Epidemiological and Molecular Evolution of the Hiv-1 Crf94: Birth of Crf132

Background: In 2018 we reported the emergence of the new HIV-1 recombinant CRF94-02BF2 involved in a large transmission cluster of 49 French MSM mostly infected in 2016-2017. This CRF94 raised concerns of enhanced virulence. Prevention actions were undertaken in the area and population affected. This study reported the molecular and epidemiological evolution of this CRF94 until June 2022. Method(s): In 2021-2022, French sequence databases were screened for patients infected with HIV-1 subtype CRF94 or similar strain. HIV subtyping was confirmed by phylogenetic analysis of genes encoding both protease and reverse transcriptase (1070bps), and integrase (696bps) using IQ-Tree. Five whole genomes, related but distinct from CRF94, were obtained with the DeepChek assay Whole Genome kits. Recombination breakpoints were estimated using RDP4 and SimPlot. Mann-Whitney and LogRank tests were used for statistical analyses to compare patients' characteristics. Result(s): In June 2022, 49 new HIV-1 sequences were collected: 14 clustered with the 49 previous CRF94, 32 formed a new cluster next to but distinct from CRF94, and 3 strains could not be classified. Analysis of 5 whole genomes from the new cluster revealed a new recombinant, the CRF132-94B, mainly consisting of CRF94 which recombined with subtype B in the POL and accessory genes. Vif gene changed from the F2 to the B subtype. Both CRF94 and 132 clusters involved >95% of MSM, mostly infected < 1 year before diagnosis. However, there were differences: 97% were diagnosed in 2013-2019 for CRF94 vs 90% in 2020-2022 for CRF132. At time of diagnosis, 33% of patients infected with CRF94 knew the Prep vs 95% for CRF132. In the cluster CRF94, patients were older (34 vs 30 years, p=0.02), had higher viral loads (5.42 vs 4.42 log10 copies/Ml;p< 0.001), a lower CD4 cell counts (358 vs 508 /mm3, p=0.002). On treatment, the patients with the CRF94 reached viremia < 50 copies/Ml significantly later than those infected with CRF132 (p=0.0002). The prevention activities targeting the CRF94 cluster could explained the few patients infected with this strain after 2018. The CRF132 is mainly located in another Paris region area, but no specific transmission place has been identified. Conclusion(s): After 2019, the CRF94 spread seems greatly slowed down but the very close CRF132-94B has given birth to a new highly active cluster in 2020- 2022, despite the COVID social-distancing and a strong knowledge of the Prep. CRF132 appears to be less virulent perhaps due to the Vif gene change. Identified breakpoints positions of the new HIV-1 CRF132-94B. GenBank accession numbers of the five references : ON901787 to ON901791.

Vaccination contre le SARS-CoV-2 avant l'introduction d'un traitement par anti-CD20 chez les patients atteints de sclerose en plaques : une protection durable ?.

Declaration de liens d'interets: Les auteurs declarent ne pas avoir de liens d'interets.Copyright © 2023

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.

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.

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.

Characteristics and outcome profile of hospitalized African patients with COVID-19: The Ethiopian context.

BACKGROUND: The COVID-19 pandemic seems to have a different picture in Africa; the first case was identified in the continent after it had already caused a significant loss to the rest of the world and the reported number of cases and mortality rate has been low. Understanding the characteristics and outcome of the pandemic in the African setup is therefore crucial. AIM: To assess the characteristics and outcome of Patients with COVID-19 and to identify determinants of the disease outcome among patients admitted to Millennium COVID-19 Care Center in Ethiopia. METHODS: A prospective cohort study was conducted among 1345 consecutively admitted RT-PCR confirmed Patients with COVID-19 from July to September, 2020. Frequency tables, KM plots, median survival times and Log-rank test were used to describe the data and compare survival distribution between groups. Cox proportional hazard survival model was used to identify determinants of time to clinical recovery and the independent variables, where adjusted hazard ratio, P-value and 95% CI for adjusted hazard ratio were used for testing significance and interpretation of results. Binary logistic regression model was used to assess the presence of a statistically significant association between disease outcome and the independent variables, where adjusted odds ratio, P-value and 95% CI for adjusted odds ratio were used for testing significance and interpretation of results. RESULTS: Among the study population, 71 (5.3%) died, 72 (5.4%) were transferred and the rest 1202 (89.4%) were clinically improved. The median time to clinical recovery was 14 days. On the multivariable Cox proportional hazard model; temperature (AHR = 1.135, 95% CI = 1.011, 1.274, p-value = 0.032), COVID-19 severity (AHR = 0.660, 95% CI = 0.501, 0.869, p-value = 0.003), and cough (AHR = 0.705, 95% CI = 0.519, 0.959, p-value = 0.026) were found to be significant determinants of time to clinical recovery. On the binary logistic regression, the following factors were found to be significantly associated with disease outcome; SPO2 (AOR = 0.302, 95% CI = 0.193, 0.474, p-value = 0.0001), shortness of breath (AOR = 0.354, 95% CI = 0.213, 0.590, p-value = 0.0001) and diabetes mellitus (AOR = 0.549, 95% CI = 0.337, 0.894, p-value = 0.016). CONCLUSIONS: The average duration of time to clinical recovery was 14 days and 89.4% of the patients achieved clinical recovery. The mortality rate of the studied population is lower than reports from other countries including those in Africa. Having severe COVID-19 disease severity and presenting with cough were found to be associated with delayed clinical recovery of the disease. On the other hand, being hyperthermic is associated with shorter disease duration (faster time to clinical recovery). In addition, lower oxygen saturation, subjective complaint of shortness of breath and being diabetic were associated with unfavorable disease outcome. Therefore, patients with these factors should be followed cautiously for a better outcome.

Anti-CD20 therapies decrease humoral immune response to SARS-CoV-2 in patients with multiple sclerosis or neuromyelitis optica spectrum disorders

Introduction: SARS-CoV-2 seroconversion rate after COVID-19 may be influenced by disease-modifying therapies (DMTs) in patients with multiple sclerosis (MS) or neuromyelitis optica spectrum disorders (NMO-SD). Objectives: To investigate the seroprevalence and the quantity of SARS-CoV-2 antibodies in a cohort of patients with MS or NMO-SD. Aims: To improve our knowledge of the impact of different DMTs on the immune response to SARS-COV2. Methods: Blood samples were collected in patients diagnosed with COVID-19 between February 19, 2020 and February 26, 2021. SARS-CoV-2 antibody positivity rates and Ig levels (anti-S IgG titer, anti-S IgA index, anti-N IgG index) were compared between DMTs groups. Multivariate logistic and linear regression models were used to estimate the influence of DMTs and other confounding variables on SARS-CoV-2 serological outcomes. Results: 119 patients (115 MS, 4 NMO, mean age: 43.0 years) were analyzed. Overall seroconversion rate was 80.6% within 5.0 (SD 3.4) months after infection. 20/21 (95.2%) patients without DMT and 66/77 (85.7%) patients on DMTs other than anti-CD20 had at least one SARS-CoV-2 Ig positivity, while this rate decreased to only 10/21 (47.6%) for patients on anti-CD20 (p < 0.001). Patients on anti-CD20 had a lower anti-S IgG titer (mean [SD], 1.4 [1.6]) relative to patients on other DMTs (2.4 [1.1]) or no DMT (2.7 [0.8] (p<0.001 by ANOVA). Being on anti-CD20 was associated with a decreased odd of positive serology (OR, 0.06 [95%CI, 0.01-0.59], p=0.01) independently from time to COVID-19, total IgG level, age, sex and COVID-19 severity. Time between last anti-CD20 infusion and COVID-19 was longer (mean [SD], 3.7 [2.0] months) in seropositive patients compared to seronegative patients (mean [SD], 1.9 [1.5] months, p=0.04). Serological data at 6 months follow-up after inclusion will be available and presented during the congress. Conclusions: SARS-CoV-2 antibody response was decreased in patients with MS or NMO-SD treated with anti-CD20 therapies. Monitoring long-term risk of reinfection and specific vaccination strategies in this population may be warranted.

Public knowledge, attitudes, and practices regarding the coronavirus disease pandemic: A cross-sectional study in the Kurdistan region, Iraq

Background/Objectives: Coronavirus disease (COVID-19) is an emerging viral respiratory disease that has currently reached apandemic status.This study aimed to assessCOVID-19 knowledge, attitudes, and practices among the Kurdishpopulation in Iraq. Methods: This cross-sectional studywas conducted fromJuly 15 to September 15, 2020 among the Kurdish population in Iraq. A total of 885 subjects were interviewed. All subjects were aged 15-75 years. Knowledgescores, attitudes, and practices of subjects were analyzed according to demographic characteristics. Results:The study subjects were largely male,the average age was31.79 years,and 41.92% subjects were from Erbil province. Approximately 85.31% subjectshad enhancedknowledge regarding disease prevention and control. The lowest subscale scores were related toclinical manifestations of the disease. Knowledge scores were significantly associated with age, place of current residence, and level of education.A large number of participants believed COVID-19 would be controlled and the fight against the pandemic would be won.Subjects' attitudes toward success differedsignificantly by demographic characteristics, except marital status. Approximately 40.03% subjects reported that they had not visited a crowded place, and 60.22% of these subjects wore face masks when leaving home. Conclusions: This study foundgood knowledge, positive attitudes, and proper practices among the general populationregarding the COVID-19 pandemic.However, community-based health campaigns in the regionshould encourage optimistic attitudes and appropriate practicesregarding virus containment and dissemination. Our findings may be used as a baseline for planning health education campaigns in the region.

Characteristics and outcome profile of Hospitalized African COVID-19 patients: The Ethiopian Context (preprint)

Background: The COVID-19 pandemic seems to have a different picture in Africa; the first case was identified in the continent after it has already caused a significant loss to the rest of the world and the reported number of cases and mortality rate has been low. Understanding the characteristics and outcome of the pandemicin the African setup is therefore crucial. Aim: To assess the characteristics and outcome of COVID-19 patients and to identify determinants of the disease outcome among patients admitted to Millennium COVID-19 Care Center in Ethiopia. Methods: A prospective cohort study was conducted among 1345 consecutively admitted RT-PCR confirmed COVID-19 patients from July to September, 2020. Frequency tables, KM plots, median survival times and Log-rank test were used to describe the data and compare survival distribution between groups. Cox proportional hazard survival model was used to identify determinants of time to clinical improvement and the independent variables, where adjusted hazard ratio, P-value and 95% CI for adjusted hazard ratio were used for testing significance and interpretation of results. Binary logistic regression model was used to assess the presence of a statistically significant association between disease outcome and the independent variables, where adjusted odds ratio, P-value and 95% CI for adjusted odds ratio were used for testing significance and interpretation of results Results: Among the study population, 71 (5.3%) died, 72 (5.4%) were transferred and the rest 1202 (89.4%) were clinically improved. The median time to clinical improvement was 14 days. On the multivariable Cox proportional hazard model; temperature (AHR= 1.135, 95% CI= 1.011, 1.274, p-value=0.032), COVID-19 severity (AHR= 0.660, 95% CI= 0.501, 0.869, p-value=0.003), and cough (AHR= 0.705, 95% CI= 0.519, 0.959, p-value=0.026) were found to be significant determinants of time to clinical improvement. On the binary logistic regression, the following factors were found to be significantly associated with disease outcome; SPO2 (AOR= 0.302, 95% CI= 0.193, 0.474, p-value=0.0001), shortness of breath (AOR= 0.354, 95% CI= 0.213, 0.590, p-value=0.0001) and diabetes mellitus (AOR= 0.549, 95% CI= 0.337, 0.894, p-value=0.016). Conclusions: The average duration of time to clinical improvement was 14 days and 89.4 % of the patients achieved clinical improvement. The mortality rate of the studied population is lower than reports from other countries including those in Africa. Having severe COVID-19 disease severity and presenting with cough were found to be associated with delayed clinical improvement ofthe disease. On the other hand, being hyperthermic is associated with shorter disease duration (faster time to clinical improvement). In addition, lower oxygen saturation and subjective complaint of shortness of breath and being diabetic were associated with unfavorable disease outcome. Therefore, patients with these factors should be followed cautiously for a better outcome.

COVID-19 Disease Severity and Determinants among Ethiopian Patients: A study of the Millennium COVID-19 Care Center (preprint)

Background: Understanding determinants of developing severe COVID-19 disease is important as studies show that severe disease is associated with worse outcomes. Objective: The study aimed to assess the determinants of COVID-19 disease severity among COVID-19 patients admitted to Millennium COVID-19 Care Center in Ethiopia. Methods: A cross-sectional study was conducted from June to August 2020 among randomly selected 686 patients. Chi-square test was used to detect the presence of a statistically significant difference in the characteristics of the patients based on disease severity (Mild Vs Moderate Vs Severe), where p-value of <0.05 was considered as having a statistically significant difference. A Multivariable multinomial logistic regression model was used to assess the presence of a significant association between the independent variables and COVID-19 disease severity where Adjusted Odds ratio (AOR), 95% CIs for AOR and P-values were used for testing significance and interpretation of results. Results: Having moderate as compared with mild disease was significantly associated with having hypertension (AOR= 2.302, 95% CI= 1.266, 4.184, p-value=0.006), diabetes mellitus (AOR=2.607, 95% CI= 1.307, 5.198, p-value=0.007 for diabetes mellitus), fever (AOR= 6.115, 95% CI= 2.941, 12.716, p-value=0.0001) and headache (AOR= 2.695, 95% CI= 1.392, 5.215, p-value=0.003). Similarly, having severe disease as compared with mild disease was associated with age group (AOR= 4.428, 95% CI= 2.497, 7.853, p-value=0.0001 for 40-59 years and AOR=18.070, 95% CI=9.292, 35.140, p-value=0.0001 for [≥] 60 years), sex (AOR=1.842, 95% CI=1.121, 3.027, p-value=0.016), hypertension (AOR= 1.966, 95% CI= 1.076, 3.593, p-value=0.028), diabetes mellitus (AOR= 3.926, 95% CI= 1.964, 7.847, p-value=0.0001), fever (AOR= 13.218, 95% CI= 6.109, 28.601, p-value=0.0001) and headache (AOR= 4.816, 95% CI= 2.324, 9.979, p-value=0.0001). In addition, determinants of severe disease as compared with moderate disease were found to be age group (AOR= 4.871, 95% CI= 2.854, 8.315, p-value=0.0001 for 40-59 years and AOR= 18.906, 95% CI= 9.838, 36.334, p-value=0.0001 for [≥] 60 years), fever (AOR= 2.161, 95% CI= 1.286, 3.634, p-value=0.004) and headache (AOR= 1.787, 95% CI= 1.028, 3.107, p-value=0.039). Conclusions: Being old, male sex, hypertension, diabetes mellitus, and having symptoms of fever and headache were found to be determinants of developing a more severe COVID-19 disease category. We recommend a better preventive practice to be set in place so that these groups of patients can be protected from acquiring the disease. And for those who are already infected, a more careful follow-up and management should be given so that complication and death can be prevented. Furthermore, considering the above non respiratory symptoms as disease severity indicator could be important.

Description clinique et diagnostique sérologique des patients présentant des symptômes persistants après suspicion d’infection à SARS-COV-2

Introduction La persistance d’une symptomatologie chez des patients suspects d’une infection à SARS-COV-2 est fréquente y compris chez des patients sans diagnostic virologique initial. L’organisation d’une consultation dite « post-COVID » initiée en mai 2020 et son évaluation constitue l’objectif de cette étude. Matériels et méthodes Étude rétrospective de cohorte des patients>18 ans, présentant une histoire clinique compatible avec une infection à SARS-COV-2, une symptomatologie persistante≥30 j du j0 et vus en consultation post-COVID entre mai–juin 2020. Le diagnostic d’infection à SARS-COV-2 a été définie par une RT-PCR SARS-COV-2 positive et/ou une sérologique positive en IgG (Architect, Abbott ;sensibilité 100 % [IC95 : 95,8–100 %] ;spécificité 99,6 % [IC95 : 99,0–99,9 %]). Les variables continues sont présentées en médiane et IQR. L’analyse présentée compare les caractéristiques des patients confirmés au SARS-COV-2 (COVID-19 positif) à ceux non confirmés (COVID-19 négatif). Résultats Un total de 83 patients (71 femmes [86 %], 46 ans [38–52]) ont consulté dans un délai 61jours (j) (49–78) après le début des symptômes. Les manifestations cliniques persistantes après j30 les plus fréquentes étaient : asthénie/myalgies (n=58, 70 %), toux (n=34, 41 %), dyspnée (n=45, 54 %) et douleur thoracique (n=43, 52 %). Parmi eux, 32/83 (39 %) avaient eu une PCR SARS-COV-2 positive et 51/83 (61 %) n’avait pas de preuve virologique d’infection. Une sérologie réalisée chez 78 patients (27 avec PCR positive antérieure et 51 sans preuve virologique) montre la présence d’Ac anti-SARS-CoV chez 37/78 (47 %) : 26/27 (97 %) des patients avec PCR initiale positive et 11/51 (22 %) des patients sans preuve virologique initiale. Au total, 43/83 (52 %) patients de la consultation post-COVID ont eu un COVID-19 confirmé. Le groupe COVID-19 positif (n=43, 33 femmes [77 %], 49 ans [44–59]) était significativement plus âgé (p=0,005) avec un délai de consultation plus court par rapport au j0 (55 j [45–70] vs 73 j [53–82], p=0,007) que les COVID-19 négatif (n=40, 29 femmes [73 %], 42 ans [35–49]) avec à j0, significativement plus souvent de la toux (n=36 [84 %] vs n=25 [63 %], p=0,028), une anosmie/dysgueusie (n=29 [67 %] vs n=8 [20 %], p<0,0001), des céphalées (n=26 [61 %] vs n=13 [33 %], p=0,010) et une hospitalisation plus fréquente (28 % vs 2,5 %, p=0,001). L’évolution clinique du groupe COVID-19 positif montrait la persistance majoritairement d’asthénie/myalgies (n=31, 72 %), toux et dyspnée (n=22, 51 %). Les manifestations d’anosmie/dysgueusie persistaient également et de façon significative par rapport au groupe COVID-19 négatif (n=10 [23 %] vs n=2 [5 %], p=0,020). Conclusion La consultation « post-COVID » a accueilli une moitié de patients confirmés au SARS-COV-2. Les manifestations les plus fréquemment rapportées étaient une asthénie, des myalgies et une symptomatologie pulmonaire. La sérologie SARS-COV-2 a permis un diagnostic rétrospectif d’infection au SARS-COV-2 chez 22 % des patients sans documentation virologique. La compréhension de cette persistance de symptômes cliniques nécessite une analyse clinicobiologique multidisciplinaire afin d’en adapter la prise en charge.