Long-term Consequences of COVID-19 and the Pandemic: Protocol for a Web-Based, Longitudinal Observational Study (DEFEAT).

BACKGROUND: With population-wide vaccination availability, the global COVID-19 pandemic entered a new phase. Despite vaccination status, some people who were infected with SARS-CoV-2 experience long-term symptoms. OBJECTIVE: In this study, we aim to characterize the long-term effects of SARS-CoV-2 infection and the pandemic. We also aim to build symptom clusters and determine risk factors for developing long COVID symptoms. Furthermore, we assess social participation and health-related quality of life in patients with long COVID and in the general population during a global pandemic. METHODS: With a mixed-methods, web-based approach, we aim to recruit 2000 people in Germany who are older than 18 years and can provide informed consent. In the quantitative arm of the study, we identify symptoms of and predictive factors for long COVID manifestations with cluster analysis and assess social participation during the pandemic with standardized questionnaires. The qualitative arm of the study uses individual interviews and focus group discussions to better understand the illness experience of persons who experience long COVID. RESULTS: Recruitment started in September 2021. Up until July 2022, we recruited approximately 4500 participants via our web-based database. CONCLUSIONS: This study aims to build an innovative, patient-centered, web-based research platform appropriate for the pandemic by minimizing physical contact between study personnel and participants. All study activities are designed to better understand the long COVID syndrome, social participation during the pandemic, and the illness experiences of persons affected by long COVID. TRIAL REGISTRATION: German Clinical Trial Registry DRKS00026007; https://tinyurl.com/yh282fkt. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/38718.

Self-reported Tinnitus and Vertigo or Dizziness in a Cohort of Adult Long COVID Patients.

Tinnitus, vertigo and dizziness are symptoms commonly reported among Long and Post COVID patients, however the severity of these symptoms has not been assessed in large trials. Therefore, in this study a large cohort of Long COVID patients was surveyed about the presence and severity of tinnitus and vertigo or dizziness symptoms. The online survey was completed by a German cohort of 1,082 adult Long COVID patients after a mean period of 43.2 weeks ± 23.4 weeks after infection. Eighty percent were not fully vaccinated (at least two vaccinations) at the time of their first COVID symptoms and 9.8% were hospitalized in the course of their acute SARS-CoV-2 infection. At the time of the survey, 60% of patients reported the presence of vertigo or dizziness with a mean severity of 4.6 ± 2.7 on a scale of 1 (least severe) to 10 (most severe) and 30% complained of tinnitus with a mean severity of 4.8 ± 3.0. Approximately one fifth of the participants with tinnitus and vertigo or dizziness, rated their symptoms to be severe. The data shown in this study confirms that tinnitus and vertigo or dizziness are common symptoms in Long COVID patients and demonstrates, that a compelling number of patients rate their symptoms as severe. The self-reported severity highlights the need for Long COVID clinics to address these symptoms effectively. We suggest a multidisciplinary diagnostic and therapeutic approach to prevent further morbidity and socioeconomic burden for Long COVID patients suffering from severe vertigo, dizziness or tinnitus.

Proteomic Profiling and T Cell Receptor Usage of Abacavir Susceptible Subjects.

Type B adverse drug reactions (ADRs) represent a significant threat as their occurrence arises unpredictable and despite proper application of the drug. The severe immune reaction Abacavir Hypersensitivity Syndrome (AHS) that arises in HIV+ patients treated with the antiretroviral drug Abacavir (ABC) strongly correlates to the presence of the human leukocyte antigen (HLA) genotype HLA-B*57:01 and discriminates HLA-B*57:01+ HIV+ patients from ABC treatment. However, not all HLA-B*57:01+ HIV+ patients are affected by AHS, implying the involvement of further patient-specific factors in the development of AHS. The establishment of a reliable assay to classify HLA-B*57:01 carriers as ABC sensitive or ABC tolerant allowed to investigate the T cell receptor (TCR) Vß chain repertoire of effector cells and revealed Vß6 and Vß24 as potential public TCRs in ABC sensitive HLA-B*57:01 carriers. Furthermore, distinct effects of ABC on the cellular proteome of ABC sensitive and tolerant volunteers were observed and suggest enhanced activation and maturation of dentritic cells (DC) in ABC sensitive volunteers. Analysis of ABC-naïve cellular proteomes identified the T cell immune regulator 1 (TCIRG1) as a potential prognostic biomarker for ABC susceptibility and the involvement of significantly upregulated proteins, particularly in peptide processing, antigen presentation, interferon (IFN), and cytokine regulation.

The incidence of first-line antiretroviral treatment changes and related factors among HIV-infected sex workers in in Nairobi, Kenya

Introduction: in many settings, several factors including adverse drug reactions and clinical failure can limit treatment choices for combined antiretroviral therapy (cART). The aim of the study was to describe the incidence of first-line cART changes and associated factors in a cohort of Kenyan sex workers.Methods: this was a retrospective review of medical records collected from 2009 to 2013. The review included records of HIV-infected patients aged ≥ 18 years, who received either stavudine or zidovudine or tenofovir disoproxil fumarate-based regimens. Using systematic random sampling, the study selected 1 500 records and censoring targeted the first incident of a drug change from the first-line cART.Results: the overall incidence rate of cART changes was 11.1 per 100 person-years within a total follow-up period of 3 427.9 person-years. Out of 380 patients who changed cART, 370 (97%) had a drug substitution and 10 (3%) switched regimens. The most commonly cited reasons for changing cART were adverse drug reactions (76%). Tenofovir disoproxil fumarate had a lower drug change rate (1.9 per 100 person years) compared to stavudine (27 per 100 person years). Using zidovudine as the reference group, stavudine-based regimens were significantly associated with an increased hazard of drug changes (adjusted hazards ratio 10.2; 95% CI: 6.02-17.2).Conclusion: these findings suggest a moderate incidence of cART changes among sex workers in Nairobi, Kenya. Individuals using stavudine were at a higher risk of experiencing a change in their cART, mostly presenting within 20 months, and primarily due to adverse drug reactions

Prevalent neuropathy in a cohort of HIV-infected Kenyan sex workers using antiretroviral drugs.

INTRODUCTION: Several risk factors including stavudine and age have been strongly associated with polyneuropathy. However, conflicting data exist on height as an independent risk factor in polyneuropathy. The objective of this study is to exclude height as an independent polyneuropathy risk factor in a cohort of human immunodeficiency virus (HIV)-infected Kenyan sex workers. METHODS: This was an analysis of prospectively collected data of treatment-naive subjects initiating either stavudine or tenofovir diphosphate fumarate or zidovudine-based antiretroviral therapy (ART) regimens from January 2008 to August 2012. Polyneuropathy was characterised as burning sensation, numbness, or dysesthesia. The study used arithmetic means of weight (kg) and height (cm) measured in duplicates using calibrated scales. RESULTS: After exclusion of duplicate data sets and un-confirmed cases of polyneuropathy, the study identified 212 patients without polyneuropathy, 14 pre-ART and 94 post-ART related polyneuropathy cases. Polyneuropathy cases were older but did not differ in demographic, clinical and laboratory parameters at baseline. There was a significant difference in first-line ART regimens with more patients on tenofovir disoproxil fumarate in the post-ART group (p=0.017). CONCLUSION: Polyneuropathy is a common disorder among HIV-infected Kenyan sex workers. These data cannot support the postulated increased risk by height after matching for gender and ART duration. Though stavudine is associated with polyneuropathy, in this study many patients previously not exposed to stavudine developed polyneuropathy. This suggests the involvement of unknown risk factors such as genetic and metabolite differences in the development of polyneuropathy.