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.

IMPORTANCEThe benefit of high-dose dexamethasone and oxygenation strategies vs standard of care for patients with severe acute hypoxemic respiratory failure (AHRF) caused by COVID-19 pneumonia is debated.OBJECTIVES To assess the benefit of high-dose dexamethasone compared with standard of care dexamethasone, and to assess the benefit of high-flow nasal oxygen (HFNO 2 ) or continuous positive airway pressure (CPAP) compared with oxygen support standard of care (O 2 SC). DESIGN, SETTING, AND PARTICIPANTSThis multicenter, placebo-controlled randomized clinical trial was conducted in 19 intensive care units (ICUs) in France from April 2020 to January 2021. Eligible patients were consecutive ICU-admitted adults with COVID-19 AHRF. Randomization used a 2 × 3 factorial design for dexamethasone and oxygenation strategies; patients not eligible for at least 1 oxygenation strategy and/or already receiving invasive mechanical ventilation (IMV) were only randomized for dexamethasone. All patients were followed-up for 60 days. Data were analyzed from May 26 to July 31, 2021.INTERVENTIONS Patients received standard dexamethasone (dexamethasone-phosphate 6 mg/d for 10 days [or placebo prior to RECOVERY trial results communication]) or high-dose dexamethasone (dexamethasone-phosphate 20 mg/d on days 1-5 then 10 mg/d on days 6-10). Those not requiring IMV were additionally randomized to O 2 SC, CPAP, or HFNO 2 . MAIN OUTCOMES AND MEASURESThe main outcomes were time to all-cause mortality, assessed at day 60, for the dexamethasone interventions, and time to IMV requirement, assessed at day 28, for the oxygenation interventions. Differences between intervention groups were calculated using proportional Cox models and expressed as hazard ratios (HRs). RESULTS Among 841 screened patients, 546 patients (median [IQR] age, years; 414 [75.8%] men) were randomized between standard dexamethasone (276 patients, including 37 patients who received placebo) or high-dose dexamethasone (270 patients). Of these, 333 patients were randomized among O 2 SC (109 patients, including 56 receiving standard dexamethasone), CPAP (109 patients, including 57 receiving standard dexamethasone), and HFNO 2 (115 patients, including 56 receiving standard dexamethasone). There was no difference in 60-day mortality between standard and high-dose dexamethasone groups (HR, 0.96 [95% CI, 0.69-1.33]; P = .79). There was no significant difference for the cumulative incidence of IMV criteria at day 28 among O 2 support groups (O 2 SC vs CPAP: HR, 1.08 [95% CI, 0.71-1.63]; O 2 SC vs HFNO 2 : HR, 1.04 [95% CI, 0.69-1.55]) or 60-day mortality (O 2 SC vs CPAP: HR, 0.97 [95% CI, 0.58-1.61; O 2 SC vs HFNO 2 : HR, 0.89 [95% CI,). Interactions between interventions were not significant. CONCLUSIONS AND RELEVANCEIn this randomized clinical trial among ICU patients with COVID-19-related AHRF, high-dose dexamethasone did not significantly improve 60-day survival. The oxygenation strategies in patients who were not initially receiving IMV did not significantly modify 28-day risk of...

Background Human Norovirus (HuNoV) has recently been identified as a major cause of diarrhea among kidney transplant recipients (KTR). Data regarding risk factors associated with the occurrence of HuNoV infection, and its long-term impact on kidney function are lacking. Methods We conducted a retrospective case-control study including all KTR with a diagnosis of HuNoV diarrhea. Each case was matched to a single control according to age and date of transplantation, randomly selected among our KTR cohort and who did not develop HuNoV infection. Risk factors associated with HuNoV infection were identified using conditional logistic regression, and survival was estimated using Kaplan-Meier estimator. Results From January 2012 to April 2018, 72 cases of NoV diarrhea were identified among 985 new KT, leading to a prevalence of HuNoV infection of 7.3%. Median time between kidney transplantation and diagnosis was 46.5 months (Inter Quartile Range [IQR]:17.8–81.5), and the median duration of symptoms 40 days (IQR: 15–66.2). Following diagnosis, 93% of the cases had a reduction of immunosuppression. During follow-up, de novo Donor Specific Antibody (DSA) were observed in 8 (9%) cases but none of the controls (p = 0.01). Acute rejection episodes were significantly more frequent among cases (13.8% versus 4.2% in controls; p = 0,03), but there was no difference in serum creatinine level at last follow-up between the two groups (p = 0.08). Pre-transplant diabetes and lymphopenia below 1000/mm3 were identified as risks factors for HuNoV infection in multivariate analysis. Conclusion HuNoV infection is a late-onset and prolonged infection among KTR. The current management, based on the reduction of immunosuppressive treatment, is responsible for the appearance of de novo DSA and an increase in acute rejection episodes.

OBJECTIVES: Acute kidney injury, acute kidney injury severity, and acute kidney injury duration are associated with both short- and long-term outcomes. Despite recent definitions, only few studies assessed pattern of renal recovery and time-dependent competing risks are usually disregarded. Our objective was to describe pattern of acute kidney injury recovery, change of transition probability over time and their risk factors. DESIGN: Monocenter retrospective cohort study. Acute kidney injury was defined according to Kidney Disease Improving Global Outcomes definition. Renal recovery was defined as normalization of both serum creatinine and urine output criteria. Competing risk analysis, time-inhomogeneous Markov model, and group-based trajectory modeling were performed. SETTING: Monocenter study. PATIENTS: Consecutive patients admitted in ICU from July 2018 to December 2018 were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three-hundred fifty patients were included. Acute kidney injury occurred in 166 patients at ICU admission, including 64 patients (38.6%) classified as acute kidney disease according to Acute Disease Quality Initiative definition and 44 patients (26.5%) who could not be classified. Cumulative incidence of recovery was 25 % at day 2 (95% CI, 18–32%) and 35% at day 7 (95% CI, 28–42%). After adjustment, need for mechanical ventilation (subdistribution hazard ratio, 0.42; 95% CI, 0.23–0.74) and severity of the acute kidney injury (stage 3 vs stage 1 subdistribution hazard ratio, 0.11; 95% CI, 0.03–0.35) were associated with lack of recovery. Group-based trajectory modeling identified three clusters of temporal changes in this setting, associated with both acute kidney injury recovery and patients’ outcomes. CONCLUSIONS: In this study, we demonstrate Acute Disease Quality Initiative to allow recovery pattern classification in 75% of critically ill patients. Our study underlines the need to take into account competing risk factors when assessing recovery pattern in critically ill patients.

Background Tumor lysis syndrome (TLS) is a life-threatening complication during the treatment of malignant neoplasia. We sought to describe characteristics and predictors of acute kidney injury (AKI), remission and mortality in high-risk TLS patients. In this retrospective monocentric study, we included all patients with the diagnosis of biological and/or clinical TLS from 2012 to 2018. The primary outcome was the prevalence of AKI during the acute phase of TLS. Secondary outcomes were overall mortality and remission of the underlying malignancy at 1 year. Results Among 153 patients with TLS, 123 (80.4%) patients experienced AKI and 83 (54.2%) required renal replacement therapy. mSOFA score (OR = 1.15, IC 95% [1.02–1.34]), age (OR = 1.05, IC 95% [1.02–1.08]) and male gender (OR = 6.79, IC 95% [2.59–19.44]) were associated with AKI. Rasburicase use (HR = 2.45, IC 95% [1.17–5.15]) was associated with remission of the underlying malignancy at 1 year. Parameters associated with mortality at 1 year were mechanical ventilation (HR = 1.96, IC 95% [1.02–3.78]), vasopressors (HR = 3.13, IC 95% [1.59–6.15]), age (HR = 1.02, IC 95% [1–1.03]), spontaneous TLS (HR = 1.65, IC 95% [1.01–2.69]) and delay of chemotherapy administration (HR = 1.01, IC 95% [1–1.03]). Conclusions AKI is highly prevalent in TLS patients. Rasburicase is associated with better outcomes regarding remission of the underlying malignancy. As rasburicase may be an indirect marker of a high degree of tumor lysis and chemosensitivity, more studies are warranted to confirm the protective role of urate oxidase. Delaying chemotherapy may be deleterious in terms of long-term outcomes.