropriate'). An evaluation of UTI diagnoses by ID specialists revealed that of the 79 UTI diagnoses, 61% were classified as probable overdiagnosis related to the COVID-19 hospitalization. The following factors were associated with UTI overdiagnosis: physicians who are unfamiliar working in an internal medicine ward, urinary incontinence, mechanical ventilation and female sex. Antimicrobial stewardship teams should focus on diagnostic stewardship of UTIs, as UTI overdiagnosis seems to be highly prevalent in admitted COVID-19 patients.

Symptomatic severe acute respiratory syndrome coronavirus 2 reinfection in a lupus patient treated with hydroxychloroquine: a case report.

BACKGROUND: Hydroxychloroquine and chloroquine have been used for hospitalized coronavirus disease 2019 patients because of their antiviral and anti-inflammatory function. However, little research has been published on the impact of the immunomodulatory effect of (hydroxy)chloroquine on humoral immunity. CASE PRESENTATION: We report a case of symptomatic severe acute respiratory syndrome coronavirus 2 reinfection, diagnosed 141 days after the first episode, in a 56-year-old man of Black African origin treated with hydroxychloroquine for lupus erythematosus. No anti-severe acute respiratory syndrome coronavirus 2 IgG antibodies could be detected 127 days after the initial episode of coronavirus disease 2019. CONCLUSIONS: The treatment with hydroxychloroquine probably explains the decreased immune response with negative serology and subsequent reinfection in our patient. As humoral immunity is crucial to fight a severe acute respiratory syndrome coronavirus 2 infection, the use of (hydroxy)chloroquine is likely to have a detrimental effect on the spread of the virus. This case emphasizes that more needs to be learned about the role of antibodies in protecting against severe acute respiratory syndrome coronavirus 2 (re)infection and the role of (hydroxy)chloroquine on humoral immunity.

Antibiotic Prescriptions Targeting Bacterial Respiratory Infections in Admitted Patients with COVID-19: A Prospective Observational Study.

INTRODUCTION: Although bacterial co- and superinfections are rarely present in patients with COVID-19, overall antibiotic prescribing in admitted patients is high. In order to counter antibiotic overprescribing, antibiotic stewardship teams need reliable data concerning antibiotic prescribing in admitted patients with COVID-19. METHODS: In this prospective observational cohort study, we performed a quantitative and qualitative evaluation of antibiotic prescriptions in patients admitted to the COVID-19 ward of a 721-bed Belgian university hospital between 1 May and 2 November 2020. Data on demographics, clinical and microbiological parameters and antibiotic consumption were collected. Defined daily doses (DDD) were calculated for antibiotics prescribed in the context of a (presumed) bacterial respiratory tract infection and converted into two indicators: DDD/admission and DDD/100 hospital bed days. A team of infectious disease specialists performed an appropriateness evaluation for every prescription. A driver analysis was performed to identify factors increasing the odds of an antibiotic prescription in patients with a confirmed COVID-19 diagnosis. RESULTS: Of 403 eligible participants with a suspected COVID-19 infection, 281 were included. In 13.8% of the 203 admissions with a COVID-19 confirmed diagnosis, antibiotics were initiated for a (presumed) bacterial respiratory tract co-/superinfection (0.86 DDD/admission; 8.92 DDD/100 bed days; 39.4% were scored as 'appropriate'). Five drivers of antibiotic prescribing were identified: history of cerebrovascular disease, high neutrophil/lymphocyte ratio in male patients, age, elevated ferritin levels and the collection of respiratory samples for bacteriological analysis. CONCLUSION: In the studied population, the antibiotic consumption for a (presumed) bacterial respiratory tract co-/superinfection was low. In particular, the small total number of DDDs in patients with confirmed COVID-19 diagnosis suggests thoughtful antibiotic use. However, antibiotic stewardship programmes remain crucial to counter unnecessary and inappropriate antibiotic use in hospitalized patients with COVID-19. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov (NCT04544072).

Diagnostic accuracy of screening tests for patients suspected of COVID-19, a retrospective cohort study.

BACKGROUND: The diagnostic gold standard for Coronavirus-2019 disease (CoViD-19) is reverse transcriptase-polymerase chain reaction (RT-PCR). However, its sensitivity might be suboptimal. The current study aims to investigate predictive factors for false-negative nasopharyngeal RT-PCR in CoViD-19 patients. Additionally, the specificity and sensitivity of RT-PCR on the nasopharyngeal swab, serology and chest computerized-tomography (CCT) as a screening tool for the diagnosis of CoViD-19 were investigated. METHODS: Medical records of patients admitted at the university hospital UZ Brussel during the CoViD-19 epidemic were reviewed. A group of CoViD-19 patients with false-negative RT-PCR was identified through scrupulous examination of medical records. Serological testing was performed through chemiluminescent microparticle assay. RESULTS: Eighteen CoViD-19 patients with 'false negative' RT-PCR were identified and compared to 51 'true positives'. Logistic regression for prediction of 'false negative' RT-PCR found significantly higher serology results at hospitalization and more intensive care unit admission in the group with false-negative testing. In a cohort of 228 patients, the sensitivity of RT-PCR for the diagnosis of CoViD-19 was 85%. The sensitivity of serology was 86% and its specificity 92%. Chest computerized-tomography (CCT) showed a sensitivity of 93%, its specificity was 62%. By combining RT-PCR and serology results any 'false negative' could be excluded. CONCLUSIONS: In this cohort, the sensitivity and specificity of RT-PCR and serology for the diagnosis of CoViD-19 were high and comparable. CCT had the highest sensitivity and confirmed its efficacy as a screening tool. CoViD-19 patients, who have a more severe presentation, might have negative RT-PCR and positive serology results.

Infections at the nexus of metabolic-associated fatty liver disease.

Metabolic-associated fatty liver disease (MAFLD) is a chronic liver disease that affects about a quarter of the world population. MAFLD encompasses different disease stadia ranging from isolated liver steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis and hepatocellular carcinoma. Although MAFLD is considered as the hepatic manifestation of the metabolic syndrome, multiple concomitant disease-potentiating factors can accelerate disease progression. Among these risk factors are diet, lifestyle, genetic traits, intake of steatogenic drugs, male gender and particular infections. Although infections often outweigh the development of fatty liver disease, pre-existing MAFLD could be triggered to progress towards more severe disease stadia. These combined disease cases might be underreported because of the high prevalence of both MAFLD and infectious diseases that can promote or exacerbate fatty liver disease development. In this review, we portray the molecular and cellular mechanisms by which the most relevant viral, bacterial and parasitic infections influence the progression of fatty liver disease and steatohepatitis. We focus in particular on how infectious diseases, including coronavirus disease-19, hepatitis C, acquired immunodeficiency syndrome, peptic ulcer and periodontitis, exacerbate MAFLD. We specifically underscore the synergistic effects of these infections with other MAFLD-promoting factors.

Evaluation of four laboratory-based SARS-CoV-2 IgG antibody immunoassays.

OBJECTIVES: To evaluate the diagnostic performances of four SARS-CoV-2 IgG antibody immunoassays. METHODS: Following immunoassays were studied: Abbott's SARS-CoV-2 IgG assay, Diasorin's Liaison SARS-CoV-2 S2/S2 IgG assay, Euroimmun's Anti-SARS-CoV-2 IgG ELISA, and Roche's Elecsys Anti-SARS-CoV-2 assay. Specificity was retrospectively evaluated with 38 samples from 2019. Sensitivity samples (n = 147) were taken from SARS-CoV-2 real-time PCR-positive patients who developed COVID-19 symptoms ten days earlier. RESULTS: Mean specificity was 96.6%. Mean sensitivity was 62.7% from ten days after onset of symptoms, 84.4% from 15 days after onset of symptoms, and 87.5% from 20 days after onset of symptoms. CONCLUSIONS: Specificity was high, while Abbott and Roche were 100% specific. Sensitivity increased over time, with Abbott and Roche having the highest sensitivity at all time points with ≥90% from 20 days after symptoms' onset. These findings may assist in selecting SARS-CoV-2 IgG antibody immunoassays for additional diagnostics, epidemiological research, and vaccine development.

Ventilator-associated bacterial pneumonia in coronavirus 2019 disease, a retrospective monocentric cohort study.

INTRODUCTION: Severe coronavirus 2019 disease (CoViD-19) may lead to respiratory failure and mechanical ventilation. Therefore, ventilator associated pneumonia (VAP) may complicate the course of the disease. The aim of the current article was to investigate possible predictive factors for bacterial VAP on a retrospective manner, in a cohort of mechanically ventilated CoViD-19 patients. Additionally, determinant factors of lethality were analyzed. METHODS: Medical records of patients hospitalized in the intensive care units (ICU) at the university hospital UZ Brussel during the epidemic were reviewed. VAP was defined following the National Healthcare Safety Network 2017 criteria. Univariate and multivariate logistic regressions analyses were performed. RESULTS: Among the 39 patients included in the study, 54% were diagnosed with bacterial VAP. Case fatality rate was 44%, but 59% of the deceased patients had a do-not-resuscitate status. Multivariate logistic regression for prediction of VAP showed significant differences in duration of ICU hospitalization and in minimal lung compliance. Additional analyses were performed on CoViD-19 patients who were affected by bacterial respiratory superinfection. The responsible pathogens correspond to the commonly found bacteria in VAP. However, 71% of the isolated germs were multi-drug resistant and bacteraemia was reported in 38%. Multivariate analyses for prediction of lethality found significant difference in SOFA score. CONCLUSIONS: Mechanically ventilated CoViD-19 patients might frequently develop VAP. Longer ICU hospitalization was associated with pulmonary superinfection in the current cohort. Moreover, decreased minimal lung compliance was correlated to VAP and higher SOFA score at VAP diagnosis was associated with lethality.

Impact of solid cancer on in-hospital mortality overall and among different subgroups of patients with COVID-19: a nationwide, population-based analysis.

BACKGROUND: Cancer seems to have an independent adverse prognostic effect on COVID-19-related mortality, but uncertainty exists regarding its effect across different patient subgroups. We report a population-based analysis of patients hospitalised with COVID-19 with prior or current solid cancer versus those without cancer. METHODS: We analysed data of adult patients registered until 24 May 2020 in the Belgian nationwide database of Sciensano. The primary objective was in-hospital mortality within 30 days of COVID-19 diagnosis among patients with solid cancer versus patients without cancer. Severe event occurrence, a composite of intensive care unit admission, invasive ventilation and/or death, was a secondary objective. These endpoints were analysed across different patient subgroups. Multivariable logistic regression models were used to analyse the association between cancer and clinical characteristics (baseline analysis) and the effect of cancer on in-hospital mortality and on severe event occurrence, adjusting for clinical characteristics (in-hospital analysis). RESULTS: A total of 13 594 patients (of whom 1187 with solid cancer (8.7%)) were evaluable for the baseline analysis and 10 486 (892 with solid cancer (8.5%)) for the in-hospital analysis. Patients with cancer were older and presented with less symptoms/signs and lung imaging alterations. The 30-day in-hospital mortality was higher in patients with solid cancer compared with patients without cancer (31.7% vs 20.0%, respectively; adjusted OR (aOR) 1.34; 95% CI 1.13 to 1.58). The aOR was 3.84 (95% CI 1.94 to 7.59) among younger patients (<60 years) and 2.27 (95% CI 1.41 to 3.64) among patients without other comorbidities. Severe event occurrence was similar in both groups (36.7% vs 28.8%; aOR 1.10; 95% CI 0.95 to 1.29). CONCLUSIONS: This population-based analysis demonstrates that solid cancer is an independent adverse prognostic factor for in-hospital mortality among patients with COVID-19. This adverse effect was more pronounced among younger patients and those without other comorbidities. Patients with solid cancer should be prioritised in vaccination campaigns and in tailored containment measurements.