Long COVID-19 symptoms: Clinical characteristics and recovery rate among non-severe outpatients over a six-month follow-up.

BACKGROUND: To describe persistent symptoms in long COVID-19 non-severe outpatients and report the 6-month clinical recovery (CR) rate. METHODS: Observational study enrolling outpatients (≥ 18 years) with confirmed non-severe COVID-19 (positive nasopharyngeal RT-PCR or presence of SARS-CoV-2 antibodies) who consulted for persistent symptoms after the first pandemic wave (March-May 2020). CR was assessed at the 6-month visit and defined as complete (no symptom), partial (persistent symptoms of lower intensity) or lack of recovery (no improvement). RESULTS: Sixty-three patients (79% women, mean age: 48 years) enrolled; main symptoms (mean 81 days after acute infection): asthenia/myalgia (77%), dyspnea (51%), headaches (35%), cough (33%). At 6 months (n=56), 30% had complete, 57% partial, and 13% lack of recovery. The proportion of patients with>2 persistent symptoms was 26% at 6 months (main symptoms: dyspnea [54%] and asthenia/myalgia [46%]). CONCLUSION: We observed a slow but high recovery rate at 6 months among these outpatients.

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.

Olfactory and gustatory dysfunctions in COVID-19 outpatients: A prospective cohort study.

OBJECTIVES: To describe the characteristics, evolution and risk factors for long-term persistence of olfactory and gustatory dysfunctions (OGD) in COVID-19 outpatients. PATIENTS AND METHODS: We conducted a prospective study in SARS-CoV-2 infected outpatients with OGD. Weekly phone interviews were set up starting from COVID-19 onset symptoms and over the course of 60 days, using standardized questionnaires that included a detailed description of general symptoms and OGD. The primary outcome was the proportion of patients with complete recovery of OGD at D30. Rate and time to recovery of OGD, as well as risk factors for late recovery (>30 days), were evaluated using Cox regression models. RESULTS: Ninety-eight outpatients were included. The median time to onset of OGD after first COVID-19 symptoms was 2 days (IQR 0-4). The 30-day recovery rate from OGD was 67.5% (95% CI 57.1-75.4) and the estimated median time of OGD recovery was 20 days (95% CI 13-26). Risk factors for late recovery of OGD were a complete loss of smell or taste at diagnosis (HR=0.26, 95% CI 0.12-0.56, P=0.0005) and age over 40 years (HR=0.56, 95% CI 0.36-0.89, P=0.01). CONCLUSIONS: COVID-19 patients with complete loss of smell or taste and over age 40 are more likely to develop persistent OGD and should rapidly receive sensorial rehabilitation.

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.

Low immune response rate of HIV-infected patients to a single injection of hepatitis A vaccine.

OBJECTIVES: We aimed to evaluate the immune response of HIV-1 positive patients to a single injection of HAV vaccine in a context of vaccine shortage during the 2017 European outbreak. METHODS: We retrospectively enrolled all HIV-1 positive patients vaccinated by a single injection of HAV vaccine Vaqta 50®. HAV serology was performed before and>30 days after the vaccine injection. RESULTS: Among the 73 patients, HIV-1 viral load was≤50 copies/mL in 93.2% of the cases. Medians of CD4 and median ratio of T CD4/CD8 cells were 658/mm3 and 0.9, respectively. A low immune response rate (59.7%) was observed among the patients. Responders had a significantly higher CD4/CD8 cell ratio than non-responders. CONCLUSIONS: A serologic control should be recommended in this population in the event of a single injection vaccination schedule. During routine follow-up, and prior to any untoward event, physicians should assess the vaccination coverage of HIV-infected patients.

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.

Kaposi sarcoma among people living with HIV in the French DAT'AIDS cohort between 2010 and 2015.

BACKGROUND: Although antiretroviral therapy (ART) has reduced the risk of Kaposi sarcoma (KS), KS cases still occur in HIV-infected people. OBJECTIVE: To describe all KS cases observed between 2010 and 2015 in a country with high ART coverage. METHODS: Retrospective study using longitudinal data from 44 642 patients in the French Dat'AIDS multicenter cohort. Patients' characteristics were described at KS diagnosis according to ART exposure and to HIV-plasma viral load (HIV-pVL) (≤50 or >50) copies/mL. RESULTS: Among the 209 KS cases diagnosed during the study period, 33.2% occurred in ART naïve patients, 17.3% in ART-experienced patients and 49.5% in patients on ART, of whom 23% for more than 6 months. Among these patients, 24 (11.5%) had HIV-pVL ≤50 cp/mL, and 16 (66%) were treated with a boosted-PI-based regimen. The distribution of KS localization did not differ by ART status nor by year of diagnosis. LIMITATIONS: Data on human herpesvirus 8, treatment modalities for KS and response rate were not collected. CONCLUSION: Half of KS cases observed in the study period occurred in patients not on ART, reflecting the persistence of late HIV diagnosis. Factors associated with KS in patients on ART with HIV-pVL ≤50 cp/mL remain to be explored.

Long-term follow-up of HIV-infected patients on dolutegravir monotherapy.

BACKGROUND: In recent years, dolutegravir monotherapy has been explored as a drug-reduced regimen for HIV patients. METHODS: This was a retrospective observational study, including patients virologically suppressed for ≥6 months, without previous virological failure (VF) under integrase inhibitors (INIs), who had been switched to dolutegravir monotherapy (50 mg/day). The primary aim was to report the proportion of VF at week 48 (W48) and week 96 (W96) of dolutegravir monotherapy. The evolution from baseline to W48 of residual viraemia on ultra-deep sequencing and HIV DNA was also evaluated. RESULTS: Sixty-one patients were included. Prior to switching to dolutegravir monotherapy, they had a median (IQR) of 15.4 (6.5-19.9) years of antiretroviral exposure, 5.8 (3.2-10.3) years of viral suppression and 687 (461-848) CD4+ cells/mm3. They remained on dolutegravir monotherapy for a median (IQR) of 100 (29-148) weeks. Forty-two out of 61 patients (68.9%) reached W48 and 32 out of 61 patients (52.5%) reached W96. VF occurred in three patients, with the emergence of INI resistance. VF occurred before W24 and in patients pre-exposed to INIs. At W48, the probability of VF (Kaplan-Meier analysis) was 5.6% (95% CI = 1.8%-16.4%). The same result was obtained at W96. Detectable residual viraemia did not increase and median HIV DNA did not change significantly (2.4 log/106 cells at baseline and 2.3 log/106 cells at W48). Dolutegravir plasma concentration was above the IC90 in 41/41 samples, from 22 patients. CONCLUSIONS: Long-term follow-up showed a low risk of VF under dolutegravir monotherapy, in a selected population of patients with previous long-term virological suppression and low HIV reservoir.