Monoclonal antibody-mediated neutralization of SARS-CoV-2 in an IRF9-deficient child.

We describe an unvaccinated child at risk for life-threatening COVID-19 due to an inherited deficiency of IRF9, which governs ISGF-3-dependent responses to type I and III interferons (IFN). She was admitted, with a high nasal SARS-CoV-2 load on day 1 of upper respiratory tract infection. She was viremic on day 2 and received casirivimab and imdevimab. Her clinical manifestations and viremia disappeared on days 3 and 4, respectively. Circulating SARS-CoV-2 virus induced the expression of IFN-stimulated genes in leukocytes on day 1, whereas the secretion of blood type I IFNs, which peaked on day 4, did not. Antibody-mediated SARS-CoV-2 neutralization is, therefore, sufficient to overcome a deficiency of antiviral IFNs.

Genomic diversity of mpox virus in Paris area (France) during the 2022 outbreak.

In May 2022, several countries reported mpox cases from patients without history of traveling to endemic areas. France was one of the most affected European countries by this outbreak. In this study, the clinical characteristics of mpox cases in France were described, and the genetic diversity of the virus was studied. Patients diagnosed with mpox infection (quantitative polymerase chain reaction ct < 28) between May 21, and July 4, 2022 and between 16th August and 10th September 2022 were included to this study. Twelve amplicons corresponding to the most polymorphic regions of the mpox genome and covering ~30 000 nucleotides were generated and sequenced using the S5 XL Ion Torrent technology to evaluate the genetic diversity of mpox sequences. One hundred and forty-eight patients were diagnosed with mpox-infection. 95% were men, 5% transgender (M-to-F), 50% were taking human immunodeficiency virus (HIV) pre-exposure prophylaxis, and 25% were HIV seropositive. One hundred and sixty-two samples (some patients had two samples) were sequenced and compared to GenBank sequences. Overall, low genetic diversity of mpox sequences was found compared with pre-epidemic Western-African sequences, with 32 distinct mutational patterns. This study provides a first glance at the mutational landscape of early mpox 2022 circulating strains in Paris (France).

Performances of ICT Toxoplasma IgG-IgM test in comparison with Vidas® toxo competition to determine the immune status against Toxoplasma gondii.

Toxoplasmosis is a ubiquitous parasitic infection caused by Toxoplasma gondii (Tg). In immunocompetent people, the infection may be asymptomatic with the induction of an immune response that may prevent reinfection or transmission to the fetus in immune pregnant woman. In immunocompromised persons or seronegative pregnant woman with a primary infection during pregnancy, the infection may result in the loss of life, sight, cognition, and motor function in the immune-compromised person or immunologically immature fetus. The objective of this study was to evaluate a new immunochromatographic test Toxoplasma ICT IgG-IgM (ICT) that allows detection of specific anti-Tg immunoglobulins G (Ig G) and M (Ig M). We included 1145 prospectively obtained sera and 376 samples selected for specificity or sensitivity studies. The performance of ICT was compared using Vidas® Toxo Competition (TXC) and Toxoscreen®. In case of discrepancy, Vidas® Toxo Ig G or Ig M and LDBIO Toxo II IgG western blot were used to establish definitive results by additional methods. Sensitivity and specificity of ICT were respectively 99.3% and 100%. In comparison, Toxoscreen®'s sensitivity was 100% and the specificity was 99.8%. TXC had a sensitivity of 98.7% with a specificity of 99.1%. ICT has excellent performance even for low Ig G titers, especially in immunocompromised patients, and confirms the specificity of isolated Ig M. This ICT provides reliable results easily and quickly. This screening technique is not designed to differentiate the Ig M from Ig G. When positive, additional tests may be necessary.

In-hospital and midterm post-discharge complications of adults hospitalised with respiratory syncytial virus infection in France, 2017-2019: an observational study.

OBJECTIVES: The purpose of this study was to describe the clinical characteristics and in-hospital and post-discharge outcomes of respiratory syncytial virus (RSV) infection among adults hospitalised with influenza-like illness (ILI) and compared against patients admitted for influenza. METHODS: Adults hospitalised with ILI were prospectively included from five French university hospitals over two consecutive winter seasons (2017/2018 and 2018/2019). RSV and influenza virus were detected by multiplex reverse transcription PCR on nasopharyngeal swabs. RSV-positive patients were compared to RSV-negative and influenza-positive hospitalised patients. Poisson regression models were used to estimate the adjusted prevalence ratio (aPR) associated with in-hospital and post-discharge outcomes between RSV and influenza infections. The in-hospital outcome was a composite of the occurrence of at least one complication, length of stay ≥7 days, intensive care unit admission, use of mechanical ventilation and in-hospital death. Post-discharge outcome included 30- and 90-day all-cause mortality and 90-day readmission rates. RESULTS: Overall, 1428 hospitalised adults with ILI were included. RSV was detected in 8% (114 of 1428) and influenza virus in 31% (437 of 1428). Patients hospitalised with RSV were older than those with influenza (mean age 73.0 versus 68.8 years, p=0.015) with a higher frequency of chronic respiratory or cardiac disease (52% versus 39%, p=0.012, and 52% versus 41%, p=0.039, respectively) and longer hospitalisation duration (median stay 8 versus 6 days, p<0.001). Anti-influenza therapies were less prescribed among RSV patients than influenza patients (20% versus 66%, p<0.001). In-hospital composite outcome was poorer in RSV patients (aPR 1.5, 95% CI 1.1-2.1) than in those hospitalised with influenza. No difference was observed for the post-discharge composite outcome (aPR 1.1, 95% CI 0.8-1.6). CONCLUSION: RSV infection results in serious respiratory illness, with worse in-hospital outcomes than influenza and with similar midterm post-discharge outcomes.

Novel mutations in antiviral multiresistant HSV-2 genital lesion: A case report.

HSV-2 antiviral resistance mainly occurs in immunocompromised patients and especially in HIV-positive individuals receiving long-term antiviral treatment. Those situations can be challenging as few alternatives are available for HSV infection management. To describe clinical and virological significance of two novel potential HSV-2 resistance mutations after treating an obese patient with a pseudotumoral genital HSV-related lesion. Consecutive different antiviral treatments were used: valacyclovir (VACV) then foscarnet (FOS) then topical cidofovir (CDV) and finally imiquimod. Under VACV, genotypic resistance testing revealed a novel mutation within viral thymidine kinase (TK, gene UL23) not previously reported but probably accounting for antiviral resistance: W89G, similar to W88R mutation reported in HSV-1 TK, known to be associated with ACV resistance for HSV-1. Under FOS, while initial mutations were still present, a second genotypic resistance testing performed on persisting lesions showed a novel mutation within viral DNA polymerase (DNA pol, gene UL30): C625R. All three antivirals used in this case are small molecules and pharmacokinetics of VACV, FOS, and CDV have not been evaluated in animals and there are very few studies in human. As small molecules are poorly bound to proteins and distribution volume is increased in obese patients, there is risk of underdosage. This mechanism is suspected to be involved in emergence of resistance mutation and further data is needed to adapt, closely to patient profile, antiviral dosage. This report describes a chronic HSV-2 genital lesion, with resistance to current antivirals and novel mutations within viral TK and DNA pol which may confer antiviral resistance.

Added value of rapid respiratory syndromic testing at point of care versus central laboratory testing: a controlled clinical trial.

BACKGROUND: Virus-associated respiratory infections are in the spotlight with the emergence of SARS-CoV-2 and the expanding use of multiplex PCR (mPCR). The impact of molecular testing as a point-of-care test (POCT) in the emergency department (ED) is still unclear. OBJECTIVES: To compare the impact of a syndromic test performed in the ED as a POCT and in the central laboratory on length of stay (LOS), antibiotic use and single-room assignment. METHODS: From 19 November 2019 to 9 March 2020, adults with acute respiratory illness seeking care in the ED of a large hospital were enrolled, with mPCR performed with a weekly alternation in the ED as a POCT (week A) or in the central laboratory (week B). RESULTS: 474 patients were analysed: 275 during A weeks and 199 during B weeks. Patient characteristics were similar. The hospital LOS (median 7 days during week A versus 7 days during week B, P = 0.29), the proportion of patients with ED-LOS <1 day (63% versus 60%, P = 0.57) and ED antibiotic prescription (59% versus 58%, P = 0.92) were not significantly different. Patients in the POCT arm were more frequently assigned a single room when having a positive PCR for influenza, respiratory syncytial virus and metapneumovirus [52/70 (74%) versus 19/38 (50%) in the central testing arm, P = 0.012]. CONCLUSIONS: Syndromic testing performed in the ED compared with the central laboratory failed to reduce the LOS or antibiotic consumption in patients with acute respiratory illness, but was associated with an increased single-room assignment among patients in whom a significant respiratory pathogen was detected.

Performance of 30 commercial SARS-CoV-2 serology assays in testing symptomatic COVID-19 patients.

We report evaluation of 30 assays' (17 rapid tests (RDTs) and 13 automated/manual ELISA/CLIA assay (IAs)) clinical performances with 2594 sera collected from symptomatic patients with positive SARS-CoV-2 rRT-PCR on a respiratory sample, and 1996 pre-epidemic serum samples expected to be negative. Only 4 RDT and 3 IAs fitted both specificity (> 98%) and sensitivity (> 90%) criteria according to French recommendations. Serology may offer valuable information during COVID-19 pandemic, but inconsistent performances observed among the 30 commercial assays evaluated, which underlines the importance of independent evaluation before clinical implementation.

HSV-1 reactivation is associated with an increased risk of mortality and pneumonia in critically ill COVID-19 patients.

BACKGROUND: Data in the literature about HSV reactivation in COVID-19 patients are scarce, and the association between HSV-1 reactivation and mortality remains to be determined. Our objectives were to evaluate the impact of Herpes simplex virus (HSV) reactivation in patients with severe SARS-CoV-2 infections primarily on mortality, and secondarily on hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP) and intensive care unit-bloodstream infection (ICU-BSI). METHODS: We conducted an observational study using prospectively collected data and HSV-1 blood and respiratory samples from all critically ill COVID-19 patients in a large reference center who underwent HSV tests. Using multivariable Cox and cause-specific (cs) models, we investigated the association between HSV reactivation and mortality or healthcare-associated infections. RESULTS: Of the 153 COVID-19 patients admitted for ≥ 48 h from Feb-2020 to Feb-2021, 40/153 (26.1%) patients had confirmed HSV-1 reactivation (19/61 (31.1%) with HSV-positive respiratory samples, and 36/146 (24.7%) with HSV-positive blood samples. Day-60 mortality was higher in patients with HSV-1 reactivation (57.5%) versus without (33.6%, p = 0.001). After adjustment for mortality risk factors, HSV-1 reactivation was associated with an increased mortality risk (hazard risk [HR] 2.05; 95% CI 1.16-3.62; p = 0.01). HAP/VAP occurred in 67/153 (43.8%) and ICU-BSI in 42/153 (27.5%) patients. In patients with HSV-1 reactivation, multivariable cause-specific models showed an increased risk of HAP/VAP (csHR 2.38, 95% CI 1.06-5.39, p = 0.037), but not of ICU-BSI. CONCLUSIONS: HSV-1 reactivation in critically ill COVID-19 patients was associated with an increased risk of day-60 mortality and HAP/VAP.

Severe Acute Respiratory Syndrome Coronavirus 2-Specific Antibody Responses in Coronavirus Disease Patients.

A new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently emerged to cause a human pandemic. Although molecular diagnostic tests were rapidly developed, serologic assays are still lacking, yet urgently needed. Validated serologic assays are needed for contact tracing, identifying the viral reservoir, and epidemiologic studies. We developed serologic assays for detection of SARS-CoV-2 neutralizing, spike protein-specific, and nucleocapsid-specific antibodies. Using serum samples from patients with PCR-confirmed SARS-CoV-2 infections, other coronaviruses, or other respiratory pathogenic infections, we validated and tested various antigens in different in-house and commercial ELISAs. We demonstrated that most PCR-confirmed SARS-CoV-2-infected persons seroconverted by 2 weeks after disease onset. We found that commercial S1 IgG or IgA ELISAs were of lower specificity, and sensitivity varied between the 2 assays; the IgA ELISA showed higher sensitivity. Overall, the validated assays described can be instrumental for detection of SARS-CoV-2-specific antibodies for diagnostic, seroepidemiologic, and vaccine evaluation studies.

Evaluation of the QIAstat-Dx Respiratory SARS-CoV-2 Panel, the First Rapid Multiplex PCR Commercial Assay for SARS-CoV-2 Detection.

In the race to contain severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), efficient detection and triage of infected patients must rely on rapid and reliable testing. In this work, we performed the first evaluation of the QIAstat-Dx respiratory SARS-CoV-2 panel (QIAstat-SARS) for SARS-CoV-2 detection. This assay is the first rapid multiplex PCR (mPCR) assay, including SARS-CoV-2 detection, and is fully compatible with a non-PCR-trained laboratory or point-of-care (PoC) testing. This evaluation was performed using 69 primary clinical samples (66 nasopharyngeal swabs [NPS], 1 bronchoalveolar lavage fluid sample [BAL], 1 tracheal aspirate sample, and 1 bronchial aspirate sample) comparing SARS-CoV-2 detection with the currently WHO-recommended reverse transcription-PCR (RT-PCR) (WHO-RT-PCR) workflow. Additionally, a comparative limit of detection (LoD) assessment was performed for QIAstat-SARS and WHO-RT-PCR using a quantified clinical sample. Compatibility of sample pretreatment for viral neutralization or viscous samples with the QIAstat-SARS system were also tested. The QIAstat-Dx respiratory SARS-CoV-2 panel demonstrated a sensitivity comparable to that of the WHO-recommended assay with a limit of detection at 1,000 copies/ml. The overall percent agreement between QIAstat-Dx SARS and WHO-RT-PCR on 69 clinical samples was 97% with a sensitivity of 100% (40/40) and specificity at 93% (27/29). No cross-reaction was encountered for any other respiratory viruses or bacteria included in the panel. The QIAstat-SARS rapid multiplex PCR panel provides a highly sensitive, robust, and accurate assay for rapid detection of SARS-CoV-2. This assay allows rapid decisions even in non-PCR-trained laboratory or point-of-care testing, allowing innovative organization.

Late viral or bacterial respiratory infections in lung transplanted patients: impact on respiratory function.

BACKGROUND: Respiratory infections are a major threat for lung recipients. We aimed to compare with a monocentric study the impact of late viral and bacterial respiratory infections on the graft function. METHODS: Patients, who survived 6 months or more following lung transplantation that took place between 2009 and 2014, were classified into three groups: a viral infection group (VIG) (without any respiratory bacteria), a bacterial infection group (BIG) (with or without any respiratory viruses), and a control group (CG) (no documented infection). Chronic lung allograft dysfunction (CLAD) and acute rejection were analysed 6 months after the inclusion in the study. RESULTS: Among 99 included lung recipients, 57 (58%) had at least one positive virological respiratory sample during the study period. Patients were classified as follows: 38 in the VIG, 25 in the BIG (among which 19 co-infections with a virus) and 36 in the CG. The BIG presented a higher initial deterioration in lung function (p = 0.05) than the VIG. But 6 months after the infection, only the VIG presented a median decrease of forced expiratory volume in 1 s; - 35 mL (IQR; - 340; + 80) in the VIG, + 140 mL (+ 60;+ 330) in the BIG and + 10 (- 84;+ 160) in the CG, p < 0.01. Acute rejection was more frequent in the VIG (n = 12 (32%)), than the BIG (n = 6 (24%)) and CG (n = 3 (8%)), p < 0.05, despite presenting no more CLAD (p = 0.21). CONCLUSIONS: Despite a less severe initial presentation, single viral respiratory infections seem to lead to a greater deterioration in lung function, and to more acute rejection, than bacterial infections.

Viral-bacterial coinfection affects the presentation and alters the prognosis of severe community-acquired pneumonia.

BACKGROUND: Multiplex polymerase chain reaction (mPCR) enables recovery of viruses from airways of patients with community-acquired pneumonia (CAP), although their clinical impact remains uncertain. METHODS: Among consecutive adult patients who had undergone a mPCR within 72 hours following their admission to one intensive care unit (ICU), we retrospectively included those with a final diagnosis of CAP. Four etiology groups were clustered: bacterial, viral, mixed (viral-bacterial) and no etiology. A composite criterion of complicated course (hospital death or mechanical ventilation > 7 days) was used. A subgroup analysis compared patients with bacterial and viral-bacterial CAP matched on the bacterial pathogens. RESULTS: Among 174 patients (132 men [76 %], age 63 [53-75] years, SAPSII 38 [27;55], median PSI score 106 [78;130]), bacterial, viral, mixed and no etiology groups gathered 46 (26 %), 53 (31 %), 45 (26 %) and 30 (17 %) patients, respectively. Virus-infected patients displayed a high creatine kinase serum level, a low platelet count, and a trend toward more frequent alveolar-interstitial infiltrates. A complicated course was more frequent in the mixed group (31/45, 69 %), as compared to bacterial (18/46, 39 %), viral (15/53, 28 %) and no etiology (12/30, 40 %) groups (p < 0.01). In multivariate analysis, the mixed (viral-bacterial) infection was independently associated with complicated course (reference: bacterial pneumonia; OR, 3.58; CI 95 %, 1.16-11; p = 0.03). The subgroup analysis of bacteria-matched patients confirmed these findings. CONCLUSIONS: Viral-bacterial coinfection during severe CAP in adults is associated with an impaired presentation and a complicated course.

Clinical characteristics of ambulatory and hospitalized patients with monkeypox virus infection: an observational cohort study.

OBJECTIVES: A global outbreak of monkeypox virus infections in human beings has been described since April 2022. The objectives of this study were to describe the clinical characteristics and complications of patients with a monkeypox infection. METHODS: All consecutive patients with a polymerase chain reaction (PCR)-confirmed monkeypox infection seen in a French referral centre were included. RESULTS: Between 21 May and 5 July 2022, 264 patients had a PCR-confirmed monkeypox infection. Among them, 262 (262/264, 99%) were men, 245 (245/259, 95%) were men who have sex with men, and 90 (90/216, 42%) practiced chemsex in the last 3 months. Seventy-three (73/256, 29%) patients were living with human immunodeficiency virus infection, and 120 (120/169, 71%) patients were taking pre-exposure prophylaxis against human immunodeficiency virus infection. Overall, 112 (112/236, 47%) patients had contact with a confirmed monkeypox case; it was of sexual nature for 95% of the contacts (86/91). Monkeypox virus PCR was positive on the skin in 252 patients, on the oropharyngeal sample in 150 patients, and on blood in eight patients. The majority of patients presented with fever (171/253, 68%) and adenopathy (174/251, 69%). Skin lesions mostly affected the genital (135/252, 54%) and perianal (100/251, 40%) areas. Overall, 17 (17/264, 6%) patients were hospitalized; none of them were immunocompromised. Complications requiring hospitalization included cellulitis (n = 4), paronychia (n = 3), severe anal and digestive involvement (n = 4), non-cardia angina with dysphagia (n = 4), blepharitis (n = 1), and keratitis (n = 1). Surgical management was required in four patients. CONCLUSION: The current outbreak of monkeypox infections has specific characteristics: it occurs in the men who have sex with men community; known contact is mostly sexual; perineal and anal areas are frequently affected; and severe complications include superinfected skin lesions, paronychia, cellulitis, anal and digestive involvement, angina with dysphagia, and ocular involvement.

Human inherited complete STAT2 deficiency underlies inflammatory viral diseases.

STAT2 is a transcription factor activated by type I and III IFNs. We report 23 patients with loss-of-function variants causing autosomal recessive (AR) complete STAT2 deficiency. Both cells transfected with mutant STAT2 alleles and the patients' cells displayed impaired expression of IFN-stimulated genes and impaired control of in vitro viral infections. Clinical manifestations from early childhood onward included severe adverse reaction to live attenuated viral vaccines (LAV) and severe viral infections, particularly critical influenza pneumonia, critical COVID-19 pneumonia, and herpes simplex virus type 1 (HSV-1) encephalitis. The patients displayed various types of hyperinflammation, often triggered by viral infection or after LAV administration, which probably attested to unresolved viral infection in the absence of STAT2-dependent types I and III IFN immunity. Transcriptomic analysis revealed that circulating monocytes, neutrophils, and CD8+ memory T cells contributed to this inflammation. Several patients died from viral infection or heart failure during a febrile illness with no identified etiology. Notably, the highest mortality occurred during early childhood. These findings show that AR complete STAT2 deficiency underlay severe viral diseases and substantially impacts survival.

CT features of community-acquired pneumonia at the emergency department.

BACKGROUND: Chest computed tomography (CT) was reported to improve the diagnosis of community-acquired pneumonia (CAP) as compared to chest X-ray (CXR). The aim of this study is to describe the CT-patterns of CAP in a large population visiting the emergency department and to see if some of them are more frequently missed on CXR. MATERIALS AND METHODS: This is an ancillary analysis of the prospective multicenter ESCAPED study including 319 patients. We selected the 163 definite or probable CAP based on adjudication committee classification; 147 available chest CT scans were reinterpreted by 3 chest radiologists to identify CAP patterns. These CT-patterns were correlated to epidemiological, biological and microbiological data, and compared between false negative and true positive CXR CAP. RESULTS: Six patterns were identified: lobar pneumonia (51/147, 35%), including 35 with plurifocal involvement; lobular pneumonia (43/147, 29%); unilobar infra-segmental consolidation (24/147, 16%); bronchiolitis (16/147, 11%), including 4 unilobar bronchiolitis; atelectasis and bronchial abnormalities (8/147, 5.5%); interstitial pneumonia (5/147, 3.5%). Bacteria were isolated in 41% of patients with lobar pneumonia-pattern (mostly Streptococcus pneumoniae and Mycoplasma pneumonia) versus 19% in other patients (p = 0.01). Respiratory viruses were equally distributed within all patterns. CXR was falsely negative in 46/147 (31%) patients. Lobar pneumonia was significantly less missed on CXR than other patterns (p = 0.003), especially lobular pneumonia and unilobar infra-segmental consolidation, missed in 35% and 58% of cases, respectively. CONCLUSION: Lobar and lobular pneumonias are the most frequent CT-patterns. Lobar pneumonia is appropriately detected on CXR and mainly due to Streptococcus pneumoniae or Mycoplasma pneumoniae. Chest CT is very useful to identify CAP in other CT-patterns. Prior the COVID pandemic, CAP was rarely responsible for interstitial opacities on CT.

Differential activation of human neutrophils by SARS-CoV-2 variants of concern.

The emerging SARS-CoV-2 virus has affected the entire world with over 600 million confirmed cases and 6.5 million deaths as of September 2022. Since the beginning of the pandemic, several variants of SARS-CoV-2 have emerged, with different infectivity and virulence. Several studies suggest an important role of neutrophils in SARS-Cov-2 infection severity, but data about direct activation of neutrophils by the virus is scarce. Here, we studied the in vitro activation of human neutrophils by SARS-CoV-2 variants of concern (VOCs). In our work, we show that upon stimulation with SARS-Cov-2 infectious particles, human healthy resting neutrophils upregulate activation markers, degranulate IL-8, produce Reactive Oxygen Species and release Neutrophil Extracellular Traps. Neutrophil activation was dependent on TLR7/8 and IRF3/STING. We then compared the activation potential of neutrophils by SARS-CoV-2 variants and showed a significantly increased activation by the Delta variant and a decreased activation by the Omicron variant as compared to the initial strain. In this study, we demonstrate that the SARS-Cov-2 virus can directly activate neutrophils in COVID-19 and that the different VOCs had differences in neutrophil activation intensity that mirror the differences of clinical severity. These data highlight the need to address neutrophil-virus interactions as a potential target for therapeutic intervention in SARS-CoV-2 infection.

Efficacy of Severe Acute Respiratory Syndrome Coronavirus-2 Vaccine in Patients With Thoracic Cancer: A Prospective Study Supporting a Third Dose in Patients With Minimal Serologic Response After Two Vaccine Doses.

INTRODUCTION: Coronavirus disease 2019 resulted in a 30% mortality rate in patients with thoracic cancer. Given that patients with cancer were excluded from serum antisevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine registration trials, it is still unknown whether they would develop a protective antispike antibody response after vaccination. This prospective vaccine monitoring study primarily aimed to assess humoral responses to the SARS-CoV-2 vaccine in patients with thoracic cancer. METHODS: SARS-CoV-2-spike antibodies were measured using the Abbot Architect SARS-CoV-2 immunoglobulin G immunoassay before the first injection of BNT162b2 mRNA vaccine, at week 4, and 2 to 16 weeks after the second vaccine dose administration. The factors associated with antibody response were analyzed. RESULTS: Overall, 306 patients, with a median age of 67.0 years (interquartile range: 58-74), were vaccinated. Of these, 283 patients received two vaccine doses at 28-day intervals. After a 6.7-month median follow-up, eight patients (2.6%) contracted proven symptomatic SARS-CoV-2 infection, with rapid favorable evolution. Of the 269 serologic results available beyond day 14 after the second vaccine dose administration, 17 patients (6.3%) were still negative (<50 arbitrary units/mL, whereas 34 (11%) were less than 300 arbitrary units/mL (12.5th percentile). In multivariate analysis, only age (p < 0.01) and long-term corticosteroid treatment (p = 0.01) were significantly associated with a lack of immunization. A total of 30 patients received a third vaccine dose, with only three patients showing persistently negative serology thereafter, whereas the others exhibited clear seroconversion. CONCLUSIONS: SARS-CoV2 vaccines were found to be efficient in patients with thoracic cancer, most of them being immunized after two doses. A third shot given to 1% of patients with persistent low antibody titers resulted in an 88% immunization rate.

Chronic use of inhaled corticosteroids in patients admitted for respiratory virus infections: a 6-year prospective multicenter study.

Inhaled corticosteroids (ICS) have been associated with increased risk of pneumonia. Their impact on respiratory virus infections is unclear. We performed a post-hoc analysis of the FLUVAC cohort, a multicenter prospective cohort study of adults hospitalized with influenza-like illness (ILI) during six consecutive influenza seasons (2012-2018). All patients were tested for respiratory virus infection by multiplex PCR on nasopharyngeal swabs and/or bronchoalveolar lavage. Risk factors were identified by logistic regression analysis. Among the 2658 patients included, 537 (20.2%) were treated with ICS before admission, of whom 282 (52.5%, 282/537) tested positive for at least one respiratory virus. Patients on ICS were more likely to test positive for non-influenza respiratory viruses (25.1% vs. 19.5%, P = 0.004), especially for adenovirus (aOR 2.36, 95% CI 1.18-4.58), and respiratory syncytial virus (aOR 2.08, 95% CI 1.39-3.09). Complications were reported in 55.9% of patients on ICS (300/537), primarily pneumonia (171/535, 32%). Among patients on chronic ICS who tested positive for respiratory virus, 14.2% (40/282) were admitted to intensive care unit, and in-hospital mortality rate was 2.8% (8/282). Chronic use of ICS is associated with an increased risk of adenovirus or RSV infections in patients admitted for ILI.

Rhinoviruses: molecular diversity and clinical characteristics.

BACKGROUND: Rhinoviruses are commonly considered simple "common cold" agents. The link between their molecular epidemiology and patient clinical presentation and outcomes remains unclear in adult populations. MATERIALS/METHODS: All nasopharyngeal or bronchoalveolar lavages were screened using multiplex PCR in 3 Parisian hospitals from January 2018 to September 2018. For all detected rhinoviruses, the VP2/VP4 region was subtyped by sequencing. RESULTS: The study included 178 unique patients who were positive for human rhinovirus (HRV). They were primarily men (56%), with a median age of 62.2 years (IQR: 46.8-71.4), frequently presenting chronic respiratory diseases (56%) and/or immunosuppression (46%). Of these, 63% were admitted for respiratory distress, including 25% for pneumonia; 95 (53%), 27 (15%), and 56 (32%) were positive for HRV-A, -B, and -C, respectively. HRV-B appeared to be more associated with immunosuppressive treatments (58% vs 30% and 36% of patients for HRV-A and -C, respectively, p = 0.038), higher coinfection rates (54% vs 34% and 23%, p = 0.03), and higher intensive care unit (ICU) admission rates (35% vs 17% and 13%, p = 0.048). Conversely, HRV-A was more frequently associated with pneumonia (54% vs 31% and 11% for HRV-B and -C, respectively, p = 0.01). CONCLUSIONS: This study highlights the high proportion of chronic respiratory diseases or immunosuppression among hospitalized patients infected with a rhinovirus. IMPORTANT: Human rhinoviruses (HRVs) are frequently detected in patients hospitalized for respiratory distress. Understanding their molecular differences is crucial to finding target treatments and improving patient outcomes.