Reduce COVID-19 Mortality Research Articles

Effects of the COVID-19 pandemic on health inequalities and mental health: effective public policies

The aim of this article is to examine the effects of the COVID-19 pandemic on health inequalities and mental disorders and to analyse the most effective public policies in containing them. COVID-19, in addition to causing the worst health crisis since World War II, has generated a severe economic recession and a rise in unemployment. The poorer socioeconomic classes have been most affected by infections and deaths caused by the SARS-CoV-2 virus due to inequalities in working, housing and area of ​​residence conditions, psychosocial factors, and unequal access to health care. The pandemic crisis, in addition to causing psychiatric and neurological problems in people who have been hospitalized, appears to have increased the risk of psychological problems through various mechanisms such as social distancing, loss of a loved one, unemployment, and economic difficulties. In many countries, however, there was no significant increase in suicides in 2020 and there have even been decreasing temporal trends. It is possible that the crisis, in addition to creating stress and social isolation, may have promoted reciprocity, interpersonal help, and greater motivation to take care of one's health.The most effective policies in reducing COVID-19 mortality have the potential to limit the most adverse effects of the pandemic on health inequalities and mental health. Thanks to vigorous preventive interventions on the territory, based on testing, tracing, isolating, timely, countries who managed best the pandemic avoided prolonged and repeated lockdowns, protected public health and the economy. However, more vigorous social protection measures are needed in favour of those populations most affected by the health crisis and its socioeconomic effects. This pandemic offers the opportunity to learn lessons on the protection of public health and stress the need to adopt a syndemic model oriented towards prevention.

Hydroxychloroquine treatment does not reduce COVID-19 mortality; underdosing to the wrong patients?

An observational study published in The Lancet Rheumatology by Christopher T Rentsch and colleagues1 showed no association between pre-exposure use of hydroxychloroquine and reduced mortality in patients with COVID-19 who also have systemic lupus erythematosus or rheumatoid arthritis. 138 440 (71·1%) participants were women, and the study population was relatively young, with 50% of the participants younger than 66 years. In a previous study,2 the death rate in patients younger than 70 years was low, and it was lower for women than men; therefore, the differences in mortality might be very difficult to appreciate in the study by Rentsch and colleagues,1 in which half of the participants are under 70 years old and more than two thirds are women.

Hydroxychloroquine treatment does not reduce COVID-19 mortality; underdosing to the wrong patients? - Authors' reply.

We thank Luis Ayerbe and colleagues for the opportunity to further discuss our Article.1 The choice of our study population—individuals with rheumatoid arthritis or systemic lupus erythematosus—was made to minimise the potential for confounding by indication when estimating the effectiveness of hydroxychloroquine use rather than investigating how to prevent severe COVID-19 in this population. The key question is whether our study had sufficient statistical power to detect a real difference in mortality, if one existed? As stated in the Article, the CIs around our key estimate (hazard ratio 1·03 [95% CI 0·80–1·33]) suggested that we could exclude substantial benefit, although a modest benefit or harm on a relative scale could not be ruled out; therefore, trials were warranted.

COVID-19: High-JAKing of the Inflammatory "Flight" by Ruxolitinib to Avoid the Cytokine Storm.

Since SARS-CoV-2 outbreak in December 2019, world health-system has been severely impacted with increased hospitalization, Intensive-Care-Unit (ICU) access and high mortality rates, mostly due to severe acute respiratory failure and multi-organ failure. Excessive and uncontrolled release of proinflammatory cytokines (cytokine release/storm syndrome, CRS) have been linked to the development of these events. The recent advancements of immunotherapy for the treatment of hematologic and solid tumors shed light on many of the molecular mechanisms underlying this phenomenon, thus rendering desirable a multidisciplinary approach to improve COVID-19 patients’ outcome. Indeed, currently available therapeutic-strategies to overcome CRS, should be urgently evaluated for their capability of reducing COVID-19 mortality. Notably, COVID-19 shares different pathogenic aspects with acute graft-versus-host-disease (aGVHD), hemophagocytic-lymphohistiocytosis (HLH), myelofibrosis, and CAR-T-associated CRS. Specifically, similarly to aGVHD, an induced tissue damage (caused by the virus) leads to increased cytokine release (TNFα and IL-6) which in turn leads to exaggerated dendritic cells, macrophages (like in HLH) and lymphocytes (as in CAR-T) activation, immune-cells migration, and tissue-damage (including late-stage fibrosis, similar to myelofibrosis). Janus Kinase (JAK) signaling represents a molecular hub linking all these events, rendering JAK-inhibitors suitable to limit deleterious effects of an overwhelming inflammatory-response. Accordingly, ruxolitinib is the only selective JAK1 and JAK2-inhibitor approved for the treatment of myelofibrosis and aGVHD. Here, we discuss, from a molecular and hematological point of view, the rationale for targeting JAK signaling in the management of COVID-19 patients and report the clinical results of a patient admitted to ICU among the firsts to be treated with ruxolitinib in Italy.

Reducing COVID-19 mortality in Senegal through community case management

Like many countries across the world, Senegal is facing a second wave of the COVID-19 pandemic with an increase in hospital admissions and deaths, putting pressure on an already overstretched health workforce. This situation requires new and innovative measures to reverse the trend and avoid overwhelming the health system. Community Case Management is a proven strategy in healthcare that could be a powerful tool in preventing severe cases and reducing deaths related to COVID-19. This proposed strategy is based on early detection of cases and home-based management by community health workers.

Predictors of COVID-19 Case Fatality Rate in Highly Populated Developed Countries During the Emergence of the Delta Variant

By September 2021 the outbreak of the COVID-19 caused 228.19 million confirmed cases and 4.7 million deaths globally. Mortality measures are frequently used to estimate the severity of a pandemic. Among them is the Case Fatality Rate (CFR). Some mathematical models were developed to estimate the impact of specific factors on the disease’s mortality. These models were developed before the COVID-19 vaccines were administrated, and therefore did not consider the vaccines influence on COVID-19 fatality. Moreover, some other factors associated with COVID-19 mortality such as diabetes and cardiovascular mortality were not included in these models. This study offers a mathematical model with some potential predictors of COVID-19 CFR during the fourth pandemic wave caused by the Delta variant. To evaluate these predictors, demographic and clinical information for 10 highly populated developed countries was retrieved from a real-time available website. Demographic data included population density, percent of population above age 65, GDP per capita, and percent of smoking. Clinical data included diabetes prevalence, cardiovascular death rate, percent of fully vaccinated population, and CFR. Single linear regressions were conducted to assess the association of each potential predictor with CFR. A backward multiple linear regression was conducted to identify the most parsimonious combination of the independent variables of this study predicting CFR. The model developed in this study suggests that percent of population above age 65, and cardiovascular death rate have a positive effect on CFR, i.e., they are associated with increased COVID-19 fatality rate during the fourth wave. In addition, GDP per capita has a negative effect on CFR, i.e. – higher GDP per capita is associated with lower fatality rate during COVID-19 fourth wave. Moreover, single linear regressions show a strong negative association between percent of fully vaccinated people in each country and CFR. This model sheds light on several potential demographic and clinical factors which may predict CFR in highly populated developed countries during the emergence of the Delta variant. Vaccination in accordance with the recommendations is recommended to reduce COVID-19 mortality.

Could Dietary Factors Reduce COVID-19 Mortality Rates? Moderating the Inflammatory State.

Could Dietary Factors Reduce COVID-19 Mortality Rates? Moderating the Inflammatory State.

PRS56 Cost-Effectiveness of Social Distancing to Reduce COVID-19 Mortality in the United States

PRS56 Cost-Effectiveness of Social Distancing to Reduce COVID-19 Mortality in the United States

CO3 Effectiveness of Government Measures to Reduce COVID-19 Mortality across 5 Different Countries

As COVID-19 cases increased in early 2020, most governments imposed social distancing and mobility restrictions. This study was designed to determine associations between government actions and new cases of fatalities, and the differences between the effectiveness of these actions across five different countries.

Chemocentric Informatics Analysis: Dexamethasone Versus Combination Therapy for COVID-19.

COVID-19 is a biphasic infectious disease with no approved vaccine or pharmacotherapy. The first drug that has shown promise in reducing COVID-19 mortality in severely-ill patients is dexamethasone, a cheap, well-known anti-inflammatory glucocorticoid, approved for the treatment of inflammatory conditions including respiratory diseases such as asthma and tuberculosis. However, about 80% of COVID-19 patients requiring oxygenation, and about 67% of patients on ventilators, are not responsive to dexamethasone therapy mainly. Additionally, using higher doses of dexamethasone for prolonged periods of time can lead to severe side effects and some patients may develop corticosteroid resistance leading to treatment failure. In order to increase the therapeutic efficacy of dexamethasone in COVID-19 patients, while minimizing dexamethasone-related complications that could result from using higher doses of the drug, we applied a chemocentric informatics approach to identify combination therapies. Our results indicated that combining dexamethasone with fast long-acting beta-2 adrenergic agonists (LABAs), such as formoterol and salmeterol, can ease respiratory symptoms hastily, until dexamethasone’s anti-inflammatory and immunosuppressant effects kick in. Our studies demonstrated that LABAs and dexamethasone (or other glucocorticoids) exert synergistic effects that will augment both anti-inflammatory and fibronectin-mediated anticoagulant effects. We also propose other alternatives to LABAs that are supported by sound systems biology evidence, such as nitric oxide. Other drugs such as sevoflurane and treprostinil interact with the SARS-CoV-2 interactome and deserve further exploration. Moreover, our chemocentric informatics approach provides systems biology evidence that combination therapies for COVID-19 will have higher chances of perturbing the SARS-CoV-2 human interactome, which may negatively impact COVID-19 disease pathways.

Cost-effectiveness of public health strategies for COVID-19 epidemic control in South Africa: a microsimulation modelling study

BackgroundHealth-care resource constraints in low-income and middle-income countries necessitate the identification of cost-effective public health interventions to address COVID-19. We aimed to develop a dynamic COVID-19 microsimulation model to assess clinical and economic outcomes and cost-effectiveness of epidemic control strategies in KwaZulu-Natal province, South Africa.MethodsWe compared different combinations of five public health interventions: health-care testing alone, where diagnostic testing is done only for individuals presenting to health-care centres; contact tracing in households of cases; isolation centres, for cases not requiring hospital admission; mass symptom screening and molecular testing for symptomatic individuals by community health-care workers; and quarantine centres, for household contacts who test negative. We calibrated infection transmission rates to match effective reproduction number (Re) estimates reported in South Africa. We assessed two main epidemic scenarios for a period of 360 days, with an Re of 1·5 and 1·2. Strategies with incremental cost-effectiveness ratio (ICER) of less than US$3250 per year of life saved were considered cost-effective. We also did sensitivity analyses by varying key parameters (Re values, molecular testing sensitivity, and efficacies and costs of interventions) to determine the effect on clinical and cost projections.FindingsWhen Re was 1·5, health-care testing alone resulted in the highest number of COVID-19 deaths during the 360-day period. Compared with health-care testing alone, a combination of health-care testing, contact tracing, use of isolation centres, mass symptom screening, and use of quarantine centres reduced mortality by 94%, increased health-care costs by 33%, and was cost-effective (ICER $340 per year of life saved). In settings where quarantine centres were not feasible, a combination of health-care testing, contact tracing, use of isolation centres, and mass symptom screening was cost-effective compared with health-care testing alone (ICER $590 per year of life saved). When Re was 1·2, health-care testing, contact tracing, use of isolation centres, and use of quarantine centres was the least costly strategy, and no other strategies were cost-effective. In sensitivity analyses, a combination of health-care testing, contact tracing, use of isolation centres, mass symptom screening, and use of quarantine centres was generally cost-effective, with the exception of scenarios in which Re was 2·6 and when efficacies of isolation centres and quarantine centres for transmission reduction were reduced.InterpretationIn South Africa, strategies involving household contact tracing, isolation, mass symptom screening, and quarantining household contacts who test negative would substantially reduce COVID-19 mortality and would be cost-effective. The optimal combination of interventions depends on epidemic growth characteristics and practical implementation considerations.FundingUS National Institutes of Health, Royal Society, Wellcome Trust.

The efficacy of IL-6 inhibitor Tocilizumab in reducing severe COVID-19 mortality: a systematic review.

BackgroundIn the absence of highly effective antiviral therapies against SARS-CoV-2, it is crucial to counter the known pathophysiological causes of severe COVID-19. Evaluating the efficacy existing drugs may expedite the development of such therapeutics. Severe COVID-19 is largely the result of a dysregulated immune response characterized by lymphocytopenia, neutrophilia and critical hypercytokinemia, or “cytokine storm,” which is largely mediated by the cytokine interleukin-6 (IL-6). The IL-6 inhibitor tocilizumab (TCZ) could potentially suppress the effects of the pro-inflammatory cytokine and thereby lower mortality from the disease. This systematic analysis aimed to investigate and synthesize existing evidence for the efficacy of TCZ in reducing COVID-19 mortality.MethodologyPubMed and SearchWorks searches were performed to locate clinical studies with primary data on TCZ treatment for severe COVID-19. Sixteen case-control studies comparing mortality between TCZ and standard of care (SOC) were identified for quantitative synthesis. The systematic analysis was pre-approved through PROSPERO (CRD42020193479).ResultsCombined mortality for the TCZ-treated and SOC groups were 26.0% and 43.4% respectively. In all but one of the studies, the odds ratio of mortality from COVID-19 pointed towards lower fatality with TCZ vs the SOC. A combined random effects odds ratio calculation yielded an odds ratio of 0.453 (95% CI [0.376–0.547], p < 0.001). Additionally, 18 uncontrolled trials were identified for qualitative analysis producing a raw combined mortality rate of 16.0%.ConclusionsImportant caveats to this research include the lack of prospective randomized control trials and the absence of data from the large COVATA study from the published literature. However, results from this systematic analysis of published research provide positive evidence for the potential efficacy of TCZ to treat severe COVID-19, validating the ethical basis and merit of ongoing randomized controlled clinical trials.

Influence of Malaria Edemicity and TB Prevalence on COVID-19 Mortality

Background: Regarding SARS-CoV-2 it is well known that a substantial percentage of adult population cannot get infected if exposed to this novel coronavirus. Several studies give primary indication of the possible role of preexisting immunity whether cross immunity or not. Possible role of latent TB and malaria have been already suggested to create innate cross heterogeneous immunity. We look for influence of these factors on COVID -19 mortality in malarious countries.Material and Methods: 80 malarious countries are enrolled in this study. Hierarchical multiple regression type of analyses is used for data analyses. TB prevalence/ 100,000 population standardized to BCG coverage rates is taken as direct factor in the test. Malaria incidence /1000 population is considered as intermediate factor and the outcome is COVID-19 mortality/ 1 million (M) population.Results: The results show with robust statistical support that standardized TB prevalence is significantly associated with reduced COVID-19 mortality. Malaria have an additional effect in reducing COVID-19 mortality with highly significant association.Conclusions: Malaria and standardized TB prevalence are statistically significant factors predicting COVID-19 mortality in negative associations.Funding Statement: No specific source of funding was utilized for the current study.Declaration of Interests: There is no conflict of interest.Ethics Approval Statement: Ethical permission is not necessary as this study analyzed publically published data and patients were not involved.

COVID-19 in Italy: An Analysis of Death Registry Data.

ABSTRACTBackgroundThere are still many unknowns about COVID-19. We do not know its exact mortality rate nor the speed through which it spreads across communities. This lack of evidence complicates the design of appropriate response policies.MethodsWe source daily death registry data for 4100 municipalities in Italy’s north and match them to Census data. We augment the dataset with municipality-level data on a host of co-factors of COVID-19 mortality, which we exploit in a differences-in-differences regression model to analyze COVID-19-induced mortality.ResultsWe find that COVID-19 killed more than 0.15% of the local population during the first wave of the epidemic. We also show that official statistics vastly underreport this death toll, by about 60%. Next, we uncover the dramatic effects of the epidemic on nursing home residents in the outbreak epicenter: in municipalities with a high share of the elderly living in nursing homes, COVID-19 mortality was about twice as high as in those with no nursing home intown.ConclusionsA pro-active approach in managing the epidemic is key to reduce COVID-19 mortality. Authorities should ramp-up testing capacity and increase contact-tracing abilities. Adequate protective equipment should be provided to nursing home residents and staff.

Cytokine release syndrome: inhibition of pro-inflammatory cytokines as a solution for reducing COVID-19 mortality.

Coronavirus disease (COVID-19) reached pandemic proportions at the beginning of 2020 and continues to be a worldwide concern. End organ damage and acute respiratory distress syndrome are the leading causes of death in severely or critically ill patients. The elevated cytokine levels in severe patients in comparison with mildly affected patients suggest that cytokine release syndrome (CRS) occurs in the severe form of the disease. In this paper, the significant role of pro-inflammatory cytokines, including IL-1, IL-6, and TNF-alpha, and their mechanism of action in the CRS cascade is explained. Potential therapeutic approaches involving anti-IL-6 and anti-TNF-alpha antibodies to fight COVID-19 and reduce mortality rate in severe cases are also discussed.

Applications of predictive modelling early in the COVID-19 epidemic

Applications of predictive modelling early in the COVID-19 epidemic

Ruxolitinib Rapidly Reduces Acute Respiratory Distress Syndrome in COVID-19 Disease. Analysis of Data Collection From RESPIRE Protocol.

Background: The Coronavirus disease (COVID-19) pandemic is causing millions of infections and hundreds of thousands of deaths worldwide. Cumulative clinical and laboratory evidence suggest that a subset of patients with severe COVID-19 may develop a cytokine storm syndrome during the course of the disease, with severe respiratory impairment requiring ventilatory support. One field of research nowadays is to identify and treat viral-induced hyperinflammation with drugs used in other clinical conditions characterized by an hyperinflammation status. These drugs might help to reduce COVID19 mortality.Methods: Ruxolitinib, a JAK1 and JAK2 inhibitor, has been successfully used to treat severe immune-mediated diseases, such as graft vs. host disease and Hemophagocytic lymphohistiocytosis. We used ruxolitinib in 18 patients with clinically progressive COVID-19 related acute respiratory distress syndrome, with a primary endpoint to rapidly reduce the degree of respiratory impairment and as a secondary endpoint to rapidly restore the PaO2/FiO2 ratio, as an evaluation of clinical status, and monitoring of drug related Adverse Events. Parameters of inflammation responses and organ functions were assessed and monitored. The treatment plan was ruxolitinib 20 mg bid for the first 48 h and subsequent two-step de-escalation at 10 mg bid and 5 mg bid for a maximum of 14 days of treatment.Results: Our data collection shows a rapid clinical response with no evolution from non-invasive ventilation to mechanical ventilation in 16/18 patients and no response in two patients (overall response rate—ORR 89%). Already after 48 h of ruxolitinib treatment 16/18 patients showed evident clinical improvement, and after 7 days of treatment 11/18 patients showed fully recovered respiratory function (pO2 > 98% in spontaneous breathing), 4/18 patients had minimal oxygen requirement (2–4 L/m), 1/18 patient showed stable disease, and 2/18 patient showed progressive disease. After 14 days, 16/18 patients showed complete recovery of respiratory function (ORR 89%). Compliance to ruxolitinib planned treatment was 100% and no serious adverse event was recorded. In our case series of 18 critically ill patients with COVID-19 and ARDS, administration of ruxolitinib resulted in a clinical improvement that concurred to modify the standard course of disease. Ruxolitinib can be a therapeutic option for patients with respiratory insufficiency in COVID-19 related ARDS. RESPIRE Study (Ruxolitinib for the treatment of acute rESPIratory distREss syndrome, ClinicalTrials.gov Identifier: NCT04361903).

Extensive Testing May Reduce COVID-19 Mortality: A Lesson From Northern Italy.

The effects of different COVID-19 swab testing policies in Italy need investigation. We examined the relationship between the number of COVID-19 swab tests (per 10,000 population) performed from February 24 through March 27 and 7-day lagged COVID-19 mortality (per 10,000 population) in four regions of northern Italy. Lombardy, Piedmont, and initially, also Emilia-Romagna, which followed recommendations for limiting swab testing to symptomatic subjects requiring hospitalization, had a much steeper increase in mortality with increasing number of tests performed than Veneto, which applied a policy of broader testing. The relationship between tests performed and mortality declined in Emilia-Romagna in coincidence with a substantial increase in the number of tests performed on March 18. When the cumulative number of tests performed was regressed linearly toward lagged mortality in Lombardy and Veneto, the slope of the regression was 133 in Veneto and 10.4 tests per one death in Lombardy. These findings suggest that the strategy adopted in Veneto, similar to that in South Korea, was effective in containing COVID-19 epidemics and should be applied in other regions of Italy and countries in Europe.

Use of seasonal influenza and pneumococcal polysaccharide vaccines in older adults to reduce COVID-19 mortality

Use of seasonal influenza and pneumococcal polysaccharide vaccines in older adults to reduce COVID-19 mortality

The effects of physical distancing on population mobility during the COVID-19 pandemic in the UK

The effects of physical distancing on population mobility during the COVID-19 pandemic in the UK