The elderly population, who have increased susceptibility to severe outcomes, have been particularly impacted by the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), leading to a global health crisis. However, definitive parameters or mechanisms underlying the severity of COVID-19 in elderly people remain unclear. Thus, this study seeks to elucidate the mechanism behind the increased vulnerability of elderly individuals to severe COVID-19. We employed an aged mouse model with a mouse-adapted SARS-CoV-2 strain to mimic the severe symptoms observed in elderly patients with COVID-19. Comprehensive analyses of the whole lung were performed using transcriptome and proteome sequencing, comparing data from aged and young mice. For transcriptome analysis, bulk RNA sequencing was conducted using an Illumina sequencing platform. Proteomic analysis was performed using mass spectrometry following protein extraction, digestion, and peptide labelling. We analysed the transcriptome and proteome profiles of young and aged mice and discovered that aged mice exhibited elevated baseline levels of inflammation and tissue damage repair. After SARS-CoV-2 infection, aged mice showed increased antiviral and inflammatory responses; however, these responses were weaker than those in young mice, with significant complement and coagulation cascade responses. In summary, our study demonstrates that the increased vulnerability of the elderly to severe COVID-19 may be attributed to an attenuated antiviral response and the overactivation of complement and coagulation cascades. Future research on antiviral and inflammatory responses is likely to yield treatments that reduce the severity of viral respiratory diseases in the elderly.

Background/Objectives: SARS-CoV-2 infection increases thrombotic events in hospitalized patients, especially those of greater severity. It has been associated with the cytokine storm and worsening renal and liver function, increased inflammatory markers, and altered coagulation markers. This study analyzes differences in inflammatory, hepatic, renal, and coagulation markers between hospitalized patients with and without COVID-19 who experienced thromboembolic events during the last three years of the pandemic. Methods: This single-center, retrospective observational study, with an inferential component and biomarker analysis, included 663 patients (600 without COVID-19, 63 with COVID-19) admitted between December 2022 and January 2023. Results: Patients with COVID-19 exhibited significantly higher mean glomerular filtration rate (GFR) (100.5 mL/min/1.73 m2; p < 0.01) and alanine aminotransferase (ALT) levels (33.0 IU/L; p < 0.01) compared to those without COVID-19. Ferritin levels were also significantly elevated in COVID-19 patients (441.1; p < 0.01), particularly those with severe disease. Conversely, troponin I was significantly higher in patients without COVID-19 (22.6 × 104 pg/mL; p < 0.001). Among COVID-19 patients, D-dimer levels were significantly higher in those not requiring intensive care unit (ICU) admission (9.0 × 103 ng/mL; p = 0.023). Multivariate analysis revealed a significant association between COVID-19 and sex. Conclusions: Overall, renal function did not differ significantly between COVID-19 and non-COVID-19 patients. However, renal function was better in patients admitted to the ICU, regardless of COVID-19 status. Troponin I levels were elevated in non-COVID-19 patients, while ferritin and ALT levels were higher in COVID-19 patients. D-dimer levels showed no significant difference between the two groups.

Cancer patients face a 4 to 7-fold higher risk of developing thrombotic events compared to individuals without cancer. This elevated risk is driven by the underlying tumour biology and the effects of cancer treatments, significantly increasing the mortality rates of these patients. While low molecular weight heparin (LMWH) is the gold standard anticoagulation, direct oral anticoagulants (DOACs) are emerging as effective alternatives. Recent clinical evidence indicates reduced recurrent VTE upon DOAC treatment compared to LMWH; however, there is limited understanding of the underlying mechanistic pathways. Of interest, extracellular vesicles (EVs), released from a multitude of cells including platelets and tumour cells, are known as potent intercellular communication mediators, capable of progressing coagulation, thrombosis, as well as tumour growth and metastasis.

We characterised the extracellular vesicles and inflammatory markers associated with hypercoagulability and thrombosis in cancer-associated thrombosis (CAT) patients, comparing those treated for 8 weeks with DOACs to those receiving LMWH. This pilot observational study recruited 28 CAT patients (21 baseline, 13 treated with DOACs, 8 treated with LMWH; 14 paired) and quantified their circulating, platelet-derived, and endothelial-derived EVs using Nanoparticle Tracking Analysis and flow cytometry. Proteomics was performed on the EV cargo and patient plasma, quantifying the inflammatory profiles of the patients under both treatment arms.

We demonstrated that DOAC treatment maintained hypercoagulable and prothrombotic EV profiles similar to LMWH treatment, showing a remarkably stable EV cargo proteome. Inflammatory profiles were also comparable between treatment arms, with a trend toward a DOAC-mediated reduction of circulating cytokines, highlighting potential anti-inflammatory effects.

This pilot study demonstrates that DOACs sustain the circulating EV and inflammatory profiles to the same extent as LMWH, supporting this clinical shift in anticoagulant treatment in the cancer setting.

This study discusses disseminated intravascular coagulation (DIC) associated with solid cancers and various vascular abnormalities, both of which generally exhibit chronic DIC patterns. Solid cancers are among the most significant underlying diseases that induce DIC. However, the severity, bleeding tendency, and progression of DIC vary considerably depending on the type and stage of the cancer, making generalization difficult. Moreover, during the process of creating these guidelines, it became apparent that despite solid cancers being a major underlying condition for DIC, there is a lack of high-quality research on DIC associated with solid cancers. Nevertheless, we developed recommendations for clinical questions (CQs) regarding the use of heparin and recombinant thrombomodulin. Additionally, statements concerning these five questions were provided. DIC associated with various vascular abnormalities, is characterized by hyperfibrinolytic activity and linked to underlying conditions such as aortic aneurysm, aortic dissection, vasculitis syndromes, and vascular malformations. These conditions must always be considered differential diagnoses when unexplained thrombocytopenia or bleeding tendencies are observed. Although no evidence was found to support the assignment of recommendation levels, three statements were made. However, traumatic vascular abnormalities have not been discussed in this context.

Sepsis is a life-threatening organ dysfunction syndrome caused by a dysregulated host immune response to pathogenic infection. Due to its high mortality rate, it has been a major global public health problem. Recent studies have shown that the formation of immunothrombosis plays as a "double-edged sword" in the pathogenesis of sepsis, and how to properly regulate immunothrombosis to avoid organ damage and end the high-inflammation state as early as possible are the key steps for sepsis therapy. Considering the complexity of sepsis therapy, the development of an effective combined therapeutic strategy is the goal of this study. First, the insoluble Panexin1 (Panx1) channel inhibitor probenecid (Prob) was prepared as nanocrystals and administered via intramuscular injection. At the same time, septic mice were intravenously injected with cefotaxime sodium through the tail vein for combination therapy. After treatment, the number of infection foci and the level of serum inflammatory factors in septic mice were significantly reduced, and also neutrophil NETosis was significantly inhibited; thus, the survival rate of septic mice was dramatically increased. Pathological analysis revealed that the combination treatment was safe and effective and could significantly reduce the formation of immunothrombosis in septic mice.

The aim of this study was to analyze whether patients with SARS-CoV-2 who received surgical tracheotomy had a lower incidence of postoperative bleeding if their LMWH was postponed or canceled on the day of surgery.

Patients with SARS-CoV-2 admitted to the intensive care units who underwent surgical tracheotomy were assessed retrospectively through their medical records. Data on comorbidity, LMWH dose, and timing were collected. Bleedings < 72 h post surgery were noted as stomal or airway bleedings.

All 101 patients included were on LMWH. Twenty-two patients had no change of dose of LMWH, 24 patients had their dose of LMWH postponed to post surgery, and 50 patients had their dose reduced to only the evening dose on the day of surgery. Twenty-six patients had a stomal bleeding, one patient had an airway bleeding, and four patients had both stomal and airway bleedings. No significant difference in the incidence of bleeding was identified between various groups of different LMWH doses or timing, reduced dose versus no change of dose, OR 1.29 (95% CI 0.42-3.92). Postponed dose versus no change of dose of LMWH, OR 1.03 (95% CI 0.28-3.75). Increasing age was correlated to a higher risk of bleeding post-surgery by an OR of 1.64 (95% CI 1.06-2.54, p = 0.026 for every 10 years added). No fatal bleeding related to surgical tracheotomy was observed.

Decreased doses of LMWH on the day of surgery were not associated with a risk reduction for post-surgical bleeding in patients with SARS-CoV-2 who received tracheotomy. Increasing age was a risk factor for post-surgical bleeding.

Retrospective, level 3.

Therapeutic plasma exchange (TPE) is the primary intervention for treating symptomatic hyperviscosity from hypergammaglobulinemia, yet its efficacy for treating hyperviscosity related to hyperfibrinogenemia is unclear.

Define the safety and efficacy of TPE for critically ill COVID-19 patients with elevated blood viscosity from hyperfibrinogenemia.

We performed a prospective randomized controlled trial in critically ill COVID-19 patients in a single US healthcare system. Patients with hyperfibrinogenemia (>800 mg/dL) or elevated plasma viscosity (2.3-3.5 centipoise [cP]) were randomized to receive TPE on 2 consecutive days or continued standard of care (SOC).

Twenty participants were enrolled, with 10 receiving TPE and 10 receiving SOC alone. Mean (±SEM) plasma viscosity decreased significantly from 2.35 cP (±0.12) to 1.61 cP (±0.03) in the TPE group and was unchanged in the SOC group (2.47 cP [±0.11] to 2.47 cP [±0.15]). Mean fibrinogen decreased from 934.0 mg/dL (±25.1) to 359.1 mg/dL (±22.5) after TPE vs from 859.6 mg/dL (±57.6) to 807.3 mg/dL (±63.1) in SOC. There was no significant difference in 28-day all-cause mortality between groups, with 2 deaths in the TPE cohort and 5 deaths in the SOC cohort (P = .13). No serious safety events related to TPE were reported. TPE significantly decreased biomarkers of inflammation (erythrocyte sedimentation rate and C-reactive protein) and endothelial activation (von Willebrand factor and factor VIII) but not hemostatic activation (prothrombin fragment 1.2, thrombin-antithrombin complex, and fibrin monomer) or immunoglobulin (IgG and IgM) levels.

TPE is safe and effective for normalizing elevated blood viscosity from hyperfibrinogenemia in COVID-19 patients. Additional studies are needed to determine the impact of TPE on overall patient outcomes, including in those with non-COVID-19 conditions associated with hyperfibrinogenemia.

This study compared the efficacy of therapeutic anticoagulation guided by anti-Xa levels vs. a D-dimer-based protocol in ICU patients with COVID-19. Given the heightened risk of thrombosis despite anticoagulation therapy in some cases, we hypothesised that anti-Xa measurement improves anticoagulation effectiveness and clinical outcomes in this population. We retrospectively analysed data from ICU patients at COVID Hospital Karaburma between April 2020 and December 2021. The primary outcome was the incidence of failed noninvasive ventilation necessitating intubation. Secondary endpoints included mortality rates, thromboembolic and bleeding complications, and anticoagulation effectiveness assessed by antifactor Xa activity. The analysis included 395 patients - 137 in the anti-Xa group and 258 in the D-dimer group. The D-dimer group showed a higher rate of failed noninvasive ventilation requiring intubation (65.7% vs. 50%, P  = 0.009). The overall mortality was 48.3%, significantly higher in the D-dimer group (52.7%) compared to the anti-Xa group (40.1%, P  = 0.02). Thromboembolic complications were lower in the anti-Xa group (2.9%) than in the D-dimer group (9.7%, P  = 0.014), with no significant difference in bleeding. Following the first LMWH administration, 70.8% of patients had anti-Xa levels below the therapeutic and 11.7% below the prophylactic range. Anti-Xa-guided anticoagulation improves survival and reduces thromboembolic complications compared to D-dimer-based treatment without increasing bleeding risk. This study highlights the potential of the anti-Xa assay in managing anticoagulation in critically ill COVID-19 patients. Our findings provide a foundation for future research on using anti-Xa measurements as a guiding tool to optimise anticoagulation therapy in other critically ill populations.

The first Polish recommendations for the management of COVID-19 were published by the Polish Society of Epidemiologists and Infectiologists (PTEiLChZ) on 31 March 2020, and the last three years ago. The emergence of new SARS-CoV-2 variants, a different course of the disease, as well as new knowledge about therapies and vaccines, requires updating diagnostic, therapeutic, and prophylactic guidelines. Despite the reduction in the threat associated with COVID-19, there is a risk of another epidemic caused by coronaviruses, which was an additional reason for developing a new version of the guidelines. In preparing these recommendations, the Delphi method was used, reaching a consensus after three survey cycles. Compared to the 2022 version, the names of the individual stages of the disease have been changed, adapting them to the realities of clinical practice, and attention was paid to the differences observed in immunosuppressed patients and in children. Some previously recommended drugs have been discontinued, including monoclonal antibodies. In addition, general principles of vaccination were presented, as well as issues related to the post-COVID syndrome.

The clinical spectrum of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is broad; it can range from asymptomatic cases to mild upper respiratory tract illness, respiratory failure, and severe multiorgan failure resulting in death. Therefore, it is important to identify the clinical course of the disease and the factors associated with mortality.

The aim of this study is to identify the risk factors associated with the severity of the disease, intensive care unit admission, and mortality in COVID-19 patients.

A total of 1075 patients with clinical and radiological findings compatible with COVID-19 pneumonia and positive SARS-CoV-2 PCR were selected and retrospectively screened. All included patients were classified according to the 7th edition of the 2019 Coronavirus Disease Guidelines published by the National Health Commission of China.

It was observed that elevated white blood count (WBC) increased the severity of COVID-19 by 3.26 times and the risk of intensive care unit (ICU) admission by 3.47 times. Patients with high D-dimer levels had a 91% increased risk, and those with high fibrinogen levels had a 2.08 times higher risk of severe disease. High C-reactive protein (CRP) values were found to increase disease severity by 6.89 times, mortality by 12.84 times, and ICU admission by 3.37 times.

Identifying the factors associated with disease severity, ICU admission, and mortality in COVID-19 patients could help reduce disability and mortality rates in pandemics.

Introduction: Severely ill COVID-19 patients receiving prophylactic-dose anticoagulation exhibit high rates of thrombosis and mortality. The escalation of anticoagulation also does not reduce mortality and has an uncertain impact on thrombosis rates. The reasons why escalated doses fail to outperform prophylactic doses in reducing risks of thrombosis and death in severely ill COVID-19 patients remain unclear. We hypothesized that escalated anticoagulation would not effectively prevent hypercoagulability and, consequently, would not reduce the risk of thrombosis and death in some severely ill patients. Methods: We conducted a prospective multicenter study that enrolled 3860 COVID-19 patients, including 1654 severely ill. They received different doses of low-molecular-weight or unfractionated heparin, and their blood coagulation was monitored with activated partial thromboplastin time, D-dimer, and Thrombodynamics. A primary outcome was hypercoagulability detected by Thrombodynamics. Blood samples were collected at the trough level of anticoagulation. Results: We found that escalated anticoagulation did not prevent hypercoagulability in 28.3% of severely ill patients at the trough level of the pharmacological activity. Severely ill patients with such hypercoagulability had higher levels of inflammation markers and better creatinine clearance compared to severely ill patients without it. Hypercoagulability detected by Thrombodynamics was associated with a 1.68-fold higher hazard rate for death and a 3.19-fold higher hazard rate for thrombosis. Elevated D-dimer levels were also associated with higher hazard rates for thrombosis and death, while shortened APTTs were not. The simultaneous use of Thrombodynamics and D-dimer data enhanced the accuracy for predicting thrombotic events and fatal outcomes in severely ill patients. Conclusions: Thrombodynamics reliably detects hypercoagulability in COVID-19 patients and can be used in conjunction with D-dimer to assess the risk of thrombosis and death in severely ill patients. The pharmacological effect of LMWH at the trough level might be too low to prevent thrombosis in some severely ill patients with severe inflammation and better creatinine clearance, even if escalated doses are used.

Gastrointestinal (GI) hemorrhage has been reported in patients with SARS-CoV-2. Although there is consensus that the infection is associated with GI sequelae, controversy remains regarding its clinical significance. Endoscopic intervention was limited during the pandemic due to safety concerns and resource constraints, which may have hindered a full assessment of the impact of GI hemorrhage on patient outcomes. This paper aims to evaluate the outcomes of patients diagnosed with SARS-CoV-2 and concurrent clinically significant GI hemorrhage.

A total of 125 patients (69 male, 56 female) over the age of 18, with signed procedural consent, were included. All met the criteria for a SARS-CoV-2 diagnosis and underwent diagnostic endoscopic intervention. Data were analyzed using the Mann-Whitney U test with Excel (Microsoft Corporation, Redmond, WA, USA) and SPSS Statistics version 25 (IBM Corp., Released 2017. IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp.).

The overall hospital length of stay was 8 ± 6 days. A subset analysis compared patients requiring ICU admission with those who did not. The average ICU length of stay was 13 ± 6 days, compared to 5 ± 3 days for non-ICU patients. Among patients who underwent esophagogastroduodenoscopy, 65% (70/108) required intervention, while 16% (3/19) of colonoscopies required intervention. There was no significant difference in underlying comorbidities or rates of non-invasive mechanical ventilation between groups. Overall mortality was 50% (62/125), with no significant difference between ICU (26/50) and non-ICU (36/75) patients (52% vs. 48%).

While studies have indicated an increased risk of GI complications in SARS-CoV-2 patients, many have not differentiated between hemorrhagic and non-hemorrhagic sequelae or accounted for the level of care. We conclude that there was higher mortality among patients requiring endoscopic intervention, regardless of their level of care or patient-specific factors.

Thromboembolic events of COVID-19 are due to hyperinflammatory process associated with hypercoagulable state. The aim of the study was to determine characteristics and clinical outcomes of patients with COVID-19 who presented with aortic thrombus.

We retrospectively conducted a single-center, descriptive study over a period of 1 year and 7 months, between June 2021 and December 2022, involving eight patients with documented SARS-CoV-2 infection associated with aortic thrombus revealed by acute limb ischemia.

The mean age of patients was 67 years with a median of 64, 5 ± 14. Of the eight included patients, six were men and two were women. Aortic thrombus was diagnosed in all cases. Six patients developed one episode of acute limb ischemia and one patient had recurrent upper and lower ischemia despite full anticoagulation whereas one patient had distal embolization with palpable pulses. In six patients, the thrombi were located in descending and abdominal aorta, while two patients presented with ascending aorta floating thrombus. Seven patients required urgent revascularization whereas medical treatment was recommended for one patient. The primary outcomes were successful in five cases, one patient had to be amputated above elbow, whereas two patients died due to a rapid deterioration of respiratory condition.

Aortic thrombosis is a rare clinical presentation in SARS-CoV-2 infection but with potentially fatal embolic complication. Physicians should maintain a high degree of clinical suspicion to diagnose thromboembolic consequences of SARS-CoV-2 infection for timely management and avoiding morbidities like ischemic stroke and major amputations.

Background and Objectives: We conducted a retrospective observational study to evaluate the impact of elevated blood glucose levels in patients with SARS-CoV-2 infection and a prior diagnosis of diabetes mellitus (DM) or newly diagnosed hyperglycemia. Materials and Methods: This study analyzed 6065 patients admitted to the COVID-19 departments of the "Marius Nasta" National Institute of Pulmonology in Bucharest, Romania, between 26 October 2020 and 5 January 2023. Of these, 813 patients (13.40%) were selected for analysis due to either a pre-existing diagnosis of DM or hyperglycemia at the time of hospital admission. Results: The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were elevated in patients with blood glucose levels exceeding 300 mg/dL. These elevations correlated with the presence of respiratory failure and increased mortality rates. Additionally, oxygen requirements were significantly higher at elevated blood glucose levels (p < 0.001), with a direct relationship between glycemia and oxygen demand. This was accompanied by lower oxygen saturation levels (p < 0.001). Maximum blood glucose levels were associated with the severity of respiratory failure (AUC 0.6, 95% CI: 0.56-0.63, p < 0.001). We identified cut-off values for blood glucose at admission (217.5 mg/dL) and maximum blood glucose during hospitalization (257.5 mg/dL), both of which were associated with disease severity and identified as risk factors for increased mortality. Conclusions: High blood glucose levels, both at admission and during hospitalization, were identified as risk factors for poor prognosis and increased mortality in patients with SARS-CoV-2 infection, regardless of whether the hyperglycemia was due to a prior diagnosis of DM or was newly developed during the hospital stay. These findings underscore the importance of glycemic control in the management of hospitalized COVID-19 patients.

The intersection of COVID-19 and cardiovascular disease (CVD) has emerged as a significant area of research, particularly in understanding the impact of antiplatelet therapies like ticagrelor and clopidogrel. COVID-19 has been associated with acute cardiovascular complications, including myocardial infarction, thrombosis, and heart failure, exacerbated by the virus's ability to trigger widespread inflammation and endothelial dysfunction. MicroRNAs (miRNAs) play a critical role in regulating these processes by modulating the gene expressions involved in platelet function, inflammation, and vascular homeostasis. This study explores the potential of miRNAs such as miR-223 and miR-126 as biomarkers for predicting resistance or responsiveness to antiplatelet therapies in COVID-19 patients with cardiovascular disease. Identifying miRNA signatures linked to drug efficacy could optimize treatment strategies for patients at high risk of thrombotic events during COVID-19 infection. Moreover, understanding miRNA-mediated pathways offers new insights into how SARS-CoV-2 exacerbates CVD, particularly through mechanisms like cytokine storms and endothelial damage. The findings of this research could lead to personalized therapeutic approaches, improving patient outcomes and reducing mortality in COVID-19-associated cardiovascular events. With global implications, this study addresses the urgent need for effective management of CVD in the context of COVID-19, focusing on the integration of molecular biomarkers to enhance the precision of antiplatelet therapy.

Nebulised unfractionated heparin may attenuate COVID-19 ARDS by reducing pulmonary microvascular thrombosis, blocking SARS-CoV-2 entry into cells, and decreasing lung inflammation. COVID-19 patients with a raised D-dimer have areas of pulmonary hypoperfusion on CT perfusion scans of the lung and have increased mortality risk.

This was a phase Ib/IIa open-label multi-centre, randomised controlled trial. The study was designed to evaluate whether nebulised unfractionated heparin decreased D-dimer concentrations, with safety as a co-primary outcome.

Forty patients were recruited, with 20 patients into each group. Mean age was 56.6 (SD 11.5) in the heparin group and 51.3 (SD 14.7) in the standard care group, while 60% of participants were male. There was no change in D-dimers from baseline to day 10 (heparin group mean change - 316.5, [SD 1840.3] and control group mean change - 321.7 [SD 3589.4]; p = 0.996). Fourteen patients suffered at least one serious adverse event, 9 patients the Heparin group and 5 in the control group. Eight patients had one or more bleeding events, 5 in the heparin group and 3 in the control group, but were no cases of pulmonary bleeding, of severe haemorrhage or of heparin-induced thrombocytopenia. Patients receiving heparin therapy had lower PaO2/FiO2 ratios, increased oxygenation indices, and decreased ROX index profiles, up to day 10. The time to separation from respiratory support, and the time to ICU or hospital discharge was similar in both groups. There were 3 deaths in the Heparin group and 2 in the control group.

Nebulised unfractionated heparin was safe and well tolerated, but did not reduce D-dimer concentrations, and worsened oxygenation indices in patients with COVID-19 ARDS.

Acute respiratory infections (ARIs) caused by viruses such as SARS-CoV-2, influenza viruses, and respiratory syncytial virus (RSV), pose significant global health challenges, particularly for the elderly and immunocompromised individuals. Substantial evidence indicates that acute viral infections can manipulate the host's epigenome through mechanisms like DNA methylation and histone modifications as part of the immune response. These epigenetic alterations can persist beyond the acute phase, influencing long-term immunity and susceptibility to subsequent infections. Post-infection modulation of the host epigenome may help distinguish infected from uninfected individuals and predict disease severity. Understanding these interactions is crucial for developing effective treatments and preventive strategies for viral ARIs. This review highlights the critical role of epigenetic modifications following viral ARIs in regulating the host's innate immune defense mechanisms. We discuss the implications of these modifications for diagnosing, preventing, and treating viral infections, contributing to the advancement of precision medicine. Recent studies have identified specific epigenetic changes, such as hypermethylation of interferon-stimulated genes in severe COVID-19 cases, which could serve as biomarkers for early detection and disease progression. Additionally, epigenetic therapies, including inhibitors of DNA methyltransferases and histone deacetylases, show promise in modulating the immune response and improving patient outcomes. Overall, this review provides valuable insights into the epigenetic landscape of viral ARIs, extending beyond traditional genetic perspectives. These insights are essential for advancing diagnostic techniques and developing innovative treatments to address the growing threat of emerging viruses causing ARIs globally.

One of the most serious complications of coronary artery stenting is restenosis and in-stent thrombosis; their prevalence can reach 20-25%. Stent thrombosis can be acute (up to 24 hours), subacute (24 hours to 30 days), late (30 days to 1 year), and very late (> 1 year after previous stenting). In the patients with COVID-19 in intensive care units, the proportion of those with elevated troponin levels reached 25%.

Evaluation of the association between COVID-19 and the development of in-stent thrombosis and restenosis of the coronary arteries based on the analysis of clinical cases and case series.

We searched the PubMed and Scopus databases for relevant case reports and case series of stent restenosis and in-stent thrombosis associated with coronavirus infection (CVI) published between 2020 and the present. Thirty-eight full-text publications were screened and manually checked for analysis. We found 10 publications describing cases of thrombosis and restenosis of stents associated with coronavirus infection, of which only 2 were case series. In total, we analyzed 22 cases.

In the structure of in-stent restenosis and thrombosis, 59.1% were very late, 9.1% were late; 18.2% were considered subacute events, and 13.6% were acute events. All cases were angiographically confirmed. The main location of restenosis or thrombosis was the left coronary artery (LAD) (51.1%), thrombosis of the right coronary artery (RCA) occurred in 27.3%, and location in circumflex artery was in 22.7%. All patients had COVID-19 confirmed by a PCR test or the presence of immunoglobulins G and M. In fourteen patients (54.5%), an X-ray examination showed the presence of bilateral polysegmental infiltration.

Analysis of publications demonstrates the association between restenosis and in-stent thrombosis in patients with coronary arteries disease (CAD) and coronavirus infection.

A heightened risk for thrombosis is a hallmark of COVID-19. Expansive clinical experience and medical literature have characterized small (micro) and large (macro) vessel involvement of the venous and arterial circulatory systems. Most events occur in patients with serious or critical illness in the hyperacute (first 1-2 weeks) or acute phases (2-4 weeks) of SARS-CoV-2 infection. However, thrombosis involving the venous, arterial, and microcirculatory systems has been reported in the subacute (4-8 weeks), convalescent (> 8-12 weeks) and chronic phases (> 12 weeks) among patients with mild-to-moderate illness. The purpose of the current focused review is to highlight the distinguishing clinical features, pathological components, and potential mechanisms of venous, arterial, and microvascular thrombosis in patients with COVID-19. The overarching objective is to better understand the proclivity for thrombosis, laying a solid foundation for screening and surveillance modalities, preventive strategies, and optimal patient management.

Background. Severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) infection during pregnancy was associated with a number of adverse pregnancy outcomes, including miscarriage, preeclampsia, preterm birth, and stillbirth. The virus persistence can last for a long time, and the consequences of a previous coronavirus infection are currently under study. Objectives. This study aimed to establish the clinical features of the course of pregnancy and childbirth in women with a history of asymptomatic coronavirus disease 2019 (COVID-19). Methods. This study was conducted in the Regional Perinatal Center N3 of Turkestan city, Kazakhstan. A total of 229 participants were enrolled comprising individuals with (n = 133, exposed group) from August to September 2021 with a history of COVID-19 and without one in the same period in 2019 (n = 96, unexposed group). Results. There is a statistically significant strong association between a history of COVID-19 and the development of oligohydramnios (φ = 0.743, p < 0.001), and medium strength between a history of COVID-19 and the presence of anemia (φ = 0.254, p < 0.001), abnormal development of the placenta (φ = 0.254, p < 0.011), cord entanglement (φ = 0.343, p = 0.000), low birth weight (φ = 0.356, p < 0.001) and stillbirth (φ = 0.293, p < 0.001). Conclusions. The past COVID-19 infection in pregnant women has long-term consequences in the form of placenta abnormal development and oligohydramnios; and, as a result, the development of adverse perinatal outcomes.

This systematic review and meta-analysis study evaluated the association between mortality due to COVID-19 and coagulative factors.

A systematic search was conducted on electronic databases including PubMed, Scopus, and the Web of Science from the beginning of the pandemic until October 2024 to identify relevant studies on COVID-19 patients and their laboratory findings related to coagulation markers and mortality outcome. Eligibility criteria were defined based on the PICO framework, and data extraction was performed by two authors independently using a standardized sheet. Statistical analysis was accomplished using the random effects model, and heterogeneity among studies was assessed using the I2 test. R and RStudio were used for statistical analysis and visualization.

Our systematic literature search yielded 6969 studies, with 48 studies meeting the inclusion criteria for our meta-analysis. The mean platelet count was significantly lower in deceased COVID-19 patients compared to survivors (20.58), while activated partial thromboplastin time (aPTT) and fibrinogen levels did not show significant differences. The pooled mean difference of D-Dimer, International Normalized Ratio (INR), and prothrombin time (PT) were significantly lower in survived patients (-2.45, -0.10, and -0.84, respectively). These findings suggest that platelet count, D-Dimer, INR, and PT may serve as potential indicators of mortality in COVID-19 patients.

The results of our systematic review and meta-analysis revealed a significant reduction in the pooled platelet count among deceased individuals when compared to survivors. However, no significant distinctions were observed in the pooled mean activated aPTT and fibrinogen levels between the deceased and survivor groups. On the other hand, there were noticeable variations in the pooled estimated mean of INR, PT, and D-Dimer levels, with significantly higher values in the deceased group compared to those who survived.

The COVID-19 pandemic has emphasized the need for effective management of severe acute respiratory distress syndrome (ARDS) using veno-venous extracorporeal membrane oxygenation (VV-ECMO). This meta-analysis aims to compare the effectiveness and outcomes of ECMO in patients with COVID-19 ARDS versus those with non-COVID ARDS, assessing its role in different respiratory virus infections.

A systematic search was conducted in PubMed, Web of Science, and other relevant databases up to June 30, 2023, to identify studies comparing ECMO use in COVID-19 and non-COVID ARDS cases. This analysis adheres to PRISMA guidelines, with studies rigorously selected based on predefined inclusion and exclusion criteria and assessed for bias using validated tools.

The meta-analysis included 24 studies with 2,121 patients, revealing that non-COVID ARDS patients treated with ECMO had a lower mortality risk compared to those with COVID-19 ARDS. Specifically, the overall pooled risk difference in survival was -0.11 (95% CI: -0.17 to -0.05, P<0.001), indicating a statistically significant advantage for non-COVID patients. The standardized mean difference for ECMO duration was significantly longer in COVID-19 patients (SMD=0.70, 95% CI: 0.32 to 1.08, P<0.001), reflecting more prolonged treatment needs.

ECMO serves as a vital intervention in severe ARDS, with differential effectiveness observed between COVID-19 and non-COVID patients. The study's findings underline the need for precise patient selection and tailored ECMO application across different viral etiologies. These insights are crucial for enhancing clinical strategies and resource allocation during ongoing and future pandemics.

Various studies have observed an association between interleukin-6 (IL-6), serum ferritin, d-dimer, and in-hospital mortality in COVID-19 patients. However, multivariate regression analysis was not done in the majority of the studies, Also, the role of interleukin-6 (IL-6), serum ferritin, and d-dimer in hospitalized COVID-19 patients was not adequately studied and reported from our region.

It was a retrospective cohort study in which the serum IL-6, serum ferritin, and d-dimer of 305 hospitalized COVID-19 patients were analyzed, and their association with mortality was determined.

In COVID-19 patients, the levels of IL-6 (P = 0.007), serum ferritin (P = 0.011), and d-dimer (P = 0.004) were significantly elevated in patients with severe SARS-CoV-2 illness (SpO2 < 90 % at admission). IL-6 levels were significantly elevated (186 pg/ml vs. 215 pg/ml, P = 0.003) in non-survivors compared to survivors. However, d-dimer (mg/ml) (P = 0.129) and serum ferritin (mg/ml) (P = 0.051) levels were similar between the two groups. The ROC curve (receiver operating characteristic curve) analysis showed a significant but poor area under the curve (AUC) between elevated IL-6 (>208 pg/ml) and in-hospital mortality (P < 0.008, AUC = 0.61). Kaplan-Meir survival analysis showed poor survival in patients with elevated IL-6 (>208 pg/ml) (Pby log-rank: 0.010) and elevated d-dimer (>1780 mg/ml) (P by log-rank: 0.036). The multivariate cox-regression analysis did not show any association between IL-6, serum ferritin, d-dimer, and in-hospital mortality (P > 0.05). Also, no association was found between serum levels of IL-6, serum ferritin, d-dimer, and the use of a ventilator (P > 0.05) and the severity of SARS-CoV-2 illness (P > 0.05) on multivariate binary logistic regression analysis.

In this study, the serum levels of IL-6, serum ferritin, and d-dimer were not associated with in-hospital mortality in hospitalized COVID-19 patients on multivariate cox-regression analysis, and were the markers of severe SARS-CoV-2 illness.

The impact of chronic oral anticoagulant (OACs) use on long-term post-discharge outcomes after coronavirus disease 2019 (COVID-19) hospitalisation remains unclear. Herein, we compared clinical outcomes up to 2-years after COVID-19 hospitalisation between patients on vitamin K antagonists (VKAs), direct-acting OACs (DOACs) and no OAC therapy.

Data from TriNetX, a global federated health research network, were used. Adult patients on VKAs, DOACs or no OAC therapy at diagnosis of COVID-19 between 20 January 2020 and 31 December 2021, who were hospitalised for COVID-19, were included. The primary outcomes were all-cause mortality, ischaemic stroke/transient ischaemic attack (TIA)/systemic embolism (SE) and the composite of intracranial haemorrhage (ICH)/gastrointestinal bleeding, at 2 years after COVID-19 hospitalisation.

We included 110,834 patients with COVID-19. Following propensity score matching (PSM), we identified a decreased mortality risk in DOAC-treated patients compared to the no OAC cohort (RR .808, 95% CI .751-.870). A higher risk of ischaemic stroke/TIA/SE was observed in VKA users compared to DOAC users (RR 1.100, 95% CI 1.020-1.220) and in VKA users compared to patients not taking OAC (RR 1.400, 95% CI 1.140-1.720). VKA use was associated with a greater risk of ICH/gastrointestinal bleeding than DOAC users (RR 1.198, 95% CI 1.066-1.347), while DOAC users had a lower risk compared to no OAC-treated patients (RR .840, 95% CI .754-.936).

COVID-19 patients taking prior DOACs were associated with lower long-term mortality risk and ICH/gastrointestinal bleeding than patients not taking OAC. Compared to patients on DOACs, VKA users were associated with higher risks of mortality, ischaemic stroke/TIA/SE and ICH/gastrointestinal bleeding.

Paxlovid is one of the most effective antiviral therapies for COVID-19 patients, but no studies have explored the efficacy predictors of this drug.

To investigate whether D-dimer could be used as a predictor of paxlovid response. Our study included 394 patients diagnosed with COVID-19 who were treated with paxlovid at Xiangya Hospital from Dec 5, 2022, to Jan 31, 2023. We analyzed the composite outcome and all-cause mortality and compared the clinical and demographic data of patients with normal and abnormal D-dimer levels.

We found that 324 patients (82.2%) with D-dimer levels were regularly compared with 70 patients (17.8%). Compared with patients with normal D-dimer levels, those with elevated D-dimer levels exhibited significantly reduced albumin levels, along with elevated levels of white blood cells, platelets, neutrophils, blood urea nitrogen, and procalcitonin. Kaplan-Meier survival curves showed that patients displaying increased D-dimer levels demonstrated a significantly higher incidence of composite disease progression within 28 days (p = 0.002) and all-cause death (p < 0.001). The multivariable adjusted Cox proportional hazard regression model also achieved consistent results in composite outcome (hazard ratio [HR] 2.21, 95% confidence interval [CI], 1.21-4.02, p = 0.009) and all-cause death (HR 8.06, 95% CI 2.74-23.71, p < 0.001).

Our findings suggested that the reduced efficacy of paxlovid could be predicted by elevated D-dimer levels in COVID-19 patients.

The COVID-19 outbreak, caused by the SARS-CoV-2 virus, was linked to significant neurological and psychiatric manifestations. This review examines the physiopathological mechanisms underlying these neuropsychiatric outcomes and discusses current management strategies. Primarily a respiratory disease, COVID-19 frequently leads to neurological issues, including cephalalgia and migraines, loss of sensory perception, cerebrovascular accidents, and neurological impairment such as encephalopathy. Lasting neuropsychological effects have also been recorded in individuals following SARS-CoV-2 infection. These include anxiety, depression, and cognitive dysfunction, suggesting a lasting impact on mental health. The neuroinvasive potential of the virus, inflammatory responses, and the role of angiotensin-converting enzyme 2 (ACE2) in neuroinflammation are critical factors in neuropsychiatric COVID-19 manifestations. In addition, the review highlights the importance of monitoring biomarkers to assess Central Nervous System (CNS) involvement. Management strategies for these neuropsychiatric conditions include supportive therapy, antiepileptic drugs, antithrombotic therapy, and psychotropic drugs, emphasizing the need for a multidisciplinary approach. Understanding the long-term neuropsychiatric implications of COVID-19 is essential for developing effective treatment protocols and improving patient outcomes.

Disseminated intravascular coagulation (DIC) is an acquired disorder characterized by systemic activation of blood coagulation, which can arise from various causes. Owing to its abrupt onset, rapid progression, and high mortality rate, DIC presents a major clinical challenge. Anticoagulant drugs, such as heparin or low-molecular-weight heparin, are the current gold standard of treatment; however, these interventions pose considerable bleeding risks. Thus, safer and more effective therapeutic strategies are urgently required. Owing to their strong anti-inflammatory and tissue repair capabilities, mesenchymal stem cell-derived exosomes (MSC-Exos) have gained considerable attention as novel therapeutic options for numerous disorders, including DIC. Their stability in diverse pathological states highlights their potential as promising candidates for DIC therapy. This review presents the latest insights on the pathogenesis of DIC and anti-inflammatory and anticoagulant properties of MSC-Exos. We aimed to elucidate the potential mechanisms by which MSC-Exos influence DIC pathogenesis. We speculate that MSC-Exos offer a multifaceted approach to DIC treatment by attenuating neutrophil extracellular trap formation, modulating M1/M2 macrophage polarization, altering Nrf2/NF-κB signalling pathway to downregulate pro-inflammatory factors, and correcting imbalances in the coagulation-fibrinolysis system through anticoagulant routes. This suggests that MSC-Exos are a potential paradigm in DIC therapy, offering novel targets and treatment modalities for DIC management.

COVID-19 pandemics increases venous thromboembolism (VTE) risk during hospitalization, despite prophylactic anticoagulation. Limited radiological diagnosis in pandemic requires a guided protocol for anticoagulant adjustment.

This retrospective cohort study was conducted at a single center as part of a quality improvement program evaluating the efficacy and safety of anticoagulation protocols. The study focused on implementing a guideline for anticoagulant dosing protocol based on dynamic changes in D-dimer levels in COVID-19 hospitalized patients. The dosing guideline allowed for dose escalation from standard prophylactic levels to escalated prophylactic or therapeutic levels, depending on the patient's risk profile for VTE. The primary endpoints included in-hospital survival comparing between fix and dynamic adjustment treatment groups. Secondary endpoints encompassed major and clinically relevant non-major bleeding (CRNMB) events, incidence of breakthrough thrombosis, length of hospitalization and ICU stay, days of mechanical ventilator use, and survival duration.

Among the 260 COVID-19-infected patients hospitalized between March 15th and June 15th, 2020. The patients received fixed anticoagulant dosage in 188, 72.3%) patients, while 72 (27.7%) were up-titrated according to the protocol. In-hospital survival at 30 days demonstrated superiority among patients whose anticoagulation was up-titrated to either escalated prophylactic or therapeutic (80.2%) compared to receiving fixed anticoagulant dosage (51.3%) (p=0.01). Bleeding events were significantly higher in up-titrate group (12.5%) compared to fixed anticoagulant dosage group (2.13%). Most of them are CRNMB.

A dynamic, D-dimer-based dose escalation of anticoagulation for hospitalized patients with COVID-19 holds promise in improving in-hospital mortality rates without a significant increase in fatal bleeding events.

Background: SARS-CoV-2 infection can lead to a potentially life-threatening condition known as SARS-CoV-2-associated multisystem inflammatory syndrome in children (MIS-C), which differs from the severe lung disease and thrombotic complications commonly seen in adults. Recently, similar cases have been identified in adults, characterized by a clinical multisystem inflammatory syndrome referred to as MIS-A, which can emerge as a late and severe complication of SARS-CoV-2 infection. Case Presentation: We report two cases of MIS-A that were recently admitted to our hospital. Both patients developed a severe multisystem inflammatory syndrome despite experiencing only mild SARS-CoV-2 infection. Key clinical features in both cases included significant systemic inflammation, prominent cardiac involvement, and thrombocytopenia. Prior SARS-CoV-2 infection was confirmed through serological testing. Treatment protocols for MIS-C, including steroids and immunoglobulins, proved effective for both patients. Conclusions: Clinicians should remain vigilant for MIS-A in the context of ongoing SARS-CoV-2 infection worldwide. This infection, even when presenting with mild or no symptoms, can progress to a life-threatening hyperinflammatory syndrome with cardiac implications if not promptly recognized and treated.

Coronavirus disease 2019 (COVID-19) is known to increase the risk of venous thromboembolism (VTE) and arterial thromboembolism (ATE). However, the incidence, predictors, and outcomes of clinical thrombosis for inpatients with COVID-19 are not well known. This study aimed to enhance our understanding of clinical thrombosis in COVID-19, its associated factors, and mortality outcomes.

Hospitalised adult (≥18 years of age) patients with COVID-19 in 2020 were retrospectively identified from the US National Inpatient Sample database. Clinical characteristics, incident VTE, ATE, and in-hospital mortality outcomes were recorded. Multivariable logistic regression was performed to identify clinical factors associated with thrombosis and in-hospital mortality in COVID-19 inpatients.

A total of 1,583,135 adult patients with COVID-19 in the year 2020 were identified from the National Inpatient Sample database; patients with thrombosis were 41% females with a mean age of 65.4 (65.1-65.6) years. The incidence of thrombosis was 6.1% (97,185), including VTE at 4.8% (76,125), ATE at 3.0% (47,790), and the in-hospital mortality rate was 13.4% (212,785). Patients with thrombosis were more likely to have respiratory symptoms of COVID-19 (76.7% vs 75%, p<0.001) compared with patients without thrombosis. The main factors associated with overall thrombosis, VTE, and ATE were paralysis, ventilation, solid tumours without metastasis, metastatic cancer, and acute liver failure. Although all thrombosis categories were associated with higher in-hospital mortality for COVID-19 inpatients in univariable analyses (p<0.001), they were not in multivariable analyses-thrombosis (odds ratio [OR] 1.24; 95% confidence interval [CI] 0.90-1.70; p=0.19), VTE (OR 0.70; 95% CI 0.52-1.00; p=0.05), and ATE (OR 1.07; 95% CI 0.92-1.25; p=0.36).

The association of COVID-19 with thrombosis and VTE increases with increasing severity of the COVID-19 disease. Risk stratification of thrombosis is crucial in COVID-19 patients to determine the necessity of thromboprophylaxis.

Pulmonary embolism is a complication of COVID-19 infection. The aim of this study is to assess prognosis and treatment response, including incidences of chronicity, relapse, and mortality among outpatients diagnosed with COVID-19-related pulmonary embolism between 2020 and 2022. A total of 101 patients with pulmonary embolism, started on anticoagulation during or within a month of COVID-19 infection, were included after testing positive by PCR. Data about comorbidities, Pulmonary Embolism Severity Index scores, PE diagnostic modalities, biochemical parameters, and transthoracic echocardiographic findings at diagnosis and at 24-month follow-up were collected. Cardiac catheterization parameters were recorded and compared between groups at diagnosis and at the 24-month follow-up. Groups were comparable with respect to gender, age, body mass index, and comorbidity score. Use of Q-SPECT for diagnosis was found significantly higher in patients with COVID-19-related pulmonary embolism (P < .001). The incidence of deep vein thrombosis was similar. In the study group, 43.6% of patients received anticoagulants for 3 months, with 49.1% using low molecular weight heparin and 50.9% using direct oral anticoagulants. At 24 months, rate of patients continuing treatment was comparable between groups. Specific pulmonary artery blockage value was found to be higher in patients with chronic thromboembolic pulmonary hypertension compared to those who demonstrated a response to pulmonary embolism treatment (P = .009). No adverse effects of anticoagulant therapy were observed during course of treatment. Over 24-month follow-up period, mortality, relapse, chronic thromboembolic hypertension and thromboembolic disease was observed in 2%, 2.2%, 4.9%, and 9.9% of patients, respectively.

The COVID-19 pandemic has intensified inquiries into the interplay between diabetes and disease severity, and the long-term impact of long-COVID. This study specifically explored the implications of different antithrombotic treatments on COVID-19 patients. It aimed to assess the long-term efficacy and safety of Vitamin K antagonists (VKA) and direct oral anticoagulants (DOACs) in mitigating thromboembolic complications in COVID-19 patients.

We conducted a study on 157 patients diagnosed with COVID-19 from August 2021 to August 2023. The study evaluated shifts in anticoagulant therapy recommendations, tracking the transition from VKA to DOACs, and analyzed associated health outcomes.

A significant shift from VKA to DOACs prescriptions was observed, especially in high-risk patients. Despite the change in antithrombotic treatments, incidences of varices and varices with hemorrhoids increased by 2.6% and 3.2%, respectively. Long-COVID was also linked to higher occurrences of diabetes and gastrointestinal diseases. Joint diseases rose by 14%, indicating persistent inflammation. Cardiomyopathies increased by 3.9%, predominantly in high-risk groups, and psychoanxiety disorders surged by 39.5%, highlighting the need for further research. DOAC usage was more common in older age groups, with a 10.2% increase in recommendations among high-risk patients (p<0.05).

The study underscores the evolving landscape of antithrombotic therapy in managing COVID-19 complications. Despite the increased use of DOACs, the rise in various health conditions suggests the necessity for personalized treatment strategies tailored to patient risk profiles.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection can lead to life-threatening clinical manifestations. Patients with cardiovascular disease (CVD) are at higher risk for severe courses of COVID-19. So far, however, there are hardly any strategies for predicting the course of SARS-CoV-2 infection in CVD patients at hospital admission. Thus, we investigated whether this prediction is achievable by prospectively analysing the blood immunophenotype of 94 nonvaccinated participants, including uninfected and acutely SARS-CoV-2-infected CVD patients and healthy donors, using a 36-colour spectral flow cytometry panel. Unsupervised data analysis revealed little differences between healthy donors and CVD patients, whereas the distribution of the cell populations changed dramatically in SARS-CoV-2-infected CVD patients. The latter had more mature NK cells, activated monocyte subsets, central memory CD4+ T cells, and plasmablasts but fewer dendritic cells, CD16+ monocytes, innate lymphoid cells, and CD8+ T-cell subsets. Moreover, we identified an immune signature characterised by CD161+ T cells, intermediate effector CD8+ T cells, and natural killer T (NKT) cells that is predictive for CVD patients with a severe course of COVID-19. Thus, intensified immunophenotype analyses can help identify patients at risk of severe COVID-19 at hospital admission, improving clinical outcomes through specific treatment.