Наукові праці. Кафедра інфекційних хвороб, дитячих інфекційних хвороб, фтизіатрії та пульмонології

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Agile transformation in a healthcare environment: the methodology of project-oriented management
(Associazione Italiana di Storia Urbana & UKRLOGOS Group LLC, 2024-04-26) Chumachenko, Igor; Bondarenko, Andriy; Dotsenko, Nataliia; Bondarenko, Olena
Chest X-ray alone is insufficient for predicting drug-resistant pulmonary tuberculosis
(Elsevier B.V., 2024-05) Pedersen, Ole Skouvig; Butova, Tetiana; Borovok, Natalia; Akymenko, Oleksandra; Sapelnik, Nadiya; Tantsura, Oleksandr; Knysh, Vitaliy; Fløe, Andreas; Butov, Dmytro
Clinical and immunological features of rotavirus infection in children infected with herpesviruses
(Group of Companies Med Expert, LLC, 2024) Sliepchenko, M.; Olkhovska, O.; Kolesnyk, Ya.; Gavrylov, A.
The basis for conducting the study was the absence in the scientific literature of works devoted to the study of clinical and immunological features of rotavirus infection (RVI) in children against the background of the latent form of herpesvirus infection (lHVI) caused by cytomegalovirus (CMV) and human herpesvirus type 6 (HHV-6). The aim - to identify clinical and immunological features of RVI in children with lHVI caused by CMV and HHV-6 that will contribute to the early diagnosis of lHVI in patients. Materials and methods. A total of 81 children aged 12-36 months with RVI were examined. The Group 1 included 33 children who were not found to be infected with any of the herpesviruses. The Group 2 included 17 children who were suffering from RVI against the background of lHVI caused by CMV. The Group 3 included 31 children suffering from RVI against the background of lHVI caused by HHV-6 type. Statistical processing of the results was carried out using the IBM® SPSS® 25.0 program for Microsoft® Windows®. The results. The presence of lHVI caused by CMV in the acute period (AP) of RVI leads to lower indicators of temperature reaction, lower frequency of vomiting, a decrease in the immunoregulatory index (IRI) against the background of an increase in the level of CD8+ T-lymphocytes. In addition to lower numbers of the temperature reaction, the level of IgA was increased in children with lHVI caused by HHV-6. During the convalescent period (CP), CMV is associated with an increase in the duration of fever and diarrhea, an increased content of CD8+ T-cell counts, and lower IRI, CD16+, CD22+ T-cells, and IgM scores. In patients with lHVI caused by HHV-6, fever, diarrhea, and catarrhal syndrome persisted longer against the background of reduced levels of IRI, CD22+ T cells, and IgM. Conclusions. lHVI is caused by CMV and HHV-6, it has different effects on clinical and immune indicators in children with RVI.
Clinical and laboratory characteristics of patients with coronavirus infection covid-19 and its comorbidity
(Клінічна та профілактична медицина, 2024) Andrusovych, Inna; Yurko, Kateryna
The coronavirus disease has reached an alarming epidemic scale with extraordinary morbidity and mortality rates for the entire world population. The majority of patients with COVID-19 note damage to the respiratory tract and state a more severe course of the disease with the development of systemic damage. A more severe course of COVID-19 is associated with the presence of comorbid diseases.
Clinical and laboratory charecteristics of patients with coronavirus infection COVID-19 and its comorbidity
(Державна наукова установа «Центр інноваційних технологій охорони здоров’я» Державного управління справами, 2024) Yurko, Kateryna; Andrusovych, Inna
Introduction. The coronavirus disease has reached an alarming epidemic scale with extraordinary morbidity and mortality rates for the entire world population. The majority of patients with COVID-19 note damage to the respiratory tract and state a more severe course of the disease with the development of systemic damage. A more severe course of COVID-19 is associated with the presence of comorbid diseases. Aim. To investigate and analyze clinical and laboratory manifestations and to determine the main comorbidities of patients with COVID-19 infection. Materials and methods. The research was carried out in accordance with bioethical norms and rules. 179 patients with COVID-19 (the main group) and 42 people of the control group were examined. Diagnosis and treatment of the COVID-19 coronavirus infection was carried out taking into account the relevant national recommendations. The average value and standard deviation were statistically determined. The probability of differences was performed using the Mann- Whitney U-test and the Wilcoxon W-test of signed ranks. The threshold value of the level of statistical significance of all calculated features was taken as 0.05 (p=0.05). Results. A high comorbidity with cardiovascular system pathology was found–40.2 %, type 2 diabetes–22.3 %, respiratory system diseases–20.7 %. Disorders of the functional state of the cardiovascular system were determined: pulse values–91.01±13.44, systolic (127.9±15.19) and diastolic (79.3±11.6) blood pressure. Changes in clinical blood analysis were noted: erythrocytes–4.38±0.65 x1012/l, hemoglobin–127.6±21.2 g/l, hematocrit–0.37±0.07, leukocytes–10.7±7, 32 x109/l, segmented (65.4±14.8 %) and rod-nuclear (9.03±9.99 %) neutrophils, platelets–226.1±90.6 x109/l, lymphocytes–20.24±12.43 %, monocytes–6.60±4.37 % and erythrocyte sedimentation rate (ESR)–25.4±14.9 mm/h. Significant (almost fourfold) increases in IL-6 levels (24.56±22.9 pg/ml) and blood glucose concentrations (7.40±3.42 mmol/l) were determined. Conclusions. A significant comorbidity of COVID-19 was determined and a significant prevalence of indicators of the functional state of the cardiovascular system and a decrease in the average levels of the quantitative composition of erythrocytes and indicators of hemoglobin and hematocrit were established. Significant leukocytosis, neutrophilia, lymphocytosis and monocytosis, significant excesses of ESR and IL-6 and blood serum glucose were determined, which confirmed the presence of a significant inflammatory reaction in response to infection with COVID-19.
Clinical predictors of blastocystosis treatment efficacy
(2024) Bodnia, Kateryna; Bodnia, Igor; Maslova, Valentyna; Ogienko, Viktoria; Pavliy, Viktoria
Improvement of methods and criteria for diagnostics of human blastocystosis and selection of drugs for etiotropic therapy remain urgent scientific tasks of the present day. Clinical manifestations of blastocystosis in humans are diverse, and in this regard, their influential role on the effectiveness of blastocystosis therapy cannot be excluded.
Clinical predictors of Вlastocystosis treatment efficacy
(Georgian Association of Business Press, 2024-04) Bodnia, I.; Bodnia, K.; Maslova, V.; Ogienko, V.; Pavliy, V.
Improvement of methods and criteria for diagnostics of human blastocystosis and selection of drugs for etiotropic therapy remain urgent scientific tasks of the present day. Clinical manifestations of blastocystosis in humans are diverse, and in this regard, their influential role on the effectiveness of blastocystosis therapy cannot be excluded. Materials and methods: To assess the predictor properties of clinical symptoms, we retrospectively analyzed them in 300 patients with blastocystosis in alternative groups: group A − with good therapeutic effect (n = 162) and group B − with satisfactory effect (n = 138). Group A included patients who had an overall regression rate of clinical symptoms ≥ 33% after 1 month from the start of treatment and ≤ 32% in group B. Results and discussions: Preliminary analysis showed that reliable differences between the groups were established for most clinical symptoms, which provided the basis for the development of a prognostic algorithm using a heterogeneous sequential Wald-Henkin procedure [19]. It was found that high prognostic informativity was shown by liver enlargement (J= 3,38), the presence of heaviness in the right subcostal area (J = 2,45), tachycardia (J = 1,76), decreased efficiency (J = 1,63), the degree of manifestation of clinical symptoms in general (J = 1,74), the nature of body temperature (J = 1,56), the presence of dizziness (J = 1,46) and duration of the disease (J = 1,07). Moderate predictive properties were characterized for the patient's age (J = 0,67) and the presence of vegeto-visceral dysfunction (J = 0,96), joint pain (J = 0,87), headache (J = 0,67), heart pain (J = 0,64), and muscle pain (J = 0,53). Low prognostic informativeness was established with regard to the presence of seizures (J = 0,42), lymphoadenopathy (J = 0,33) and spleen enlargement (J = 0,30). No predictor value was found for symptoms such as abdominal pain syndrome (J = 0,09), memory impairment (J = 0,008), skin manifestations (J = 0,04), jaundice (J = 0,02), and patient gender (J = 0,01). The testing of the predictive algorithm on the training group (n=300) established its high efficiency, as the erroneous predictions amounted to 3% and did not exceed the specified (5%; p < 0.05) level of reliability. Correct predictions amounted to 77% and uncertain predictions amounted to 20% of cases. Conclusions: Using the heterogeneous sequential Wald Genkin procedure, an algorithm was created to predict the effectiveness of therapy for patients with blastocystosis, which determined the values of the prognostic coefficients of each gradation of indicators and their general prognostic information content. The highest prognostic informativeness was found for clinical symptoms such as liver enlargement (J = 3,38), right subcostal heaviness (J = 2,45), tachycardia (J = 1,76), degree of manifestation of clinical symptoms (J = 1,74) and body temperature (J = 1,56). Testing the algorithm at 95% reliability level on the training group (n=300) revealed its high efficiency, as the erroneous predictions amounted to 3% and did not exceed the specified (5%; p < 0,05) reliability level. Correct predictions amounted to 77% and uncertain predictions amounted to 20% of cases.
Concomitant pathology of patients with COVID-19 infection
(Perfect Publishing, 2024) Andrusovych, Inna
Many studies have shown that a more severe course of COVID-19 is associated with the presence of comorbidities. Thus, the risk of hospitalization in patients with bronchial asthma is 1.5 times higher, and in patients with chronic kidney disease and diabetes mellitus - 4 and 3 times higher, respectively. Among the risk factors that significantly affect the deterioration of COVID-19, the researchers consider the following: older age, male gender, and comorbidities. For example, in the presence of concomitant hypertension, the risk of mortality increases by at least 1.7-3.5 times, and in the presence of grade I-II obesity - by 3 times. According to Pranata et al, cardiovascular and cerebrovascular pathology was the leading comorbidity in patients with COVID-19. Another meta-analysis by Pranata et al. showed the impact of concomitant hypertension on the course of COVID-19: hypertension was significantly associated with total negative outcomes of COVID-19: hazard ratio (HR) = 2.11 [95.0% confidence intervals (CI) 1.85-2.40], p < 0.001.
Conditions for the expansion of СOVID-19 in the regions of the Northern part of Ukraine Conditions for the expansion of СOVID-19 in Ukraine
(2023-09-07) Korzh, Alexei; Georgiyants, Marine; Podavalenko, Alla; Nessonova, Tetyana; Maslova, Valentyna; Bereznyakov, Vladislav; Asoyan, Irina
Background: The intensity of the COVID-19 epidemic process in the administrative territories of Ukraine differs. Risk factors for the spread of this infection have not been sufficiently studied, which prevents the development of adequate preventive and anti-epidemic measures at the local level. Objectives: Conduct an epidemiological analysis of the incidence of COVID-19 in the regions of the Northern part of Ukraine and identify the leading risk factors for spread. Material and Methods: The incidence of COVID-19 was analyzed for 73 weeks and 28 predictors. Fourier’s spectral analysis, Feature Selection and Variable Filtering method of the Data mining module, Irwin’s method, integral visual coefficient was used. Results. There were two rises in the incidence of COVID-19, the cyclicity was 18 - 24 weeks. The conditions for the spread of COVID-19 cases in the regions of the Northern part have been established, namely: the number of people and the elderly in the family, demographic and migration processes. Violation of regime-restrictive measures leads to abnormal rises in morbidity. Conclusions. The epidemic situation in the Northern part remains volatile, as there are conditions for the spread of COVID-19 that cannot be eliminated, as well as some, that need to be developed (tourism, demographic processes, financing, etc.). Therefore, compliance with restrictive measures and vaccination of the population of the region remain the main preventive measures.
Correction: The role of centre and country factors on process and outcome indicators in critically ill patients with hospital-acquired bloodstream infections
(Springer Verlag, 2024) Buetti, Niccolò; Tabah, Alexis; Setti, Nour; Ruckly, Stéphane; Barbier, François; Akova, Murat; Aslan, Abdullah Tarik; Leone, Marc; Bassetti, Matteo; Morris, Andrew Conway; Arvaniti, Kostoula; Paiva, José‑Artur; Ferrer, Ricard; Qiu, Haibo; Montrucchio, Giorgia; Cortegiani, Andrea; Kayaaslan, Bircan; De Bus, Liesbet; De Waele, Jan J.; Timsit, Jean‑François; Sokhan, Anton
Correlations between clinical, laboratory and instrumental characteristics of patients with COVID-19 infection
(2024) Andrusovych, Inna
COVID-19 is a leading disease in terms of prevalence (more than 100 million cases) and mortality (more than 10.0%). Most often, COVID-19 is accompanied by hemostatic disorders (manifestations of COVID-19-associated coagulopathy) and blood coagulation.
Damage to the respiratory system of patients SARS-CoV-2 associated with COVID-19 infection
(Міжнародний центр наукових досліджень, 2024) Andrusovych, Inna
Corona virus disease (COVID-19) is associated with a number of clinical conditions mainly of the respiratory system, including both mild lesions of the upper respiratory tract and severe viral pneumonia. Manifestations of interstitial pneumonia are determined among at least 14.0% of infected patients, which has a significant chance of developing into a severe acute respiratory syndrome with subsequent need for intensive therapy. In addition, damage to peripheral pulmonary vessels and vessels involved in gas exchange significantly affects the balance of ventilation and perfusion, which causes the development of hypoxemia and requires a change in the patient's position during oxygenation.
Determination of the degree of inflammatory response in patients with COVID-19 infection by interleukin-6 levels
(MDPC Publishing, 2024) Andrusovych, Inna
An inflammatory reaction and subsequent severe organ damage play an undeniable role in the pathogenesis of disorders in patients with COVID-19 infection. Clinically, this is manifested by severe acute respiratory syndrome, which is characterized by diffuse damage to the alveoli at the level of hyaline membranes. The immune response in this case can manifest itself in the form of a cytokine storm: in the vast majority of patients, there is a significant increase in the levels of interleukin (IL)-6, IL-17A and tumor necrosis factor-α.
Drug-Resistant Tuberculosis, Georgia, Kazakhstan, Kyrgyzstan, Moldova, and Ukraine, 2017–2022
(Centers for Disease Control and Prevention (CDC), 2024-04-04) Dahl, Victor Naestholt; Butova, Tetiana; Rosenthal, Alex; Grinev, Alina; Gabrielian, Andrei; Vashakidze, Sergo; Shubladze, Natalia; Toxanbayeva, Bekzat; Chingissova, Lyailya; Crudu, Valeriu; Chesov, Dumitru; Kalmambetova, Gulmira; Saparova, Gulbarchyn; Wejse, Christian Morberg; Butov, Dmytro
In 2021, the World Health Organization recommended new extensively drug-resistant (XDR) and pre-XDR tuberculosis (TB) definitions. In a recent cohort of TB patients in Eastern Europe, we show that XDR TB as currently defined is associated with exceptionally poor treatment outcomes, considerably worse than for the former definition (31% vs. 54% treatment success).
Dynamics of clinical and laboratory indicators of patients with COVID-19 against the backdrop of treatment
(2024) Andrusovych, Inna
The article presents the results of the analysis of the dynamics of the main indicators of the blood coagulation system and cytokines (IL-6, D-dimers, C-reactive protein and procalcitonin) on the background of thromboprophylaxis in patients with COVID-19. The aim of our study was to determine the dynamics of the main indicators of the blood coagulation system and cytokines in the setting of thromboprophylaxis. The study was conducted at the Department of Infectious and Pediatric Infectious Diseases, Parasitology, Phthisiology and Pulmonology of the Kharkiv National Medical University and at the Municipal Non-Profit Enterprise "Kharkiv Regional Infectious Diseases Hospital" of the Kharkiv Regional Council, in 2020–2024 with compliance of the existing recommendations of bioethical norms and rules. All patients singed informed consent. We examined 179 patients aged 20–88 years (average age of [58.75±13.82] years) with COVID-19. The diagnosis of COVID-19 was confirmed by enzyme-linked im-munosorbent assay and polymerase chain reaction. Medical and statistical calculations were performed using the SPSS 25.0 software package. The mean value and standard square devia-tion were calculated. The probability of differences was determined using the Mann-Whitney U-test with a threshold value of statistical significance of p=0.05. According to the results of the study, a significant (p<0.001) dynamic of restoration of D-Dimers’ levels was noted against the background of the applied therapy (on days 9–10, a decrease of 166.3 Fibrinogen Equivalent Unit (FEU), ng/ml, and on days 12–15 – of 376.7 FEU, ng/ml) and procalcitonin (on days 6–7 the content was by 0.04 ng/ml, p=0.006; on days 10–11 – 0.01 ng/ml, p<0.001; on days 12–15 – also 0.01 ng/ml, p=0.027).
Effect of adequacy of empirical antibiotic therapy for hospital-acquired bloodstream infections on intensive care unit patient prognosis: a causal inference approach using data from the Eurobact2 study
(Elsevier B.V., 2024) Loiodice, Ambre; Bailly, Sebastien; Ruckly, Stephane; Buetti, Niccolo; Barbier, François; Staiquly, Quentin; Tabah, Alexis; Timsit, Jean-François; Sokhan, A.; Burma, Ya.
Objectives: Hospital-acquired bloodstream infections (HA-BSI) in the intensive care unit (ICU) are common life-threatening events. We aimed to investigate the association between early adequate antibiotic therapy and 28-day mortality in ICU patients who survived at least 1 day after the onset of HA-BSI. Methods: We used individual data from a prospective, observational, multicentre, and intercontinental cohort study (Eurobact2). We included patients who were followed for - 1 day and for whom time-to appropriate treatment was available. We used an adjusted frailty Cox proportional-hazard model to assess the effect of time-to-treatment-adequacy on 28-day mortality. Infection- and patient-related variables identified as confounders by the Directed Acyclic Graph were used for adjustment. Adequate therapy within 24 hours was used for the primary analysis. Secondary analyses were performed for adequate therapy within 48 and 72 hours and for identified patient subgroups. Results: Among the 2418 patients included in 330 centres worldwide, 28-day mortality was 32.8% (n ¼ 402/1226) in patients who were adequately treated within 24 hours after HA-BSI onset and 40% (n ¼ 477/1192) in inadequately treated patients (p < 0.01). Adequacy within 24 hours was more common in young, immunosuppressed patients, and with HA-BSI due to Gram-negative pathogens. Antimicrobial adequacy was significantly associated with 28-day survival (adjusted Hazard Ratio (aHR), 0.83; 95% CI, 0.72e0.96; p 0.01). The estimated population attributable fraction of 28-day mortality of inadequate therapy was 9.15% (95% CI, 1.9e16.2%). Discussion: In patients with HA-BSI admitted to the ICU, the population attributable fraction of 28-day mortality of inadequate therapy within 24 hours was 9.15%. This estimate should be used when
Epidemiological characteristics and impact of sepsis on survival after osteoporotic pelvic fracture in Austria
(Nature Publishing Group, 2024) Sokhan, Anton; Haschka, Judith; Reichardt, Berthold; Zwerina, Jochen; Kocijan, Roland; Behanova, Martina
We performed a retrospective nationwide register-based cohort study which included all in-hospital patients aged≥ 50 with pelvic fracture (PF) between 2010 and 2018 inAustria. We identified patients who were hospitalized with sepsis within 180 days following a PF event.Aetiology of sepsis was divided by unspecified, gram positive, gram negative and other. Among 59,081 patients hospitalized with PF between 2010 and 2018 we identified 619 (1.05%) patients who were hospitalized with sepsis within 180 days following PF.The cumulative incidence risk of sepsis within 180 days after PF was significantly higher in males (1.4%, 95% CI 1.2%-1.5%) as compared to females (0.92%, 95% CI 0.83%-1.0%), p< 0.001. In the cohort of patients with sepsis, the one-year mortality was 50.4%. Mortality risk was greater for patients who developed sepsis, independently of age, sex and comorbidity status (HR 3.12, 95% CI 2.83–3.44, p< 0.001) as compared to patients without sepsis.With a very high one year mortality risk among those who develop sepsis, our study emphasizes the substantial impact of sepsis on long term survival in fractured patients.These findings underscore the critical need for sepsis prevention and early detection and management to mitigate its detrimental effects on patient outcomes.
Features of blood coagulation indicators in surgical patients with a confirmed diagnosis of COVID- 19
(European Surgery, 2024-05-16) Andrusovych, Inna; Korolevska, Anna; Komarchuk, I.
Timely and accurate assessment of the state of the hemostasis system in patients with the different severity of the course of COVID-19 is the key to the correct appointment appropriate volume of anticoagulant therapy in order to prevent complications disease. Thromboelastography is a non-invasive method evaluation of the hemostasis system – not only provides data on the state of the links thrombus formation, but also the processes of fibrinolysis, a comprehensive assessment of which can contribute to the personalized selection of anticoagulant therapy. The aim of the research. Determine the relationship between the difficulty of the course and the tension of the system hemostasis in patients with different course of the COVID-19 coronavirus disease.
Features of the course of toxoplasmic encephalitis in hiv-infected patients
(2024) Veliieva, Tunzala; Bodnia, Kateryna; Makarenko, Valentyna; Pavliy, V.; Krokhmal, I.
This article presents the results of a retrospective analysis of clinical characteristics and examination outcomes in 23 patients with toxoplasmic encephalitis (TE) among HIV-infected individuals. Among the examined individuals, 11 (47.8%) were men and 12 (52.2%) were women. The patients' ages ranged from 31 to 55 years, with an average age of 37.5 ± 0.38 years. The average CD4+ lymphocyte count was 102.5 ± 21.2 cells/μl, and the HIV RNA load in plasma was 292,773.8 ± 113,180 copies/mL. All patients were confirmed to have stage 4 HIV infection (according to the CDC classification, 1993). Toxoplasmosis infection was confirmed by blood serology (presence of anti-Toxoplasma IgG antibodies via ELISA), and toxoplasmic encephalitis was diagnosed through MRI with characteristic focal brain changes. According to our analysis toxoplasmic encephalitis in HIV-infected patients develops gradually, with cognitive and psychiatric disorders as primary manifestations, followed by focal neurological impairments (hemiparesis, seizures, speech problems). All HIV patients with detected Toxoplasma antibodies at the onset of the disease can be considered at risk for developing toxoplasmic encephalitis. TE in the brain manifests when CD4+ cell levels drop below 200 cells/μL and is characterized by polysymptomatic presentation, with an average of 5.67±0.37 symptoms in our patients. The data from our correlation analysis between altered blood parameters and the presence of symptoms in TE among HIV-infected patients showed that the greater the severity, activity, and duration of toxoplasmic infection (indicated by eosinophilia), the more diverse the symptoms. This, in turn, leads to an increase in ESR, the development of leukocytopenia, and hypochromic anemia.
Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021
(Lancet Publishing Group, 2024-04-03) Naghavi, M.; Ong, K.L.; Aali, A.; Sokhan, A.; Wool, E.E.; Murray, C.J.L.
Background Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. Methods The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model—a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates- with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality—which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. Findings The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2–100·0) per 100000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1–290·7] per 100000 population) and Latin America and the Caribbean (195·4 deaths [182·1–211·4] per 100000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4–48·8] per 100000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3–37·2] per 100000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7–9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. Interpretation Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere.