The impact of COVID-19 vaccination for mental well-being.

We examine the impact of vaccination against Covid-19 for mental health. Our estimates suggest that vaccination led to a significant and substantive improvement in mental health. These positive impacts were however concentrated on those most at risk of hospitalisation and death from Covid-19, namely older and clinically vulnerable groups. Our proposed explanation is that in the absence of vaccination, anxiety about contracting COVID-19 has a deleterious impact on the mental health of this cohort. On the other hand, vaccination was much less impactful for the mental health of those least at risk from Covid-19. This may help to explain vaccine hesitancy amongst young people. For this group, a lack of uptake may be principally due to a lack of perceived benefits (and indeed perceived costs) for their own well-being as opposed to vaccine hesitancy.

Clinical Trial Subgroup Analyses to Investigate Clinical and Immunological Outcomes of Convalescent Plasma Therapy in Severe COVID-19.

Objective: To assess the clinical and immunological benefits of passive immunization using convalescent plasma therapy (CPT). Materials and Methods: A series of subclass analyses were performed on the previously published outcome data and accompanying clinical metadata from a completed randomized controlled trial (RCT) (Clinical Trial Registry of India, number CTRI/2020/05/025209). The subclass analyses were performed on the outcome data and accompanying clinical metadata from a completed RCT (patient recruitment between May 15, 2020 and October 31, 2020). Data on the plasma abundance of a large panel of cytokines from the same cohort of patients were also used to characterize the heterogeneity of the putative anti-inflammatory function of convalescent plasma (CP) in addition to passively providing neutralizing antibodies. Results: Although the primary clinical outcomes were not significantly different in the RCT across all age groups, significant immediate mitigation of hypoxia, reduction in hospital stay, and significant survival benefit were registered in younger (<67 years in our cohort) patients with severe coronavirus disease 2019 and acute respiratory distress syndrome on receiving CPT. In addition to neutralizing the antibody content of CP, its anti-inflammatory proteome, by attenuation of the systemic cytokine deluge, significantly contributed to the clinical benefits of CPT. Conclusion: Subgroup analyses revealed that clinical benefits of CPT in severe coronavirus disease 2019 are linked to the anti-inflammatory protein content of CP apart from the anti-severe acute respiratory syndrome coronavirus 2 neutralizing antibody content.

Plasma Gradient of Soluble Urokinase-Type Plasminogen Activator Receptor Is Linked to Pathogenic Plasma Proteome and Immune Transcriptome and Stratifies Outcomes in Severe COVID-19.

Disease caused by SARS-CoV-2 coronavirus (COVID-19) led to significant morbidity and mortality worldwide. A systemic hyper-inflammation characterizes severe COVID-19 disease, often associated with acute respiratory distress syndrome (ARDS). Blood biomarkers capable of risk stratification are of great importance in effective triage and critical care of severe COVID-19 patients. Flow cytometry and next-generation sequencing were done on peripheral blood cells and urokinase-type plasminogen activator receptor (suPAR), and cytokines were measured from and mass spectrometry-based proteomics was done on plasma samples from an Indian cohort of COVID-19 patients. Publicly available single-cell RNA sequencing data were analyzed for validation of primary data. Statistical analyses were performed to validate risk stratification. We report here higher plasma abundance of suPAR, expressed by an abnormally expanded myeloid cell population, in severe COVID-19 patients with ARDS. The plasma suPAR level was found to be linked to a characteristic plasma proteome, associated with coagulation disorders and complement activation. Receiver operator characteristic curve analysis to predict mortality identified a cutoff value of suPAR at 1,996.809 pg/ml (odds ratio: 2.9286, 95% confidence interval 1.0427-8.2257). Lower-than-cutoff suPAR levels were associated with a differential expression of the immune transcriptome as well as favorable clinical outcomes, in terms of both survival benefit (hazard ratio: 0.3615, 95% confidence interval 0.1433-0.912) and faster disease remission in our patient cohort. Thus, we identified suPAR as a key pathogenic circulating molecule linking systemic hyperinflammation to the hypercoagulable state and stratifying clinical outcomes in severe COVID-19 patients with ARDS.

Nature and Dimensions of Systemic Hyperinflammation and its Attenuation by Convalescent Plasma in Severe COVID-19.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), has led to significant morbidity and mortality. While most suffer from mild symptoms, some patients progress to severe disease with acute respiratory distress syndrome (ARDS) and associated systemic hyperinflammation. METHODS: First, to characterize key cytokines and their dynamics in this hyperinflammatory condition, we assessed abundance and correlative expression of a panel of 48 cytokines in patients progressing to ARDS as compared to patients with mild disease. Then, in an ongoing randomized controlled trial of convalescent plasma therapy (CPT), we analyzed rapid effects of CPT on the systemic cytokine dynamics as a correlate for the level of hypoxia experienced by the patients. RESULTS: We identified an anti-inflammatory role of CPT independent of its neutralizing antibody content. CONCLUSIONS: Neutralizing antibodies, as well as reductions in circulating interleukin-6 and interferon-γ-inducible protein 10, contributed to marked rapid reductions in hypoxia in response to CPT. CLINICAL TRIAL REGISTRY OF INDIA: CTRI/2020/05/025209. http://www.ctri.nic.in/.

The interaction of ethnicity and deprivation on COVID-19 mortality risk: a retrospective ecological study.

Black, Asian and Minority Ethnic (BAME) populations are at an increased risk of developing COVID-19 and consequentially more severe outcomes compared to White populations. The aim of this study was to quantify how much of the disproportionate disease burden can be attributed to ethnicity and deprivation as well as its interaction. An ecological study was conducted using data derived from the Office for National Statistics data at a Local Authority District (LAD) level in England between 1st March and 17th April 2020. The primary analysis examined how age adjusted COVID-19 mortality depends on ethnicity, deprivation, and the interaction between the two using linear regression. The secondary analysis using spatial regression methods allowed for the quantification of the extent of LAD spillover effect of COVID-19 mortality. We find that in LADs with the highest deprivation quartile, where there is a 1 percentage point increase in "Black-African (regression coefficient 2.86; 95% CI 1.08-4.64)", "Black-Caribbean (9.66: 95% CI 5.25-14.06)" and "Bangladeshi (1.95: 95% CI 1.14-2.76)" communities, there is a significantly higher age-adjusted COVID-19 mortality compared to respective control populations. In addition, the spatial regression results indicated positive significant correlation between the age-adjusted mortality in one LAD and the age-adjusted mortality in a neighbouring LAD, suggesting a spillover effect. Our results suggest targeted public health measures to support those who are deprived and belong to BAME communities as well as to encourage restricted movement between different localities to limit disease propagation.

The effect of COVID - 19 pandemic on global stock market volatility: Can economic strength help to manage the uncertainty?

Stock markets across the world have exhibited varying degrees of volatility following the recent COVID-19 pandemic. We have examined the effect of this pandemic on stock market volatility and whether economic strength, measured by a set of selected country-level economic characteristics and factors such as economic resilience, intensity of capitalism, level of corporate governance, financial development, monetary policy rate and quality of health system, can potentially mitigate the possible detrimental effect of the global pandemic on stock market volatility. Using data from 34 developed and emerging markets, we have found that these country-level economic characteristics and factors do help to reduce the volatility arising due to the virus pandemic. The results of this paper are important as policymakers can use these economic factors to set policy responses to tackle extraordinary heat in the global stock market in order to avoid any possible future financial crisis.