Outcome of SARS-CoV-2 infection is linked to MAIT cell activation and cytotoxicity.

Immune system dysfunction is paramount in coronavirus disease 2019 (COVID-19) severity and fatality rate. Mucosal-associated invariant T (MAIT) cells are innate-like T cells involved in mucosal immunity and protection against viral infections. Here, we studied the immune cell landscape, with emphasis on MAIT cells, in cohorts totaling 208 patients with various stages of disease. MAIT cell frequency is strongly reduced in blood. They display a strong activated and cytotoxic phenotype that is more pronounced in lungs. Blood MAIT cell alterations positively correlate with the activation of other innate cells, proinflammatory cytokines, notably interleukin (IL)-18, and with the severity and mortality of severe acute respiratory syndrome coronavirus 2 infection. We also identified a monocyte/macrophage interferon (IFN)-α-IL-18 cytokine shift and the ability of infected macrophages to induce the cytotoxicity of MAIT cells in an MR1-dependent manner. Together, our results suggest that altered MAIT cell functions due to IFN-α-IL-18 imbalance contribute to disease severity, and their therapeutic manipulation may prevent deleterious inflammation in COVID-19 aggravation.

Evaluation of the Specificity of the 2023 Duke-International Society of Cardiovascular Infectious Diseases Classification for Infective Endocarditis.

BACKGROUND: The 2023 Duke-ISCVID (International Society of Cardiovascular Infectious Diseases) classification is a new diagnostic tool for infective endocarditis, updating the 2000 modified Duke and the 2015 European Society for Cardiology (ESC) classifications. In comparison, its sensitivity is higher; however, its specificity remains to be evaluated and compared to that of the 2 other classifications in endocarditis suspected patients. METHODS: We retrospectively collected the characteristics of patients hospitalized in Bichat University's Hospital, Paris, in 2021, who had been evaluated for clinical suspicion of endocarditis, have had at least a transthoracic echocardiography, 2 pairs of blood cultures, 3-month follow-up and in whom endocarditis diagnosis was finally rejected. All patients were classified by 2000 modified Duke, 2015 ESC and 2023 Duke-ISCVID, as though the endocarditis diagnosis had not been rejected. RESULTS: In total, 130 patients' charts were analyzed. Mean age was 62 years, 84 (64.6%) were male, 39 (30.0%) had prosthetic cardiac valve or valve repair, 21 (16.2%) cardiac implanted electronic device, and 30 (23.1%) other cardiac conditions. Overall, 5, 2, and 5 patients were falsely classified as definite endocarditis with the 2000 modified Duke, 2015 ESC, and 2023 Duke-ISCVID classifications, respectively. The corresponding specificities were 96.2% (95% confidence interval [CI] [90.8%, 98.6%]), 98.5% (95% CI [93.9%, 99.7%]), and 96.2% (95% CI [90.8%, 98.6%]). The rates of possible endocarditis were of 38%, 35%, and 35% in the 3 classifications, respectively. CONCLUSIONS: The 2023 Duke-ISCVID classification is highly specific for ruling out the diagnosis of definite infective endocarditis in patients who had been evaluated for IE.

Efficacy of vancomycin lock therapy for totally implantable venous access port-related infection due to coagulase-negative staphylococci in 100 patients with cancer.

OBJECTIVES: Data on the efficacy of vancomycin catheter lock therapy (VLT) for conservative treatment of totally implantable venous access port-related infections (TIVAP-RI) due to CoNS are scarce. The aim of this study was to evaluate the effectiveness of VLT in the treatment of TIVAP-RI due to CoNS in cancer patients. METHODS: This prospective, observational, multicentre study included adults with cancer treated with VLT for a TIVAP-RI due to CoNS. The primary endpoint was the success of VLT, defined as no TIVAP removal nor TIVAP-RI recurrence within 3 months after initiation of VLT. The secondary endpoint was 3 month mortality. Risk factors for VLT failure were also analysed. RESULTS: One hundred patients were included [men 53%, median age 63 years (IQR 53-72)]. Median duration of VLT was 12 days (IQR 9-14). Systemic antibiotic therapy was administered in 87 patients. VLT was successful in 44 patients. TIVAP could be reused after VLT in 51 patients. Recurrence of infection after completion of VLT occurred in 33 patients, among which TIVAP was removed in 27. Intermittent VLT (antibiotic solution left in place in the TIVAP lumen part of the time) was identified as a risk factor for TIVAP-RI recurrence. At 3 months, 26 deaths were reported; 1 (4%) was related to TIVAP-RI. CONCLUSIONS: At 3 months, success of VLT for TIVAP-RI due to CoNS was low. However, removing TIVAP was avoided in nearly half the patients. Continuous locks should be preferred to intermittent locks. Identifying factors of success is essential to select patients who may benefit from VLT.

Prognosis of rash and chilblain-like lesions among outpatients with COVID-19: a large cohort study.

In a large regional observational cohort study of adult (≥ 18 years), outpatients with COVID-19, prevalence, characteristics, and outcome of patients with rash and/or chilblain-like lesions (CLL), compared with population without cutaneous features, were studied. In total, 28,957 outpatients were included; the prevalence of rash and CCL were 9.5% and 3.7%, respectively. Presence of rash was significantly associated with presence of asthenia, shivers or myalgia, respiratory and gastro-intestinal symptoms, and anosmia/ageusia. The presence of CCL was associated with chest pain, chest oppression, nausea/vomiting, and anosmia/ageusia. Patients with CCL were significantly less prone to an unfavourable outcome (hospitalization or death).

Covidom, a Telesurveillance Solution for Home Monitoring Patients With COVID-19.

In a matter of months, COVID-19 has escalated from a cluster of cases in Wuhan, China, to a global pandemic. As the number of patients with COVID-19 grew, solutions for the home monitoring of infected patients became critical. This viewpoint presents a telesurveillance solution-Covidom-deployed in the greater Paris area to monitor patients with COVID-19 in their homes. The system was rapidly developed and is being used on a large scale with more than 65,000 registered patients to date. The Covidom solution combines an easy-to-use and free web application for patients (through which patients fill out short questionnaires on their health status) with a regional control center that monitors and manages alerts (triggered by questionnaire responses) from patients whose health may be deteriorating. This innovative solution could alleviate the burden of health care professionals and systems while allowing for rapid response when patients trigger an alert.

Use of covid-19 convalescent plasma to treat patients admitted to hospital for covid-19 with or without underlying immunodeficiency: open label, randomised clinical trial.

Objective: To evaluate the efficacy of covid-19 convalescent plasma to treat patients admitted to hospital for moderate covid-19 disease with or without underlying immunodeficiency (CORIPLASM trial). Design: Open label, randomised clinical trial. Setting: CORIMUNO-19 cohort (publicly supported platform of open label, randomised controlled trials of immune modulatory drugs in patients admitted to hospital with moderate or severe covid-19 disease) based on 19 university and general hospitals across France, from 16 April 2020 to 21 April 2021. Participants: 120 adults (n=60 in the covid-19 convalescent plasma group, n=60 in the usual care group) admitted to hospital with a positive SARS-CoV2 test result, duration of symptoms <9 days, and World Health Organization score of 4 or 5. 49 patients (n=22, n=27) had underlying immunosuppression. Interventions: Open label randomisation to usual care or four units (200-220 mL/unit, 2 units/day over two consecutive days) of covid-19 convalescent plasma with a seroneutralisation titre >40. Main outcome measures: Primary outcomes were proportion of patients with a WHO Clinical Progression Scale score of ≥6 on the 10 point scale on day 4 (higher values indicate a worse outcome), and survival without assisted ventilation or additional immunomodulatory treatment by day 14. Secondary outcomes were changes in WHO Clinical Progression Scale scores, overall survival, time to discharge, and time to end of dependence on oxygen supply. Predefined subgroups analyses included immunosuppression status, duration of symptoms before randomisation, and use of steroids. Results: 120 patients were recruited and assigned to covid-19 convalescent plasma (n=60) or usual care (n=60), including 22 (covid-19 convalescent plasma) and 27 (usual care) patients who were immunocompromised. 13 (22%) patients who received convalescent plasma had a WHO Clinical Progression Scale score of ≥6 at day 4 versus eight (13%) patients who received usual care (adjusted odds ratio 1.88, 95% credible interval 0.71 to 5.24). By day 14, 19 (31.6%) patients in the convalescent plasma group and 20 (33.3%) patients in the usual care group needed ventilation, additional immunomodulatory treatment, or had died. For cumulative incidence of death, three (5%) patients in the convalescent plasma group and eight (13%) in the usual care group died by day 14 (adjusted hazard ratio 0.40, 95% confidence interval 0.10 to 1.53), and seven (12%) patients in the convalescent plasma group and 12 (20%) in the usual care group by day 28 (adjusted hazard ratio 0.51, 0.20 to 1.32). In a subgroup analysis performed in patients who were immunocompromised, transfusion of covid-19 convalescent plasma was associated with mortality (hazard ratio 0.39, 95% confidence interval 0.14 to 1.10). Conclusions: In this study, covid-19 convalescent plasma did not improve early outcomes in patients with moderate covid-19 disease. The efficacy of convalescent plasma in patients who are immunocompromised should be investigated further. Trial registration: ClinicalTrials.gov NCT04345991.

Prevention of SARS-CoV-2 transmission during a large, live, indoor gathering (SPRING): a non-inferiority, randomised, controlled trial.

BACKGROUND: Mass indoor gatherings were banned in early 2020 to prevent the spread of SARS-CoV-2. We aimed to assess, under controlled conditions, whether infection rates among attendees at a large, indoor gathering event would be similar to those in non-attendees, given implementation of a comprehensive prevention strategy including antigen-screening within 3 days, medical mask wearing, and optimised ventilation. METHODS: The non-inferiority, prospective, open-label, randomised, controlled SPRING trial was done on attendees at a live indoor concert held in the Accor Arena on May 29, 2021 in Paris, France. Participants, aged 18-45 years, recruited via a dedicated website, had no comorbidities, COVID-19 symptoms, or recent case contact, and had had a negative rapid antigen diagnostic test within 3 days before the concert. Participants were randomly allocated in a 2:1 ratio to the experimental group (attendees) or to the control group (non-attendees). The allocation sequence was computer-generated by means of permuted blocks of sizes three, six, or nine, with no stratification. The primary outcome measure was the number of patients who were SARS-CoV-2-positive by RT-PCR test on self-collected saliva 7 days post-gathering in the per-protocol population (non-inferiority margin <0·35%). This trial is registered with ClinicalTrials.gov, NCT04872075. FINDINGS: Between May 11 and 25, 2021, 18 845 individuals registered on the dedicated website, and 10 953 were randomly selected for a pre-enrolment on-site visit. Among 6968 who kept the appointment and were screened, 6678 participants were randomly assigned (4451 were assigned to be attendees and 2227 to be non-attendees; median age 28 years; 59% women); 88% (3917) of attendees and 87% (1947) of non-attendees complied with follow-up requirements. The day 7 RT-PCR was positive for eight of the 3917 attendees (observed incidence, 0·20%; 95% CI 0·09-0·40) and three of the 1947 non-attendees (0·15%; 0·03-0·45; absolute difference, 95% CI -0·26% to 0·28%), findings that met the non-inferiority criterion for the primary endpoint. INTERPRETATION: Participation in a large, indoor, live gathering without physical distancing was not associated with increased SARS-CoV-2-transmission risk, provided a comprehensive preventive intervention was implemented. FUNDING: French Ministry of Health. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Tocilizumab plus dexamethasone versus dexamethasone in patients with moderate-to-severe COVID-19 pneumonia: A randomised clinical trial from the CORIMUNO-19 study group.

Background: In moderate-to-severe COVID-19 pneumonia, dexamethasone (DEX) and tocilizumab (TCZ) reduce the occurrence of death and ventilatory support. We investigated the efficacy and safety of DEX+TCZ in an open randomized clinical trial. Methods: From July 24, 2020, through May 18, 2021, patients with moderate-to-severe COVID-19 pneumonia requiring oxygen (>3 L/min) were randomly assigned to receive DEX (10 mg/d 5 days tapering up to 10 days) alone or combined with TCZ (8 mg/kg IV) at day 1, possibly repeated with a fixed dose of 400 mg i.v. at day 3. The primary outcome was time from randomization to mechanical ventilation support or death up to day 14, analysed on an intent-to-treat basis using a Bayesian approach. ClinicalTrials.gov number, NCT04476979. Findings: A total of 453 patients were randomized, 3 withdrew consent, 450 were analysed, of whom 226 and 224 patients were assigned to receive DEX or TCZ+DEX, respectively. At day 14, mechanical ventilation or death occurred in 32/226 (14%) and 27/224 (12%) in the DEX and TCZ+DEX arms, respectively (hazard ratio [HR] 0·85, 90% credible interval [CrI] 0·55 to 1·31). At day 14, the World health Organization (WHO) clinical progression scale (CPS) was significantly improved in the TCZ+DEX arm (OR 0·69, 95% CrI, 0·49 to 0.97). At day 28, the cumulative incidence of oxygen supply independency was 82% in the TCZ+DEX arms and 72% in the DEX arm (HR 1·36, 95% CI 1·11 to 1·67). On day 90, 24 deaths (11%) were observed in the DEX arm and 18 (8%) in the TCZ+DEX arm (HR 0·77, 95% CI 0·42-1·41). Serious adverse events were observed in 25% and 21% in DEX and TCZ+DEX arms, respectively. Interpretation: Mechanical ventilation need and mortality were not improved with TCZ+DEX compared with DEX alone. The safety of both treatments was similar. However, given the wide confidence intervals for the estimate of effect, definitive interpretation cannot be drawn. Funding: Programme Hospitalier de Recherche Clinique [PHRC COVID-19-20-0151, PHRC COVID-19-20-0029], Fondation de l'Assistance Publique - Hôpitaux de Paris (Alliance Tous Unis Contre le Virus) and from Fédération pour la Recherche Médicale" (FRM). Tocilizumab was provided by Roche.

Time to resolution of respiratory and systemic coronavirus disease 2019 symptoms in community setting.

OBJECTIVES: To assess the time to resolution of respiratory and systemic symptoms and their associated factors in outpatients during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Cohort study including adult outpatients, managed with Covidom, a telesurveillance solution, with RT-PCR-confirmed diagnosis, from 9 March 2020 until 23 February 2021. Follow up was 30 days after symptom onset. RESULTS: Among the 9667 patients included, mean age was 43.2 ± 14.0 years, and 67.5% were female (n = 6522). Median body mass index (BMI) was 25.0 kg/m2 (interquartile range 22.1-28.8 kg/m2). Main co-morbidities were: hypertension (12.9%; n = 1247), asthma (11.0%; n = 1063) and diabetes mellitus (5.5%; n = 527). The most frequent symptom during follow up was dyspnoea (65.1%; n = 6296), followed by tachypnoea (49.9%; n = 4821), shivers (45.6%; n = 4410) and fever (36.7%; n = 3550). Median times to resolution of systemic and respiratory symptoms were 3 days (95% CI 2-4 days) and 7 days (95% CI 6-8 days), respectively. Ultimately, 17.2% (95% CI 15.7%-18.8%) still presented respiratory symptoms at day 30. Longer time to respiratory symptom resolution was associated with older age, increased BMI, chronic obstructive pulmonary disease, coronary artery disease, asthma and heart failure. Regarding systemic symptoms, coronary artery disease, asthma, age above 40 years and elevated BMI were associated with longer time to resolution. CONCLUSIONS: Time to symptom resolution among outpatients with COVID-19 seemed shorter for systemic than respiratory symptoms. Prolonged respiratory symptoms were common at day 30. Risk factors associated with later resolution included age, and cardiovascular and pulmonary diseases.

Is the term "anti-anaerobic" still relevant?

For decades, the term "anti-anaerobic" has been commonly used to refer to antibiotics exhibiting activity against anaerobic bacteria, also designated as anaerobes. This term is used in various situations ranging from infections associated with well-identified pathogens like Clostridioides difficile, or Fusobacterium necrophorum in Lemierre's syndrome, that require specific antibiotic treatments to polymicrobial infections generally resulting from the decreased permeability of anatomical barriers (e.g., intestinal translocation and stercoral peritonitis) or infectious secondary localizations (e.g., brain abscess and infectious pleurisy). In these cases, the causal bacteria generally remain unidentified and the antimicrobial treatment is empirical. However, major progress in the knowledge of human bacterial microbiotas in the last 10 years has shown how diverse are the species involved in these communities. Here, we sought to reappraise the concept of anti-anaerobic spectrum in the light of recent advances in the microbiota field. We first highlight that the term anaerobic itself does not represent the tremendous diversity of the bacteria it spans, and then we stress that the antibiotic susceptibility profiles for most anaerobic bacteria remain unaddressed. Furthermore, we provide examples challenging the relevance of the "anti-anaerobic" spectrum from a clinical and ecological perspective.

Correction: Characteristics associated with COVID-19 or other respiratory viruses' infections at a single-center emergency department.

[This corrects the article DOI: 10.1371/journal.pone.0243261.].

Factors associated with single-room assignment among patients admitted through the emergency department during influenza epidemics.

INTRODUCTION: Every winter, emergency departments (EDs) face overcrowding with patients presenting influenza-like symptoms, and organisational issues such as single room assignment and droplet precautions to avoid hospital-acquired influenza. Our main objective was to assess the impact of PCR results and patient's severity on single room assignment. METHODS: All patients admitted to Bichat-Claude Bernard Hospital through the ED and tested for influenza by PCR (GenXpert, Cepheid) or (FilmArray, BioMérieux) on a nasopharyngeal swab were retrospectively included during three influenza seasons (2015-2018. RESULTS: Of 1,330 included patients, 278 (20.9%) had a positive PCR for influenza. The median time to obtain a PCR result was 19 hours, and 238 (18.3%) patients were assigned a single room. Among patients with positive and negative influenza PCR, 22.3% and 16.7% were assigned a single room (p = 0.03). The multivariable analysis was performed on the two first epidemic periods, excluding the third epidemic because of the concomitant use of influenza immune-chromatic test. Only level 1 of the Emergency severity index (ESI) (aOR, 1.9; 95% CI, 1.3-2.8; p < 0.01) was associated with single-room assignment. PCR result was not statistically associated with the decision of single room assignment (aOR, 1.4; 95%CI, 1.0-1.4; p = 0.07). CONCLUSION: A PCR positive for influenza was not significantly associated with single-room assignment. Less than one quarter of influenza patients were adequately assigned a single room, likely due to the long turnaround time of PCR result and other conflicting indications for single room-assignment. Accelerating biological diagnosis could improve single-room assignment.

Characteristics associated with COVID-19 or other respiratory viruses' infections at a single-center emergency department.

BACKGROUND: Rapid identification of patients with high suspicion of COVID-19 will become a challenge with the co-circulation of multiple respiratory viruses (RVs). We have identified clinical or biological characteristics to help distinguish SARS-CoV-2 from other RVs. METHODS: We used a prospective cohort including all consecutive patients admitted through the emergency department's (ED) and presenting respiratory symptoms from November 2019 to April 2020. Patients were tested for RV using multiplex polymerase chain reaction (mPCR) and SARS-CoV-2 RT-PCR. RESULTS: 203/508 patients were positive for an RV during the non-SARS-CoV-2 epidemic period (November to February), and 268/596 patients were SARS-CoV-2 positive during the SARS-CoV-2 epidemic (March to April). Younger age, male gender, fever, absence of expectoration and absence of chronic lung disease were statistically associated with SARS-CoV-2 detection. Combining these variables allowed for the distinguishing of SARS-CoV-2 infections with 83, 65, 75 and 76% sensitivity, specificity, PPV and NPV, respectively. CONCLUSION: Patients' characteristics associated with a positive PCR are common between SARS-CoV-2 and other RVs, but a simple discrimination of strong SARS-CoV-2 suspicion with a limited set of clinical features seems possible. Such scoring could be useful but has to be prospectively evaluated and will not eliminate the need for rapid PCR assays.

SARS-COV2 infection in 30 HIV-infected patients followed-up in a French University Hospital.

INTRODUCTION: An acute respiratory disease caused by a novel coronavirus (SARSCOV2) is spreading from China since January 2020. Surprisingly, few cases of Covid-19 have been reported in people living with HIV (PLWHIV). METHODS: Here we present a series of 30 PLWHIV diagnosed for SARS-COV2 infection. The principal outcome was to describe clinical characteristics of this population. RESULTS: Eighteen (60%) patients were men, 10/30 (33,3%) women and 2/30 (6,7%) transgender women. Median age was 53,7 years (range 30-80 years) and 23/30 patients (76,7%) were born in a foreign country (out of France). The most common comorbidities were cardiovascular disease (11/30, 36,7%), hypertension (11/30, 36,7%), diabetes (9/30,30%) obesity (7/30, 23%) and chronic renal disease (5/30, 16,7%). Twenty (66,7%) patients presented overweight. Five patients (16,7%) had a Charlson comorbidity (Quan et al., 2011) score ≥3. Twenty-seven (90%) patients were virologically suppressed.CD4 count was >500cell/mm 3 in 23/30 (76,6%) patients. An antiviral treatment for SARS-COV2 was administered, in addition to HIV treatment, in 5/30 patients (16,3%). Twenty-four patients (80%) recovered from covid-19, 3/30 (10%) required invasive mechanical ventilation, 2/30 (6,7%) patients died and 4/30 (13,3%) patients were still hospitalized. CONCLUSIONS: Most of the patients were virologically suppressed with CD4>500 mm3. Risk factors were the same as those described in other SARS-COV2 series, suggesting that HIV infection is probably not an independent risk factor for covid-19.

A strobe multicenter descriptive study of 55 infectious aortitis.

Infectious aortitis (IA) is a rare and severe disease. The treatment classically associates open surgery with prolonged antibiotic therapy. This study aimed to describe clinical characteristics, medical and surgical supports in a large and current series of IA.We conducted a retrospective multicenter study of native aorta IA, between 2000 and 2019. Inclusion criteria were the presence of a microorganism on blood culture, aortic sample or any other validated technique and structural anomaly in imaging.We included 55 patients (85% men), with a median age of 65. Microbiology data substantially differed from previous studies with 12 Gram-negative rods IA, of which only 3 due to Salmonella spp., 24 Gram-positive cocci IA of which 12 Streptococcus spp., and 18 IA due to intracellular growth and/or fastidious microorganisms, of which 8 Coxiella burnetii, 3 Treponema pallidum, and 5 tuberculosis suspicious cases. Fifteen patients (27%) presented with thoracic IA, 31 (56%) with abdominal IA, and 9 (16%) with thoraco-abdominal IA. Eight patients had no surgery, 41 underwent open surgery, only 4 endovascular aneurysm repair, and 2 a combination of these 2 techniques. Nine patients died before 1-month follow-up. There was no difference in the mortality rate between the different types of germ or localization of IA.The variety of germs involved in IA increases. Positron emission tomography-computed tomography scan is a very useful tool for diagnosis. Surgery is still mainly done in open approach and a prospective multicenter study seems necessary to better determine the place of endovascular aneurysm repair versus open surgery.