Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is constantly mutating and spreading globally, posing a great threat to people's lives and health. The main protease of SARS-CoV-2 (Mpro, also called 3CLpro) is an attractive drug target for SARS-CoV-2, due to its crucial role in processing the viral replication. Here, we showed that chondroitin sulfate (CS) from pig, cattle and shark efficaciously inhibits Mpro activity of SARS-CoV-2 with half maximal inhibitory concentrations (IC50) of 0.148, 0.121 and 0.119 μM, respectively, through a fluorescence resonance energy transfer (FRET) assay. The inhibition pattern of CSs against Mpro activity is competitive inhibition, with inhibition constants (Ki) of CSs derived from pig, bovine and shark are 0.111, 0.096, and 0.107 μM, respectively, indicating significant inhibitory effects of CSs on Mpro activity. Protein fluorescence quenching demonstrated that porcine, bovine and shark CSs strongly bind to Mpro protein with dissociation constants (KD) of 28.31, 28.47 and 20.66 μM at 25 °C at a physiological condition, respectively, mainly through van der Waals and hydrogen bond interactions. Molecular docking and dynamics analysis provides an insight into structural information of the binding of the CSs with Mpro protein. Our findings suggested that CSs from different origins might be a promising food ingredient for the prevention of the SARS-CoV-2 infection.

COronaVIrus Disease-2019 (COVID-19) is associated with a hypercoagulable state. Intracardiac thrombosis is a potentially serious complication but has seldom been evaluated in COVID-19 patients. We assessed the incidence, associated factors, and outcomes of COVID-19 patients with intracardiac thrombosis. In 2020, COVID-19 inpatients were identified from the National Inpatient Sample (NIS) database. Data on clinical characteristics, intracardiac thrombosis, and adverse outcomes were collected. Multivariable logistic regression was used to identify factors associated with intracardiac thrombosis, in-hospital mortality, and morbidities. In 2020, 1,683,785 COVID-19 inpatients (mean age 63.8 years, 32.2% females) were studied. Intracardiac thrombosis occurred in 0.10% (1830) of cases. In-hospital outcomes included 13.2% all-cause mortality, 3.5% cardiovascular mortality, 2.6% cardiac arrest, 4.4% acute coronary syndrome (ACS), 16.1% heart failure, 1.3% stroke, and 28.3% acute kidney injury (AKI). Key factors for intracardiac thrombosis were congestive heart failure history and coagulopathy. Intracardiac thrombosis independently linked to higher risks of all-cause mortality (odds ratio [OR]: 3.32 (2.42-4.54)), cardiovascular mortality (OR: 2.95 (1.96-4.44)), cardiac arrest (OR: 2.04 (1.22-3.43)), ACS (OR: 1.62 (1.17-2.22)), stroke (OR: 3.10 (2.11-4.56)), and AKI (OR: 2.13 (1.68-2.69)), but not heart failure. While rare, intracardiac thrombosis in COVID-19 patients independently raised in-hospital mortality and morbidity risks.

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.

COVID-19, caused by the SARS-CoV-2 virus, is not only characterized by respiratory symptoms but is also associated with a wide range of systemic complications, including significant hematologic abnormalities. This is a comprehensive review of the current literature, using PubMed and Google Scholar, on the pathophysiology and incidence of thromboembolic events in COVID-19 patients and thromboprophylaxis. COVID-19 infection induces a prothrombotic state in patients through the dysregulation of the renin-angiotensin-aldosterone system (RAAS), endothelial dysfunction, elevated von Willebrand factor (vWF), and a dysregulated immune response involving the complement system and neutrophil extracellular traps (NETs). As a result, thromboembolic complications have emerged in COVID-19 cases, occurring more frequently in severe cases and hospitalized patients. These thrombotic events affect both venous and arterial circulation, with increased incidences of deep venous thrombosis (DVT), pulmonary embolism (PE), systemic arterial thrombosis, and myocardial infarction (MI). While DVT and PE are more common, the literature highlights the potential lethal consequences of arterial thromboembolism (ATE). This review also briefly examines the ongoing discussions regarding the use of anticoagulants for the prevention of thrombotic events in COVID-19 patients. While theoretically promising, current studies have yielded varied outcomes: Some suggest potential benefits, whereas others report an increased risk of bleeding events among hospitalized patients. Therefore, further large-scale studies are needed to assess the efficacy and safety of anticoagulants for thromboprophylaxis in COVID-19 patients.

In some reports, antiphospholipid antibodies (aPL) prevalence is higher in COVID-19 patients. This study intended to compare aPL prevalence between COVID-19 patients and healthy controls, and differences in aPL types using meta-analysis.

This work retrieved published literature about association between COVID-19 and aPL from Embase, Web of Science, PubMed, and The Cochrane Library databases. The observation group was COVID-19 patients, and the control group was healthy individuals. Outcome measures contained any of following aPLs: classic aPL: anti-cardiolipin antibodies (aCL) and anti-β2-glycoprotein-1 antibodies (Anti-β2GP1); other non-criteria aPL: anti-phosphatidylserine/prothrombin antibodies (aPS/PT) and anti-annexin-V antibodies (AnV). Meta-analysis was done on Review Manager 5.4.

10 studies involving 2288 patients were deemed eligible for inclusion. The results of the meta-analysis showed that the prevalence of Classic aPL and Any aPL in the COVID-19 group was significantly higher than in the healthy group (Classic aPL, RR = 2.55, 95 % CI = 1.83-3.55, P < 0.00001; Any aPL, RR = 2.34, 95 % CI = 1.46-3.77, P = 0.0005). Anti-β2GP1 IgA antibodies were the most common aPL in COVID-19 patients, with a significantly higher prevalence than in the healthy group (RR = 4.26, 95 % CI = 2.84-6.40, P < 0.00001). The prevalence of the four types of IgM aPL was significantly higher in the COVID-19 group compared to the healthy group, while there was no significant difference in aPL IgG between the two groups.

The prevalence of aPL in COVID-19 patients was significantly higher than in the healthy control group. IgM aPL was more easily detectable in the early stages of COVID-19 infection, while IgG aPL may be of more concern in the later time points of the immune epidemiology following SARS-CoV-2 infection.

Presently, numerous studies have demonstrated that long-term cardiovascular changes after Coronavirus Disease 2019(COVID-19) infection should be considered. The study was aimed to explore the risk factors for post COVID-19 long-term cardiovascular symptoms.

This retrospective observational cross-sectional study involved 204 COVID-19 patients who were admitted to Yantaishan Hospital from January 1, 2023 to January 31, 2023. Demographic and laboratory data were collected and compared between patients who experienced post COVID-19 long-term cardiovascular symptoms and those who did not. Logistic regression analysis was used to identify the risk factors associated with the occurrence of post COVID-19 long-term cardiovascular symptoms.

Fifty-two participants presented Post COVID-19 cardiovascular symptoms, while the remaining 152 individuals did not show any such symptoms including chest pain, chest tightness, shortness of breath, palpitations, dyspnea, exercise intolerance, and postural tachycardia syndrome. In comparison to the group without post COVID-19 long-term cardiovascular symptoms, the group with post COVID-19 long-term cardiovascular symptoms exhibited a significantly higher prevalence of anxiety and depression (25.0% vs. 4.6%, p = 0.000), as well as significantly elevated C-reactive protein (42.3 mg/L vs. 20.3 mg/L, p = 0.014) and D-dimer (0.3 mg/L vs. 0.22 mg/L, p = 0.024). Anxiety and depression (odds ratio [OR] = 6.403, 95% confidence interval [CI]:2.180-18.809, p = 0.001), C-reactive protein (OR = 1.009, 95%CI:1.003-1.015, p = 0.006), D-dimer (OR = 1.455, 95%CI:1.004-2.109, p = 0.048), and LDL-C (OR = 1.780, 95%CI:1.043-3.040, p = 0.035) were identified as independent risk factors for post COVID-19 long-term cardiovascular symptoms.

Anxiety and depression, C-reactive protein, D-dimer, and LDL-C levels are associated with the development of post COVID-19 long-term cardiovascular symptoms.

The aim of the present study was to identify more effective laboratory markers to assess the severity of corona virus disease 2019 and predict the progression of the disease by collecting more laboratory markers and variables.

In this study, most risk factors, including epidemiological characteristics, blood cell counts, cytokines, and infection markers, were collected from 126 patients with COVID-19 to assess their predictive value.

The area under curve (AUC) of Albumin (Alb) to fibrinogen (Fib) ratio (AFR) (0.791), Lactate dehydrogenase (LDH) (0.792), myoglobin (MYO) (0.795), C-reactive protein (CRP) (0.801) and lymphocyte count (0.859) were higher than other markers to distinguish severe from non-severe patients in receiver operating characteristic (ROC) analysis. In the univariate logistic regression analysis, thirty-six out of 46 risk factors, including 34 laboratory markers, were significantly associated with increased odds of severe patients. Multivariate logistic regression analysis showed that the CD19+ lymphocyte count, MYO, LDH, and AFR were associated with increased odds of severe disease. Moreover, Lymphocyte count and AFR levels increased, LDH and CRP levels decreased during hospitalization in recovered severe patients, whereas severe lymphocytopenia and continuously increasing LDH levels were observed in deteriorated patients. AFR level increased and CRP level decreased before the disease worsened in the deteriorated patients; however, when the patients deteriorated, AFR decreased and CRP increased significantly.

CD19+ lymphocyte count, MYO, LDH, and AFR are independent biomarkers for early identification of severe COVID-19. Lymphocyte count, AFR, LDH, and CRP levels were helpful in predicting the clinical progression of the disease.\.

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.

Coagulopathy and thromboembolic events are associated with poor outcomes in coronavirus disease 2019 (COVID-19) patients. There is conflicting evidence on the effects of chronic anticoagulation on mortality and severity of COVID-19 disease.

To summarize the body of evidence on the effects of pre-hospital anticoagulation on outcomes in COVID-19 patients.

A Literature search was performed on LitCovid PubMed, WHO, and Scopus databases from inception (December 2019) till June 2023 for original studies reporting an association between prior use of anticoagulants and patient outcomes in adults with COVID-19. The primary outcome was the risk of thromboembolic events in COVID-19 patients taking anticoagulants. Secondary outcomes included COVID-19 disease severity, in terms of intensive care unit admission or invasive mechanical ventilation/intubation requirement in patients hospitalized with COVID-19 infection, and mortality. The random effects models were used to calculate crude and adjusted odds ratios (aORs) with 95% confidence intervals (95%CIs).

Forty-six observational studies met our inclusion criteria. The unadjusted analysis found no association between prior anticoagulation and thromboembolic event risk [n = 43851, 9 studies, odds ratio (OR)= 0.67 (0.22, 2.07); P = 0.49; I 2 = 95%]. The association between prior anticoagulation and disease severity was non-significant [n = 186782; 22 studies, OR = 1.08 (0.78, 1.49); P = 0.64; I 2 = 89%]. However, pre-hospital anticoagulation significantly increased all-cause mortality risk [n = 207292; 35 studies, OR = 1.72 (1.37, 2.17); P < 0.00001; I 2 = 93%]. Pooling adjusted estimates revealed a statistically non-significant association between pre-hospital anticoagulation and thromboembolic event risk [aOR = 0.87 (0.42, 1.80); P = 0.71], mortality [aOR = 0.94 (0.84, 1.05); P = 0.31], and disease severity [aOR = 0.96 (0.72, 1.26); P = 0.76].

Prehospital anticoagulation was not significantly associated with reduced risk of thromboembolic events, improved survival, and lower disease severity in COVID-19 patients.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection represented a disruptive pathology that emerged in late 2019 with profound implications ranging from individual health to health systems and world economy. Our study aimed to evaluate clinical, biochemical and computerized tomography (CT) parameters values in determining the severity of pulmonary embolism (PE) associated with COVID-19.

We performed an observational cohort study evaluating demographic, clinical, biochemical, coagulation markers, as well as CT imaging parameters.

In our study on 186 patients with COVID-19, we found that 31 patients (16,66%) had pulmonary embolism. Significant correlations for the patients with PE were detected in C-reactive protein, lactate dehydrogenase, serum ferritin, IL-6, serum myoglobin, NT-proBNP, D-dimers, serum proteins, transaminases as well as white cell blood counts. Patients with pulmonary embolism had a more severe lung involvement, with thrombi distribution mainly involving the lower lobes.

Early identification of PE is an important step for timely and efficient treatment in the intensive care management of COVID-19 patients. Our study showed that high plasmatic values of lactate dehydrogenase, ferritin, IL-6, white blood cells and D-dimers and low proteins serum levels are strongly linked with COVID-19-associated pulmonary embolism.

Background The mortality and morbidity of thrombotic events in patients with coronavirus disease 2019 (COVID-19) are increasing worldwide. The clinical impact of prophylactic anticoagulation regimens among these patients in Iran remains unclear. This study aimed to evaluate the use of prophylactic anticoagulants and outcomes among COVID-19 patients admitted to a tertiary referral hospital. Methodology Patients diagnosed with COVID-19 and hospitalized between March 20 and June 20, 2020, were included in this longitudinal study after obtaining informed consent. Demographic and clinical data were collected from the hospital information system and medical records. Outcomes during this period were also evaluated. The data were entered into the preparation checklist and analyzed using SPSS version 24 software (IBM Corp., Armonk, NY, USA), employing chi-square, Fisher's exact, and Mann-Whitney U tests. Results Of the 831 enrolled patients, 51.9% were female, and 10.6% needed to be admitted to the intensive care unit (ICU). The mean age of the patients was 57.16 ± 17.32 years, and the mortality rate was estimated to be 9.4%. Mortality rates were significantly higher at older ages, in men, patients with ICU admission, severe pulmonary involvement, malignancy, airway obstruction, ischemic heart disease, and previous cerebrovascular accidents. ICU admission and mortality were statistically significantly higher in those who received concurrent prophylactic anticoagulants and aspirin than in other individuals. Conclusions Our study demonstrated that administering prophylactic aspirin with or without anticoagulant agents in COVID-19 patients did not reduce mortality rates or ICU transfers. However, it is worth noting that anticoagulant prescription was associated with a decrease in ICU admissions, which could potentially alleviate the significantly higher mortality rates observed among ICU patients in this study. Further research is needed to explore the potential benefits of anticoagulants in COVID-19 treatment.

Recent studies elucidate that coronavirus disease 2019 (COVID-19) patients may face a higher risk of cardiovascular complications. This study aimed to evaluate association of COVID-19 with the risk of pulmonary embolism (PE) or deep vein thrombosis (DVT). This nationwide population-based retrospective cohort study included Korean adult citizens between January 2021 and March 2022 from the Korea Disease Control and Prevention Agency COVID-19 National Health Insurance Service cohort. The Fine and Gray's regression with all-cause death as a competing event was adopted to evaluate PE and DVT risks after COVID-19. This study included a total of 1,601,835 COVID-19 patients and 14,011,285 matched individuals without COVID-19. The risk of PE (adjusted hazard ratio [aHR], 6.25; 95% confidence interval [CI], 3.67-10.66; p < 0.001) and DVT (aHR, 3.05; 95% CI, 1.75-5.29; p < 0.001) was higher in COVID-19 group in individuals without complete COVID-19 vaccination. In addition, individuals with complete COVID-19 vaccination still had a higher risk of COVID-19-related PE (aHR, 1.48; 95% CI, 1.15-1.88; p < 0.001). However, COVID-19 was not a significant risk factor for DVT among those with complete COVID-19 vaccination. COVID-19 was identified as an independent factor that elevated PE and DVT risks, especially for individuals without complete COVID-19 vaccination.

Background/Objectives: Although SARS-CoV-2 infection is a significant risk factor for venous thromboembolism (VTE), data on the impact of the use of non-invasive ventilation support (NIVS) to mitigate the risk of VTE during hospitalization are scarce. Methods: Data for 1471 SARS-CoV-2 patients, hospitalized in a single hub during the first pandemic wave, were collected from clinical records, including symptom duration and type, information on lung abnormalities on chest computed tomography (CT), laboratory parameters and the use of NIVS. Determining VTE occurrence during hospital stays was the main endpoint. Results: Patients with VTE (1.8%) had an increased prevalence of obesity (26% vs. 11%), diabetes (41% vs. 21%), higher CHA2DS2VASC score (4, IQR 2-5 vs. 3, IQR 1-4, age- and sex-adjusted, p = 0.021) and cough (65% vs. 44%) and experienced significantly higher rates of NIVS (44% vs. 8%). Using a stepwise multivariate logistic regression model, the prevalence of electrocardiogram abnormalities (odds ratio (OR) 2.722, 95% confidence interval (CI) 1.039-7.133, p = 0.042), cough (OR 3.019, 95% CI 1.265-7.202, p = 0.013), CHA2DS2-VASC score > 3 (OR 3.404, 95% CI 1.362-8.513, p = 0.009) and the use of NIVS (OR 15.530, 95% CI 6.244-38.627, p < 0.001) were independently associated with a risk of VTE during hospitalization. NIVS remained an independent risk factor for VTE even after adjustment for the period of admission within the pandemic wave. Conclusions: Our study suggests that NIVS is a risk factor for VTE during hospitalization in SARS-CoV-2 patients. Future studies should assess the optimal prophylactic strategy against VTE in patients with a SARS-CoV-2 infection candidate to non-invasive ventilatory support.

COVID-19 infection confers an increased risk of coagulation dysfunction (1) predisposing to thromboembolism in many anatomical sites including the gastrointestinal tract (GIT) (2). This study investigates the clinical presentation and outcome in patients presenting with concurrent COVID-19 infection and gastrointestinal tract ischaemia. Furthermore, differentiation and comparisons are drawn between those with arterial and venous aetiology for mesenteric ischaemia.

A systematic search was undertaken on EMBASE, PubMed, and MEDLINE. Two independent reviewers screened titles, abstracts, and full-text articles according to the inclusion criteria and extracted relevant data. Data analyses were conducted using Excel®.

Forty-one studies were included in the data analyses, yielding 44 patients. Twenty-six patients had mesenteric arterial occlusion, sixteen patients had mesenteric venous occlusion, and two patients had both arterial and venous mesenteric occlusion. All patients had concurrent COVID-19 infection. The survival rate in patients with arterial aetiology was 38.5% in contrast to 68.8% in patients with venous aetiology. Twelve patients (29.3%) experienced respiratory symptoms in the community before the onset of gastrointestinal symptoms, and five (12.2%) developed gastrointestinal symptoms during their inpatient stay for COVID-19 pneumonitis.

Acute mesenteric ischaemia presents a clinical challenge to diagnose due to its non-specific symptoms. Concurrent COVID-19 infection with its predominant respiratory symptoms adds a further challenge in recognising the non-specific symptoms of mesenteric ischaemia. Our study draws attention to the increased thromboembolic risk posed by COVID-19 infection and the need for a high index of suspicion to aid prompt diagnosis and management of acute mesenteric ischaemia, even in the post-pandemic era.

Thromboembolism is reported to be up to 27% in COVID-19 patients due to SARS-CoV-2 infection. Dysregulated systemic inflammation and various patient traits play a vital role in thrombosis progression.

To assess odds and associated factors for thrombosis development among Lebanese COVID-19 patients.

This was a case-control retrospective study conducted in January-May 2021. Patients infected with COVID-19 and developed thrombosis were classified as cases and patients who were thrombosis-free identified as control. A questionnaire assessed socio-demographics, clinical parameters, and WHO COVID-19 disease severity.

Among 267 patients, 26 (9.7%) developed thrombosis and the majority of thrombosis 34.6% was myocardial infarction, and the least (3.8%) was for catheter-related thrombosis. Results showed that the risk of thrombosis development is higher in patients with previous thromboembolic event (OR = 9.160) and previous intake of anti-hypertensive medications at home (OR = 3.116). However, females (OR = 0.330; CI: 0.118-0.925), intake of anticoagulants during hospital admission (OR = 0.126; CI: 0.053-0.300) and non-severe COVID-19 were at lower thrombosis risk (OR = 0.273). Patients who developed thromboembolic events had longer hospital stay (OR = 0.077).

Patients with COVID-19 and thromboembolism were at higher risk of mortality as compared to patients with COVID-19 but without thromboembolism. The use of anticoagulants significantly reduced the risk for thromboembolism.

This study assessed medication patterns for inpatients at a central hospital in Portugal and explored their relationships with clinical outcomes in COVID-19 cases.

A retrospective study analyzed inpatient medication data, coded using the Anatomical Therapeutic Chemical classification system, from electronic patient records. It investigated the association between medications and clinical severity outcomes such as ICU admissions, respiratory/circulatory support needs, and hospital discharge status, including mortality (identified by ICD-10-CM/PCS codes). Multivariate analyses incorporating demographic data and comorbidities were used to adjust for potential confounders and understand the impact of medication patterns on disease progression and outcomes.

The analysis of 2688 hospitalized COVID-19 patients (55.3% male, average age 62.8 years) revealed a significant correlation between medication types and intensity and disease severity. Cases requiring ICU admission or ECMO support often involved blood and blood-forming organ drugs. Increased use of nervous system and genitourinary hormones was observed in nonsurvivors. Corticosteroids, like dexamethasone, were common in critically ill patients, while tocilizumab was used in ECMO cases. Medications for the alimentary tract, metabolism, and cardiovascular system, although widely prescribed, were linked to more severe cases. Invasive mechanical ventilation correlated with higher usage of systemic anti-infectives and musculoskeletal medications. Trends in co-prescribing blood-forming drugs with those for acid-related disorders, analgesics, and antibacterials were associated with intensive interventions and worse outcomes.

The study highlights complex medication regimens in managing severe COVID-19, underscoring specific drug patterns associated with critical health outcomes. Further research is needed to explore these patterns.

SARS-CoV-2 has been known remarkably since December 2019 as a strain of pathogenic coronavirus. Starting from the earlier stages of the COVID-19 pandemic until now, we have witnessed many cases of neurological damage caused by SARS-CoV-2. There are many studies and research conducted on COVID-19-positive-patients that have found brain-related abnormalities with clear neurological symptoms, ranging from simple headaches to life-threatening strokes. For treating neurological damage, knowing the actual pathway or mechanism of causing brain damage via SARS-CoV-2 is very important. For this reason, we have tried to explain the possible pathways of brain damage due to SARS-CoV-2 with mechanisms and illustrations. The SARS-CoV-2 virus enters the human body by binding to specific ACE2 receptors in the targeted cells, which are present in the glial cells and CNS neurons of the human brain. It is found that direct and indirect infections with SARS-CoV-2 in the brain result in endothelial cell death, which alters the BBB tight junctions. These probable alterations can be the reason for the excessive transmission and pathogenicity of SARS-CoV-2 in the human brain. In this precise review, we have tried to demonstrate the neurological symptoms in the case of COVID-19-positive-patients and the possible mechanisms of neurological damage, along with the treatment options for brain-related abnormalities. Knowing the transmission mechanism of SARS-CoV-2 in the human brain can assist us in generating novel treatments associated with neuroinflammation in other brain diseases.

Developmental biology is intricately regulated by epigenetics and metabolism but the mechanisms are not completely understood. The situation becomes even more complicated during diseases where all three phenomena are dysregulated. A salient example is COVID-19, where the death toll exceeded 6.96 million in 4 years, while the virus continues to mutate into different variants and infect people. Early evidence during the pandemic showed that the host's immune and inflammatory responses to COVID-19 (like the cytokine storm) impacted the host's metabolism, causing damage to the host's organs and overall physiology. The involvement of angiotensin-converting enzyme 2 (ACE2), the pivotal host receptor for the SARS-CoV-2 virus, was identified and linked to epigenetic abnormalities along with other contributing factors. Recently, studies have revealed stronger connections between epigenetics and metabolism in COVID-19 that impact development and accelerate aging. Patients manifest systemic toxicity, immune dysfunction and multi-organ failure. Single-cell multiomics and other state-of-the-art high-throughput studies are only just beginning to demonstrate the extent of dysregulation and damage. As epigenetics and metabolism directly impact development, there is a crucial need for research implementing cutting-edge technology, next-generation sequencing, bioinformatics analysis, the identification of biomarkers and clinical trials to help with prevention and therapeutic interventions against similar threats in the future.

COVID-19 (Coronavirus disease 2019) pandemic is the main medical problem around the world from the end of 2019. We found until now many symptoms of this disease, but one of the most problematic was thrombosis. Wide recommendation on COVID-19 treatment was pharmacological thromboprophylaxis. In some papers we found that clinicians face the problem of bleeding in those patients. Is still unknown that coronavirus could led to the coagulopathy.

We described case report of patient who with COVID-19 disease present femoral nerve palsy caused by the iliopsoas hematoma. There were no deviations in coaguology parameters, patient got standard thromboprophylaxis, besides above probably COVID-19 was risk factor of hematoma formation. Non-operative treatment was applied, thrombophylaxis was discontinued. In the follow up in the radiological exam we saw reduction of the haematoma and patient report decrease of symptoms.

We should assess individually patient with COVID-19 according to thrombosis risk factors. Probably we should be more careful in ordering thrombophylaxis medications in COVID-19 patients.

Despite the great impact of severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2), we still lack techniques that allow us to anticipate the natural history of the disease in order to avoid or shorten the clinical period of the disease. The values of nine cytokines were measured in COVID-19+ patients admitted to the Hospital Universitario Reina Sofía (HURS) using flow cytometry. The cytokines measured are IL-1ß, IL-6, MCP-1, IP-10, IL-10, IL-8, IL-12, IFN-γ and TNF-α. Given the absence of previous studies on cytokine values in healthy patients using the flow cytometry technique, and the low availability of resources in the first waves of COVID-19, a control group was lacking, all resources were employed for monitoring sick patients. However, this study has revealed a greater increase in two specific cytokines, which are also found to be higher than the rest in healthy patients: MCP-1 and IP-10, which are mainly responsible for cytokine storm and post-disease thrombosis.

The association between the severity of COVID-19 and gastrointestinal (GI) bleeding is unknown. This study aimed to determine whether the severity of COVID-19 is a risk factor for GI bleeding.

A multicentre, retrospective cohort study was conducted on hospitalised patients with COVID-19 between January 2020 and December 2021. The severity of COVID-19 was classified according to the National Institute of Health severity classification. The primary outcome was the occurrence of GI bleeding during hospitalisation. The main analysis compared the relationship between the severity of COVID-19 and the occurrence of GI bleeding. Multivariable logistic regression analysis was performed to evaluate the association between the severity of COVID-19 and the occurrence of GI bleeding.

12 044 patients were included. 4165 (34.6%) and 1257 (10.4%) patients had severe and critical COVID-19, respectively, and 55 (0.5%) experienced GI bleeding. Multivariable analysis showed that patients with severe COVID-19 had a significantly higher risk of GI bleeding than patients with non-severe COVID-19 (OR: 3.013, 95% CI: 1.222 to 7.427). Patients with critical COVID-19 also had a significantly higher risk of GI bleeding (OR: 15.632, 95% CI: 6.581 to 37.130). Patients with severe COVID-19 had a significantly increased risk of lower GI bleeding (OR: 10.349, 95% CI: 1.253 to 85.463), but the risk of upper GI bleeding was unchanged (OR: 1.875, 95% CI: 0.658 to 5.342).

The severity of COVID-19 is associated with GI bleeding, and especially lower GI bleeding was associated with the severity of COVID-19. Patients with severe or critical COVID-19 should be treated with caution as they are at higher risk for GI bleeding.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can manifest itself in several ways, including coagulopathy and thrombosis. These complications can be the first and sometimes only manifestations of SARS-CoV-2 infection and can occur early or late in the course of the disease. However, these symptoms are more prevalent in hospitalized patients with venous thromboembolism, particularly those admitted to intensive care units. Moreover, various forms of arterial and venous thrombosis, or micro- or macro-vasculature embolisms, have been reported during the current pandemic. They have led to harmful consequences, such as neurological and cardiac events, nearly all resulting from the hypercoagulable state caused by this viral infection. The severe hypercoagulability observed in patients with COVID-19 accounts for most cases of the disease that become critical. Therefore, anticoagulants seem to be one of the most vital therapeutics for treating this potentially life-threatening condition. In the current paper, we present a thorough review of the pathophysiology of COVID-19-induced hypercoagulable state and the use of anticoagulants to treat SARS-CoV-2 infections in different patient groups, as well as their pros and cons.

Respiratory failure is the primary cause of death in patients with COVID-19, whereas coagulopathy is associated with excessive inflammation and multiorgan failure. Neutrophil extracellular traps (NETs) may exacerbate inflammation and provide a scaffold for thrombus formation.

The goal of this study was to determine whether degradation of NETs by recombinant human DNase-I (rhDNase), a safe, Food and Drug Administration-approved drug, reduces excessive inflammation, reverses aberrant coagulation, and improves pulmonary perfusion after experimental acute respiratory distress syndrome (ARDS).

Intranasal poly(I:C), a synthetic double-stranded RNA, was administered to adult mice for 3 consecutive days to simulate a viral infection, and these subjects were randomized to treatment arms, which received either an intravenous placebo or rhDNase. The effects of rhDNase on immune activation, platelet aggregation, and coagulation were assessed in mice and donor human blood.

NETs were observed in bronchoalveolar lavage fluid and within regions of hypoxic lung tissue after experimental ARDS. The administration of rhDNase mitigated peribronchiolar, perivascular, and interstitial inflammation induced by poly(I:C). In parallel, rhDNase degraded NETs, attenuated platelet-NET aggregates, reduced platelet activation, and normalized the clotting time to improve regional perfusion, as observed using gross morphology, histology, and microcomputed tomographic imaging in mice. Similarly, rhDNase reduced NETs and attenuated platelet activation in human blood.

NETs exacerbate inflammation and promote aberrant coagulation by providing a scaffold for aggregated platelets after experimental ARDS. Intravenous administration of rhDNase degrades NETs and attenuates coagulopathy in ARDS, providing a promising translational approach to improve pulmonary structure and function after ARDS.

The purpose of this study was to assess the efficacy of transarterial embolization in COVID-19 patients with an arterial bleeding and to investigate differences between various patient groups concerning survival.

We retrospectively reviewed COVID-19 patients undergoing transarterial embolization due to an arterial bleeding in a multicenter study from April 2020 to July 2022 and analyzed the technical success of embolization and survival rate. 30-day survival between various patient groups was analyzed. The Chi- square test and Fisher's exact test were used for testing association between the categorical variables.

53 COVID-19 patients (age: 57.3 ± 14.3 years, 37 male) received 66 angiographies due to an arterial bleeding. The initial embolization was technically successful in 98.1% (52/53). In 20.8% (11/53) of patients, additional embolization was necessary due to a new arterial bleeding. A majority of 58.5% (31/53) had a severe course of COVID-19 infection necessitating ECMO-therapy and 86.8% (46/53) of patients received anticoagulation. 30-day survival rate in patients with ECMO-therapy was significantly lower than without ECMO-therapy (45.2% vs. 86.4%, p = 0.004). Patients with anticoagulation did not have a lower 30-day survival rate than without anticoagulation (58.7% vs. 85.7%, p = 0.23). COVID-19 patients with ECMO-therapy developed more frequently a re-bleeding after embolization than non-ECMO-patients (32.3% vs. 4.5%, p = 0.02).

Transarterial embolization is a feasible, safe, and effective procedure in COVID-19 patients with arterial bleeding. ECMO-patients have a lower 30-day survival rate than non-ECMO-patients and have an increased risk for re-bleeding. Treatment with anticoagulation could not be identified as a risk factor for higher mortality.

Recent studies have reported the impact of previous COVID-19 infection on the early clinical outcome after total knee arthroplasty (TKA). However, the timing of infection before the surgery was not constant and a study on patients with COVID-19 infection within 1 week after TKA is lacking. This study aimed to determine the effect of COVID-19 infection within one week after TKA on the postoperative outcomes and to compare the early clinical outcomes to those who were not infected with COVID-19 before and after surgery. No significant differences were observed between the two groups in terms of clinical outcomes or complications. The length of the hospital stay (LOS) was significantly longer for the COVID-19 group than for the non-COVID-19 group (p < 0.05). The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were higher for the study group on postoperative days 9 and 12 than for those in the control group (p < 0.05). However, D-dimer levels were not significantly different between the two groups. We should cautiously consider that COVID-19 infection within 1 week after TKA may be associated with increased ESR, CRP levels, and length of hospital stay, but they are not associated with the worsening of early clinical outcomes or the occurrence of complications.

This study aimed to evaluate the prevalence, causes, medical interventions, and mortality outcome of acute gastrointestinal bleeding (AGIB) among COVID-19 patients hospitalized during the delta pandemic in Vietnam.

The medical records of COVID-19 patients hospitalized in a tertiary hospital in Vietnam from July to October 2021 were retrospectively collected. Data regarding age, sex, comorbidities, COVID-19 severity, onset time of AGIB, therapeutic interventions for AGIB, and mortality outcome were analyzed.

Of 1567 COVID-19 inpatients, 56 (3.6%) had AGIB. The independent risk factors for AGIB in COVID-19 inpatients included age (OR = 1.03, 95% CI: 1.01-1.04, p = .003), male sex (OR = 1.86, 95% CI: 1.06-3.26, p = .03), chronic liver disease (OR = 6.21, 95% CI: 2.97-13.00, p < .001), and chronic kidney disease (OR = 2.17, 95% CI: 1.01-4.65, p = .047). Among 34 AGIB patients undergoing endoscopy, upper AGIB was determined in 24 (70.6%) patients. Peptic ulcer disease and hemorrhagic erosive gastritis were the most common causes (64.7%, 22/34). The therapeutic interventions for AGIB included blood transfusion (76.8%, 43/56), endoscopic hemostasis (23.5%, 8/34), and surgery (1.8%, 1/56). The mortality rate in the AGIB group was significantly higher than that in the non-AGIB group (46.4% vs. 27.7%, OR = 2.26, 95% CI: 1.32-3.87, p = .002). However, the majority (76.9%) of deaths in COVID-19 inpatients with AGIB were not bleeding-related.

Age, male sex, chronic liver disease, and chronic kidney disease are risk factors for AGIB among COVID-19 inpatients. Peptic ulcer disease is the most common cause. COVID-19 inpatients with AGIB have a higher risk of mortality, but a large percentage of deaths are not bleeding-related.

Coronavirus 2019 (COVID-19) patients are at risk of thrombosis. Literature that compares the effectiveness of enoxaparin to unfractionated heparin (UFH) in COVID-19 patients is scarce.

We aimed to evaluate the effectiveness and safety of enoxaparin compared with UFH when used at their standard/intermediate dosing in COVID-19 patients.

This was a retrospective study conducted at a large COVID-19 center located in Eastern Province, Saudi Arabia. Confirmed COVID-19 cases (≥18 years old) admitted between January and December 2020 were randomly screened for inclusion. Exclusion criteria were patients receiving therapeutic anticoagulation, on chronic anticoagulation, had active bleeding, a platelet count <25 × 109/L, or an incomplete electronic file. The primary endpoint was the occurrence of any thrombotic event (pulmonary embolism, deep venous thrombosis, stroke, or myocardial infarction) or mortality. Secondary endpoints were major or minor bleeding. We applied inverse propensity score weighting (IPTW) with survival analysis to analyze the primary endpoint. Logistic regression was used for the secondary endpoint.

A total of 980 patients were included (enoxaparin, n = 470 and UFH, n = 510) with a mean age (±SD) of 47.7 (± 12.3) for the enoxaparin arm and 52 (±13.9) for the UFH arm. There was a statistically significant difference in the primary endpoint with an adjusted hazard ratio (aHR) of 0.46 (95%CI: 0.22 to 0.96, P = 0.039) in favor of the enoxaparin arm. There was no statistically significant difference in major or minor bleeding rates between the two arms.

When compared with UFH, enoxaparin was associated with a significant reduction in thrombotic events or mortality among COVID-19 patients. The results need confirmation from randomized controlled trials.

The COVID-19 pandemic remains the pre-eminent global health problem, and yet after more than three years there is still no prophylactic agent against the disease aside from vaccines. The objective of this study was to evaluate whether pre-existing, outpatient medications approved by the US Food and Drug Administration (FDA) reduce the risk of hospitalization due to COVID-19. This was a retrospective cohort study of patients from across the United States infected with COVID-19 in the year 2020. The main outcome was adjusted odds of hospitalization for COVID-19 amongst those positive for the infection. Outcomes were adjusted for known risk factors for severe disease. 3,974,272 patients aged 18 or older with a diagnosis of COVID-19 in 2020 met our inclusion criteria and were included in the analysis. Mean age was 50.7 (SD 18). Of this group, 290,348 patients (7.3%) were hospitalized due to COVID-19, similar to the CDC's reported estimate (7.5%). Four drugs showed protective effects against COVID-19 hospitalization: rosuvastatin (aOR 0.91, p = 0.00000024), empagliflozin-metformin (aOR 0.69, p = 0.003), metformin (aOR 0.97, p = 0.017), and enoxaparin (aOR 0.88, p = 0.0048). Several pre-existing medications for outpatient use may reduce severity of disease and protect against COVID-19 hospitalization. Well-designed clinical trials are needed to assess the efficacy of these agents in a therapeutic or prophylactic setting.

Little is known about the role played by anticoagulants in COVID-19.

The aim of this study was to assess the impact of previous anticoagulant treatment on risk of hospitalization due to COVID-19, progression to severe COVID-19 and susceptibility to COVID-19 infection.

We conducted a multiple population-based case-control study in northwest Spain, in 2020, to assess (1) risk of hospitalization: cases were all patients admitted due to COVID-19 with PCR confirmation, and controls were a random matched sample of subjects without a positive PCR; (2) progression: cases were hospitalized COVID-19 subjects, and controls were all non-hospitalized COVID-19 patients; and (3) susceptibility: cases were patients with a positive PCR (hospitalized and non-hospitalized), and the controls were the same as for the hospitalization model. Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using a generalized linear mixed model.

The consumption of antivitamin K and direct-acting anticoagulants apparently was not associated with the risk of progression to severe COVID-19 (OR 0.93 [95% CI 0.74-1.17] and OR 1.04 [95% CI 0.79-1.36], respectively). Antivitamin K anticoagulants were associated with a significantly lower risk of hospitalization (OR 0.77 [95% CI 0.64-0.93]), which, in part, can be explained by a decreased risk of susceptibility to infection (OR 0.83 [95% CI 0.74-0.92]). The use of direct-acting anticoagulants was not associated with the risk of hospitalization, although it also seems to decrease susceptibility (OR 0.85 [95% CI 0.74-0.98]). It has also been observed that low-molecular-weight heparins were associated with an increased risk of progression to severe COVID-19 (OR 1.25 [95% CI 1.01-1.55]).

The results of this study have shown that antivitamin K anticoagulants and direct-acting anticoagulants do not increase the risk of progression to more severe stages. Antivitamin K consumption was associated with a lower risk of hospitalization and susceptibility to infection.

Since the beginning of the pandemic, a recommendation was made for the use of anticoagulants in high-risk hospitalized patients. This therapeutic approach has positive and negative effects regarding the outcome of the disease. Anticoagulant therapy prevents thromboembolic events, but it can also lead to spontaneous hematoma formation, or be accompanied by massive active bleeding. We present a 63-year-old COVID-19-positive female patient with a massive retroperitoneal hematoma and spontaneous left inferior epigastric artery injury.

Congenital heart disease (CHD) is the most prevalent congenital defect in newborn infants. Due to the various types of heart abnormalities, CHD can have a wide range of symptoms. Cardiac lesions comprise a range of different types and accordingly varying severities. It is highly helpful to classify CHD into cyanotic and acyanotic heart diseases. In this review, we are investigating the course of Coronavirus disease 2019 (COVID-19) in cyanotic CHD patients. The infection may directly or indirectly affect the heart by affecting the respiratory system and other organs. The effect on the heart that is pressure- or volume-overloaded in the context of CHD is theoretically more severe. Patients with CHD are at a higher risk of mortality from COVID-19 infection or suffering worse complications. While the anatomic complexity of CHD does not seem to predict the severity of infection, patients with worse physiological stages are more susceptible such as cyanosis and pulmonary hypertension. Patients with CHD exhibit continuous hypoxemia and have lower oxygen saturations because of a right-to-left shunt. Such individuals run the danger of rapidly deteriorating in the event of respiratory tract infections with inadequate oxygenation. Additionally, these patients have a higher risk of paradoxical embolism. Hence, critical care should be given to cyanotic heart disease patients with COVID-19 in comparison to acyanotic patients and this is through proper management, close observation, and adequate medical therapy.

The COVID-19 pandemic, which has a prominent social and economic impact worldwide, shows a largely unexplained male bias for the severity and mortality of the disease. Loss of chromosome Y (LOY) is a risk factor candidate in COVID-19 due to its prior association with many chronic age-related diseases, and its impact on immune gene transcription.

Publicly available scRNA-seq data of PBMC samples derived from male patients critically ill with COVID-19 were reanalyzed, and LOY status was added to the annotated cells. We further studied LOY in whole blood for 211 COVID-19 patients treated at intensive care units (ICU) from the first and second waves of the pandemic. Of these, 139 patients were subject to cell sorting for LOY analysis in granulocytes, low-density neutrophils (LDNs), monocytes, and PBMCs.

Reanalysis of available scRNA-seq data revealed LDNs and monocytes as the cell types most affected by LOY. Subsequently, DNA analysis indicated that 46%, 32%, and 29% of critically ill patients showed LOY above 5% cut-off in LDNs, granulocytes, and monocytes, respectively. Hence, the myeloid lineage that is crucial for the development of severe COVID-19 phenotype is affected by LOY. Moreover, LOY correlated with increasing WHO score (median difference 1.59%, 95% HDI 0.46% to 2.71%, p=0.025), death during ICU treatment (median difference 1.46%, 95% HDI 0.47% to 2.43%, p=0.0036), and history of vessel disease (median difference 2.16%, 95% HDI 0.74% to 3.7%, p=0.004), among other variables. In 16 recovered patients, sampled during ICU stay and 93-143 days later, LOY decreased significantly in whole blood and PBMCs. Furthermore, the number of LDNs at the recovery stage decreased dramatically (median difference 76.4 per 10,000 cell sorting events, 95% HDI 55.5 to 104, p=6e-11).

We present a link between LOY and an acute, life-threatening infectious disease. Furthermore, this study highlights LOY as the most prominent clonal mutation affecting the myeloid cell lineage during emergency myelopoiesis. The correlation between LOY level and COVID-19 severity might suggest that this mutation affects the functions of monocytes and neutrophils, which could have consequences for male innate immunity.

The global community has been affected by the coronavirus disease 2019 (COVID-19), which emerged in December 2019. Since then, many studies have been conducted on cardiovascular diseases (CVDs) and COVID-19. The aim of this study was to perform a bibliometric and visual analysis of the published relationship between CVDs and COVID-19.

1,890 publications were retrieved from the Web of Science Core Collection database on January 5, 2022. Microsoft Office Excel and CiteSpace were then used to carry out scientometric analysis on the relevant literature according to seven aspects: document type, countries/regions, institutions, authors, journals, references, and keywords.

The research on CVDs and COVID-19 is currently in a period of rapid development, with China, USA, England, and Italy leading the field. There is active cooperation between most countries and institutions. Harvard Medical School stands out among the many institutions not only for the largest number of publications, but also for their high quality. Banerjee A, Solomon SD and Narula J are three representative authors in this field. Frontiers in Cardiovascular Medicine was the journal with the highest number of published studies, and The Lancet was the most cited journal. Two documents with a high degree of significance in this field were identified. Popular research topics in this field are specific diseases, such as acute coronary syndrome and heart failure; pathogenesis related to ACE2, insulin resistance and pericyte; the specific therapeutic drug chloroquine; and clinical characteristics, physical activity, and mental health. ACE2 and NF-κB will be the focus of future research.

This study provides useful information for the research of CVDs and COVID-19, including potential collaborators, popular research topics, and a reference for more extensive and in-depth research in the future.

SARS-COV-2, in most cases, only generates a mild acute respiratory disease. However, patients with severe disease show an exaggerated response of the immune system, creating a pro-inflammatory state, which could cause abnormalities in the coagulation system that increases mortality. Latin American countries, specially those with limited resources, have few studies about clinical features, coagulation and inflammatory biomarkers that could be useful at admission to assess poor outcomes.

The objective of this study is to describe the clinical features, coagulation, and inflammatory biomarkers, and identify risk factors at admission that are associated poor outcomes in Honduran population.

A cohort study was conducted. 210 patients were included, which 105 died during hospitalization due to COVID-19 and 105 were discharged alive, between September 2020 and January 2021. Clinical and laboratorial data was retrospectively collected.

57,6% of the population were male. The median age was 58 years. The median time between symptom onset and hospital admission was 6 days. D-dimer median was higher in the dead group compared with the alive group. Poor prognosis factors in the Cox multivariable model were male gender, age, symptom's duration, obesity and an elevated d dimer at admission.

In low-middle income countries, the assessment of these clinical and laboratory tools, especially in those with risk factors for prothrombotic states, could help clinicians to correctly stratify disease prognosis, establish a baseline to evaluate further evolution, and also predict outcomes, thus improving patient management.

As long as the coronavirus disease-2019 (COVID-19) pandemic continues, new variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) with altered antigenicity will emerge. The development of vaccines that elicit robust, broad, and durable protection against SARS-CoV-2 variants is urgently required. We have developed a vaccine consisting of the attenuated vaccinia virus Dairen-I (DIs) strain platform carrying the SARS-CoV-2  S gene (rDIs-S). rDIs-S induced neutralizing antibody and T-lymphocyte responses in cynomolgus macaques and human angiotensin-converting enzyme 2 (hACE2) transgenic mice, and the mouse model showed broad protection against SARS-CoV-2 isolates ranging from the early-pandemic strain (WK-521) to the recent Omicron BA.1 variant (TY38-873). Using a tandem mass tag (TMT)-based quantitative proteomic analysis of lung homogenates from hACE2 transgenic mice, we found that, among mice subjected to challenge infection with WK-521, vaccination with rDIs-S prevented protein expression related to the severe pathogenic effects of SARS-CoV-2 infection (tissue destruction, inflammation, coagulation, fibrosis, and angiogenesis) and restored protein expression related to immune responses (antigen presentation and cellular response to stress). Furthermore, long-term studies in mice showed that vaccination with rDIs-S maintains S protein-specific antibody titers for at least 6 months after a first vaccination. Thus, rDIs-S appears to provide broad and durable protective immunity against SARS-CoV-2, including current variants such as Omicron BA.1 and possibly future variants.