Seroprevalence and placental transfer of SARS-CoV-2 antibodies in unvaccinated pregnant women.

PURPOSE: Pregnant women are at risk of severe SARS-CoV-2 infection, potentially leading to obstetric and neonatal complications. Placental transfer of antibodies directed to SARS-CoV-2 may be protective against neonatal COVID-19, but this remains to be studied. We aimed to determine the seroprevalence of SARS-CoV-2 antibodies in a population of unvaccinated pregnant women and to determine the placental transfer of these antibodies. METHODOLOGY: A total of 1197 unvaccinated women with mostly unknown pre-study SARS-CoV-2 infection status, were tested at delivery for SARS-CoV-2 spike protein IgG antibodies during the first year of the pandemic. Umbilical cord samples were collected and assessed for seropositivity if the mother was seropositive. Maternal characteristics, pregnancy and neonatal outcomes and data on SARS-CoV-2 infection were extracted from medical records. RESULTS: Specific IgG were detected in 258 women (21.6%). A significant placental transfer to the newborn was observed in 81.3% of cases. The earlier in the 2nd and 3rd trimesters that the mother had contracted the disease and the more symptomatic she was, the greater the likelihood of transplacental transfer of IgG to her newborn. CONCLUSION: Approximately one in five women had detectable anti-SARS-CoV-2 spike protein IgG antibodies at delivery during the first year of the pandemic, and these antibodies were significantly transferred to their fetuses. This research provides further evidence to better understand the dynamics of the placental transfer of SARS-CoV-2 IgG antibodies from mothers to their newborns, which is necessary to improve vaccination strategies.

Impact of Human Immunodeficiency Virus and Recreational Drugs on Cognitive Functions.

BACKGROUND: This prospective study characterizes the structural and metabolic cerebral correlates of cognitive impairments found in a preclinical setting that considers the lifestyle of young European men exposed to human immunodeficiency virus (HIV), including recreational drugs. METHODS: Simultaneous structural brain magnetic resonance imaging (MRI) and positron emission tomography using [18F]-fluorodeoxyglucose (FDG-PET) were acquired on a hybrid PET-MRI system in 23 asymptomatic young men having sex with men with HIV (HIVMSM; mean age, 33.6 years [range, 23-60 years]; normal CD4+ cell count, undetectable viral load). Neuroimaging data were compared with that of 26 young seronegative men under HIV preexposure prophylaxis (PrEPMSM), highly well matched for age and lifestyle, and to 23 matched young seronegative men (controls). A comprehensive neuropsychological assessment was also administered to the HIVMSM and PrEPMSM participants. RESULTS: HIVMSM had lower performances in executive, attentional, and working memory functions compared to PrEPMSM. No structural or metabolic differences were found between those 2 groups. Compared to controls, HIVMSM and PrEPMSM exhibited a common hypometabolism in the prefrontal cortex that correlated with the level of recreational drug use. No structural brain abnormality was found. CONCLUSIONS: Abnormalities of brain metabolism in our population of young HIVMSM mainly relate to recreational drug use rather than HIV per se. A complex interplay between recreational drugs and HIV might nevertheless be involved in the cognitive impairments observed in this population.

A public health value-based healthcare paradigm for HIV.

BACKGROUND: HIV patients face considerable acute and chronic healthcare needs and battling the HIV epidemic remains of the utmost importance. By focusing on health outcomes in relation to the cost of care, value-based healthcare (VBHC) proposes a strategy to optimize quality of care and cost-efficiency. Its implementation may provide an answer to the increasing pressure to optimize spending in healthcare while improving patient outcomes. This paper describes a pragmatic value-based healthcare framework for HIV care. METHODS: A value-based HIV healthcare framework was developed during a series of roundtable discussions bringing together 16 clinical stakeholder representatives from the Belgian HIV reference centers and 2 VBHC specialists. Each round of discussions was focused on a central question translating a concept or idea to the next level of practical implementation: 1) how can VBHC principles be translated into value-based HIV care drivers; 2) how can these value-based HIV care divers be translated into value-based care objectives and activities; and 3) how can value-based HIV care objectives and activities be translated into value-based care indicators. Value drivers were linked to concrete objectives and activities using a logical framework approach. Finally, specific, measurable, and acceptable structure, process and outcomes indicators were defined to complement the framework. RESULTS: Our framework identifies 4 core value areas where HIV care would benefit most from improvements: Prevention, improvement of the cascade of care, providing patient-centered HIV care and sustaining a state-of-the-art HIV disease management context. These 4 core value areas were translated into 12 actionable core value objectives. For each objective, example activities were proposed. Indicators are suggested for each level of the framework (outcome indicators for value areas and objectives, process indicators for suggested activities). CONCLUSIONS: This framework approach outlines how to define a patient- and public health centered value-based HIV care paradigm. It proposes how to translate core value drivers to practical objectives and activities and suggests defining indicators that can be used to track and improve the framework's implementation in practice.

Clinical characteristics and outcomes of COVID-19 in people living with HIV in Belgium: A multicenter, retrospective cohort.

The aim of this study was to describe the clinical characteristics and outcomes of coronavirus disease 2019 (COVID-19) among people living with HIV (PLWH) in Belgium. We performed a retrospective multicenter cohort analysis of PLWH with either laboratory-confirmed, radiologically diagnosed, or clinically suspected COVID-19 between February 15, 2020 and May 31, 2020. The primary endpoint was outcome of COVID-19. Secondary endpoints included rate of hospitalization and length of hospital stay and rate of Intensive Care Unit (ICU) admission and mechanical ventilation. One hundred and one patients were included in this study. Patients were categorized as having either laboratory-confirmed (n = 65), radiologically-diagnosed (n = 3), or clinically suspected COVID-19 (n = 33). The median age was 51.3 years (interquartile range [IQR] 41.3-57.3) and 44% were female. Ninety-four percent of patients were virologically suppressed and 67% had a CD4+ cell count more than or equal to 500 cells/µl. Overall, 46% of patients required hospitalization and the median length of hospital stay was 6 days (IQR 3-15). Age more than or equal to 50 years, Black Sub-Saharan African patients, and being on an integrase strand transfer inhibitor-based regimen were associated with being hospitalized. ICU admission and mechanical ventilation was required for 15% and 10% of all patients respectively. Overall, 9% of patients died while 78 (77%) patients made a full recovery. HIV patients with COVID-19 experienced a high degree of hospitalization despite having elevated CD4+ cell counts and a high rate of virologic suppression. Matched case-control studies are warranted to measure the impact that HIV may have on patients with COVID-19.

Structural and metabolic brain abnormalities in COVID-19 patients with sudden loss of smell.

OBJECTIVES: Sudden loss of smell is a very common symptom of coronavirus disease 19 (COVID-19). This study characterizes the structural and metabolic cerebral correlates of dysosmia in patients with COVID-19. METHODS: Structural brain magnetic resonance imaging (MRI) and positron emission tomography with [18F]-fluorodeoxyglucose (FDG-PET) were prospectively acquired simultaneously on a hybrid PET-MR in 12 patients (2 males, 10 females, mean age: 42.6 years, age range: 23-60 years) with sudden dysosmia and positive detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on nasopharyngeal swab specimens. FDG-PET data were analyzed using a voxel-based approach and compared with that of a group of healthy subjects. RESULTS: Bilateral blocking of the olfactory cleft was observed in six patients, while subtle olfactory bulb asymmetry was found in three patients. No MRI signal abnormality downstream of the olfactory tract was observed. Decrease or increase in glucose metabolism abnormalities was observed (p < .001 uncorrected, k ≥ 50 voxels) in core olfactory and high-order neocortical areas. A modulation of regional cerebral glucose metabolism by the severity and the duration of COVID-19-related dysosmia was disclosed using correlation analyses. CONCLUSIONS: This PET-MR study suggests that sudden loss of smell in COVID-19 is not related to central involvement due to SARS-CoV-2 neuroinvasiveness. Loss of smell is associated with subtle cerebral metabolic changes in core olfactory and high-order cortical areas likely related to combined processes of deafferentation and active functional reorganization secondary to the lack of olfactory stimulation.

Unspecific post-mortem findings despite multiorgan viral spread in COVID-19 patients.

BACKGROUND: Post-mortem studies can provide important information for understanding new diseases and small autopsy case series have already reported different findings in COVID-19 patients. METHODS: We evaluated whether some specific post-mortem features are observed in these patients and if these changes are related to the presence of the virus in different organs. Complete macroscopic and microscopic autopsies were performed on different organs in 17 COVID-19 non-survivors. Presence of SARS-CoV-2 was evaluated with immunohistochemistry (IHC) in lung samples and with real-time reverse-transcription polymerase chain reaction (RT-PCR) test in the lung and other organs. RESULTS: Pulmonary findings revealed early-stage diffuse alveolar damage (DAD) in 15 out of 17 patients and microthrombi in small lung arteries in 11 patients. Late-stage DAD, atypical pneumocytes, and/or acute pneumonia were also observed. Four lung infarcts, two acute myocardial infarctions, and one ischemic enteritis were observed. There was no evidence of myocarditis, hepatitis, or encephalitis. Kidney evaluation revealed the presence of hemosiderin in tubules or pigmented casts in most patients. Spongiosis and vascular congestion were the most frequently encountered brain lesions. No specific SARS-CoV-2 lesions were observed in any organ. IHC revealed positive cells with a heterogeneous distribution in the lungs of 11 of the 17 (65%) patients; RT-PCR yielded a wide distribution of SARS-CoV-2 in different tissues, with 8 patients showing viral presence in all tested organs (i.e., lung, heart, spleen, liver, colon, kidney, and brain). CONCLUSIONS: In conclusion, autopsies revealed a great heterogeneity of COVID-19-associated organ injury and the remarkable absence of any specific viral lesions, even when RT-PCR identified the presence of the virus in many organs.

High uptake of pre-exposure prophylaxis (PrEP) during early roll-out in Belgium: results from surveillance reports.

Background Since 1 June 2017, oral pre-exposure prophylaxis (PrEP) could be prescribed and reimbursed in Belgium as prophylactic medication for people who are at increased risk of HIV acquisition. The aim of this study was to determine the uptake of daily and event-driven PrEP in Belgium during the first 9 months of roll-out. METHODS: Routine aggregated data on the number of reimbursement requests and the number of boxes of Truvada (Gilead Sciences, Cambridge, UK) delivered for PrEP through the Belgian pharmacies were obtained from the National Institute for Health and Disability Insurance. We also collected aggregated data from seven Aids Reference Centres (ARCs) currently providing most of the PrEP care in Belgium. RESULTS: From 1 June 2017 to 28 February 2018, 1352 requests for reimbursement were approved by the National Institute for Health and Disability Insurance. Almost 98% of those who bought at least one box of 30 tablets of emtricitabine 200mg/tenofovir disoproxil fumarate 300mg (FTC/TDF) in a Belgian pharmacy were male, and most (67%) were between 30 and 50 years of age. According to data obtained from ARCs, the proportion of those choosing event-driven PrEP initially ranged between 29% and 73%. CONCLUSIONS: The uptake of PrEP in Belgium since the start of the roll-out in June 2017 has been high, and almost entirely limited to men who have sex with men, of whom 43% initially prefer a non-daily regimen. A better understanding is needed as to why other populations, such as sub-Saharan African migrants, are not accessing PrEP, as well as the development of a more sustainable PrEP delivery model.

Screening for Chlamydia trachomatis and Neisseria gonorrhoeae Infections in Men Who Have Sex With Men: Diagnostic Accuracy of Nucleic Acid Amplification Test on Pooled Urine, Anorectal, and Pharyngeal Specimens.

Neisseria gonorrhoeae and Chlamydia trachomatis screening was performed in a cohort of 100 men who have sex with men. A nucleic acid amplification test on a pooled sample of first-pass urine, pharyngeal, and anorectal specimens was compared with results on nonpooled samples. Despite an excellent agreement (Cohen κ, 0.932), pooling specimens reduced test sensitivity to 89.5%.

Deep dermatophytosis and inherited CARD9 deficiency.

BACKGROUND: Deep dermatophytosis is a severe and sometimes life-threatening fungal infection caused by dermatophytes. It is characterized by extensive dermal and subcutaneous tissue invasion and by frequent dissemination to the lymph nodes and, occasionally, the central nervous system. The condition is different from common superficial dermatophyte infection and has been reported in patients with no known immunodeficiency. Patients are mostly from North African, consanguineous, multiplex families, which strongly suggests a mendelian genetic cause. METHODS: We studied the clinical features of deep dermatophytosis in 17 patients with no known immunodeficiency from eight unrelated Tunisian, Algerian, and Moroccan families. Because CARD9 (caspase recruitment domain-containing protein 9) deficiency has been reported in an Iranian family with invasive fungal infections, we also sequenced CARD9 in the patients. RESULTS: Four patients died, at 28, 29, 37, and 39 years of age, with clinically active deep dermatophytosis. No other severe infections, fungal or otherwise, were reported in the surviving patients, who ranged in age from 37 to 75 years. The 15 Algerian and Tunisian patients, from seven unrelated families, had a homozygous Q289X CARD9 allele, due to a founder effect. The 2 Moroccan siblings were homozygous for the R101C CARD9 allele. Both alleles are rare deleterious variants. The familial segregation of these alleles was consistent with autosomal recessive inheritance and complete clinical penetrance. CONCLUSIONS: All the patients with deep dermatophytosis had autosomal recessive CARD9 deficiency. Deep dermatophytosis appears to be an important clinical manifestation of CARD9 deficiency. (Funded by Agence Nationale pour la Recherche and others.).

Reasons for not starting antiretroviral therapy in HIV-1-infected individuals: a changing landscape.

PURPOSE: A cross-sectional survey was conducted to better understand why chronically HIV-1-infected individuals stratified by CD4 count (≤349; 350-499; ≥500 cells/µL) were not on antiretroviral therapy (ART). METHODS: Before the consultation, treatment-naive patients and their physicians independently completed a 90-item-questionnaire about barriers and their readiness to start/defer ART. The study was carried out at 34 sites in nine countries in Europe and Australia. RESULTS: Between December 2011 and October 2012, 508 pairs of patient- and physician-questionnaires were completed. 426 (84 %) patients were male and 39 (8 %), 138 (27 %), and 330 (65 %) were in the three stratified groups based on CD4 count, respectively. In the category 'Body and symptoms' the most commonly identified reason for patients not to start was: "As long as I feel good I don't have to take medication" (44 %). Less than 20 % of respondents indicated fears of side effects and toxicity or problems to manage pills. Most patients were in the lowest stage of treatment-readiness (N = 323, 68 %), especially patients with CD4 cells ≥500 cells/µL (N = 240, 79 %). Physicians answered in 92 (18 %) cases that ART was not indicated for CD4 cells <500 cells/µL. Main reasons for physicians not starting treatment for these patients were their perception that patients were 'too depressed' (13 %) or that they had not known them long enough (13 %). CONCLUSIONS: Nowadays patient-barriers to ART are commonly related to health-and treatment-beliefs compared to fear of toxicity or ART manageability in the past. This new barrier pattern seems to reflect the era of well tolerated, easier ART regimens and has to be considered in light of the new recommendations to treat all HIV-infected individuals regardless of the CD4 cell count.

Contribution of a heparin-binding haemagglutinin interferon-gamma release assay to the detection of Mycobacterium tuberculosis infection in HIV-infected patients: comparison with the tuberculin skin test and the QuantiFERON-TB Gold In-tube.

BACKGROUND: The screening and treatment of latent tuberculosis (TB) infection reduces the risk of progression to active disease and is currently recommended for HIV-infected patients. The aim of this study is to evaluate, in a low TB incidence setting, the potential contribution of an interferon-gamma release assay in response to the mycobacterial latency antigen Heparin-Binding Haemagglutinin (HBHA-IGRA), to the detection of Mycobacterium tuberculosis infection in HIV-infected patients. METHODS: Treatment-naïve HIV-infected adults were recruited from 4 Brussels-based hospitals. Subjects underwent screening for latent TB using the HBHA-IGRA in parallel to a classical method consisting of medical history, chest X-ray, tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube (QFT-GIT). Prospective clinical and biological follow-up ensued, with repeated testing with HBHA-IGRA. A group of HIV-infected patients with clinical suspicion of active TB was also recruited and tested with the HBHA-IGRA. Multiplex analysis was performed on the culture supernatants of this in-house assay to identify test read-outs alternative to interferon-gamma that could increase the sensitivity of the test. RESULTS: Among 48 candidates enrolled for screening, 9 were identified with latent TB by TST and/or QFT-GIT results. Four of these 9 patients and an additional 3 screened positive with the HBHA-IGRA. This in-house assay identified all the patients that were positive for the TST and showed the best concordance with the presence of a M. tuberculosis exposure risk. During follow-up (median 14 months) no case of active TB was reported and HBHA-IGRA results remained globally constant. Fourteen HIV-infected patients with clinical suspicion of active TB were recruited. Active TB was confirmed for 6 of them among which 3 were HBHA-IGRA positive, each with very high interferon-gamma concentrations. All patients for whom active TB was finally excluded, including 2 non-tubercular mycobacterial infections, had negative HBHA-IGRA results. Multiplex analysis confirmed interferon-gamma as the best read-out. CONCLUSIONS: The HBHA-IGRA appears complementary to the QuantiFERON-TB Gold In-Tube for the screening of latent TB in HIV-infected patients. Large-scale studies are necessary to determine whether this combination offers sufficient sensitivity to dismiss TST, as suggested by our results. Furthermore, HBHA-IGRA may help in the diagnosis work-up of clinical suspicions of active TB.

Effect of screening for Neisseria gonorrhoeae and Chlamydia trachomatis on incidence of these infections in men who have sex with men and transgender women taking HIV pre-exposure prophylaxis (the Gonoscreen study): results from a randomised, multicentre, controlled trial.

BACKGROUND: Guidelines recommend screening for Neisseria gonorrhoeae and Chlamydia trachomatis at three anatomical sites (urethra, anus, and pharynx) every 3 months (3 × 3) in men who have sex with men (MSM) and transgender women taking HIV pre-exposure prophylaxis (PrEP). We present the first randomised controlled trial to compare the effect of screening versus non-screening for N gonorrhoeae and C trachomatis on the incidence of these infections in MSM and transgender women taking PrEP. METHODS: A multicentre, randomised, controlled trial of 3 × 3 screening for N gonorrhoeae and C trachomatis versus non-screening was done among MSM and transgender women taking PrEP in five HIV reference centers in Belgium. Participants attended the PrEP clinics quarterly for 12 months. N gonorrhoeae and C trachomatis was tested at each visit in both arms, but results were not provided to the non-screening arm, if asymptomatic. The primary outcome was incidence rate of N gonorrhoeae and C trachomatis infections in each arm, assessed in the per-protocol population. Non-inferiority of the non-screening arm was proven if the upper limit of the 95% CI of the incidence rate ratio (IRR) was lower than 1·25. This trial is registered with ClinicalTrials.gov, NCT04269434, and is completed. FINDINGS: Between Sept 21, 2020, and June 4, 2021, 506 participants were randomly assigned to the 3 × 3 screening arm and 508 to the non-screening arm. The overall incidence rate of N gonorrhoeae and C trachomatis was 0·155 cases per 100 person-days (95% CI 0·128-0·186) in the 3 × 3 screening arm and 0·205 (95% CI 0·171-0·246) in the non-screening arm. The incidence rate was significantly higher in the non-screening arm (IRR 1·318, 95% CI 1·068-1·627). Participants in the non-screening arm had a higher incidence of C trachomatis infections and symptomatic C trachomatis infections. There were no significant differences in N gonorrhoeae infections. Participants in the non-screening arm consumed significantly fewer antimicrobial drugs. No serious adverse events were reported. INTERPRETATION: We failed to show that non-screening for N gonorrhoeae and C trachomatis is non-inferior to 3 × 3 screening in MSM and transgender women taking PrEP in Belgium. However, screening was associated with higher antibiotic consumption and had no effect on the incidence of N gonorrhoeae. Further research is needed to assess the benefits and harms of N gonorrhoeae and C trachomatis screening in this population. FUNDING: Belgian Health Care Knowledge Centre.

IL-12Rß1 deficiency and disseminated Mycobacterium tilburgii disease.

Mycobacterium tilburgii rarely causes disseminated disease. We describe a case of M. tilburgii infection in an otherwise healthy 33-year-old woman, who was found to carry bi-allelic mutations of the gene encoding the ß1 chain of the IL-12 receptor.

Distinct socioeconomic profile of patients hospitalised with severe COVID-19 and prepandemic respiratory infections in Brussels's deprived areas: a case-control study.

OBJECTIVE: Belgium has been hit harder by COVID-19 than other countries in Europe. While clinical risk factors are well studied, socioeconomic risk factors remained underexplored. This study's objective was to analyse the social and clinical profile of patients hospitalised for COVID-19 during the two waves of 2020, compared with a control population in 2019 in two hospitals located in Brussels' most deprived area. DESIGN AND METHODS: We did a case-control study by using the minimal clinical data set in two Brussels hospitals. All patients hospitalised for COVID-19 in 2020, divided into two waves (n=3220), were compared with all patients hospitalised for viral pneumonia and respiratory diseases in 2019 (control population n=2950). Multinomial regression models were used to estimate the relative risk ratios of the association between the COVID-19 hospitalised populations (waves 1 and 2) and risk factors (social and clinical) stratified by age. RESULTS: Patients under 65 years of age and hospitalised for COVID-19 presented significantly higher rates (relative rate ratio (95% CI)), especially for the first wave, of obesity 1.6 (1.2-2.2), African nationalities 1.4 (1.0-1.8), lack of health insurance 1.6 (1.3-2.1), living in high-density population areas 1.6 (1.3-2.1) and low incomes 1.7 (1.4-2.1), compared with the control population For patients over 65 years of age, we did not observe significant excess of COVID-19 hospitalisations for any risk factors, except diabetes during for the second wave but we have a significant excess mortality rate than the control population for both waves (p<0.002). CONCLUSIONS: The social and clinical profile of patients hospitalised for COVID-19 compared with a population hospitalised for viral respiratory diseases differed between age groups and waves. For younger patients, risk factors were linked to patients' precarious situations. This study underlines the role of selected social health determinants and the importance of routinely collecting social data, along with clinical data, particularly among vulnerable populations.

Social and clinical risk factors associated with hospitalized COVID-19 patients in Brussels's deprived and multiethnic areas.

BACKGROUND: In Belgium, the Brussels-Capital region was severely affected by the COVID-19 epidemic. Various hypotheses were mentioned in order to explain Brussels' excess disease spreading and mortality rate, but socioeconomic risk factors are increasingly recognized. This study's objective was to analyze clinical and social profiles of patients hospitalized for COVID-19, by nationality groups, in two hospitals located in Brussels's deprived and multiethnic areas. METHODS: Data covered hospitalized COVID-19 patients from two Brussels hospitals (n = 787) between the 1st of March 2020 and the 31st of June 2020. Social data was collected using hospital records, and clinical data was extracted from hospitals' COVID-19 databases. Multivariable logistic regression models were used to estimate the odds ratios (OR) of the association between two outcomes (Intensive Care Unit admission and mortality) and risk factors (social and clinical). RESULTS: Patients from Sub-Saharan Africa were younger, had a higher prevalence of obesity, lacked health insurance, and had the highest proportion of Intensive Care Unit (ICU) admission (27.7%) but the lowest mortality rates than other nationality groups. Patients from North Africa had a higher prevalence of diabetes compared to other nationality groups and a high proportion of European patients came from nursing homes. Patients deprived of health insurance had a higher risk of ICU admission compared to those who had insurance (OR IC95%; 1,9 1.1-3.6, p = 0.03). Other risk factors as sex and obesity were significantly associated to ICU admission and, age and hypertension were significantly associated to mortality. CONCLUSION: Social and clinical profile of the patients differs between the nationality groups, and some risk factors for Intensive Care Unit admission and mortality were linked to more patients' precarious situation as the availability of health insurance. This study underlines the role of selected social health determinants and the importance of routinely collecting social along with clinical data.

Next-generation sequencing: what are the needs in routine clinical microbiology? A survey among clinicians involved in infectious diseases practice.

Background: The translation of Next-Generation Sequencing (NGS) from research to clinical microbiology is increasing rapidly, but its integration into routine clinical care struggles to catch-up. A challenge for clinical laboratories is that the substantial investments made in the required technologies and resources must meet both current and forthcoming needs. Methods: To get a clinical perspective of these needs, we have sent a survey to infectious diseases clinicians of five hospitals, covering the following topics: NGS knowledge, expected syndromes and patients foreseen to benefit from NGS, and expected impact on antimicrobial prescription. Results: According to clinicians, benefits of NGS are mostly expected in neurological and respiratory infections diagnostics. Conclusion: A better dialog between microbiologists and clinicians about hopes and limits of NGS in microbiology may help identifying key investments needed for clinical laboratories, today and tomorrow.

Characteristics and outcomes of an international cohort of 600 000 hospitalized patients with COVID-19.

BACKGROUND: We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, one of the world's largest international, standardized data sets concerning hospitalized patients. METHODS: The data set analysed includes COVID-19 patients hospitalized between January 2020 and January 2022 in 52 countries. We investigated how symptoms on admission, co-morbidities, risk factors and treatments varied by age, sex and other characteristics. We used Cox regression models to investigate associations between demographics, symptoms, co-morbidities and other factors with risk of death, admission to an intensive care unit (ICU) and invasive mechanical ventilation (IMV). RESULTS: Data were available for 689 572 patients with laboratory-confirmed (91.1%) or clinically diagnosed (8.9%) SARS-CoV-2 infection from 52 countries. Age [adjusted hazard ratio per 10 years 1.49 (95% CI 1.48, 1.49)] and male sex [1.23 (1.21, 1.24)] were associated with a higher risk of death. Rates of admission to an ICU and use of IMV increased with age up to age 60 years then dropped. Symptoms, co-morbidities and treatments varied by age and had varied associations with clinical outcomes. The case-fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients and was on average 21.5%. CONCLUSIONS: Age was the strongest determinant of risk of death, with a ∼30-fold difference between the oldest and youngest groups; each of the co-morbidities included was associated with up to an almost 2-fold increase in risk. Smoking and obesity were also associated with a higher risk of death. The size of our international database and the standardized data collection method make this study a comprehensive international description of COVID-19 clinical features. Our findings may inform strategies that involve prioritization of patients hospitalized with COVID-19 who have a higher risk of death.

Human type I IFN deficiency does not impair B cell response to SARS-CoV-2 mRNA vaccination.

Inborn and acquired deficits of type I interferon (IFN) immunity predispose to life-threatening COVID-19 pneumonia. We longitudinally profiled the B cell response to mRNA vaccination in SARS-CoV-2 naive patients with inherited TLR7, IRF7, or IFNAR1 deficiency, as well as young patients with autoantibodies neutralizing type I IFNs due to autoimmune polyendocrine syndrome type-1 (APS-1) and older individuals with age-associated autoantibodies to type I IFNs. The receptor-binding domain spike protein (RBD)-specific memory B cell response in all patients was quantitatively and qualitatively similar to healthy donors. Sustained germinal center responses led to accumulation of somatic hypermutations in immunoglobulin heavy chain genes. The amplitude and duration of, and viral neutralization by, RBD-specific IgG serological response were also largely unaffected by TLR7, IRF7, or IFNAR1 deficiencies up to 7 mo after vaccination in all patients. These results suggest that induction of type I IFN is not required for efficient generation of a humoral response against SARS-CoV-2 by mRNA vaccines.

Exposure to SARS-CoV-2 in Hospital Environment: Working in a COVID-19 Ward Is a Risk Factor for Infection.

Aims. Health care workers (HCWs) are at risk of acquiring the Severe Acute Respiratory Syndrome Coronavirus 2 Infection (SARS-CoV-2). The aim of the study is to determine the SARS-CoV-2 positivity rates during the first epidemiologic peak among HCWs of a south Belgian hospital and to identify risks factors for infection. Methods. All hospital staff who worked during the first epidemiological peak were asked to answer a questionnaire regarding demographical data, function, type of working unit, type of contact with patients, eventual symptomatology, and the positivity of reverse transcription-polymerase chain reaction (RT-PCR) testing or immunoassay. Results. A total of 235 questionnaires were collected; 90 (38%) HCWs tested positive for SARS-CoV-2 from either RT-PCR or immunoassay testing. The positivity rate of HCWs between wards was statistically different (p = 0.004) and was higher in COVID-19 wards than Intensive Care Unit (ICU) and Emergency Department (ED). A total of 114 (49%) HCWs presented SARS-CoV-2-compatible symptomatology; 79 (88%) were positive on either RT-PCR or immunoassay testing; 74 (37%) HCWs were unable to work during the studied period; 5 were hospitalized. No deaths were reported. Multivariate logistic regression modeling showed that having symptoms was highly associated with test positivity (OR 23.3, CI 11.1, 53.1, p-value < 0.001). Working in a COVID-19 ward against working in ICU or ED was also predictive of positivity among HCWs (OR 3.25, CI 1.50, 7.28, p-value = 0.003). Discussion and Conclusions. This study shows a higher positivity rate compared to already reported positivity rates among HCWs. Reported differences in positivity rates depend on many factors, such as local crisis intensity, screening strategy, training in use of self-protective equipment, and study selection bias. HCWs working in COVID-19 wards, in comparison to ED and ICU, seemed at greater risk of being infected in this study. This could be explained by the disparity of HCWs' experience in handling self-protective equipment and knowledge in infection prevention. Hence, care should be taken in proper training for less-experienced HCWs during hospital epidemics. The latter could increase HCWs' protection and consequently decrease work absenteeism, ensuring enhanced continuity of patient care during hospital crisis. Rapid quarantine of symptomatic HCWs could reduce contamination rates, as having symptoms was highly associated with test positivity in this study.

Distinct antibody repertoires against endemic human coronaviruses in children and adults.

Four endemic human coronaviruses (HCoVs) are commonly associated with acute respiratory infection in humans. B cell responses to these "common cold" viruses remain incompletely understood. Here we report a comprehensive analysis of CoV-specific antibody repertoires in 231 children and 1168 adults using phage immunoprecipitation sequencing. Seroprevalence of antibodies against endemic HCoVs ranged between approximately 4% and 27% depending on the species and cohort. We identified at least 136 novel linear B cell epitopes. Antibody repertoires against endemic HCoVs were qualitatively different between children and adults in that anti-HCoV IgG specificities more frequently found among children targeted functionally important and structurally conserved regions of the spike, nucleocapsid, and matrix proteins. Moreover, antibody specificities targeting the highly conserved fusion peptide region and S2' cleavage site of the spike protein were broadly cross-reactive with peptides of epidemic human and nonhuman coronaviruses. In contrast, an acidic tandem repeat in the N-terminal region of the Nsp3 subdomain of the HCoV-HKU1 polyprotein was the predominant target of antibody responses in adult donors. Our findings shed light on the dominant species-specific and pan-CoV target sites of human antibody responses to coronavirus infection, thereby providing important insights for the development of prophylactic or therapeutic monoclonal antibodies and vaccine design.