26 August, 2023

Tensor decomposition reveals coordinated multicellular patterns of transcriptional variation that distinguish and stratify disease individuals -

Tissue- and organism-level biological processes often involve coordinated action of multiple distinct cell types. Current computational methods for the analysis of single-cell RNA-sequencing (scRNA-seq) data, however, are not designed to capture co-variation of cell states across samples, in part due to the low number of biological samples in most scRNA-seq datasets. Recent advances in sample multiplexing have enabled population-scale scRNA-seq measurements of tens to hundreds of samples. To take advantage of such datasets, here we introduce a computational approach called single-cell Interpretable Tensor Decomposition (scITD). This method extracts “multicellular gene expression patterns” that capture how sample-specific expression states of a cell type are correlated with the expression states of other cell types. Such multicellular patterns can reveal molecular mechanisms underlying coordinated changes of different cell types within the tissue, and can be used to stratify individuals in a clinically-relevant and reproducible manner. We first validated the performance of scITD using in vitro experimental data and simulations. We then applied scITD to scRNA-seq data on peripheral blood mononuclear cells (PBMCs) from 115 patients with systemic lupus erythematosus and 56 healthy controls. We recapitulated a well-established pan-cell-type signature of interferon-signaling that was associated with the presence of anti-dsDNA autoantibodies and a disease activity index. We further identified a novel multicellular pattern linked to nephritis, which was characterized by an expansion of activated memory B cells along with helper T cell activation. Our approach also sheds light on ligand-receptor interactions potentially mediating these multicellular patterns. As validation, we demonstrated that these expression patterns also stratified donors from a pediatric SLE dataset by the same phenotypic attributes. Lastly, we found the interferon multicellular pattern and others to be conserved in a COVID-19 dataset, pointing to the presence of both general and disease-specific patterns of inter-individual immune variation. Overall, scITD is a flexible method for exploring co-variation of cell states in multi-sample single-cell datasets, which can yield new insights into complex non-cell-autonomous dependencies that define and stratify disease.

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Hydroxychloroquine: balancing the needs of LMICs during the COVID-19 pandemic -

I want to thank the Editor for bringing attention to the effect of a potential shortage of hydroxychloroquine (HCQ) on existing patients with autoimmune diseases during the current COVID-19 crisis [1]. The drug has shown some promising results against SARS-CoV-2, although more testing needs to be done. However, hydroxychloroquine is also an effective medication for patients with autoimmune disorders like systemic lupus erythematosus [2].

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Conspiracies will not pay you off -

Using a representative sample of 1682 Slovaks, the study investigated antecedents and negative consequences for personal finances of the endorsement of conspiracy theories. As a part of the first wave of a longitudinal study monitoring social and psychological impacts of the COVID-19 pandemic, participants responded to questions concerning their socio-demographic status, generic conspiracy mentality, COVID-related conspiracies, financial wellbeing, predictions about economic situation and willingness to change financial behaviour. The results show that people who experience more financial anxiety and consider their socio-economic status as lower endorse conspiracy theories more often. They are also more pessimistic about economic development in general and, unlike in models without conspiracy theories, less likely to make adaptive decisions that could alleviate precarious economic conditions they experience. By linking the endorsement of conspiracy theories with precarious economic conditions, the study offers a preliminary explanation of the uncontrollable spread of conspiracy theories in countries with high prevalence of economic insecurity such as Slovakia. The findings have far-reaching practical implications for developing tailored interventions protecting those most vulnerable from endorsing conspiracies and, consequently, from making decisions that would further perpetuate poverty and financial anxiety.

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RCT-based Social Return on Investment (SROI) of a home exercise programme for people with early dementia comparing in-person and blended delivery before and during the COVID-19 pandemic -

Background: Regular exercise and community engagement may slow the rate of function loss for people with dementia. However, the evidence is uncertain regarding the cost-effectiveness and social return on investment (SROI) of home exercise with community referral for people with dementia. This study aimed to compare the social value generated from the in-person PrAISED programme delivered before March 2020 with a blended PrAISED programme delivered after March 2020. Methods: SROI analysis was conducted alongside a randomised controlled trial (RCT). Of 205 patient participants and their carers who completed cost data, 61 completed an in-person programme before March 2020. Due to COVID-19 pandemic restrictions, 144 patient participants completed a blended programme consisting of a combination of in-person visits, phone calls and video conferencing with multidisciplinary team (MDT) members. SROI analysis compared in-person and blended delivery formats. Five relevant and material outcomes were identified: three outcomes for patient participants (fear of falling, health-related quality of life, and social connection); one outcome for carer participants (carer strain index), and one outcome for the NHS (health service resource use). Data were collected at baseline and a 12-month follow-up. Results: The in-person PrAISED programme generated SROI ratios ranging from 0.58 Great Britain Pound (GBP) to 2.33 GBP for every 1 GBP invested. In-person PrAISED patient participants gained social value from improved health-related quality of life, social connection, and less fear of falling. In-person PrAISED carer participants acquired social value from less carer strain. The NHS gained benefit from less health care service resource use. However, the blended PrAISED programme generated lower SROI ratios ranging from a negative ratio to 0.08 GBP : 1 GBP. Conclusion: Compared with the blended programme, the PrAISED in-person programme generated higher SROI ratios for people with early dementia. During the COVID-19 pandemic and its restrictions, a blended delivery of the programme and the curtailment of community activities resulted in lower SROI ratios during this period. An in-person PrAISED intervention with community referral is likely to provide better value for money than a blended one with limited community referral, despite the greater costs of the former.

🖺 Full Text HTML: RCT-based Social Return on Investment (SROI) of a home exercise programme for people with early dementia comparing in-person and blended delivery before and during the COVID-19 pandemic

Risk factors for SARS-Cov-2 infection at a United Kingdom electricity-generating company: a test-negative design case-control study -

Objectives Identify workplace risk factors for SARS-Cov-2 infection, using data collected by a United Kingdom electricity-generating company. Methods Using a test-negative design case-control study we estimated the odds ratios (OR) of infection by job category, site, test reason, sex, vaccination status, vulnerability, site outage, and site COVID-19 weekly risk rating, adjusting for age, test date and test type. Results From an original 80,077 COVID-19 tests, there were 70,646 included in the final analysis. Most exclusions were due to being visitor tests (5,030) or tests after an individual first tested positive (2,968). Women were less likely to test positive than men (OR=0.71; 95% confidence interval=0.58-0.86). Test reason was strongly associated with positivity and although not a cause of infection itself, due to differing test regimes by area it was a strong confounder for other variables. Compared to routine tests, tests due to symptoms were highest risk (94.99; 78.29-115.24), followed by close contacts (16.73; 13.80-20.29) and looser work contacts 2.66 (1.99-3.56). After adjustment, we found little difference in risk by job category, but some differences by site with three sites showing substantially lower risks, and one site showing higher risks in the final model. Conclusions Infection risk was not associated with job category. Vulnerable individuals were at slightly lower risk, tests during outages were higher risk, vaccination showed no evidence of an effect on testing positive, and site COVID-19 risk rating did not show an ordered trend in positivity rates.

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Mucosal antibody responses to SARS-CoV-2 booster vaccination and breakthrough infection -

Coronavirus disease 2019 (COVID-19) vaccines have saved millions of lives. However, variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged causing large numbers of breakthrough infections. These developments necessitated the rollout of COVID-19 vaccine booster doses. It has been reported that mucosal antibody levels in the upper respiratory tract, especially for secretory IgA (sIgA), correlate with protection from infection with SARS-CoV-2. However, it is still unclear how high levels of mucosal antibodies can be induced. In this study, we measured serum IgG, saliva IgG and saliva sIgA responses in individuals who received COVID-19 mRNA booster vaccinations or who experienced breakthrough infections. We found that mRNA booster doses could induce robust serum and saliva IgG responses, especially in individuals who had not experienced infections before, but saliva sIgA responses were weak. In contrast, breakthrough infections in individuals who had received the primary mRNA vaccination series induced robust serum and saliva IgG as well as saliva sIgA responses. Individuals who had received a booster dose and then had a breakthrough infection showed low IgG induction in serum and saliva but still responded with robust saliva sIgA induction. These data suggest that upper respiratory tract exposure to antigen is an efficient way of inducing mucosal sIgA while exposure via intramuscular injection is not.

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An After-Action Review of COVID-19 Cases and Mitigation Measures at US Mission India, March 2020-July 2021 -

Introduction Between March 2020-June 2021, over 30 million COVID-19 cases were reported in India. We assessed the COVID-19 response across the US Mission India (US Embassy New Delhi, US Consulates – Mumbai, Hyderabad, Chennai and Kolkata) to plan future mitigation efforts and fill gaps in knowledge about COVID-19 transmission in a unique community like the US Mission. Method We described COVID-19 mitigation activities undertaken by the five US Mission India posts and conducted a secondary analysis of case investigation and contact tracing program data collected by the Health Unit from March 2020–July 2021. Results US Mission in India, in collaboration with multiple internal agencies, initiated COVID-19 mitigation activities in March 2020. Activities included educational sessions, training for infection prevention and control, health and safety assessments, and the development of standard operating procedures (SOPs). The Health Unit and US CDC India office initiated COVID-19 case investigations and conducted contact tracing. Between March 2020-July 2021, 636 COVID-19 cases (72% males), including 48 clusters (size range 2-10 cases), were reported. Overall case fatality rate was 1.5%. Of case patients, 82% (523) were Indians, and 18% (113) were Americans. On presentation, 22% (138/625) of cases were asymptomatic. The median time from symptom onset to notification to the Health Unit was three days (Interquartile range 1-5). The Health Unit identified 2,484 contacts (positivity rate 25%). Frequency of case presentation in the US Mission India closely resembled the pattern of COVID-19 waves in India. The attack rates ranged over the time period between 10-19%, the highest at 19% in Delhi. Conclusions COVID-19 mitigation strategies were implemented in collaboration with multiple agencies and helped prevent the transmission of COVID-19 and large COVID-19 clusters in the US Mission India.

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Host behaviour driven by awareness of infection risk amplifies the chance of superspreading events -

We demonstrate that heterogeneity within host populations in the perceived risks associated with infection can amplify the chance that superspreading occurs during the crucial, early stages of an epidemic. Under our behavioural model, individuals who are less concerned about the risks of infection are more likely to be infected and to attend larger sized events. For directly communicable diseases, such as COVID-19, this leads to infections being introduced at rates above the population prevalence to events that are most conducive to superspreading, for fixed overall transmission levels. We develop a computational framework for evaluating within-event risks and derive a small-scale reproduction number to measure how introductions and transmission heterogeneities determine the number of infections resulting from an event of given duration. This generalises earlier frameworks and both quantifies and clarifies how event-scale dynamics depend on population-level characteristics. As event duration and size increase, our reproduction number converges to the widely used basic reproduction number, R0. We show that even moderate levels of heterogeneity in the perceived risks associated with infection can substantially increase the risk that disproportionately large numbers of infections are generated at larger events, as compared to assuming homogeneous perceptions of risk across the host population. Behavioural dynamics, which remain understudied in the context of epidemiological modelling, are essential to consider when assessing the risk posed by an invading pathogen in the early stages of an infectious disease epidemic.

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Protection conferred by COVID-19 vaccination, prior SARS-CoV-2 infection, or hybrid immunity against Omicron-associated severe outcomes among community-dwelling adults -

Introduction: We assessed protection conferred by COVID-19 vaccines and/or prior SARS-CoV-2 infection against Omicron-associated severe outcomes during successive sublineage-predominant periods. Methods: We used a test-negative design to estimate protection by vaccines and/or prior infection against hospitalization/death among community-dwelling, PCR-tested adults aged >50 years in Ontario, Canada between January 2, 2022 and June 30, 2023. Multivariable logistic regression was used to estimate the relative change in the odds of hospitalization/death with each vaccine dose (2-5) and/or prior PCR-confirmed SARS-CoV-2 infection (compared with unvaccinated, uninfected subjects) up to 15 months since the last vaccination or infection. Results: We included 18,526 cases with Omicron-associated severe outcomes and 90,778 test-negative controls. Vaccine protection was high during BA.1/BA.2 predominance, but was generally <50% during periods of BA.4/BA.5 and BQ/XBB predominance without boosters. A third/fourth dose transiently increased protection during BA.4/BA.5 predominance (third-dose, 6-month: 68%, 95%CI 63%-72%; fourth-dose, 6-month: 80%, 95%CI 77%-83%), but was lower and waned quickly during BQ/XBB predominance (third-dose, 6-month: 59%, 95%CI 48%-67%; 12-month: 49%, 95%CI 41%-56%; fourth-dose, 6-month: 62%, 95%CI 56%-68%, 12-months: 51%, 95%CI 41%-56%). Hybrid immunity conferred nearly 90% protection throughout BA.1/BA.2 and BA.4/BA.5 predominance, but was reduced during BQ/XBB predominance (third-dose, 6-month: 60%, 95%CI 36%-75%; fourth-dose, 6-month: 63%, 95%CI 42%-76%). Protection was restored with a fifth dose (bivalent; 6-month: 91%, 95%CI 79%-96%). Prior infection alone did not confer lasting protection. Conclusion: Protection from COVID-19 vaccines and/or prior SARS-CoV-2 infections against severe outcomes is reduced when immune-evasive variants/subvariants emerge and may also wane over time. Our findings support a variant-adapted booster vaccination strategy with periodic review.

🖺 Full Text HTML: Protection conferred by COVID-19 vaccination, prior SARS-CoV-2 infection, or hybrid immunity against Omicron-associated severe outcomes among community-dwelling adults

Should Health Communication During the SARS-CoV-2 Pandemic Emphasize Self- or Other-Focused Impacts of Mitigation Behaviors? Insights from Two Message Matching Studies -

Mask-wearing, social distancing, and vaccination remain effective ways to mitigate the spread of COVID-19. Yet, many hesitate to enact some or all these preventive behaviors. We created three persuasive messages—framed to promote benefits to either 1) oneself, 2) close-others, or 3) distant-others—to determine whether the effectiveness of these messages varied based on personality differences (specifically independent/interdependent self-construal and chronic construal level). In two online experiments (N = 862), we measured individual differences and showed participants one of the three messages. Consistent interactions between interdependent self-construal and message conditions showed that those high in interdependent self-construal responded most positively to the self-focused messages promoting mask-wearing, social distancing, and COVID-19 vaccination. Those low in interdependent self-construal responded most negatively to the self-focused messages. Although no interaction effect was observed for independent self-construal, and inconsistent evidence emerged for construal level, other-focused messages performed either better or equally well to the self-focused messages for most participants and may thus be promising for future public health communication efforts.

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Respiratory symptoms after coalmine fire and pandemic: a longitudinal analysis of the Hazelwood Health Study adult cohort -

Background Extreme but discrete fine particle <2.5μm (PM_2.5) exposure is associated with higher prevalence of respiratory symptoms. It is unknown whether these effects abate, persist, or worsen over time, nor whether COVID-19 exacerbates PM_2.5 effects. Methods We analysed longitudinal survey data from a cohort residing near a 2014 coalmine fire in regional Australia. A 2016/2017 survey included n=4,056 participants, of whom n=612 were followed-up in 2022. Items include questions about 7 respiratory symptoms, history of COVID-19, and time-location diaries that were combined with geospatial models of fire-related PM_2.5. Associations were examined using logistic and mixed-effects logistic regressions. Results PM_2.5 exposure predicted higher prevalence of chronic cough and current wheeze 2-3 years post-fire. At the 2022 follow-up, PM_2.5 exposure was associated with worsening prevalence of chronic cough and possibly current wheeze. While were no detectable interaction effects between PM_2.5 and COVID-19, participants with a history of COVID-19 exhibited more significant associations between PM_2.5 exposure and respiratory symptoms. Discussion Short-term but extreme PM_2.5 may increase the long-term prevalence of chronic cough, while COVID-19 may exacerbate the effect on other respiratory symptoms.

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The Risk of Mpox (Monkeypox) Importation and Subsequent Outbreak Potential in Mainland China: A Retrospective Statistical Modelling Study -

The 2022 mpox outbreak has spread rapidly across multiple countries in the non-endemic region, mainly among men who have sex with men (MSM), while China only has limited recorded importation and no local outbreak. We constructed probabilistic models to simulate the risk of mpox importation in mainland China, with the help of reported monkeypox cases during this multi-country outbreak and the international air-travel data. And we further evaluated the mpox outbreak potential given that undetected mpox infections were introduced into men who have sex with men, considering different transmissibility, population immunity and population activity. We found that the reduced international air-travel volume and stringent border entry policy decreased about 94% and 69% mpox importations respectively. Once a mpox case is introduced into active MSM population with almost no population immunity, the risk of triggering local transmission is estimated at 42%, and would rise to >95% with over six cases. Our study demonstrates the key role of the reduced international air-travel volume and stringent border entry policy during the COVID-19 pandemic on reducing mpox importations, and the subsequent risk of triggering local outbreaks among MSM.

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Serological surveillance reveals a high exposure to SARS-CoV-2 and altered immune response among COVID-19 unvaccinated Cameroonian individuals -

Background Surveillance of COVID-19/SARS-CoV-2 dynamics is crucial to understanding natural history and providing insights into the population’s exposure risk and specific susceptibilities. This study investigated the seroprevalence of SARS-CoV-2 antibodies, its predictors, and immunological status among unvaccinated patients in Cameroon. Materials and Methods A multicentre cross-sectional study was conducted between January and September 2022 in the town of Douala. Patients were consecutively recruited, and data of interest were collected using a questionnaire. Blood samples were collected to determine Immunoglobin titres (IgM and IgG) by ALFA, CD4+ cells by flow cytometry, and interferon gamma (IFN- γ) and interleukin-6 (IL-6) by ELISA. Results A total of 342 patients aged 41.5 ± 13.9 years were included. Most participants (75.8%) were asymptomatic. The overall prevalence of IgM and IgG was 49.1% and 88.9%, respectively. Ageusia and anosmia have displayed the highest positive predictive values (90.9% and 82.4%) and specificity (98.9% and 98.3%). The predictors of IgM seropositivity were being aged 60 – 70 years (aOR = 0.54, p = 0.02) and ageusia (aOR = 9.31, p = 0.01), whereas those of IgG seropositivity included health facility (aOR = 0.23, p = 0.02) and ageusia (aOR = 0.21, p = 0.04). CD4+, IFN-γ, and IL-6 were impaired in seropositive individuals, with a confounding role of socio-demographic factors or comorbidities. Conclusion Although the WHO declared the end of COVID-19 as a public health emergency, the findings of this study indicate the need for continuous surveillance to adequately control the disease in Cameroon.

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Modelling the Interplay between Responsive Individual Vaccination Decisions and the Spread of SARS-CoV-2 -

The uptake of COVID-19 vaccines remains low despite their high effectiveness. Epidemic models that represent decision-making psychology can provide insight into the potential impact of vaccine promotion interventions in the context of the COVID-19 pandemic. We coupled a network-based mathematical model of SARS-CoV-2 transmission in Georgia, USA with a social-psychological vaccination decision-making model in which vaccine side effects, post-vaccination infections, and other unidentified community-level factors could “nudge” individuals towards vaccine resistance while hospitalization spikes could nudge them towards willingness. Combining an increased probability of hospitalization-prompted resistant-to-willing switches with a decreased probability of willing-to-resistant switches prompted by unidentified community-level factors increased vaccine uptake and decreased SARS-CoV-2 incidence by as much as 30.7% and 24.0%, respectively. The latter probability had a greater impact than the former. This illustrates the disease prevention potential of vaccine promotion interventions that address community-level factors influencing decision-making and anticipate the case curve instead of reacting to it.

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COVID-19 vaccine hesitancy and conspiracy beliefs in Togo: Findings from two cross-sectional surveys -

Togo is a low-income country in West Africa. Estimates suggest that only 25% of the Togolese population have received at least one dose of any COVID-19 vaccine by June 2023. Whilst the early phase of the pandemic vaccine rollout across 2021 was dominated by higher-income countries taking much of the available supply, there have long been sufficient supplies for all nations. Thus, there remains a need to understand reasons for low uptake in countries such as Togo. Two cross-sectional telephone surveys of Togo residents were conducted in December 2020 and January 2022. These surveys asked questions around perceptions of COVID-19, trust in public health messaging, belief in conspiracy theories, and hesitancy around COVID-19 vaccination. Analyses here focus on unvaccinated respondents. Across Survey 1 (N = 1430) and Survey 2 (N = 212), 65% of respondents were men, 47% lived in Lomé (capital city of Togo), 25% completed higher education, 67% were married, and 69% were Christian. Between Surveys 1 and 2, overall hesitancy (33.0% to 58.0%) and beliefs in conspiracy theories (29% to 65%) significantly increased. Using logistics regression, governmental mistrust was the strongest significant predictor of hesitancy (OR: 2.90). Participants who indicated agreement or uncertainty with at least one conspiracy belief also predicted greater vaccine hesitancy (OR: 1.36). Proactive approaches to public health messaging, that better understand reasons for hesitancy across different demographics, can support uptake of COVID-19 vaccinations within Togo. This includes health promotion campaigns that use locally and nationally trusted knowledge providers (e.g. the health service or religious leaders) for greatest effectiveness at reducing impact of misinformation. Key future research should focus around knowledge gaps and areas of mistrust created by the pandemic, such as the impact of misinformation upon routine immunisation uptake.

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