SARS-CoV-2 Variants Impact on Key Signaling Pathways Metamorphoses into Severity

The Severe Acute Respiratory Syndrome Coronavirus-2 causes a dreadful Coronavirus Disease namely COVID-19. Respiratory system is the primary target of the virus. It also impairs other major organs such as kidney, heart, liver, brain etc. Multiple novel variants of SARS-CoV-2 have appeared since the SARS-CoV-2 pandemic occurred which are linked to increased virulence, disease transmission and severity. The virus attacks the host signalling pathways to maintain a favourable environment for its spread. The present study focuses on the comprehensive analysis of major signaling pathways affected due to several variants of SARS-CoV-2 leading to abnormalities in cell growth and differentiation. The information was curated from the weblinks of several platforms like WHO, CDC, PANGO, Nextstrain clade and GISAID clade. The data on signaling pathways and comorbidities was generated by screening of different research and review articles. SARS-CoV-2 consolidates the cytoskeleton of the host for effective cell invasion and modulates the transcription processes to enable the translation of viral protein(s). These events lead to significant increase and prolonged hyper inflammation. Further, a decreased interferon (IFN) response along with increased interleukin production leading to cytokine storm is observed. Deregulation of interleukin pathways, TNF-alpha signalling through JAK/STAT-3 signalling, MAPK1, mTOR, PI3K are few other signalling pathways that are affected on SARS-CoV-2 infection. This review represents a comprehensive analysis of the vigorous life cycle of SARS CoV-2, its different variants affecting host signalling pathways which eventually cause dysfunctioning of several organs and development of comorbidities.

Effects of Porcine deltacoronavirus on the transduction pathway of the innate immune signal

Porcine deltacoronavirus (PDCOV) is a new type of pig intestinal coronavirus, which targets pig small intestinal epithelial cells to cause severe enteritis. After infecting the host, PDCoV finishes its proliferation in the host cell by antagonism or escape the innate immune signaling transduction pathway. In order to understand the action mechanism of PDCOV 0n the congenital immune signal transduction pathways, this paper reviews the effects of PDCOV on RLR, Jak-STAT, MAPK and mitochondrial signaling pathway to clarify the relationship between PDCOV and host innate immune signaling transduction pathways in order to provide help for the prevention and treatment of PDCOV infection.

IDDF2023-ABS-0045 Spatiotemporal immune landscape of Mas-driven pro-inflammatory microenvironment with hyperactivated glycolysis in acetaminophen-induced liver injury

IDDF2023-ABS-0045 Figure 1 IDDF2023-ABS-0045 Figure 2 IDDF2023-ABS-0045 Figure 3 IDDF2023-ABS-0045 Figure 4

Immune response induced by novel coronavirus infection.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has been prominent around the world since it was first discovered, affecting more than 100 million people. Although the symptoms of most infected patients are not serious, there is still a considerable proportion of patients who need hospitalization and even develop fatal symptoms such as cytokine storms, acute respiratory distress syndrome and so on. Cytokine storm is usually described as a collection of clinical manifestations caused by overactivation of the immune system, which plays an important role in tissue injury and multiorgan failure. The immune system of healthy individuals is composed of two interrelated parts, the innate immune system and the adaptive immune system. Innate immunity is the body's first line of defense against viruses; it can quickly perceive viruses through pattern recognition receptors and activate related inflammatory pathways to clear pathogens. The adaptive immune system is activated by specific antigens and is mainly composed of CD4+ T cells, CD8+ T cells and B cells, which play different roles in viral infection. Here, we discuss the immune response after SARS-CoV-2 infection. In-depth study of the recognition of and response of innate immunity and adaptive immunity to SARS-CoV-2 will help to prevent the development of critical cases and aid the exploration of more targeted treatments.

COVID-19 and informal settlements - implications for water, sanitation and health in India and Indonesia.

Informal settlements are home to over 1 billion people worldwide and are characterised by high population densities and poor environmental conditions. The authors identify the impact of COVID-19 on existing water and sanitation practices and potential pathways for the transmission of COVID-19 in informal settlements in India and Indonesia. In the short term, there is an urgent need for mobile and contactless hand washing, washing/bathing facilities and toilets. In the long term, COVID-19 provides an opportunity to invest in centralised water and sanitation networked solutions appropriate for high-density settings to integrate those settlements into cities and improve environmental conditions and health in these cities.

Synthesis and Antiviral Efficacy of Pyrimidine Analogs Targeting Viral Pathways

To date, viruses are known to cause chronic to acute pathogenesis. Nevertheless, antiviral drugs have been known for their medicinal applications for the last few decades to treat infections caused by these pathogens. Despite advancements in the field of vaccination and antiviral drugs, there is a need for a molecule that can eradicate or control viral infection without getting resistance from pathogens will be a real challenge. This review covers possible ways to treat viral infections with pyrimidine and its mimics compared to known antiviral drugs. A comprehensive study of the report accomplished synthetic routes of pyrimidine analogs and their target-specific antiviral potential. The present review article covers literature from 2018 to 2022.

Discovering common pathogenic processes between COVID-19 and HFRS by integrating RNA-seq differential expression analysis with machine learning.

Zoonotic virus spillover in human hosts including outbreaks of Hantavirus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) imposes a serious impact on the quality of life of patients. Recent studies provide a shred of evidence that patients with Hantavirus-caused hemorrhagic fever with renal syndrome (HFRS) are at risk of contracting SARS-CoV-2. Both RNA viruses shared a higher degree of clinical features similarity including dry cough, high fever, shortness of breath, and certain reported cases with multiple organ failure. However, there is currently no validated treatment option to tackle this global concern. This study is attributed to the identification of common genes and perturbed pathways by combining differential expression analysis with bioinformatics and machine learning approaches. Initially, the transcriptomic data of hantavirus-infected peripheral blood mononuclear cells (PBMCs) and SARS-CoV-2 infected PBMCs were analyzed through differential gene expression analysis for identification of common differentially expressed genes (DEGs). The functional annotation by enrichment analysis of common genes demonstrated immune and inflammatory response biological processes enriched by DEGs. The protein-protein interaction (PPI) network of DEGs was then constructed and six genes named RAD51, ALDH1A1, UBA52, CUL3, GADD45B, and CDKN1A were identified as the commonly dysregulated hub genes among HFRS and COVID-19. Later, the classification performance of these hub genes were evaluated using Random Forest (RF), Poisson Linear Discriminant Analysis (PLDA), Voom-based Nearest Shrunken Centroids (voomNSC), and Support Vector Machine (SVM) classifiers which demonstrated accuracy >70%, suggesting the biomarker potential of the hub genes. To our knowledge, this is the first study that unveiled biological processes and pathways commonly dysregulated in HFRS and COVID-19, which could be in the next future used for the design of personalized treatment to prevent the linked attacks of COVID-19 and HFRS.

Coupling Random Forest, Allometric Scaling, and Cellular Automata to Predict the Evolution of LULC under Various Shared Socioeconomic Pathways

Accurately estimating land-use demand is essential for urban models to predict the evolution of urban spatial morphology. Due to the uncertainties inherent in socioeconomic development, the accurate forecasting of urban land-use demand remains a daunting challenge. The present study proposes a modeling framework to determine the scaling relationship between the population and urban area and simulates the spatiotemporal dynamics of land use and land cover (LULC). An allometric scaling (AS) law and a Markov (MK) chain are used to predict variations in LULC. Random forest (RF) and cellular automata (CA) serve to calibrate the transition rules of change in LULC and realize its micro-spatial allocation (MKCA(RF-AS)). Furthermore, this research uses several shared socioeconomic pathways (SSPs) as scenario storylines. The MKCA(RF-AS) model is used to predict changes in LULC under various SSP scenarios in Jinjiang City, China, from 2020 to 2065. The results show that the figure of merit (FoM) and the urban FoM of the MKCA(RF-AS) model improve by 3.72% and 4.06%, respectively, compared with the MKCA(ANN) model during the 2005-2010 simulation period. For a 6.28% discrepancy between the predicted urban land-use demand and the actual urban land-use demand over the period 2005-2010, the urban FoM degrades by 21.42%. The growth of the permanent urban population and urban area in Jinjiang City follows an allometric scaling law with an exponent of 0.933 for the period 2005-2020, and the relative residual and R-2 are 0.0076 and 0.9994, respectively. From 2020 to 2065, the urban land demand estimated by the Markov model is 19.4% greater than the urban area predicted under scenario SSP5. At the township scale, the different SSP scenarios produce significantly different spatial distributions of urban expansion rates. By coupling random forest and allometric scaling, the MKCA(RF-AS) model substantially improves the simulation of urban land use.

Fantasy Leadership and the Reality of Practice

The large discourses about leadership have created understandings that are often glamorous, dramatic, and devoid of the skills real leaders use in everyday practice. Fantastic depictions of leadership in the zeitgeist also perpetuate notions that leadership is a seemingly effortless endeavor devoid of disciplined training and reliant on "natural talents.” This discussion extends understandings of leadership within the extraordinary times of the COVID-19 pandemic. A dialectic approach was applied to the literature focused on stoicism (Epictetus, The discourses of Epictetus: the handbook, fragments. Everyman's Library, London, 1995), resiliency (Duggan B, Theurer B. Resilient leadership 2.0: leading with Calm conviction, and clarity in anxious times. Infinity Publishing, New York, 2017), and neurobiology (Hanson R. Dr Rick Hanson: hardwiring happiness [Video File]. Retrieved from: https://www.youtube.com/watch?time_continue=641andv=jpuDyGgIeh0andfeature=emb_logo, 2013;Hart AW. Educ Urban Soc 22:153-169, 1990;Hanson, 2020). This effort was framed in a naturalistic lens, which allowed emphasis on the everydayness of individual leadership practices and the deconstruction of the relationship between stoicism and resiliency. Major insights from the chapter include identifying differences between fantasy leadership and authentic practice and defining specific resiliency skills as a central contour of everyday leadership. © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022.

Glycyrrhizin inhibits swine acute diarrhea syndrome coronavirus infection via the HMGB1/TLR4/JNK signal pathway

Swine acute diarrhea syndrome coronavirus (SADS-CoV), a newly discovered enteric coronavirus, is the etiological agent that causes severe clinical diarrhea and intestinal pathological damage in piglets. In this study, Vero E6 and IPI-2I cells were pretreated with different concentrations of glycyrrhizin (GLY) for 2 hours, and then infected with different concentrations of SADSCoV, aiming to investigate the inhibitory effect of GLY on SADS-CoV. Western blot and TCID50 results revealed a significantly decreased N protein expression and viral titer, indicating that GLY can inhibit the infection of SADS-CoV. Vero E6 and IPI-2I cells were pretreated with different concentrations of GLY for 2 hours and infected with SADS-CoV. Western blot results showed that when the concentration of GLY was 0.8 mmol/L, the expression of N protein decreased significantly, indicating that GLY inhibited the invasion of the virus. At first, cells were treated with 0.4 mmol/L GLY, and cell samples were collected at 2 hours, 6 hours and 12 hours after being infected with SADS-CoV for analysis, and the expression of N protein were found to be significantly reduced at all points, indicating that GLY had a significant inhibitory effect on the replication of the virus. GLY is a competitive inhibitor of high mobility group box 1 (HMGB1), and the receptors of HMGB1 mainly include TLR4 and RAGE. Based on this fact, the mutant plasmid at the key sites of HMGB1 (C45S, C106S, C45/106S) and the siRNA of the RAGE receptor were transfected to Vero E6 cells and infected with SADS-CoV, and the cell supernatant and samples were harvested. The western blot and TCID50 results showed that the expression of N protein and the virus titer were decreased, suggesting that GLY exerts its function by affecting the binding of HMGB1/TLR4/RAGE during SADS-CoV infection. To further explore the signaling pathway through which GLY functions, Vero E6 and IPI-2I cells were inoculated with SADS-CoV, and cell samples were harvested, western blot was used to detect the changes of MAPK proteins. The results showed that the protein expression levels of p-p38, p-JNK and p-ERK were up-regulated in the early and late stages, indicating that the MAPK pathway was activated by SADS-CoV infection. Vero E6 and IPI-2I were pretreated with different concentrations of GLY and TLR4 inhibitor TAK for 2 hours and infected with SADS-CoV. Protein samples were harvested and analysed by western blot which showed a decreased p-JNK and N proteins, while other proteins showed no significant changes. These results indicated that GLY and TAK regulated the phosphorylation of JNK but did not regulate the phosphorylation of p38 and ERK. Also, Vero E6 cells were treated with HMGB1 antibody, the siRNA of HMGB1 and HMGB1 mutants plasmid, and infected with SADS-CoV. Protein samples were harvested, western blot results showed that phosphorylation of JNK decreased, indicating that HMGB1 affected JNK phosphorylation. Finally, Vero E6 and IPI-2I cells were pretreated with different concentrations of JNK inhibitor SP600125 to infect SADS-CoV, western blot, TCID50 and IFA results showed that the expression of N protein and virus titer, as well as virus replication were reduced, indicating that SP600125 inhibited virus replication. In conclusion, our results revealed that GLY can inhibit in vitro replication of SADS- CoV, mainly through the HMGB1/TLR4/JNK signaling pathway. The discovery of this pathway provides theoretical support for the research of novel anti-SADS-CoV drugs.

Multi-scale Mechanisms of Maxing Shigantang in Treating Pneumonia Based on Transcriptomic Data.

Objective: Pneumonia is an infectious inflammation of the alveoli,distal airway,and interstitium caused by bacterial,viral,and other pathogens. Maxing Shigantang,originated from Treatise On Cold Damage Diseases,is a classic prescription for treating pneumonia,with significant clinical efficacy. However,its treatment mechanism is still elusive. Method(s): In that paper,the transcriptome-based multi-scale network pharmacology was used to reveal the overall pharmacological mechanism of Maxing Shigantang in treating pneumonia from six scales of tissue,cell,pathological process,biological process,signaling pathway, and target. Result(s):At the tissue level,Maxing Shigantang mainly acted on the focal tissue of pneumonia-lung and the main inflammatory immune tissues-blood and spleen. Analysis of cell,pathological process and biological process suggested that Maxing Shigantang could treat pneumonia by reversing inflammatory and immune functions and improving cardiopulmonary and vascular injury caused by pneumonia. Analysis of signaling pathway and target showed that Maxing Shigantang regulated inflammatory immune response pathways such as "coronavirus disease-COVID-19" and "Toll-like receptor signaling pathway",and related targets such as "MAPKAPK3" and "NRG1". Conclusion(s):This paper,from molecular to tissue levels,indicated Maxing Shigantang treated pneumonia mainly by regulating inflammatory immune response and improving cardiopulmonary and vascular injury.Copyright © 2023, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.

Therapeutic drugs targeting the novel coronavirus cytokine storm signaling pathways

Cytokine storm is one of the mechanisms causing acute respiratory distress syndrome and multiple organ failure in COVID-19. As an important prognostic factor, cytokines have gradually become a hotspot in the research on treatment of COVID-19 in recent years. Based on literature regarding the key cytokines, related signaling pathways and existing therapeutic drugs of COVID-19 cytokine storm, this article summarizes the therapeutic drugs for COVID-19 that block the cytokine storm signaling pathways. After summarizing and analyzing the latest research results, it is proposed that therapeutic drugs with stronger targeting capacity could be the focus of COVID-19 drug development in the future, and different treatment regimens should be adopted for different patients.

The effects of COVID-19 on European healthcare provision for working-age adults with major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is a leading cause of disability worldwide, and yet delivery of care for this illness is rife with gaps. The COVID-19 pandemic has had far reaching implications for every facet of healthcare, and MDD is no exception. This scoping review aimed to ascertain the impacts of COVID-19 on the delivery of MDD care in Europe, as well as to evaluate any novel MDD care strategies trialled in this period. METHODS: We searched the PubMed and PsycINFO databases up to January 2022 with a strategy centred around COVID-19 and MDD. Full texts of eligible studies examining working-age adults and conducted in Europe were evaluated against several criteria. All outcomes were then extracted and a narrative synthesis was constructed to summarise identified themes. RESULTS: Of 1,744 records identified in our search, 11 articles were eligible for inclusion in the review. In general, these studies reported a decrease in treatment rates, access to care, and perceived access to care during the COVID-19 pandemic. In addition, digital interventions trialled during the pandemic were broadly well-received by users, though their efficacy in improving MDD care was ambiguous. CONCLUSIONS: Despite a limited number of pertinent studies, this scoping review identified a trend of exacerbated treatment gaps in MDD care during the pandemic. Several of our pre-specified gaps, including delays to detection or treatment of depression and rates of follow-up contacts, remained unexplored in the context of COVID-19. This highlights the need for further investigation to obtain a full understanding of the relationship between COVID-19 and MDD care in Europe.

Сases of lacrimal system affection after Coronavirus infection

In the present article, cases of lacrimal apparatus conditions emerging after a new Coronavirus infection COVID-19. The aim of the study is to determine the causes of epiphora in patients after Coronavirus infection. 26 patients (30 eyes) were examined, aged from 28 to 70 years, complaining of tearing, which emerged for the first time ever not earlier than 5–14 days from the onset of the laboratory-confirmed Coronavirus infection COVID-19, which had a mild or a moderately severe course and was accompanied by anosmia. In patients, following conditions of the lacrimal system were revealed: in 22 patients, there were pathological changes of the horizontal portion of lacrimal pathways;in 6 people dry eye syndrome was diagnosed: in 3 people, it was of mild severity, manifested by hyperlacrimia, 3 people had moderate severity of the dry eye syndrome. As concomitant, following signs were revealed: in 7 patients — rhinologic conditions were present, in 2 people — neurologic signs. In the examined group of patients with epiphora, we found that in 1.5–3 month after Coronavirus infection COVID-19 with anosmia, as a common sign of the disease in more than a half of cases, a development of pathological changes of the horizontal portion of lacrimal pathways was revealed. © 2022, Eco-Vector LLC. All rights reserved.

Measuring the Impact of COVID-19 on Hospital Care Pathways

Care pathways in hospitals around the world reported significant disruption during the recent COVID-19 pandemic but measuring the actual impact is more problematic. Process mining can be useful for hospital management to measure the conformance of real-life care to what might be considered normal operations. In this study, we aim to demonstrate that process mining can be used to investigate process changes associated with complex disruptive events. We studied perturbations to accident and emergency (A &E) and maternity pathways in a UK public hospital during the COVID-19 pandemic. Co-incidentally the hospital had implemented a Command Centre approach for patient-flow management affording an opportunity to study both the planned improvement and the disruption due to the pandemic. Our study proposes and demonstrates a method for measuring and investigating the impact of such planned and unplanned disruptions affecting hospital care pathways. We found that during the pandemic, both A &E and maternity pathways had measurable reductions in the mean length of stay and a measurable drop in the percentage of pathways conforming to normative models. There were no distinctive patterns of monthly mean values of length of stay nor conformance throughout the phases of the installation of the hospital's new Command Centre approach. Due to a deficit in the available A &E data, the findings for A &E pathways could not be interpreted. © 2023, The Author(s).

Smart Mirror Activated by User's Face Recognition with Simulation of Artificial Intelligence Classifier

This paper presented a simple and easy-To-use intelligent mirror with the activated function by face recognition. Firstly, the function of face recognition was realized by the OpenMV platform, and the recognition information was transmitted to the main controller, i.e., Loongson 1C Zhilong development board. The main controller connected to the Django server through the distant communication function of ESP8266 module. The user's schedules were acquisitioned by such a communication pathway and analyzed by the main controller. Finally, the recognized user's business or traveling schedule was shown on a screen located in the rear of a semitransparent mirror. For strangers of this smart mirror, the successful rate of strangers was 100%. For the user, the successful rate of strangers was 90% and accuracy of user's recognition was 100% in 120 times of tests. Furthermore, Adaptive Neuro Fuzzy Inference System supports a nice performance for Automatic classification in computer simulation. The COVID-19 pandemic is still threatening human beings. A smart mirror with the function of face recognition activation is a non-Touching solution for avoiding the infections to support an idea for elevating human health. © 2023 Global IT Research Institute (GiRI).

Transcriptomic approaches in COVID-19: From infection to vaccines

Transcriptomics technologies have enabled the rapid response to the coronavirus disease 2019 (COVID-19) pandemic. A variety of platforms including oligonucleotide microarrays, RNA sequencing (RNA-seq), and single-cell RNA-seq (scRNA-seq) have been applied to the most diverse set of samples acquired from cell cultures, organoids, and animal models experimentally infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as well as from cells, tissues, and biofluids from COVID-19 patients. In this chapter, we will discuss transcriptomic approaches used to determine the aspects of SARS-CoV-2 structure, entry and replication, understand host responses to infection, identify diagnostic signatures, discovery, and repurpose drugs, and to elucidate the protective correlates of vaccination. © 2023 Elsevier Inc. All rights reserved.

Care trajectories of COVID-19 patients: from preventive measures to rehabilitation

This study aims to analyze the care trajectories of patients diagnosed with COVID-19 who were hospitalized and are currently undergoing rehabilitation regarding their use of and access to the healthcare network (HN). An evaluative, qualitative study was carried out based on interviews with patients in the city of Niteroi, Rio de Janeiro State, Brazil. The care trajectories were reconstructed at three different occasions that express their experiences with the healthcare and support network during the pandemic: prevention, support and diagnosis measures;hospitalization;post-COVID-19 care, rehabilitation and support. The results indicate that the main source of information about COVID-19 was TV newscasts. Preventive hygiene measures were the most widely adopted. The family was the main support network. There was no waiting time for admission to the municipal referral hospital. Hospitalization was very well evaluated in terms of user embracement, multidisciplinary care, virtual visits and daily contact between doctor and family members. A post-discharge "care vacuum" was identified, with no follow-up by primary health care (PHC) and other public services. Low-cost health insurance plans and private specialized post-COVID-19 services were frequently and spontaneously sought until the implementation of the rehabilitation service. In summary, solitary and discontinuous care trajectories of individuals and families shed light on several challenges to the health system, including guaranteed access to coordinated PHC and expanded offer of specialized public services and rehabilitation, aligned with the principles of humanized care, in addition to the maintenance of social support measures.Copyright © 2023 Fundacao Oswaldo Cruz. All rights reserved.

Interplay of Vitamin D and SIRT1 in Tissue-Specific Metabolism-Potential Roles in Prevention and Treatment of Non-Communicable Diseases Including Cancer.

The importance of the prevention and control of non-communicable diseases, including obesity, metabolic syndrome, type 2 diabetes, cardiovascular diseases, and cancer, is increasing as a requirement of the aging population in developed countries and the sustainability of healthcare. Similarly, the 2013-2030 action plan of the WHO for the prevention and control of non-communicable diseases seeks these achievements. Adequate lifestyle changes, alone or with the necessary treatments, could reduce the risk of mortality or the deterioration of quality of life. In our recent work, we summarized the role of two central factors, i.e., appropriate levels of vitamin D and SIRT1, which are connected to adequate lifestyles with beneficial effects on the prevention and control of non-communicable diseases. Both of these factors have received increased attention in relation to the COVID-19 pandemic as they both take part in regulation of the main metabolic processes, i.e., lipid/glucose/energy homeostasis, oxidative stress, redox balance, and cell fate, as well as in the healthy regulation of the immune system. Vitamin D and SIRT1 have direct and indirect influence of the regulation of transcription and epigenetic changes and are related to cytoplasmic signaling pathways such as PLC/DAG/IP3/PKC/MAPK, MEK/Erk, insulin/mTOR/cell growth, proliferation; leptin/PI3K-Akt-mTORC1, Akt/NFĸB/COX-2, NFĸB/TNFα, IL-6, IL-8, IL-1ß, and AMPK/PGC-1α/GLUT4, among others. Through their proper regulation, they maintain normal body weight, lipid profile, insulin secretion and sensitivity, balance between the pro- and anti-inflammatory processes under normal conditions and infections, maintain endothelial health; balance cell differentiation, proliferation, and fate; and balance the circadian rhythm of the cellular metabolism. The role of these two molecules is interconnected in the molecular network, and they regulate each other in several layers of the homeostasis of energy and the cellular metabolism. Both have a central role in the maintenance of healthy and balanced immune regulation and redox reactions; therefore, they could constitute promising targets either for prevention or as complementary therapies to achieve a better quality of life, at any age, for healthy people and patients under chronic conditions.

Characterising the treatment of thromboembolic events after COVID-19 vaccination in 4 European countries and the US: An international network cohort study.

Background: Thrombosis with thrombocytopenia syndrome (TTS) has been identified as a rare adverse event following some COVID-19 vaccines. Various guidelines have been issued on the treatment of TTS. We aimed to characterize the treatment of TTS and other thromboembolic events (venous thromboembolism (VTE), and arterial thromboembolism (ATE) after COVID-19 vaccination and compared to historical (pre-vaccination) data in Europe and the US. Methods: We conducted an international network cohort study using 8 primary care, outpatient, and inpatient databases from France, Germany, Netherlands, Spain, The United Kingdom, and The United States. We investigated treatment pathways after the diagnosis of TTS, VTE, or ATE for a pre-vaccination (background) cohort (01/2017-11/2020), and a vaccinated cohort of people followed for 28 days after a dose of any COVID-19 vaccine recorded from 12/2020 onwards). Results: Great variability was observed in the proportion of people treated (with any recommended therapy) across databases, both before and after vaccination. Most patients with TTS received heparins, platelet aggregation inhibitors, or direct Xa inhibitors. The majority of VTE patients (before and after vaccination) were first treated with heparins in inpatient settings and direct Xa inhibitors in outpatient settings. In ATE patients, treatments were also similar before and after vaccinations, with platelet aggregation inhibitors prescribed most frequently. Inpatient and claims data also showed substantial heparin use. Conclusion: TTS, VTE, and ATE after COVID-19 vaccination were treated similarly to background events. Heparin use post-vaccine TTS suggests most events were not identified as vaccine-induced thrombosis with thrombocytopenia by the treating clinicians.