Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with droplets and contact as the main means of transmission. Since the first case appeared in Wuhan, China, in December 2019, the outbreak has gradually spread nationwide. Up to now, according to official data released by the Chinese health commission, the number of newly diagnosed patients has been declining, and the epidemic is gradually being controlled. Although most patients have mild symptoms and good prognosis after infection, some patients developed severe and die from multiple organ complications. The pathogenesis of SARS-CoV-2 infection in humans remains unclear. Immune function is a strong defense against invasive pathogens and there is currently no specific antiviral drug against the virus. This article reviews the immunological changes of coronaviruses like SARS, MERS and other viral pneumonia similar to SARS-CoV-2. Combined with the published literature, the potential pathogenesis of COVID-19 is inferred, and the treatment recommendations for giving high-doses intravenous immunoglobulin and low-molecular-weight heparin anticoagulant therapy to severe type patients are proposed.
1 January 2015 in Journal of the International AIDS Society
Introduction: Absolute CD4 T cell count and plasma viral load have been established as predictors of HIV disease progression, and CD4 T cell count is used as an indicator for initiation of antiretroviral therapy. Following long‐term therapy, patients generally present with significant CD4 T cell recovery contrasting with persistently elevated CD8 T cell counts, which leads to a partial restoration of CD4:CD8 ratio. This review focuses on the relevance of the CD4:CD8 ratio on clinical outcomes, immune dysfunction and HIV reservoir size in long‐term treated patients.Method: We conducted a comprehensive literature review of publications in English language using major electronic databases. Our search was focused on factors contributing to CD4:CD8 T cell ratio and clinical outcome in adult HIV‐positive patients in the context of treated infection.Discussion: Low CD4:CD8 ratio has been linked to ageing and acts as a predictor of mortality in the general population. This ratio may represent the combined effects of inflammation and immunological changes called “inflammaging.” Although the mechanisms underlying partial correction of the CD4:CD8 ratio and persistently elevated CD8 T cell count in long‐term treated patients remain poorly understood, it has been recently indicated that patients with optimal CD4 T cell recovery and low CD4:CD8 ratio still harbour increased immune activation, an immune senescent phenotype and have a higher risk of non‐AIDS morbidity and mortality. This review reconsiders CD4:CD8 ratio in the light of advances in the understanding of immune dysfunction and examines its pathophysiological features and implications on clinical outcome and HIV reservoir size in long‐term treated HIV‐positive adults.Conclusion: The CD4:CD8 ratio can contribute to the immunological evaluation of treated patients in a long‐term follow‐up and may be applied for monitoring both immune dysfunction and viral reservoir size in immune‐based clinical trials.
1 January 2016 in Journal of the International AIDS Society
Introduction: HIV infection leads to a disturbed T‐cell homeostasis, featured by a depletion of CD4 T‐cells and a persistent elevation of CD8 T‐cells over disease progression. Most effort of managing HIV infection has been focused on CD4 T‐cell recovery, while changes in the CD8 compartment were relatively underappreciated in the past.Methods: A comprehensive literature review of publications in English language was conducted using major electronic databases. Our search was focused on factors contributing to CD8 T‐cell dynamics in HIV infection and following antiretroviral therapy (ART).Discussion: Normalization of CD8 counts is seldom observed even with optimal CD4 recovery following long‐term treatment. Initiation of ART in primary HIV infection leads to enhanced normalization of CD8 count compared with long‐term ART initiated in chronic infection. Importantly, such CD8 elevation in treated HIV infection is associated with an increased risk of inflammatory non‐AIDS‐related clinical events independent of CD4 T‐cell recovery. The mechanisms underlying CD8 persistence remain largely unknown, which may include bystander activation, exhaustion and immunosenescence of CD8 T‐cells. The information provided herein will lead to a better understanding of factors associated with CD8 persistence and contribute to the development of strategies aiming at CD8 normalization.Conclusions: Persistence of CD8 T‐cell elevation in treated HIV‐infected patients is associated with an increased risk of non‐AIDS‐related events. Now that advances in ART have led to decreased AIDS‐related opportunistic diseases, more attention has been focused on reducing non‐AIDS events and normalizing persistent CD8 T‐cell elevation.
Background. CD8 T-cell counts remain elevated in human immunodeficiency virus (HIV) infection even after long-term antiretroviral therapy (ART), which is associated with an increased risk of non–AIDS-related events. We assessed the impact of ART initiation in early versus chronic HIV infection on trajectories of CD8 cell counts over time. Methods. Of 280 individuals enrolled during primary HIV infection (PHI), 251 were followed up for 24 months; 84 started ART before 6 months of infection (eART), 49 started between 6 and 24 months, and 118 remained untreated. Plasma HIV viral load (VL), CD4 and CD8 cell counts were assessed at each study visit. CD8 counts were also examined in 182 age-matched HIV-infected individuals who started ART during chronic infection and maintained undetectable plasma VL for ≥5 years. Results. At PHI baseline, higher CD8 cell counts were associated with more recent infection (P = .02), higher CD4 cell counts (P < .001), and higher VL (P < .001). The CD8 count in the eART group decreased from 797 to 588 cells/µL over 24 months (P < .001), to a level lower than that in untreated PHI (834 cells/µL; P = .004) or in long-term–treated patients with chronic HIV infection (743 cells/µL; P = .047). More prominent CD4 T-cell recovery was observed in the eART group than in the delayed ART group. Conclusions. ART initiated in early HIV infection is associated with improved resolution of CD8 T-cell elevation compared with long-term ART initiated in chronic infection. Early ART may help reduce the risk of non–AIDS-related events by alleviating this elevation.
Introduction: Guidelines regarding antiretroviral therapy (ART) initiation in HIV infection have varied over time, with the 2015 World Health Organization recommendation suggesting ART initiation at the time of diagnosis regardless of CD4 T‐cell counts. Herein, we investigated the influence of socio‐demographic and clinical factors in addition to time trends on early ART initiation among participants of the Montreal Primary HIV Infection Study.Methods: The Montreal Primary HIV Infection Study is a prospective cohort established in three community medical centres (CMCs) and two university medical centres (UMCs). Recently diagnosed HIV‐infected adults were categorized as receiving early (vs. delayed) ART if ART was initiated within 180 days of the baseline visit. Associations between early ART initiation and socio‐demographic, socio‐economic and behavioural information were examined. Independent associations of factors linked with early ART initiation were determined using multivariable binary logistic regression analysis.Results: A total of 348 participants had a documented date of HIV acquisition of <180 days. The median interquartile range (IQR) age of participants was 35 (28; 42) years and the majority were male (96%), having paid employment (63%), men who have sex with men (MSM) (78%) and one to four sexual partners in the last three months (70%). Participants presented with a median IQR HIV plasma viral load of 4.6 (3.7; 5.3) log10 copies/ml, CD4 count of 510 (387; 660) cells/μl and were recruited in CMCs (52%) or UMCs (48%). Early ART initiation was observed in 47% of the participants and the trend followed a V‐shaped curve with peaks in 1996 to 1997 (89%) and 2013 to 2015 (88%) with a dip in 2007 to 2009 (22%). Multivariable analyses showed that having a paid employment adjusted odds ratio (aOR: 2.43; 95% CI: 1.19, 4.95), lower CD4 count (aOR per 50 cell increase: 0.93; 95% CI: 0.87, 0.99) and care at UMCs (aOR: 2.03; 95% CI: 1.06 to 3.90) were independently associated with early ART initiation.Conclusions: Early ART initiation during primary HIV infection was associated with diminished biological prognostic factors and calendar time mirroring evolution of treatment guidelines. In addition, socio‐economic factors such as having a paid employment, contribute to early ART initiation in the context of universal access to care in Canada.