Public Perceptions and Attitudes Toward COVID-19 Nonpharmaceutical Interventions Across Six Countries: A Topic Modeling Analysis of Twitter Data.

BACKGROUND: Nonpharmaceutical interventions (NPIs) (such as wearing masks and social distancing) have been implemented by governments around the world to slow the spread of COVID-19. To promote public adherence to these regimes, governments need to understand the public perceptions and attitudes toward NPI regimes and the factors that influence them. Twitter data offer a means to capture these insights. OBJECTIVE: The objective of this study is to identify tweets about COVID-19 NPIs in six countries and compare the trends in public perceptions and attitudes toward NPIs across these countries. The aim is to identify factors that influenced public perceptions and attitudes about NPI regimes during the early phases of the COVID-19 pandemic. METHODS: We analyzed 777,869 English language tweets about COVID-19 NPIs in six countries (Australia, Canada, New Zealand, Ireland, the United Kingdom, and the United States). The relationship between tweet frequencies and case numbers was assessed using a Pearson correlation analysis. Topic modeling was used to isolate tweets about NPIs. A comparative analysis of NPIs between countries was conducted. RESULTS: The proportion of NPI-related topics, relative to all topics, varied between countries. The New Zealand data set displayed the greatest attention to NPIs, and the US data set showed the lowest. The relationship between tweet frequencies and case numbers was statistically significant only for Australia (r=0.837, P<.001) and New Zealand (r=0.747, P<.001). Topic modeling produced 131 topics related to one of 22 NPIs, grouped into seven NPI categories: Personal Protection (n=15), Social Distancing (n=9), Testing and Tracing (n=10), Gathering Restrictions (n=18), Lockdown (n=42), Travel Restrictions (n=14), and Workplace Closures (n=23). While less restrictive NPIs gained widespread support, more restrictive NPIs were perceived differently across countries. Four characteristics of these regimes were seen to influence public adherence to NPIs: timeliness of implementation, NPI campaign strategies, inconsistent information, and enforcement strategies. CONCLUSIONS: Twitter offers a means to obtain timely feedback about the public response to COVID-19 NPI regimes. Insights gained from this analysis can support government decision making, implementation, and communication strategies about NPI regimes, as well as encourage further discussion about the management of NPI programs for global health events, such as the COVID-19 pandemic.

The high frequency of autoantibodies in HIV patients declines on antiretroviral therapy.

Autoantibodies have been described in samples from HIV positive patients, but the effects of antiretroviral therapy (ART) remain unclear. In a retrospective longitudinal study, we applied clinical assays for autoantibodies to sera collected from 13 HIV positive patients as they began ART with <210 CD4 T-cells/µL and over 2 years on treatment. Twelve of the 13 patients had at least one autoantibody. The frequency peaked before ART (21 from 156 assays) and declined to 8/143 positive reactions after 2 years. As anti-smooth muscle (ASM) antibodies remained common, these assays were applied to HIV patients (n = 67) who had <50 copies HIV RNA/mL plasma after 13 (2-17) years on ART, and healthy controls (n = 55). The frequency of ASM was high in these patients and correlated with levels of total IgG. Hence the high frequency of autoantibodies before ART declined, but did not disappear, with successful therapy. Autoantibody levels may reflect B-cell hyperactivity in patients stable on ART.

Persistence of Activated and Adaptive-Like NK Cells in HIV+ Individuals despite 2 Years of Suppressive Combination Antiretroviral Therapy.

Innate immune dysfunction persists in HIV+ individuals despite effective combination antiretroviral therapy (cART). We recently demonstrated that an adaptive-like CD56dim NK cell population lacking the signal transducing protein FcRγ is expanded in HIV+ individuals. Here, we analyzed a cohort of HIV+ men who have sex with men (MSM, n = 20) at baseline and following 6, 12, and 24 months of cART and compared them with uninfected MSM (n = 15) to investigate the impact of cART on NK cell dysfunction. Proportions of NK cells expressing markers of early (CD69+) and late (HLA-DR+/CD38+) activation were elevated in cART-naïve HIV+ MSM (p = 0.004 and 0.015, respectively), as were FcRγ- NK cells (p = 0.003). Using latent growth curve modeling, we show that cART did not reduce levels of FcRγ- NK cells (p = 0.115) or activated HLA-DR+/CD38+ NK cells (p = 0.129) but did reduce T cell and monocyte activation (p < 0.001 for all). Proportions of FcRγ- NK cells were not associated with NK cell, T cell, or monocyte activation, suggesting different factors drive CD56dim FcRγ- NK cell expansion and immune activation in HIV+ individuals. While proportions of activated CD69+ NK cells declined significantly on cART (p = 0.003), the rate was significantly slower than the decline of T cell and monocyte activation, indicating a reduced potency of cART against NK cell activation. Our findings indicate that 2 years of suppressive cART have no impact on CD56dim FcRγ- NK cell expansion and that NK cell activation persists after normalization of other immune parameters. This may have implications for the development of malignancies and co-morbidities in HIV+ individuals on cART.

Low level autoantibodies can be frequently detected in the general Australian population.

The aim of this study was to determine the prevalence and type of autoantibodies in a general Australian population cohort. Samples collected from 198 individuals included in a cross sectional Busselton Health Study were tested using autoantibody assays routinely performed at Clinical Immunology, PathWest Laboratory Medicine, Western Australia. At least one autoantibody was detected in 51.5% of individuals (males = 45.1%, females = 58.3%). The most frequently detected serum autoantibodies were anti-beta-2-glycoprotein I (12.1%) followed by anti-smooth muscle (11.6%) and anti-thyroid peroxidase (8.6%). Vasculitis associated anti-neutrophil cytoplasmic antibodies were present in 5.1%, while anti-nuclear antibodies were detected in 8.6% of individuals. Notably, 65% of positive results were detected at low levels with the exception of anti-myeloperoxidase and anti-beta 2 glycoprotein I IgG antibodies. Autoantibodies are commonly detected at low levels in a predominantly Australian or European population cohort. No large Australian study has yet provided these data for contemporary routine tests. This paper gives important information on the background frequency of autoantibodies in the general population. Due to the nature of this study we are unaware of whether these individuals have subsequently developed an autoimmune disease, however this was not clinically diagnosed at the time of sample collection.

Short Communication: Do Cytomegalovirus Antibody Levels Associate with Age-Related Syndromes in HIV Patients Stable on Antiretroviral Therapy?

HIV(+) persons stable on antiretroviral therapy (ART) face early onset of age-related diseases. This may arise from a high burden of cytomegalovirus (CMV). To address the role of CMV, we investigated univariate and multivariate associations between markers of systemic and endothelial inflammation, vascular damage, insulin resistance (IR), neurocognitive decline, and antibodies reactive with CMV. In this study, HIV(+) participants (n = 91) aged >45 years with <50 copies HIV RNA/ml plasma after >2 years on ART were assessed for cardiovascular risk (the D:A:D algorithm), type II diabetes (the HOMA-IR index), and neurocognitive performance. Blood samples were assayed for lipids, T cells, insulin, glucose, C-reactive protein, CX3CL1, sTNF-R1, total immunoglobulin G (IgG), and antibodies reactive with CMV lysate, glycoprotein B, or immediate-early-1. Levels of antibodies detected with the three antigens were tightly correlated. Levels of CMV lysate antibody were higher in patients than in age-matched healthy controls and reflected their nadir CD4 T-cell count (p = .001), total IgG (p = .02), and age (p = .08). Levels of CMV lysate antibody correlated with D:A:D score (p = .04), neurocognitive performance (p = .045), and fasting insulin (p = .02). In multivariable analyses, some associations reflected the effect of age, but CMV lysate antibody and CD8 T-cell counts were significant predictors of the HOMA-IR index (R(2) = 0.09, p = .01) independent of age. We conclude that associations between levels of CMV antibodies, cardiovascular risk, and neurocognitive health in HIV(+) patients stable on ART are moderated by age-associated increases in response to CMV, while CMV antibodies may be independently linked with IR.

The immunological footprint of CMV in HIV-1 patients stable on long-term ART.

BACKGROUND: Most HIV-infected persons are cytomegalovirus (CMV) seropositive and retain latent virus that can be reactivated by immune activation. Their T cell populations express markers reflecting a late stage of differentiation, but the contributions of HIV and CMV to this profile are unclear. We investigated the immunological "footprint" of CMV in HIV patients who had a history of extreme immunodeficiency but were now stable on antiretroviral therapy (ART). RESULTS: Twenty CMV seropositive HIV patients >50 years old with nadir CD4 T-cell counts <200 cells/µl were studied after >12 years on ART. 16 CMV seropositive and 9 CMV seronegative healthy controls were included. CMV antibody titres were higher in HIV patients than controls (P < 0.001-0.003). Levels of soluble B-cell activating factor (sBAFF) were elevated in patients (P = 0.002) and correlated with levels of CMV antibodies (P = 0.03-0.002), with no clear relationship in controls. CD8 T-cell IFNγ responses to the IE1 peptide (VLE) remained elevated in HIV patients (P = 0.005). The CD57(+)CD45RA(+)CD27(-) phenotype of CD8 T-cells correlated with age (r = 0.60, P = 0.006), antibodies against CMV IE1 protein (r = 0.44, P = 0.06) and CD4 T-cell IFNγ response to CMV lysate (r = 0.45, P = 0.05). CONCLUSIONS: Humoral and T-cell responses to CMV remained elevated in HIV patients after >12 years on ART. Age and presence of CMV disease influenced CD8 T-cell phenotypes. Elevated levels of sBAFF may be a consequence of HIV disease and contribute to high titres of CMV antibody.

The use of humoral responses as a marker of CMV burden in HIV patients on ART requires consideration of T-cell recovery and persistent B-cell activation.

OBJECTIVES: Elevated humoral responses to cytomegalovirus (CMV) associate with increased risk of cardiovascular disease (CVD) in HIV patients on antiretroviral therapy (ART). To better understand the persistence of CMV humoral responses in relation to CVD, we determined trends in CMV antibody levels over the first 10 years on ART. DESIGN: We describe longitudinal analyses of plasma from 13 HIV patients commencing ART with <210 CD4 T-cells/µL and 27 controls. Antibodies reactive with CMV (fibroblast lysate, gB and IE-1 antigens), EBV-VCA, and HIVgp41 were quantitated. B-cell activation was assessed via total IgG and sBAFF. Inflammation was assessed via sTNF-RI and sCD14. RESULTS: Amongst CMV seropositive HIV patients, levels of antibody reactive with CMV (P = 0.03) and EBV-VCA (P = 0.02) peaked after 1 year on ART. Levels of total IgG, sCD14, and sTNF-RI declined to approximate those in controls after 10 years, but sBAFF (P = 0.0002), EBV-VCA (P = 0.001), and CMV (P = 0.0004) antibodies remained elevated. A strong correlation between sBAFF and CMVgB antibody was seen at 10 years (R = 0.93, P = 0.0009) and verified in a second cohort. CONCLUSIONS: CMV antibody titres peak on ART and remain high. A correlation between CMV antibody and sBAFF suggests a role for HIV-induced B-cell pathology that may affect its use as a marker of CMV burden.