The Effect of Coronavirus Outbreak on the Utilization of Coronary Revascularization Procedures: An Interrupted Time Series Analysis.

The coronavirus disease 19 (COVID-19) pandemic represented a great challenge for health systems, which had to quickly readapt and dedicate most of their resources to managing this crisis. The postponement of programmed interventions such as coronary revascularization procedures represented a critical issue in the first wave of the COVID-19 pandemic, especially in the hardest-hit countries such as Spain. However, the precise consequences of the delay of coronary revascularizations are not clearly determined. In the present work, interrupted time series (ITS) analysis was used to evaluate the utilization rates and assessment of the risk profiles of patients receiving two main coronary revascularization procedures (percutaneous coronary intervention-PCI and coronary artery bypass graft-CABG) and compared them in the periods before and after March 2020 using the Spanish National Hospital Discharge Database (SNHDD). Our results show that the abrupt reorganization of hospital care that represented the first wave of COVID-19 in March 2020 in Spain led to a reduction in cases, which was accompanied by an increase in the risk profile of CABG patients, but not PCI. On the other hand, the risk profile of both coronary revascularization procedures began before the pandemic, showing a significant temporal trend toward an increase in the risk profile. Future works should be directed to study and validate our results, evaluating other databases, regions, or countries.

Association of CYP24A1 Gene rs6127099 (A > T) Polymorphism with Lower Risk to COVID-19 Infection in Kazakhstan.

In December 2019, SARS-CoV-2 was identified in Wuhan, China. Infection by SARS-CoV-2 causes coronavirus disease 2019 (COVID-19), which is characterized by fever, cough, dyspnea, anosmia, and myalgia in many cases. There are discussions about the association of vitamin D levels with COVID-19 severity. However, views are conflicting. The aim of the study was to examine associations of vitamin D metabolism pathway gene polymorphisms with symptomless COVID-19 susceptibility in Kazakhstan. The case-control study examined the association between asymptomatic COVID-19 and vitamin D metabolism pathway gene polymorphisms in 185 participants, who previously reported not having COVID-19, were PCR negative at the moment of data collection, and were not vaccinated. A dominant mutation in rs6127099 (CYP24A1) was found to be protective of asymptomatic COVID-19. Additionally, the G allele of rs731236 TaqI (VDR), dominant mutation in rs10877012 (CYP27B1), recessive rs1544410 BsmI (VDR), and rs7041 (GC) are worth consideration since they were statistically significant in bivariate analysis, although their independent effect was not found in the adjusted multivariate logistic regression model.

Analysis of differential gene expression of pro-inflammatory cytokines in the nasopharyngeal milieu of mild & severe COVID-19 cases.

INTRODUCTION: A subset of individuals with COVID-19 can suffer from a severe form of the disease requiring breathing support for respiratory failure and even death due to disease complications. COVID-19 disease severity can be attributed to numerous factors, where several studies have associated changes in the expression of serum pro-inflammatory cytokines with disease severity. However, very few studies have associated the changes in expression of pro-inflammatory changes in the nasopharyngeal milieu with disease severity. Therefore, in the current study, we performed differential gene expression analysis of various pro-inflammatory cytokines in the nasopharyngeal milieu of mild & severe COVID-19 cases. MATERIAL AND METHOD: For this retrospective, cross-sectional study, a total of 118 nasopharyngeal swab samples, previously collected from mild and severe (based on the WHO criteria) COVID-19 patients were used. A real-time qPCR was performed to determine the viral loads and also evaluate the mRNA expression of eight cytokines (IL-1, IL-2, IL-4, IL-6, IL-10, IFN-γ, TGF-ß1, and TNF-α). Subsequently, an unpaired T-test was applied to compare the statistical difference in mean expression of viral loads and each cytokine between the mild and severe groups, while the Pearson correlation test was applied to establish a correlation between disease severity, viral load, and cytokines expression. Similarly, a multivariable logistic regression analysis was performed to assess the relationship between different variables from the data and disease severity. RESULTS: Out of 118 samples, 71 were mild, while 47 were severe. The mean viral load between the mild and severe groups was comparable (mild group: 27.07± 5.22; severe group: 26.37 ±7.89). The mRNA expression of cytokines IL-2, IL-6, IFN- γ, and TNF-α was significantly different in the two groups (p<0.05), where the Log2 normalized expression of IL-2, IL-6, IFN- γ, and TNF-α was found to be 2.2-, 16-, 2.3-, and 1.73-fold less in the severe group as compared to the mild group. Furthermore, we also observed a significant positive correlation between all the cytokines in the severe group. The multivariate analysis showed a significant relationship between age, IL-6, and disease severity. CONCLUSION: This decreased expression of certain cytokines (IL-2, IL-6, TNF-α, and IFN-γ) in the nasopharyngeal milieu may be considered early biomarkers for disease severity in COVID-19 patients.

Recapping the Features of SARS-CoV-2 and Its Main Variants: Status and Future Paths.

Over the two years that we have been experiencing the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic, our challenges have been the race to develop vaccines and the difficulties in fighting against new variants due to the rapid ability of the virus to evolve. In this sense, different organizations have identified and classified the different variants that have been emerging, distinguishing between variants of concern (VOC), variants of interest (VOI), or variants under monitoring (VUM). The following review aims to describe the latest updates focusing on VOC and already de-escalated variants, as well as to describe the impact these have had on the global situation. Understanding the intrinsic properties of SARS-CoV-2 and its interaction with the immune system and vaccination is essential to make out the underlying mechanisms that have led to the appearance of these variants, helping to determine the next steps for better public management of this pandemic.

Overview of coronavirus pandemic

During the last months of 2019, numerous cases of respiratory illness such as pneumonia and acute respiratory distress syndrome were described in Wuhan, the capital city of Hubei province in China. At the same time, several research groups identified and reported the etiological agent, that included within the Coronaviridae family and the order Nidovirales, named SARS-CoV-2. Subsequently, the pathological and clinical status caused by the pathogen is commonly known as Coronavirus disease 2019 (COVID-19). In a short period, the outbreak of emerging spread across the world. Therefore the World Health Organization declared a public health emergency of international concern on January 30, 2020, and as a pandemic on March 11, 2020. Many different public health and epidemiological studies have been published since the COVID-19 outbreak, but fatality rates (those that relate the number of cases to mortality) are difficult to assess with certainty. Mean and median case-fatality rates worldwide are near to 3% and 2%, respectively. The median infection fatality calculated from serologic prevalence varies from 0.00% to 1.63% but is mostly estimated between 0.27% and 0.9%. These indexes are influenced by geographic location, socioeconomic status, sex, age, and health conditions, among others.

Towards an Accurate Estimation of COVID-19 Cases in Kazakhstan: Back-Casting and Capture-Recapture Approaches.

Background and Objectives: Coronavirus disease 19 (COVID-19) has emerged as the most devastating syndemic of the 21st century, with worrisome and sustained consequences for the entire society. Despite the relative success of vaccination programs, the global threat of the novel coronavirus SARS-CoV-2 is still present and further efforts are needed for its containment and control. Essential for its control and containment is getting closer to understanding the actual extent of SARS-CoV-2 infections. Material and Methods: We present a model based on the mortality data of Kazakhstan for the estimation of the underlying epidemic dynamic-with both the lag time from infection to death and the infection fatality rate. For the estimation of the actual number of infected individuals in Kazakhstan, we used both back-casting and capture-recapture methods. Results: Our results suggest that despite the increased testing capabilities in Kazakhstan, official case reporting undercounts the number of infections by at least 60%. Even though our count of deaths may be either over or underestimated, our methodology could be a more accurate approach for the following: the estimation of the actual magnitude of the pandemic; aiding the identification of different epidemiological values; and reducing data bias. Conclusions: For optimal epidemiological surveillance and control efforts, our study may lead to an increased awareness of the effect of COVID-19 in this region and globally, and aid in the implementation of more effective screening and diagnostic measures.

Seropositivity of SARS-CoV-2 in the Population of Kazakhstan: A Nationwide Laboratory-Based Surveillance.

The data on seroprevalence of anti-SARS-CoV-2 antibodies in Kazakhstani population are non-existent, but are needed for planning of public health interventions targeted to COVID-19 containment. The aim of the study was to estimate the seropositivity of SARS-CoV-2 infection in the Kazakhstani population from 2020 to 2021. We relied on the data obtained from the results from "IN VITRO" laboratories of enzyme-linked immunosorbent assays for class G immunoglobulins (IgG) and class M (IgM) to SARS-CoV-2. The association of COVID-19 seropositivity was assessed in relation to age, gender, and region of residence. Additionally, we related the monitoring of longitudinal seropositivity with COVID-19 statistics obtained from Our World in Data. The total numbers of tests were 68,732 for SARS-CoV-2 IgM and 85,346 for IgG, of which 22% and 63% were positive, respectively. The highest rates of positive anti-SARS-CoV-2 IgM results were seen during July/August 2020. The rate of IgM seropositivity was the lowest on 25 October 2020 (2%). The lowest daily rate of anti-SARS-CoV-2 IgG was 17% (13 December 2020), while the peak of IgG seropositivity was seen on 6 June 2021 (84%). A longitudinal serological study should be envisaged to facilitate understanding of the dynamics of the epidemiological situation and to forecast future scenarios.

Mortality predictors of hospitalized patients with COVID-19: Retrospective cohort study from Nur-Sultan, Kazakhstan.

BACKGROUND: First reported case of Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) in Kazakhstan was identified in March 2020. Many specialized tertiary hospitals in Kazakhstan including National Research Cardiac Surgery Center (NRCSC) were re-organized to accept coronavirus disease 2019 (COVID-19) infected patients during summer months of 2020. Although many studies from worldwide reported their experience in treating patients with COVID-19, there are limited data available from the Central Asia countries. The aim of this study is to identify predictors of mortality associated with COVID-19 in NRCSC tertiary hospital in Nur-Sultan, Kazakhstan. METHODS: This is a retrospective cohort study of patients admitted to the NRCSC between June 1st-August 31st 2020 with COVID-19. Demographic, clinical and laboratory data were collected from electronic records. In-hospital mortality was assessed as an outcome. Patients were followed-up until in-hospital death or discharge from the hospital. Descriptive statistics and factors associated with mortality were assessed using univariate and multivariate logistic regression models. RESULTS: Two hundred thirty-nine admissions were recorded during the follow-up period. Mean age was 57 years and 61% were males. Median duration of stay at the hospital was 8 days and 34 (14%) patients died during the hospitalization. Non-survivors were more likely to be admitted later from the disease onset, with higher fever, lower oxygen saturation and increased respiratory rate compared to survivors. Leukocytosis, lymphopenia, anemia, elevated liver and kidney function tests, hypoproteinemia, elevated inflammatory markers (C-reactive protein (CRP), ferritin, and lactate dehydrogenase (LDH)) and coagulation tests (fibrinogen, D-dimer, international normalized ratio (INR), and activated partial thromboplastin time (aPTT)) at admission were associated with mortality. Age (OR 1.2, CI:1.01-1.43), respiratory rate (OR 1.38, CI: 1.07-1.77), and CRP (OR 1.39, CI: 1.04-1.87) were determined to be independent predictors of mortality. CONCLUSION: This study describes 14% mortality rate from COVID-19 in the tertiary hospital. Many abnormal clinical and laboratory variables at admission were associated with poor outcome. Age, respiratory rate and CRP were found to be independent predictors of mortality. Our finding would help healthcare providers to predict the risk factors associated with high risk of mortality. Further investigations involving large cohorts should be provided to support our findings.

SARS-CoV-2 PCR-positive and PCR-negative cases of pneumonia admitted to the hospital during the peak of COVID-19 pandemic: analysis of in-hospital and post-hospital mortality.

BACKGROUND: During the spike of COVID-19 pandemic in Kazakhstan (June-2020), multiple SARS-CoV-2 PCR-test negative pneumonia cases with higher mortality were reported by media. We aimed to study the epidemiologic characteristics of hospitalized PCR-test positive and negative patients with analysis of in-hospital and post-hospital mortality. We also compare the respiratory disease characteristics between 2019 and 2020. METHODS: The study population consist of 17,691 (March-July-2020) and 4600 (March-July-2019) hospitalized patients with respiratory diseases (including COVID-19). The incidence rate, case-fatality rate and survival analysis for overall mortality (in-hospital and post-hospital) were assessed. RESULTS: The incidence and mortality rates for respiratory diseases were 4-fold and 11-fold higher in 2020 compared to 2019 (877.5 vs 228.2 and 11.2 vs 1.2 per 100,000 respectively). The PCR-positive cases (compared to PCR-negative) had 2-fold higher risk of overall mortality. We observed 24% higher risk of death in males compared to females and in older patients compared to younger ones. Patients residing in rural areas had 66% higher risk of death compared to city residents and being treated in a provisional hospital was associated with 1.9-fold increased mortality compared to those who were treated in infectious disease hospitals. CONCLUSION: This is the first study from the Central Asia and Eurasia regions, evaluating the mortality of SARS-CoV-2 PCR-positive and PCR-negative respiratory system diseases during the peak of COVID-19 pandemic. We describe a higher mortality rate for PCR-test positive cases compared to PCR-test negative cases, for males compared to females, for elder patients compared to younger ones and for patients living in rural areas compared to city residents.

New Approach to Managing the COVID-19 Pandemic in a Complex Tertiary Care Medical Center in Madrid, Spain.

The coronavirus disease 2019 (COVID-19) pandemic is putting health-care systems under unprecedented stress to accommodate unexpected numbers of patients forcing a quick re-organization. This article describes the staff management experience of a third level referral hospital in the city of Madrid, Spain, one of the cities and hospitals with the largest number of COVID-19 cases.A newly created COVID-19-specific clinical management unit (CMU) coordinated all clinical departments and conducted real-time assessments of the availability and needs of medical staff, alongside the hospital's general management board. The CMU was able to (i) redeploy up to 285 physicians every week to bolster medical care in COVID-19 wards and forecast medical staff requirements for the upcoming week so all departments could organize their work while coping with COVID-19 needs, (ii) overview all clinical activities conducted in a medicalized hotel, and (iii) recruit a team of roughly 90 volunteer medical students to accelerate data collection and evidence generation.The main advantage of a CMU composed by a member of every job category-its ability to generate rapid, locally adapted responses to unexpected challenges-made it perfect for the unprecedented increase in health-care need generated by the COVID-19 pandemic.

Clinical characteristics and risk factors for disease severity and mortality of COVID-19 patients with diabetes mellitus in Kazakhstan: A nationwide study.

BACKGROUND: Diabetes mellitus (DM) is associated with higher risk of developing infectious disease and COVID-19 is not the exception. There is a need to generate more data on clinical characteristics and risks of COVID19 patients presenting with DM. In this retrospective study we aimed to report on demographic features, clinical data, and outcomes of COVID-19 patients with DM in comparison with age- and sex-matched patients without DM. METHODS: This was a retrospective study that relied on the nationwide data on all COVID-19 patients who were diagnosed from 14 March to 18 April, 2020. Overall, there were 31 cases with DM for which we randomly matched 4 patients without DM by age and sex. RESULTS: COVID-19 patients with associated DM had less beneficial outcomes and more severe disease course both at hospital admission and final diagnosis, as compared with the age and sex-matched non-DM patients. Diabetics were more predisposed to impaired breathing (29.0 % versus 4.9 % in controls), nausea/vomiting (6.5 % versus 0 % in controls) and weakness/lethargy (45.2 % versus 26.0 % in controls). Finally, 48.4 % of diabetics showed the signs of pneumonia on CT scans versus 20.3 % of non-diabetics (p = 0.001), and 32.3 % of DM patients were admitted to intensive care units as compared with just 5.7 % of non-DM patients (p<0.001). CONCLUSION: There is a need to envisage early status monitoring and supportive care in this vulnerable category of patients to enable better prognosis.

Population Health and Health Services: Old Challenges and New Realities in the COVID-19 Era.

(1) Background: Health services that were already under pressure before the COVID-19 pandemic to maximize its impact on population health, have not only the imperative to remain resilient and sustainable and be prepared for future waves of the virus, but to take advantage of the learnings from the pandemic to re-configure and support the greatest possible improvements. (2) Methods: A review of articles published by the Special Issue on Population Health and Health Services to identify main drivers for improving the contribution of health services on population health is conducted. (3) Health services have to focus not just on providing the best care to health problems but to improve its focus on health promotion and disease prevention. (4) Conclusions: Implementing innovative but complex solutions to address the problems can hardly be achieved without a multilevel and multisectoral deliberative debate. The CHRODIS PLUS policy dialog method can help standardize policy-making procedures and improve network governance, offering a proven method to strengthen the impact of health services on population health, which in the post-COVID era is more necessary than ever.