Réactivation de tuberculose après traitement immunomodulateur pour une infection sévère à SARS-CoV-2 Reactivation of tuberculosis after immunomodulatory treatment for severe SARS-CoV-2 infection

Résumé Nous rapportons deux cas de réactivation tuberculeuse après COVID-19 sous corticostéroïdes et tocilizumab. Ils ont présenté une lymphopénie, des signes cliniques limités, une présentation radiologique inhabituelle mais des prélèvements microbiologiques positifs. Le dépistage de l'infection tuberculeuse latente (ITL) étant inapproprié dans ce contexte, il faudrait discuter de la traiter systématiquement chez des patients les plus à risque en cas de traitement immunomodulateur.

Réactivation de tuberculose après traitement immunomodulateur pour une infection sévère à SARS-CoV-2

Résumé Nous rapportons deux cas de réactivation tuberculeuse après COVID-19 sous corticostéroïdes et tocilizumab. Ils ont présenté une lymphopénie, des signes cliniques limités, une présentation radiologique inhabituelle mais des prélèvements microbiologiques positifs. Le dépistage de l'infection tuberculeuse latente (ITL) étant inapproprié dans ce contexte, il faudrait discuter de la traiter systématiquement chez des patients les plus à risque en cas de traitement immunomodulateur. We report cases of tuberculosis reactivation after COVID-19 treated with corticosteroids and tocilizumab. Both patients had lymphopenia and limited clinical signs. Radiological findings were unusual but microbiological samples were positive. As screening for latent tuberculosis with IGRA seems unappropriate in this context, latent tuberculosis treatment should be discussed while introducing immunomodulatory treatment for patients at risk.

Sociodemographic characteristics and transmission risk factors in patients hospitalized for COVID-19 before and during the lockdown in France.

BACKGROUND: The efficacy of lockdown in containing the COVID-19 pandemic has been reported in different studies. However, the impact on sociodemographic characteristics of individuals infected with SARS-CoV-2 has not been evaluated. The aim of this study was to describe the changes in sociodemographic characteristics of patients hospitalized for COVID-19 and to compare the transmission risk factors of COVID-19 before and during lockdown in France. METHODS: An observational retrospective study was conducted in a University Hospital in Paris, France. Data from patients hospitalized for COVID-19 in the Infectious Diseases Department between February 26 and May 11, 2020 were collected. The study population was divided into 2 groups: group A of patients infected before lockdown, and group B of patients infected during lockdown, considering a maximum incubation period of 14 days. Sociodemographic characteristics and transmission risk factors were compared between the 2 groups using Student's t-test for continuous variables and Chi-2 test or Fisher exact test for categorical variables. RESULTS: Three hundred eighty-three patients were included in the study, 305 (79.6%) in group A and 78 (20.4%) in group B. Patients in group A were significantly younger (60.0 versus (vs) 66.5 years (p = 0.03)). The professionally active population was larger in group A (44.3% vs 24.4%). There were significantly more non-French-speaking people in group B (16.7% vs 6.6%, p <  0.01). Most patients from group A had individual accommodation (92.8% vs 74.4%, p <  0.01). Contact with a relative was the main transmission risk factor in both groups (24.6% vs 33.3%, p = 0.16). Recent travel and large gathering were found only in group A. The proportion of people living in disadvantaged conditions, such as homeless people or people living in social housing, was significantly higher in group B (11.5% vs 4.3%, p = 0.03) as was the proportion of institutionalized individuals (14.1% vs 3.0%, p <  0.01). CONCLUSIONS: In this study conducted in patients hospitalized for COVID-19 in Paris, France, the likelihood of being infected despite the lockdown was higher for people who do not speak French, live in social housing, are homeless or institutionalized. Targeted measures have to be implemented to protect these populations.

Chronic use of renin-angiotensin-aldosterone system blockers and mortality in COVID-19: A multicenter prospective cohort and literature review.

AIMS: The role of renin-angiotensin-aldosterone system (RAAS) blockers on the course of coronavirus disease 2019 (COVID-19) is debated. We assessed the association between chronic use of RAAS blockers and mortality among inpatients with COVID-19 and explored reasons for discrepancies in the literature. METHODS AND RESULTS: We included adult hypertensive patients from a prospective nationwide cohort of 3512 inpatients with COVID-19 up to June 30, 2020. Cox proportional hazard models with various adjustment or propensity weighting methods were used to estimate the hazard ratios (HR) of 30-day mortality for chronic users versus non-users of RAAS blockers. We analyzed data of 1160 hypertensive patients: 719 (62%) were male and 777 (67%) were older than 65 years. The main comorbidities were diabetes (n = 416, 36%), chronic cardiac disease (n = 401, 35%), and obesity (n = 340, 29%); 705 (61%) received oxygen therapy. We recorded 135 (11.6%) deaths within 30 days of diagnosis. We found no association between chronic use of RAAS blockers and mortality (unadjusted HR = 1.13, 95% CI [0.8-1.6]; propensity inverse probability treatment weighted HR = 1.09 [0.86-1.39]; propensity standardized mortality ratio weighted HR = 1.08 [0.79-1.47]). Our comprehensive review of previous studies highlighted that significant associations were mostly found in unrestricted populations with inappropriate adjustment, or with biased in-hospital exposure measurement. CONCLUSION: Our results do not support previous concerns regarding these drugs, nor a potential protective effect as reported in previous poorly designed studies and meta-analyses. RAAS blockers should not be discontinued during the pandemic, while in-hospital management of these drugs will be clarified by randomized trials. NCT04262921.

Cytomegalovirus proctitis as a complication of COVID-19 with immunosuppressive treatments.

We report a case of reactivated biopsy-proven cytomegalovirus proctitis complicating the course of severe COVID-19 pneumonia treated with dexamethasone, anakinra and lopinavir/ritonavir. No other contributing factor was found than iatrogenic immunosuppression and COVID-19 immune dysregulation. We draw attention to the immunosuppressive risk when treating severe COVID-19 pneumonia with immunomodulators.

Association between renin-angiotensin-aldosterone system blockers and outcome in coronavirus disease 2019: analysing in-hospital exposure generates a biased seemingly protective effect of treatment.

OBJECTIVE: The role of renin-angiotensin-aldosterone system (RAAS) blockers during the coronavirus disease 2019 (COVID-19) pandemic is a matter of controversies. Studies based on in-hospital exposure have suggested a beneficial effect of these drugs, unlike those based on chronic exposure. We aimed to analyse RAAS blocker prescription before and during hospital stay in patients with COVID-19, and the corresponding outcomes, to explain these discrepant results. METHODS: In a retrospective cohort study conducted in 347 patients hospitalized for COVID-19 (Bichat Hospital, Paris, France, 23 January-29 April 2020), RAAS blocker exposure, as well as timing and reason for treatment modifications, were collected. The association between exposure and mortality within 30 days of hospital admission was analysed using logistic regression analysis adjusted for age, sex, and comorbidities. RESULTS: Median age was 61 [interquartile range, 51-72] years, 209 (60%) were male, 169 (49%) had a history of treated hypertension, and 117 (34%) received a RAAS blocker prior to hospitalization. RAAS blockers were discontinued within the first 7 days of hospital admission in 33% of previously treated patients (mostly driven by severity of the disease), with a corresponding mortality rate of 33%. Mortality was 8% when treatment was maintained or introduced, and 12% in patients never exposed. Adjusted odds ratios for association between exposure and mortality were 0.62 (95% confidence interval 0.25-1.48) based on chronic exposure and 0.25 (0.09-0.65) based on in-hospital exposure. CONCLUSION: A 'healthy user-sick stopper' bias influences RAAS blocker prescription after hospital admission for COVID-19, and explains the seemingly favourable outcome associated with in-hospital treatment.

Arterial Thrombotic Events in Adult Inpatients With COVID-19.

OBJECTIVE: To evaluate the clinical course of and risk factors for arterial thrombotic events in adult inpatients with coronavirus disease 2019 (COVID-19). METHODS: All consecutive adult patients admitted for COVID-19 infection in a referral center in France and discharged from the hospital between April 1 and April 30, 2020, were included. All arterial thrombotic events that occurred through discharge were considered for analysis. Epidemiologic, demographic, clinical, laboratory, treatment, and outcome data were extracted from electronic medical records with use of a standardized data collection form. RESULTS: Overall, 531 COVID-19+ patients were analyzed. Among them, 30 (5.6%) experienced arterial thrombotic events. Arterial thrombotic events in the setting of COVID-19 infection happened at a median of 11 (5-20) days after the first symptoms of infection; occurred in high-risk patients according to traditional cardiovascular risk factors; had an atypical pattern, such as thrombosis of the aorta, upper limb, or renal arteries or cerebral microvasculopathy in 7 (23.3%) cases; and were associated with an in-hospital mortality rate of 40%. Arterial thrombotic events increased the risk of death by 3-fold in COVID-19+ patients (hazard ratio, 2.96; 95% CI, 1.4 to 4.7; P=.002). A subdistribution survival hazard model showed that a concentration of D-dimer above 1250 ng/mL increased the risk of arterial thrombotic events in COVID-19+ patients by more than 7 (subdistribution hazard ratio, 7.68; 95% CI, 2.9 to 20.6; P<.001). CONCLUSION: A dramatically high rate of in-hospital death was observed in patients who suffered arterial thrombotic events in the setting of COVID-19 infection. A D-dimer level above 1250 ng/mL at entry may identify COVID-19+ patients at risk for arterial thrombotic events.

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.

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.

Case report study of the first five COVID-19 patients treated with remdesivir in France.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as the virus responsible for the coronavirus disease 2019 (COVID-19) outbreak worldwide. Data on treatment are scare and parallels have been made between SARS-CoV-2 and other coronaviruses. Remdesivir is a broad-spectrum antiviral with efficient in vitro activity against SARS-CoV-2. Evidence of clinical improvement in patients with severe COVID-19 treated with remdesivir is controversial. The aim of this study was to describe the clinical outcomes and virological monitoring of the first five COVID-19 patients admitted to the intensive care unit of Bichat-Claude Bernard University Hospital, Paris, France, for severe pneumonia related to SARS-CoV-2 and treated with remdesivir. Quantitative reverse transcription PCR was used to monitor SARS-CoV-2 in blood plasma and the lower and upper respiratory tract. Among the five patients treated, two needed mechanical ventilation and one needed high-flow cannula oxygen. A significant decrease in SARS-CoV-2 viral load in the upper respiratory tract was observed in most cases, but two patients died with active SARS-CoV-2 replication in the lower respiratory tract. Plasma samples were positive for SARS-CoV-2 in only one patient. Remdesivir was interrupted before the initialy planned duration in four patients, two because of alanine aminotransferase elevations (3 to 5 normal range) and two because of renal failure requiring renal replacement. This case series of five COVID-19 patients requiring intensive care unit treatment for respiratory distress and treated with remdesivir, highlights the complexity of remdesivir use in such critically ill patients.