Persistent low-level viraemia in antiretroviral treatment-experienced patients is not linked to viral resistance or inadequate drug concentrations.

OBJECTIVES: To assess genotypic sensitivity scores (GSSs), plasma antiretroviral concentrations (PACs) and immunovirological outcomes at Week 96 (W96) in patients with persistent low-level viraemia (LLV). METHODS: On 1 January 2017, we analysed data from patients on three-drug regimens with persistent LLV defined as at least two consecutive plasma viral loads (pVLs) between 21 and 200 copies/mL (including one pVL of ≥50 copies/mL), at the Pitié-Salpêtrière Hospital. Outcomes were: GSS, PACs and HIV-DNA load at study entry; and virological status and proportion of patients with resistance-associated mutations (RAMs) at W96. RESULTS: Fifty-seven patients were included, with median age of 52.6 years (IQR 45.2-57.9), last CD4 count of 658 cells/mm3 (IQR 462-909) and total ART duration of 10.2 years (IQR 5.7-15.2). LLV duration was 14.0 months (IQR 5.5-22.3). GSS was 3 in 46/57 (81%) patients and PACs were adequate in 53/57 (93%) patients. Median total HIV-DNA was 2.65 log10 copies/106 cells (IQR 2.44-2.86). During follow-up, 26/57 (46%) had experienced ART modifications. At W96, 38/57 (67%) patients remained with LLV, 15/60 (26%) had achieved confirmed pVL of <20 copies/mL and 4/57 (7%) had virological failure. The four virological failures were due to three ART interruptions and one incomplete adherence (selection of Y181C RAM). No factors (patient characteristics at study entry, GSS, PACs, total HIV-DNA load and ART modification) were associated with W96 viral outcome, except for time from HIV diagnosis and the LLV duration at study entry. CONCLUSIONS: A substantial number of patients harbouring LLV had no resistance to ART and adequate PACs. Two-thirds of these patients remained with this LLV status.

COVID-19-related encephalopathy: a case series with brain FDG-positron-emission tomography/computed tomography findings.

AIM: The aim of this paper is to describe the clinical features of COVID-19-related encephalopathy and their metabolic correlates using brain 2-desoxy-2-fluoro-D-glucose (FDG)-positron-emission tomography (PET)/computed tomography (CT) imaging. BACKGROUND AND PURPOSE: A variety of neurological manifestations have been reported in association with COVID-19. COVID-19-related encephalopathy has seldom been reported and studied. METHODS: We report four cases of COVID-19-related encephalopathy. The diagnosis was made in patients with confirmed COVID-19 who presented with new-onset cognitive disturbances, central focal neurological signs, or seizures. All patients underwent cognitive screening, brain magnetic resonance imaging (MRI), lumbar puncture, and brain 2-desoxy-2-fluoro-D-glucose (FDG)-positron-emission tomography (PET)/computed tomography (CT) (FDG-PET/CT). RESULTS: The four patients were aged 60 years or older, and presented with various degrees of cognitive impairment, with predominant frontal lobe impairment. Two patients presented with cerebellar syndrome, one patient had myoclonus, one had psychiatric manifestations, and one had status epilepticus. The delay between first COVID-19 symptoms and onset of neurological symptoms was between 0 and 12 days. None of the patients had MRI features of encephalitis nor significant cerebrospinal fluid (CSF) abnormalities. SARS-CoV-2 RT-PCR in the CSF was negative for all patients. All patients presented with a consistent brain FDG-PET/CT pattern of abnormalities, namely frontal hypometabolism and cerebellar hypermetabolism. All patients improved after immunotherapy. CONCLUSIONS: Despite varied clinical presentations, all patients presented with a consistent FDG-PET pattern, which may reflect an immune mechanism.

Prevalence and factors associated with symptom persistence: A prospective study of 429 mild COVID-19 outpatients.

INTRODUCTION: Persistent symptoms have recently emerged as a clinical issue in COVID-19. We aimed to assess the prevalence and risk factors in symptomatic non-hospitalized individuals with mild COVID-19. METHODS: We performed a prospective cohort study of symptomatic COVID-19 outpatients, from March to May 2020, with weekly phone calls from clinical onset until day 30 and up to day 60 in case of persistent symptoms. The main outcomes were the proportion of patients with complete recovery at day 30 and day 60 and factors associated with persistent symptoms. RESULTS: We enrolled 429 individuals mostly women (72.5%) and healthcare workers (72.5%), with a median age of 41.6 years [IQR 30-51.5]. Symptoms included: cough (69.7%), asthenia (68.8%), anosmia (64.8%), headaches (64.6%), myalgia (62.7%), gastrointestinal symptoms (61.8%), fever (61.5%), and ageusia (60.8%). Mean duration of disease was 27 days (95%CI: 25-29). The rate of persistent symptoms was 46.8% at day 30 and 6.5% at day 60 consisting in asthenia (32.6%), anosmia (32.6%), and ageusia (30.4%). The probability of complete recovery was 56.3% (95%CI: 51.7-61.1) at day 30 and 85.6% (95%CI: 81.2-89.4) at day 60. Factors associated with persistent symptoms were age>40 (HR 0.61), female sex (HR 0.70), low cycle threshold (HR 0.78), and ageusia (HR 0.59). CONCLUSIONS: COVID-19 - even in its mild presentation - led to persistent symptoms (up to one month) in nearly half of individuals. Identification of risk factors such as age, gender, ageusia and viral load is crucial for clinical management and argues for the development of antiviral agents.

Clinical, biological and radiological features, 4-week outcomes and prognostic factors in COVID-19 elderly inpatients.

OBJECTIVE: To describe clinical, biological, radiological presentation and W4 status in COVID-19 elderly patients. PATIENTS AND METHODS: All patients ≥ 70 years with confirmed SARS-CoV-2 infection and hospitalized in the Infectious Diseases department of the Pitié-Salpêtrière hospital, Paris, France, from March 1st to April 15th 2020 were included. The primary outcome was death four weeks after hospital admission. Data on demographics, clinical features, laboratory tests, CT-scan findings, therapeutic management and complications were collected. RESULTS: All in all, 100 patients were analyzed, including 49 patients ≥ 80 years. Seventy percent had ≥2 comorbidities. Respiratory features were often severe as 48% needed oxygen support upon admission. Twenty-eight out of 43 patients (65%) with a CT-scan had mild to severe parenchymal impairment, and 38/43 (88%) had bilateral impairment. Thirty-two patients presented respiratory distress requiring oxygen support ≥ 6 liters/minute. Twenty-four deaths occurred, including 21 during hospitalization in our unit, 2 among the 8 patients transferred to ICU, and one at home after discharge from hospital, leading to a global mortality rate of 24% at W4. Age, acute renal failure and respiratory distress were associated with mortality at W4. CONCLUSION: A substantial proportion of elderly COVID-19 patients with several comorbidities and severe clinical features survived, a finding that could provide arguments against transferring the most fragile patients to ICU.

[Hepatitis B virus infection: Natural history, clinical manifestations and therapeutic approach]. / Infection par le virus de l'hépatite B : histoire naturelle, manifestations cliniques et principes thérapeutiques.

Chronic hepatitis B infection remains a major public-health problem, with approximately 260 million world-wide cases of infection. Recent advances in the understanding of the natural history of chronic hepatitis B infection have led to progress in the care of infected patients. Sustained viral suppression is now possible for a majority of treated patients and is associated with a decrease in the morbidity and mortality attributable to cirrhosis and hepatocellular carcinoma. Complete cure is however not yet possible, due to the long-term persistence of viral DNA in hepatocytes of treated patients. Assessing the risk of viral reactivation in patients receiving immunosuppressive therapy is an increasingly frequent situation in clinical practice and its management is guided by both the patient's serological status and the potency of the immunosuppressive regimen. This review aims to present the clinical and biological presentations of chronic hepatitis B infection, the modalities of antiviral treatment, and how to assess the risk of viral reactivation in patients receiving immunosuppressive therapy.