Long COVID-19 is marked by persistent symptoms beyond the acute phase, necessitating a deeper understanding of mortality risk factors for effective management. Plasma proteins hold promise as prognostic markers, offering insights into disease progression and aiding in mortality risk assessment.

A total of 240 patients and 89 healthy controls were enrolled for this study. Two months post-COVID follow-up, patients were categorized as survivors (n = 212) and non-survivors (n = 28). Plasma samples underwent 2-dimensional Gel Electrophoresis (2DE) for protein separation, followed by LC-MS/MS for protein identification, and validation was performed using ELISA. Proteomic data analysis was conducted using Mascot version 2.3.02 and Samespots software 4.5.1. Statistical analyses were carried out using GraphPad Prism and IBM SPSS.

LC-MS/MS identified fibrinogen (Spot 14; 52.15 kDa/5.32 pI; protein score 2293) and haptoglobin (Spot 08; 45.86 kDa/6.56 pI; protein score 453) as prospective predictive biomarkers. ELISA results confirmed increased plasma levels of fibrinogen and haptoglobin in severe cases (P < 0.001 for both) and non-survivors (P < 0.01 and P < 0.0086, respectively). ROC analysis showed haptoglobin had moderate predictive power for mortality (AUC = 0.68; P = 0.0025), surpassing fibrinogen (AUC = 0.62; P = 0.0374).

Plasma fibrinogen and haptoglobin are promising biomarkers for assessing disease severity and mortality risk in long COVID. These findings highlight their potential for prognostic applications, warranting further research into their mechanistic roles in COVID-19 and broader clinical implications.

COVID-19 is a disease that affects people globally. Beyond affecting the respiratory system, COVID-19 patients are at an elevated risk for both venous and arterial thrombosis. This heightened risk contributes to an increased probability of acute complications, including acute myocardial infarction (AMI) and acute ischemic stroke (AIS). Given the unclear relationship between COVID-19, AMI, and AIS, it is crucial to gain a deeper understanding of their associations and potential molecular mechanisms. This study aims to utilize bioinformatics to analyze gene expression data, identify potential therapeutic targets and biomarkers, and explore the role of immune cells in the disease.

This study employed three Gene Expression Omnibus (GEO) datasets for analysis, which included data on COVID-19, AMI and AIS. We performed enrichment analysis on the co-DEGs for these three diseases to clarify gene pathways and functions, and also examined the relationship between co-DEGs and immune infiltration. Machine learning techniques and protein-protein interaction networks (PPI) were used to identify hub genes within the co-DEGs. Finally, we employed a dual validation strategy integrating independent GEO datasets and in vitro experiments with human blood samples to comprehensively assess the reliability of our experimental findings.

We identified 88 co-DEGs associated with COVID-19, AMI and AIS. Enrichment analysis results indicated that co-DEGs were significantly enriched in immune inflammatory responses related to leukocytes and neutrophils. Immune infiltration analysis revealed significant differences in immune cell populations between the disease group and the normal group. Finally, genes selected through machine learning methods included: CLEC4E, S100A12, and IL1R2. Based on the PPI network, the top ten most influential DEGs were identified as MMP9, TLR2, TLR4, ITGAM, S100A12, FCGR1A, CD163, FCER1G, FPR2, and CLEC4D. The integration of the protein-protein interaction (PPI) network with machine learning techniques facilitated the identification of S100A12 as a potential common biomarker for early diagnosis and a therapeutic target for all three diseases. Ultimately, validation of S100A12 showed that it was consistent with our experimental results, confirming its reliability as a biomarker. Moreover, it demonstrated good diagnostic performance for the three diseases.

We employed bioinformatics methods and machine learning to investigate common diagnostic biomarkers and immune infiltration characteristics of COVID-19, AMI and AIS. Functional and pathway analyses indicated that the co-DEGs were primarily enriched in immune inflammatory responses related to leukocytes and neutrophils. Through two machine learning approaches and the PPI network, and subsequent validation and evaluation, we identified S100A12 as a potential common therapeutic target and biomarker related to immune response that may influence these three diseases.

Thrombophilia, characterized by an imbalance between fibrinolysis and coagulation leading to inappropriate blood clotting, is a significant medical condition. The CDC has designated it as an underdiagnosed, serious, and potentially preventable disorder, contributing to an estimated 600,000-900,000 cases and 100,000 deaths annually in the United States. These figures surpass the combined annual mortality of AIDS, breast cancer, and motor vehicle accidents. The pathogenesis of thrombophilia involves complex interactions between genetic predispositions, such as mutations in Factor V Leiden, Factor II, MTHFR, and Serpine-1, and environmental factors, including unhealthy lifestyles, prolonged hospitalization, obesity, and cancer. Prevalence of specific genetic mutations varies across populations. Additional risk factors include age, family history, and pregnancy, with recent attention to increased susceptibility in SARS-CoV-2 infection. While molecular diagnostic techniques are available, there remains a need for robust, cost-effective, and accurate screening methods for large populations. This systematic review provides an updated overview of thrombophilia, encompassing pathophysiology, epidemiology, genetic and environmental risk factors, coagulation cascade, population-specific mutation prevalence, and diagnostic approaches. By synthesizing clinical and molecular evidence, this review aims to guide researchers, hematologists, and clinicians in the diagnosis and management of thrombophilia.

Acute surgical abdomen is characterized by intense, sudden abdominal pain due to intra-abdominal conditions requiring prompt surgical intervention. The coronavirus disease 2019 (COVID-19) pandemic has led to various complications related to the disease's complex pathophysiological mechanisms, hence the hypothesis of COVID-19-induced acute abdominal surgical pathologies. The connection between acute surgical abdomen and COVID-19 involves two primary mechanisms. First, there is the presence of angiotensin-converting enzyme 2 (ACE2) receptors in multiple abdominal organs. This facilitates the cytokine storm through direct viral injury and inflammation. Second, the hypercoagulable state induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) increases the thrombotic risk within abdominal vessels, which can subsequently lead to ischemia. ACE2 receptors are notably expressed in the gastric, duodenal, and rectal epithelium, with SARS-CoV-2 viral RNA and nucleocapsid proteins detected in these tissues. The inflammatory response results in significant endothelial damage, activating coagulation pathways that cause monocellular infiltration, lymphocytic inflammation, and uncontrolled coagulation. These findings highlight the need for further research to clarify how COVID-19 leads to acute abdominal pathologies. Understanding these mechanisms is vital for improving clinical management and patient outcomes during future health crises and in the aftermath of the pandemic.

Nontraumatic intracerebral hemorrhage (ICH) is a devastating form of stroke with high mortality and morbidity. The COVID-19 pandemic introduced additional complexities and challenges in managing ICH. This study evaluates the impact of concurrent COVID-19 infection on the demographics, outcomes, and resource use of patients with ICH. The primary outcome was in-hospital mortality, and secondary outcomes included neurological and systemic complications, length of stay, and cost of hospitalization.

The National Inpatient Sample database was screened to identify patients with and without COVID-19 infection and ICH from 2020 to 2022. Sociodemographic characteristics, comorbidities, and clinical severity were compared between the two groups. Multivariate logistic regression was used to calculate adjusted odds ratios (aORs) for the preselected outcomes. A p value of < 0.05 was considered statistically significant.

A total of 99,780 patients with ICH were included, of whom 4917 (4.9%) had concomitant COVID-19 infection. COVID-19-positive patients with ICH were younger (median 66 [interquartile range (IQR) 55-76] vs. 68 [IQR 57-78], years), more likely to identify as Black (25.6 vs. 23.5%) or Hispanic (17.1 vs. 10.9%), and more frequently in the lower quartile of median household income (31.4 vs. 29.2%) (p < 0.05 for all). Distinct multivariate regression models adjusted for demographics, baseline comorbidities, and ICH severity revealed that COVID-19 infection was independently associated with higher odds of in-hospital mortality (aOR 2.432; 95% confidence interval [CI] 2.273-2.602), systemic complications (aOR 1.527; 95% CI 1.432-1.628), longer hospital stay (aOR 2.115; 95% CI 1.957-2.286), and higher hospitalization costs (aOR 1.256; 95% CI 1.162-1.357). In contrast, COVID-19 infection was also associated with lower odds of neurological complications (aOR 0.811; 95% CI 0.76-0.865).

COVID-19 exacerbated the existing disparities in ICH, disproportionately affecting younger, socioeconomically disadvantaged, and minority populations. Additionally, patients with ICH with concomitant COVID-19 infection experienced worse clinical outcomes and greater healthcare resource use. These findings highlight the impact that the pandemic had on patients with acute neurological conditions, particularly among more vulnerable populations.

The COVID-19 (C-19) pandemic has highlighted the significance of understanding the long-term effects of this disease on the quality of life of those infected. Long COVID-19 (L-C19) presents as persistent symptoms that continue beyond the main illness period, usually lasting weeks to years. One of the lesser-known but significant aspects of L-C19 is its impact on neuropsychiatric manifestations, which can have a profound effect on an individual's quality of life. Research shows that L-C19 creates neuropsychiatric issues such as mental fog, emotional problems, and brain disease symptoms, along with sleep changes, extreme fatigue, severe head pain, tremors with seizures, and pain in nerves. People with cognitive problems plus fatigue and mood disorders experience great difficulty handling everyday activities, personal hygiene, and social interactions. Neuropsychiatric symptoms make people withdraw from social activity and hurt relationships, thus causing feelings of loneliness. The unpredictable state of L-C19 generates heavy psychological pressure through emotional suffering, including depression and anxiety. Neuropsychiatric changes such as cognitive impairment, fatigue, and mood swings make it hard for people to work or study effectively, which decreases their output at school or work and lowers their job contentment. The purpose of this narrative review is to summarize the clinical data present in the literature regarding the neuropsychiatric manifestations of L-C19, to identify current methods of diagnosis and treatment that lead to correct management of the condition, and to highlight the impact of these manifestations on patients' quality of life.

The impact of high positive end-expiratory pressure (PEEP) ventilation and the optimization of PEEP titration in COVID-19-induced acute respiratory distress syndrome (ARDS) continues to be a subject of debate. In this systematic review, we investigated the effects of varying PEEP settings on patients with severe ARDS primarily resulting from COVID-19 (C-ARDS).

Does higher or lower PEEP improve the outcomes in COVID-19 ARDS? Does individually titrated PEEP lead to better outcomes compared with PEEP set by standardised (low and high ARDS network PEEP tables) approaches? Does the individually set PEEP (best PEEP) differ from PEEP set according to the standardised approaches (low and high ARDS network PEEP tables)?

Systematic review of observational studies without metaanalysis.

We performed an extensive systematic literature search in Cochrane COVID-19 Study Register (CCSR), PubMed, Embase.com, Web of Science Core Collection, World Health Organization COVID-19 Global literature on coronavirus disease, World Health Organization International Clinical Trials Registry Platform (ICTRP), medRxiv, Cochrane Central Register of Controlled Trials until 24/01/2024.

Ventilated adult patients (≧18 years) with C-ARDS.

We screened 16 026 records, evaluated 119 full texts, and included 12 studies (n = 1431 patients) in our final data synthesis, none of them being a randomised controlled trial. The heterogeneity of study procedures and populations did not allow conduction of a meta-analysis. The results of those studies that compared lower and higher PEEP strategies in C-ARDS were ambiguous pointing out either positive effects on oxygenation with high levels of PEEP, or negative changes in lung mechanics.

The available evidence does not provide sufficient guidance for recommendations on optimal PEEP settings in C-ARDS. In general, well designed platform studies are needed to answer the questions raised in this review and, in particular, to investigate the use of individualised PEEP titration techniques and the inclusion of patients with different ARDS entities, severities and disease stages.

Our systematic review protocol was registered with the international prospective register of systematic reviews (PROSPERO 2021: CRD42021260303).

Background: Multiple studies have linked COVID-19 to a higher incidence of thromboembolic disorders. However, the association of COVID-19 with other potentially life-threatening complications, such as splanchnic vein thrombosis, is less well understood. This study aims to assess the prevalence, patient characteristics, clinical presentation, and outcomes of patients with portal vein thrombosis (PVT) and COVID-19. Methods: This was a retrospective observational study. From all positive patients for a reverse-transcription polymerase chain reaction (RT-PCR) swab test from March 2020 to June 2020, we included those who were older than 18 years, had received abdominal contrast-enhanced computed tomography (CT) in the 6 months following the positive RT-PCR swab, and had no previously known splanchnic vein thrombosis. Results: A total of 60 patients with abdominal CT were selected from all those positive for SARS-CoV-2 (n = 2987). The prevalence of PVT was 3/60 (5%). The mean age was 66.1 ± 16.5 years and 51.7% were male. In two of the three patients, there was no underlying pathology as a risk factor for PVT and one of them presented cirrhosis. The number of days from the start of COVID-19 symptoms until the PVT diagnosis were 21, 12, and 10 days. Anticoagulation treatment achieved recanalization in 100% of cases. During a mean follow-up of 803 days, none of the patients experienced long-term complications. Conclusions: Portal vein thrombosis is uncommon, and its incidence may be higher in COVID-19 patients. A greater understanding of the features of this disease in the context of COVID-19 could aid towards its diagnosis and allow for early detection and management.

To evaluate how ventilatory support, the duration of invasive ventilatory support use and lung mechanics are related to barotrauma development in patients who are severely infected with COVID-19 and who are admitted to the intensive care unit and develop pulmonary barotrauma.

Retrospective cohort study of patients who were severely infected with COVID-19 and who developed pulmonary barotrauma secondary to mechanical ventilation.

This study included 60 patients with lung barotrauma who were divided into two groups: 37 with early barotrauma and 23 with late barotrauma. The early barotrauma group included more individuals who needed noninvasive ventilation (62.2% versus 26.1%, p = 0.01). The tidal volume/kg of predicted body weight on the day of barotrauma was measured, and 24 hours later, it was significantly greater in the late barotrauma group than in the early barotrauma group. During the day, barotrauma was accompanied by plateau pressure and driving pressure accompanied by tidal volume, which significantly increased in the late barotrauma group. According to the SAPS 3, patients in the early barotrauma group had more pulmonary thromboembolism and more severe illness. However, the intensive care unit mortality rates did not significantly differ between the two groups (66.7% for early barotrauma versus 76.9% for late barotrauma).

We investigated the effect of respiratory mechanics on barotrauma in patients with severe COVID-19 and found that 25% of patients were on nonprotective ventilation parameters when they developed barotrauma. However, 50% of patients were on protective ventilation parameters, suggesting that other nonventilatory factors may contribute to barotrauma.

The coronavirus disease 2019 (COVID-19) pandemic has not only challenged global health systems but also spurred intense scientific inquiry into its pathophysiology. Among the multifaceted aspects of the disease, coagulation abnormalities have emerged as a significant contributor to morbidity and mortality. From endothelial dysfunction to dysregulated immune responses, various factors contribute to the hypercoagulable state seen in severe COVID-19 cases. The dysregulation of coagulation in COVID-19 extends beyond traditional thromboembolic events, encompassing a spectrum of abnormalities ranging from microvascular thrombosis to disseminated intravascular coagulation (DIC). Endothelial injury induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection triggers a cascade of events involving platelet activation, coagulation factor consumption, and fibrinolysis impairment. Moreover, the virus direct effects on immune cells and the cytokine storm further exacerbate the prothrombotic milieu. Unraveling this intricate web of interactions between viral pathogenesis and host responses is essential for elucidating novel therapeutic targets and refining existing management strategies for COVID-19-associated coagulopathy. In the quest to unravel the complex interplay between coagulation and COVID-19, numerous clinical and laboratory studies have yielded invaluable insights into potential biomarkers, prognostic indicators, and therapeutic avenues. Anticoagulation therapy has emerged as a cornerstone in the management of severe COVID-19, although optimal dosing regimens and patient selection criteria remain subjects of ongoing investigation. Additionally, innovative approaches such as targeting specific components of the coagulation cascade or modulating endothelial function hold promise for future therapeutic development.

It is well-described that the coronavirus disease 2019 (COVID-19) infection is associated with an increased risk of thrombotic complications. While there have been many cases of pulmonary emboli and deep vein thrombosis in these patients, reports of COVID-19 associated portal vein thrombosis (PVT) have been uncommon. We present a unique case of concomitant PVT and splenic artery thrombosis in a COVID-19 patient.

A 77-year-old-male with no history of liver disease presented with three days of left-sided abdominal pain. One week earlier, the patient was diagnosed with mildly symptomatic COVID-19 and was treated with nirmatrelvir/ritonavir. Physical exam revealed mild right and left lower quadrant tenderness, but was otherwise unremarkable. Significant laboratory findings included white blood cell count 12.5 K/μL, total bilirubin 1.6 mg/dL, aminoaspartate transferase 40 U/L, and alanine aminotransferase 61 U/L. Computed tomography of the abdomen and pelvis revealed acute PVT with thrombus extending from the distal portion of the main portal vein into the right and left branches. Also noted was a thrombus within the distal portion of the splenic artery with resulting splenic infarct. Hypercoagulable workup including prothrombin gene analysis, factor V Leiden, cardiolipin antibody, and JAK2 mutation were all negative. Anticoagulation with enoxaparin was initiated, and the patient's pain improved. He was discharged on apixaban.

It is quite uncommon for PVT to present simultaneously with an arterial thrombotic occlusion, as in the case of our patient. Unusual thrombotic manifestations are classically linked to hypercoagulable states including malignancy and hereditary and autoimmune disorders. Viral infections such as Epstein-Barr virus, cytomegalovirus, viral hepatitis, and COVID-19 have all been found to increase the risk of splanchnic venous occlusions, including PVT. In our patient, prompt abdominal imaging led to early detection of thrombus, early treatment, and an excellent outcome. This case is unique in that it is the second known case within the literature of simultaneous PVT and splenic artery thrombosis in a COVID-19 patient.

COVID-19 is a new infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). Since the outbreak in December 2019, it has caused an unprecedented world pandemic, leading to a global human health crisis. Although SARS CoV-2 mainly affects the lungs, causing interstitial pneumonia and severe acute respiratory distress syndrome, a number of patients often have extensive clinical manifestations, such as gastrointestinal symptoms, cardiovascular damage and renal dysfunction.

This review article discusses the pathogenic mechanisms of cardiovascular damage in COVID-19 patients and provides some useful suggestions for future clinical diagnosis, treatment and prevention.

An English-language literature search was conducted in PubMed and Web of Science databases up to 12th April, 2024 for the terms "COVID-19", "SARS CoV-2", "cardiovascular damage", "myocardial injury", "myocarditis", "hypertension", "arrhythmia", "heart failure" and "coronary heart disease", especially update articles in 2023 and 2024. Salient medical literatures regarding the cardiovascular damage of COVID-19 were selected, extracted and synthesized.

The most common cardiovascular damage was myocarditis and pericarditis, hypertension, arrhythmia, myocardial injury and heart failure, coronary heart disease, stress cardiomyopathy, ischemic stroke, blood coagulation abnormalities, and dyslipidemia. Two important pathogenic mechanisms of the cardiovascular damage may be direct viral cytotoxicity as well as indirect hyperimmune responses of the body to SARS CoV-2 infection.

Cardiovascular damage in COVID-19 patients is common and portends a worse prognosis. Although the underlying pathophysiological mechanisms of cardiovascular damage related to COVID-19 are not completely clear, two important pathogenic mechanisms of cardiovascular damage may be the direct damage of the SARSCoV-2 infection and the indirect hyperimmune responses.

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a global health crisis with significant neurological implications. While initially characterized by respiratory symptoms, COVID-19 has been increasingly recognized for its diverse neurological manifestations, including encephalopathy, stroke, peripheral neuropathies, and neuropsychiatric disorders. Understanding the neurological landscape of COVID-19 is essential for elucidating its pathophysiology, optimizing clinical management, and improving patient outcomes. This comprehensive review provides insights into the etiopathogenesis, clinical manifestations, diagnostic approaches, management strategies, and prognostic implications of neurological involvement in COVID-19. Mechanistic insights highlight the multifactorial nature of neurological complications involving direct viral invasion, immune-mediated mechanisms, and thrombotic events. Diagnostic challenges underscore the importance of a multidisciplinary approach to patient care, while management strategies emphasize early recognition and appropriate intervention. Long-term neurological sequelae and prognostic factors are also examined, emphasizing the need for comprehensive follow-up and rehabilitation services. Finally, recommendations for future research prioritize efforts to elucidate underlying mechanisms, identify biomarkers, and evaluate rehabilitative interventions. By addressing these challenges, we can better understand and mitigate the neurological consequences of the ongoing COVID-19 pandemic.

SARS-CoV-2 infection and COVID-19 vaccination can both lead to serious cardiac conditions such as myocarditis, arrhythmia, acute myocardial infarction, and coagulopathy. Further studies are needed to better understand the risks and benefits of COVID-19 vaccination, and to determine the best course of action for individuals with preexisting heart conditions.

The current knowledge and challenges in understanding vaccine-associated heart issues concerning the COVID-19 pandemic are briefly summarized, highlighting similar cardiac conditions caused by either SARS-CoV-2 infection or COVID-19 vaccination and the potential clinical impacts.

The short-term risks of severe cardiovascular side effects following COVID-19 vaccination are relatively low. However, further studies are needed to determine whether adverse vaccination events outweigh the long-term benefits in specific groups of individuals. Since cardiac inflammation, blood pressure dysregulation, coagulopathy, acute myocardial infarction, or arrhythmia could be the consequences of either SARS-CoV-2 infection or COVID-19 vaccination, clinical questions should be asked whether the COVID-19 vaccine worsens the condition in persons with preexisting heart diseases. It is important to carefully assess the potential risks and benefits of COVID-19 vaccination, especially for individuals with preexisting heart conditions, and to continue monitoring and studying the long-term effects of vaccination on cardiovascular health.

The coronavirus disease 2019 (COVID-19) has impacted health globally. Cumulative evidence points to long-term effects of COVID-19 such as cardiovascular and cognitive disorders, diagnosed in patients even after the recovery period. In particular, micrometer-sized blood clots and hyperactivated platelets have been identified as potential indicators of long COVID. Here, we resolve microclot structures in the plasma of patients with different subphenotypes of COVID-19 in a label-free manner, using 3D digital holo-tomographic microscopy (DHTM). Based on 3D refractive index (RI) tomograms, the size, dry mass, and prevalence of microclot composites were quantified and then parametrically differentiated from fibrin-rich microclots and platelet aggregates in the plasma of COVID-19 patients. Importantly, fewer microclots and platelet aggregates were detected in the plasma of healthy controls compared to COVID-19 patients. Our imaging and analysis workflow is built around a commercially available DHT microscope capable of operation in clinical settings with a 2 h time period from sample preparation and data acquisition to results.

Inflammation is a complex pathophysiological process underlying many clinical conditions. Platelets contribute to the thrombo-inflammatory response. Platelet P2Y12 receptors amplify platelet activation, potentiating platelet aggregation, degranulation and shape change. The contents of platelet alpha granules, in particular, act directly on leucocytes, including mediating platelet-leucocyte aggregation and activation via platelet P-selectin. Much evidence for the role of platelet P2Y12 receptors in inflammation comes from studies using antagonists of these receptors, such as the thienopyridines clopidogrel and prasugrel, and the cyclopentyltriazolopyrimidine ticagrelor, in animal and human experimental models. These suggest that antagonism of P2Y12 receptors decreases markers of inflammation with some evidence that this reduces incidence of adverse clinical sequelae during inflammatory conditions. Interpretation is complicated by pleiotropic effects such as those of the thienopyridines on circulating leucocyte numbers and of ticagrelor on adenosine reuptake. The available evidence suggests that P2Y12 receptors are prominent mediators of inflammation and P2Y12 receptor antagonism as a potentially powerful strategy in a broad range of inflammatory conditions. LINKED ARTICLES: This article is part of a themed issue on Platelet purinergic receptor and non-thrombotic disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.4/issuetoc.

Background: COVID-19 usually complicates respiratory failure; microvascular, macrovascular, and renal complications are common. Both micro and macrovascular complications are associated with multi-organ dysfunction and in-hospital mortality. Thrombotic microangiopathy (TMA) causes microvascular thromboses associated with organ failure, including acute kidney injury (AKI). Materials and Methods: This Retrospective Cohort study included 100 COVID-19 patients with thrombocytopenia, followed up in a university hospital's intensive care unit (ICU). The primary endpoints were in-hospital mortality or discharge from the hospital and assessing the occurrence of TMA and AKI during the hospitalization. The effect of thrombotic microangiopathy and acute kidney injury on mortality was investigated using logistic regression models in Stata software version 12.1. Results: The TMA and AKI were associated with in-hospital mortality in COVID-19 patients presenting with thrombocytopenia in multivariate regression analysis, adjusted for other variables. The effect of AKI on mortality was obtained (adjusted OR 4.09, 95% CI: 1.33-12.53, p = 0.01). Moreover, the odds of mortality due to TMA were ten-fold higher in the patients who had TMA than those who did not (adjusted OR 10.26, 95% CI: 1.26-83.76, p = 0.03). Conclusion: We outlined TMA in COVID-19 patients, which could be responsible for kidney injury and mortality in critically COVID-19 patients.

Little information is available regarding incidence and severity of pulmonary embolism (PE) across the periods of ancestral strain, Alpha, Delta, and Omicron variants. The aim of this study is to investigate the incidence and severity of PE over the dominant periods of ancestral strain and Alpha, Delta, and Omicron variants. We hypothesized that the incidence and the severity by proximity of PE in patients with the newer variants and vaccination would be decreased compared with those in ancestral and earlier variants. Patients with COVID-19 diagnosis between March 2020 and February 2022 and computed tomography pulmonary angiogram performed within a 6-week window around the diagnosis (-2 to +4 weeks) were studied retrospectively. The primary endpoints were the associations of the incidence and location of PE with the ancestral strain and each variant. Of the 720 coronavirus disease 2019 patients with computed tomography pulmonary angiogram (58.6 ± 17.2 years; 374 females), PE was diagnosed among 42/358 (12%) during the ancestral strain period, 5/60 (8%) during the Alpha variant period, 16/152 (11%) during the Delta variant period, and 13/150 (9%) during the Omicron variant period. The most proximal PE (ancestral strain vs variants) was located in the main/lobar arteries (31% vs 6%-40%), in the segmental arteries (52% vs 60%-75%), and in the subsegmental arteries (17% vs 0%-19%). There was no significant difference in both the incidence and location of PE across the periods, confirmed by multivariable logistic regression models. In summary, the incidence and severity of PE did not significantly differ across the periods of ancestral strain and Alpha, Delta, and Omicron variants.

The newly introduced COVID-19 vaccines have reduced disease severity and hospitalizations. However, they do not significantly prevent infection or transmission. In the same context, measuring IgM and IgG antibody levels is important, but it does not provide information about the status of the mucosal immune response. This article describes a comprehensive mapping of IgA epitopes of the S protein, its cross-reactivity, and the development of an ELISA-peptide assay.

IgA epitope mapping was conducted using SPOT synthesis and sera from RT-qPCR COVID-19-positive patients. Specific and cross-reacting epitopes were identified, and an evolutionary analysis from the early Wuhan strain to the Omicron variant was performed using bioinformatics tools and a microarray of peptides. The selected epitopes were chemically synthesized and evaluated using ELISA-IgA.

A total of 40 IgA epitopes were identified with 23 in S1 and 17 in the S2 subunit. Among these, at least 23 epitopes showed cross-reactivity with DENV and other organisms and 24 showed cross-reactivity with other associated coronaviruses. Three MAP4 polypeptides were validated by ELISA, demonstrating a sensitivity of 90-99.96% and a specificity of 100%. Among the six IgA-RBD epitopes, only the SC/18 epitope of the Omicron variants (BA.2 and BA.2.12.1) presented a single IgA epitope.

This research unveiled the IgA epitome of the S protein and identified many epitopes that exhibit cross-reactivity with DENV and other coronaviruses. The S protein of variants from Wuhan to Omicron retains many conserved IgA epitopes except for one epitope (#SCov/18). The cross-reactivity with DENV suggests limitations in using the whole S protein or the S1/S2/RBD segment for IgA serological diagnostic tests for COVID-19. The expression of these identified specific epitopes as diagnostic biomarkers could facilitate monitoring mucosal immunity to COVID-19, potentially leading to more accurate diagnoses and alternative mucosal vaccines.

COVID-19 induces endotheliitis and one of the main complications is enhanced coagulation. The incidence of pulmonary embolism (PE) in COVID-19 (CPE) has increased and clinical features for a rigorous analysis still need to be determined. Thus, we evaluated the clinical characteristics in CPE and the immune infiltration that occurred. Between January 1 and December 31, 2021, 38 patients were affected by CPE (9 ICU, 19 males/19 females, 70.18 ± 11.24 years) out of 459 COVID-19 cases. Controls were subjects who were evaluated for PE between January 1 2015, and December 31, 2019 (92 patients, 9 ICU, 48 males/45 females, 69.55 ± 16.59 years). All patients underwent complete physical examination, pulmonary computed tomography, laboratory tests, D-dimer, and blood gas analysis. There were no differences in laboratory tests or D-dimer. In patients with CPE, pO2, alveolar-arterial oxygen difference (A-aDO2), oxygen saturation %, and the ratio between arterial partial pressure of oxygen (PaO2) and fraction of inspired oxygen (FiO2), P/F, were significantly increased. There were no differences in PaCO2. Platelet count was inversely correlated to P/F (r = - 0.389, p = 0.02) but directly to A-aDO2 (r = 0.699, p = 0.001) only in patients with CPE. Histology of lung biopsies (7 CPE/7 controls) of patients with CPE showed an increase in CD15+ cells, HMGB1, and extracellular MPO as a marker of NETosis, while no significant differences were found in CD3+, CD4+, CD8+, and intracellular MPO. Overall, data suggest that CPE has a different clinical setting. Reduced oxygen content and saturation described in Patients with CPE should not be considered a trustworthy sign of disease. Increased A-aDO2 may indicate that CPE involves the smallest vessels as compared to classical PE. The significant difference in NETosis may suggest the mechanism related to thrombi formation.

Coronavirus disease 2019 (COVID-19) is linked with major coagulation disorders, especially higher risk of developing pulmonary embolism (PE). Our study summarizes COVID-19 patients' management with concomitant PE during the first weeks of pandemic and underlines the importance of D-dimer concentration assessment at admission in terms of prognosis.

Study group consisted of 107 outpatients (mean age 68.91 ​± ​12.83 years) admitted to the Temporary COVID-19 Hospital in Bialystok, Poland with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and suspicion of PE based on elevated D-dimer concentration (>500 ​μg/l) and/or low saturation rate (<90%). The clinical follow-up lasted 6 months. Death or re-hospitalization were used as composite clinical endpoint (CEP).

Cumulative incidence of PE was 62.3% (73/107 patients). Most of the patients were in the intermediate PE risk group according to the pulmonary embolism severity index (PESI) score. The mean total computed tomography (CT) lung involvement of COVID-19 findings was 48.42 ​± ​27.71%. Neither D-dimers nor NT-proBNP concentrations correlated significantly with the percentage of lung abnormalities in CT. Patients with baseline D-dimer concentration higher than 1429 ​μg/l had worse prognosis in 6-months observation, log-rank test, p ​= ​0.009.

Ongoing SARS-CoV-2 infection along with massive involvement of lung tissue and concomitant thrombi in pulmonary arteries are challenging for physicians. It seems that simple D-dimer concentration assessment at admission may be a helpful tool not only to predict PE but also to estimate the long-term prognosis.

To assess sociodemographic, medical complexity, and outcomes of persons receiving care at inpatient rehabilitation facilities (IRFs) with and without a diagnosis of COVID-19.

A retrospective cohort study using electronic medical record (EMR) data from 138 IRFs across 34 states and Puerto Rico.

N/A.

IRF EMR data for 212,663 patients discharged between 04/01/2020 and 05/31/2021 (N=212,663), of which 16,199 (COVID-19 group) had a primary or secondary COVID-19 diagnosis based upon ICD codes set (ICD-10 codes U07.1, B94.8, Z86.19, Z86.16).

Four categories: (a) sociodemographic, (b) medical complexity, (c) process, that is, standard IRF processes, and clinical outcomes (collected routinely as part of administrative reporting), and (d) functional outcomes. Patients with missing functional data associated with short/incomplete stays (n=623) were excluded from analysis of functional outcomes category only. Standard descriptive analysis techniques were employed for comparing categorical and continuous variables between groups.

Statistically significant differences were noted between the COVID-19 group and non-COVID groups for race (26.0% vs 19.7% non-minority, P<.001), Case Mix Index (1.49 vs 1.46, P<.001), Center for Medicare and Medicaid Services 60% rule qualification (79.0% vs 73.4%, P<.001), time to onset (24.3 vs 18.0 days, P<.001), length of stay (14.2 vs 12.9 days, P<.001), and discharge disposition (to community: 75.3% vs 81%, P<.001; to acute care facility: 15.6% vs 10.8%, P<.001). The COVID-19 group had higher frequency of respiratory and cardiovascular disease, diabetes, encephalopathy, morbid obesity, and critical illness neuropathy and myopathy. Clinically insignificant differences were noted for age, sex, depression, and cognitive assessment. Ability to participate and functional outcomes were comparable between the groups.

There are significant differences between the COVID-19 and non-COVID group in some sociodemographic, medical complexity, process and clinical outcomes, but not in functional outcomes. The ability to participate in the IRF-required intensity of therapy services along with attainment of comparable levels of functional outcomes supports the benefit of IRFs for persons with COVID-19.

COVID-19 is associated with an increased risk of venous thromboembolism (VTE). This study examined the prevalence of VTE among acute ischaemic stroke (AIS) patients with and without a history of COVID-19.

We identified AIS hospitalisations of Medicare fee-for-service (FFS) beneficiaries aged ≥65 years from 1 April 2020 to 31 March 2022. We compared the prevalence and adjusted prevalence ratio of VTE among AIS patients with and without a history of COVID-19.

Among 283 034 Medicare FFS beneficiaries with AIS hospitalisations, the prevalence of VTE was 4.51%, 2.96% and 2.61% among those with a history of hospitalised COVID-19, non-hospitalised COVID-19 and without COVID-19, respectively. As compared with patients without a history of COVID-19, the prevalence of VTE among patients with a history of hospitalised or non-hospitalised COVID-19 were 1.62 (95% CI 1.54 to 1.70) and 1.13 (95% CI 1.03 to 1.23) times greater, respectively.

There appeared to be a notably higher prevalence of VTE among Medicare beneficiaries with AIS accompanied by a current or prior COVID-19. Early recognition of coagulation abnormalities and appropriate interventions may help improve patients' clinical outcomes.

Microvascular thrombosis is a typical symptom of COVID-19 and shows similarities to thrombosis. Using a microfluidic imaging flow cytometer, we measured the blood of 181 COVID-19 samples and 101 non-COVID-19 thrombosis samples, resulting in a total of 6.3 million bright-field images. We trained a convolutional neural network to distinguish single platelets, platelet aggregates, and white blood cells and performed classical image analysis for each subpopulation individually. Based on derived single-cell features for each population, we trained machine learning models for classification between COVID-19 and non-COVID-19 thrombosis, resulting in a patient testing accuracy of 75%. This result indicates that platelet formation differs between COVID-19 and non-COVID-19 thrombosis. All analysis steps were optimized for efficiency and implemented in an easy-to-use plugin for the image viewer napari, allowing the entire analysis to be performed within seconds on mid-range computers, which could be used for real-time diagnosis.

Coronavirus disease 19 (COVID-19) has shown to be an infectious disease affecting not only of the respiratory system, but also cardiovascular system leading to different COVID-19-associated vasculopathies. Venous and arterial thromboembolic events have been frequently described among hospitalized patients with COVID-19 and inflammatory vasculopathic changes have also been observed. Several of the reported COVID-19 associated vasculopathies exhibit differences on epidemiology, clinical characteristics and outcome compared to non-COVID-19 types. This review focuses on the epidemiology, clinical, diagnostic and therapeutic characteristics as well as outcome data of COVID-19 associated thromboembolic events and inflammatory vasculopathies, elaborating similarities and differences with non-COVID-19 cohorts.

Infection with viral pneumonia (PNA) is known to offset the coagulation cascade. Recent studies assessing novel SARS-CoV-2 infection observed a high frequency of systemic thrombotic events resulting in ambiguity if severity of infection or specific viral strain drive thrombosis and worsen clinical outcomes. Furthermore, limited data exists addressing SARS-CoV-2 in underrepresented patient populations.

Assess clinical outcomes events and death in patients diagnosed with SARS-CoV-2 pneumonia compared to patients with other types of viral pneumonia.

Retrospective cohort study evaluated electronic medical records in adult patients admitted to University of Illinois Hospital and Health Sciences System (UIHHSS) with primary diagnosis of SARS-CoV-2 PNA or other viral (H1N1 or H3N2) PNA between 10/01/2017 and 09/01/2020. Primary composite outcome was the following event incidence rates: death, ICU admission, infection, thrombotic complications, mechanical ventilation, renal replacement therapy, and major bleeding.

Of 257 patient records, 199 and 58 patients had SARS-CoV-2 PNA and other viral PNA, respectively. There was no difference in primary composite outcome. Thrombotic events (n = 6, 3%) occurred solely in SARS-CoV-2 PNA patients in the ICU. A significantly higher incidence of renal replacement therapy (8.5% vs 0%, p=0.016) and mortality (15.6% vs 3.4%, p=0.048) occurred in the SARS-CoV-2 PNA group. Multivariable logistic regression analysis revealed age, presence of SARS-CoV-2, and ICU admission, aOR 1.07, 11.37, and 41.95 respectively, was significantly associated with mortality risk during hospitalization; race and ethnicity were not.

Low overall incidence of thrombotic events occurred only in the SARS-CoV-2 PNA group. SARS-CoV-2 PNA may lead to higher incidence of clinical events than those observed in H3N2/H1N1 viral pneumonia, and that race/ethnicity does not drive mortality outcomes.

Covid-19 is linked with the development of cardio-metabolic disorders, including dyslipidemia, dysregulation of high-density lipoprotein (HDL), and low-density lipoprotein (LDL). Furthermore, SARS-Co-2 infection is associated with noteworthy changes in lipid profile, which is suggested as a possible biomarker to support the diagnosis and management of Covid-19.

This paper adopts the literature review method to obtain information about how Covid-19 affects high-risk group patients and may cause severe and critical effects due to the development of acute lung injury and acute respiratory distress syndrome. A narrative and comprehensive review is presented.

Reducing HDL in Covid-19 is connected to the disease severity and poor clinical outcomes, suggesting that high HDL serum levels could benefit Covid-19. SARS-CoV-2 binds HDL, and this complex is attached to the co-localized receptors, facilitating viral entry. Therefore, SARS-CoV-2 infection may induce the development of dysfunctional HDL through different mechanisms, including induction of inflammatory and oxidative stress with activation of inflammatory signaling pathways. In turn, the induction of dysfunctional HDL induces the activation of inflammatory signaling pathways and oxidative stress, increasing Covid-19 severity.

Covid-19 is linked with the development of cardio-metabolic disorders, including dyslipidemia in general and dysregulation of high-density lipoprotein and low-density lipoprotein. Therefore, the present study aimed to overview the causal relationship between dysfunctional high-density lipoprotein and Covid-19.

Coronavirus disease 2019 (COVID-19), a global pandemic, has infected approximately 10% of the world's population. This comprehensive review aimed to determine the prevalence of various neurological disorders in COVID-19 without overlapping meta-analysis errors.

We searched for meta-analyses on neurological disorders following COVID-19 published up to March 14, 2023. We obtained 1,184 studies, of which 44 meta-analyses involving 9,228,588 COVID-19 patients were finally included. After confirming the forest plot of each study and removing overlapping individual studies, a re-meta-analysis was performed using the random-effects model.

The summarized combined prevalence of each neurological disorder is as follows: stroke 3.39% (95% confidence interval, 1.50-5.27), dementia 6.41% (1.36-11.46), multiple sclerosis 4.00% (2.50-5.00), epilepsy 5.36% (-0.60-11.32), Parkinson's disease 0.67% (-1.11-2.45), encephalitis 0.66% (-0.44-1.77), and Guillain-Barré syndrome 3.83% (-0.13-7.80). In addition, the mortality risk of patients with comorbidities of COVID-19 is as follows: stroke OR 1.63 (1.23-2.03), epilepsy OR 1.71 (1.00-2.42), dementia OR 1.90 (1.31-2.48), Parkinson's disease OR 3.94 (-2.12-10.01).

Our results show that the prevalence and mortality risk may increase in some neurological diseases during the COVID-19 pandemic. Future studies should elucidate the precise mechanisms for the link between COVID-19 and neurological diseases, determine which patient characteristics predispose them to neurological diseases, and consider potential global patient management.

Galectin-3 (Gal-3), multifunctional protein plays important roles in inflammatory response, infection and fibrosis. The goal of study was to determine the association of Gal-3, immune response, clinical, biochemical, and radiographic findings with COVID-19 severity. Study included 280 COVID-19 patients classified according to disease severity into mild, moderate, severe and critical group. Cytokines, clinical, biochemical, radiographic data and peripheral blood immune cell make up were analyzed. Patients in critical group had significantly higher serum level of Gal-3, IL-1β, TNF-α, IL-12, IL-10 compared to the patients in less severe stages of disease. Strong positive correlation was detected between Gal-3 and IL-1β, moderate positive correlation between Gal-3, TNF-α and IL-12, moderate negative correlation between Gal-3, IL-10/IL-1β and IL-10/TNF-α. Moderate positive correlation noted between Gal-3 and urea, D dimer, CXR findings. Strong negative correlation detected between Gal-3 and p0₂, Sa0_2, and moderate negative correlation between Gal-3, lymphocyte and monocyte percentage. In the peripheral blood of patients with more severe stages of COVID-19 we detected significantly increased percentages of CD56^- CD3⁺TNF-α⁺T cells and CD56^- CD3⁺Gal-3⁺T cells and increased expression of CCR5 in PBMCs. Our results predict Gal-3 as an important marker for critical stage of COVID-19. Higher expression of Gal-3, TNF-α and CCR5 on T cells implicate on promoting inflammation and more severe form of disease.

A man in his late 50s was admitted with a 10-day history of right frontotemporal headache, left arm and leg weakness, and a sudden decline in visual acuity in the right eye. The patient had recent exposure to COVID-19 infection and tested positive for the same on admission. A CT scan of the head done on arrival demonstrated a subarachnoid haemorrhage in the right central sulcus with an underlying superior sagittal sinus thrombosis. No other known risk factors for central venous sinus thrombosis could be identified. The patient had a normal level of consciousness on admission clinically; however, he was in severe pain. A collective decision was made to administer anticoagulants to the patient with heparin after carefully deliberating the risk-to-benefit ratio of a superior sagittal thrombus with an associated subarachnoid haemorrhage. Our patient recovered and was discharged after 2 weeks on warfarin. We present this case to highlight the potential risks of hypercoagulable and neurotropic complications of COVID-19 infections, with special emphasis on cerebral venous thrombosis.

Background: Echocardiographic Pulmonary to Left Atrial Ratio (ePLAR) represents an accurate and sensitive non-invasive tool to estimate the trans-pulmonary gradient. The prognostic value of ePLAR in hospitalized patients with COVID-19 remains unknown. We aimed to investigate the predictive value of ePLAR on in-hospital mortality in patients with COVID-19. Methods: One hundred consecutive patients admitted to two Italian institutions for COVID-19 undergoing early (<24 h) echocardiographic examination were included; ePLAR was determined from the maximum tricuspid regurgitation continuous wave Doppler velocity (m/s) divided by the transmitral E-wave: septal mitral annular Doppler Tissue Imaging e′-wave ratio (TRVmax/E:e′). The primary outcome measure was in-hospital death. Results: patients who died during hospitalization had at baseline a higher prevalence of tricuspid regurgitation, higher ePLAR, right-side pressures, lower Tricuspid Annular Plane Systolic Excursion (TAPSE)/ systolic Pulmonary Artery Pressure (sPAP) ratio and reduced inferior vena cava collapse than survivors. Patients with ePLAR > 0.28 m/s at baseline showed non-significant but markedly increased in-hospital mortality compared to those having ePLAR ≤ 0.28 m/s (27% vs. 10.8%, p = 0.055). Multivariate Cox regression showed that an ePLAR > 0.28 m/s was independently associated with an increased risk of death (HR 5.07, 95% CI 1.04−24.50, p = 0.043), particularly when associated with increased sPAP (p for interaction = 0.043). Conclusions: A high ePLAR value at baseline predicts in-hospital death in patients with COVID-19, especially in those with elevated pulmonary arterial pressure. These results support an early ePLAR assessment in patients admitted for COVID-19 to identify those at higher risk and potentially guide strategies of diagnosis and care.

The study aimed to determine how physicians' professional and institutional characteristics affect their treatment approaches for COVID-19 antiviral and supportive treatment, as well as their demographic characteristics and participation in COVID-19 trainings that may influence these orientations.

After researching the literature and conducting interviews with the experts, a questionnaire was prepared. The convenience sampling method was used to distribute the questionnaire online to 408 physicians across the nation in January 2021. Exploratory factor analysis was used to verify the research scale, and the Cronbach's Alpha test was used to confirm its reliability. During the data analysis, descriptive and inferential statistical tests were used.

It was observed that the physicians were willing to give COVID-19 patients the antivirals but hesitant to provide and suggest supportive care. The training status for COVID-19 treatment was varied. Female physicians prescribed more antiviral drugs than male physicians, received more training, and scored higher across the scale than male physicians ( p = 0.001). The treatment approaches of physicians varied according to their specializations ( p = 0.002) all over the scale.

The publication of current Ministry of Health guidelines on a variety of themes related to COVID-19 treatment, as seen in Turkey, is both beneficial and important. However, because all physicians, regardless of specialty, are affected by current and will be in the future pandemics, it is necessary to design and maintain a continuous training program on pandemics and their management for all physicians.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been demonstrated as a major risk factor in inducing coronary stent thrombosis due to its propensity to create a pro-thrombotic state. This review explores the mechanisms that may contribute to the increased thrombosis risk seen in COVID-19. Furthermore, we discuss the patient and haematological factors that predispose to an increased risk of stent thrombosis, as well as the role of certain antiplatelet and anticoagulation therapies, including ticagrelor and enoxaparin, that may reduce the likelihood and severity of in-stent thrombosis, in SARS-CoV-2 infection. To counter the proinflammatory and pro-thrombotic state shown in COVID-19, anti-thrombotic therapy in the future may be optimised using point-of-care platelet inhibition testing and inflammation-modifying therapies. Large-scale randomised trials with long-term follow-up are increasingly necessary to assess the intersection of COVID-19 and stent optimisation as well as the reduction of stent thrombosis after drug-eluting stent (DES) implantation.

Fibrin-rich clot formation in thrombo-occlusive pathologies is currently treated by systemic administration of plasminogen activators (e.g. tPA), to convert fibrin-associated plasminogen to plasmin for fibrinolytic action. However, this conversion is not restricted to clot site only but also occurs on circulating plasminogen, causing systemic fibrinogenolysis and bleeding risks. To address this, past research has explored tPA delivery using clot-targeted nanoparticles.

We designed a nanomedicine system that can (1) target clots via binding to activated platelets and fibrin, (2) package plasmin instead of tPA as a direct fibrinolytic agent, and (3) release this plasmin triggered by thrombin for clot-localized action.

Clot-targeted thrombin-cleavable nanoparticles (CTNPs) were manufactured using self-assembly of peptide-lipid conjugates. Plasmin loading and its thrombin-triggered release from CTNPs were characterized by UV-visible spectroscopy. CTNP-targeting to clots under flow was studied using microfluidics. Fibrinolytic effect of CTNP-delivered plasmin was studied in vitro using BioFlux imaging and D-dimer analysis and in vivo in a zebrafish thrombosis model.

Plasmin-loaded CTNPs significantly bound to clots under shear flow and showed thrombin-triggered enhanced release of plasmin. BioFlux studies confirmed that thrombin-triggered plasmin released from CTNPs rendered fibrinolysis similar to free plasmin, further corroborated by D-dimer analysis. In the zebrafish model, CTNP-delivered plasmin accelerated time-to-recanalization, or completely prevented occlusion when infused before thrombus formation.

Considering that the very short circulation half-life (<1 second) of plasmin prevents its systemic use but also makes it safer without off-target drug effects, clot-targeted delivery of plasmin using CTNPs can enable safer and more efficacious fibrinolytic therapy.

Severe acute respiratory syndrome Coronavirus-2 invades the cells via ACE2 receptor and damages multiple organs of the human body. Understanding the pathological manifestation is mandatory to endure the rising post-infection sequel reported in patients with or without comorbidities.

Our descriptive review emphasises the direct, indirect and post-infection damages due to COVID-19. We have performed an electronic database search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines with selective inclusion and exclusion criteria.

The included studies substantiated the extensive damages in the multiple organs due to direct and indirect consequences of COVID-19. After an apparent recovery, the prolonged presentation of the symptoms manifests as post-COVID that can be related with persisting viral antigens and dysregulated immune response.

A few of the symptoms of respiratory, cardiovascular, and neuropsychiatric systems that persist or reappear as post-COVID manifestations. Vaccination and preventive programs will effectively reduce the prevalence but, the post-COVID, a multisystem manifestation, will be a significant tribulation to the medical profession. However, the issue can be managed by implementing public health programs, rehabilitation services, and telemedicine virtual supports to raise awareness and reduce panic.

Severe coronavirus disease-19 (COVID-19) has been associated with fibrin-mediated hypercoagulability and thromboembolic complications. To evaluate potential biomarkers of coagulopathy and disease severity in COVID-19, we measured plasma levels of eight biomarkers potentially associated with coagulation, fibrinolysis, and platelet function in 43 controls and 63 COVID-19 patients, including 47 patients admitted to the intensive care unit (ICU) and 16 non-ICU patients. COVID-19 patients showed significantly elevated levels of fibrinogen, tissue plasminogen activator (t-PA), and its inhibitor plasminogen activation inhibitor 1 (PAI-1), as well as ST2 (the receptor for interleukin-33) and von Willebrand factor (vWF) compared to the control group. We found that higher levels of t-PA, ST2, and vWF at the time of admission were associated with lower survival rates, and that thrombotic events were more frequent in patients with initial higher levels of vWF. These results support a predictive role of specific biomarkers such as t-PA and vWF in the pathophysiology of COVID-19. The data provide support for the case that hypercoagulability in COVID-19 is fibrin-mediated, but also highlights the important role that vWF may play in the genesis of thromboses in the pathophysiology of COVID-19. Interventions designed to enhance fibrinolysis might prove to be useful adjuncts in the treatment of coagulopathy in a subset of COVID-19 patients.

Coronavirus disease-19 (COVID-19) patients are prone to thrombotic complications that may increase morbidity and mortality. These complications are thought to be driven by endothelial activation and tissue damage promoted by the systemic hyperinflammation associated with COVID-19. However, the exact mechanisms contributing to these complications are still unknown. To identify additional mechanisms contributing to the aberrant clotting observed in COVID-19 patients, we analyzed platelets from COVID-19 patients compared to those from controls using mass spectrometry. We identified increased serum amyloid A (SAA) levels, an acute-phase protein, on COVID-19 patients' platelets. In addition, using an in vitro adhesion assay, we showed that healthy platelets adhered more strongly to wells coated with COVID-19 patient serum than to wells coated with control serum. Furthermore, inhibitors of integrin aIIbβ3 receptors, a mediator of platelet-SAA binding, reduced platelet adhesion to recombinant SAA and to wells coated with COVID-19 patient serum. Our results suggest that SAA may contribute to the increased platelet adhesion observed in serum from COVID-19 patients. Thus, reducing SAA levels by decreasing inflammation or inhibiting SAA platelet-binding activity might be a valid approach to abrogate COVID-19-associated thrombotic complications.

Background: Thrombotic conditions triggered by SARS-CoV-2 virus can result in high mortality, especially in pregnant women as they are already in a hypercoagulability state. This thereby leads to excessive inflammation that will increase the risk of thromboembolic (TE) complications. Objective: The aim of this study is to review the prevalence of thromboembolic complications such as deep venous thrombosis, pulmonary embolism, and intervillous thrombosis, and their preventive strategies among pregnant women infected with COVID-19. Method: The articles were retrieved from online databases PubMed and ScienceDirect published from February 2020 to April 2022. Findings: A total of 5249 participants including 5128 pregnant women and 121 placentas from 19 studies were identified for having TE complications after being infected with COVID-19. The types of TE complications that developed within pregnant women were disseminated intravascular coagulation (DIC) (n = 44, 0.86%), unmentioned thromboembolic complications (TE) (n = 14, 0.27%), intervillous thrombosis (IVT) (n = 9, 0.18%), pulmonary embolism (PE) (n = 6, 0.12%), COVID-19 associated coagulopathy (CAC) (n = 5, 0.10%), and deep venous thrombosis (DVT) (n = 2, 0.04%). Whereas the prevalence of TE complications reported from studies focusing on placenta were IVT (n = 27, 22.3%), subchorionic thrombus (SCT) (n = 9, 7.44%), and placental thrombosis (n = 5, 4.13%). Thromboprophylaxis agent used among pregnant women include low molecular weight heparin (LMWH) at prophylactic dose (n = 9). Conclusions: The prevalence of thromboembolic complications among pregnant women infected by COVID-19 is low with DIC being the most common form and placental thrombosis being the least common form of TE complications that occurred within pregnant women infected with COVID-19. Anticoagulation, in particular LMWH (variable dose), is frequently used to prevent TE complications.

The coronavirus disease 2019 (COVID-19) continues to be a devastating disease for the elderly population, especially in long-term care facilities, and it presents with varying clinical presentations. We have ample evidence that COVID-19 can predispose to deep vein thrombosis (DVT) and pulmonary embolism (PE) during an active infection. Still, very few cases of DVT have been reported after recovery from COVID-19. The imbalance of the coagulation cascade and the increased release of certain coagulation factors play an essential role in promoting hypercoagulability and vascular endothelial dysfunction. It leads to a rise in the level of fibrin degradation products, D-dimers, which can remain elevated for up to several weeks, even after recovery. It has been suggested that the risk of DVT occurring after recovering from COVID-19 remains high for up to three months. We report a case of a 77-year-old long-term care female resident at a nursing facility, ambulatory at baseline, who was noted to be COVID-19 positive upon routine facility-wide testing per department of health guidelines. She was asymptomatic during her 10-day quarantine period. D-dimer levels during routine labs were high (initial D-dimer level of 1.87 mg/L FEU {normal value: 0.19-0.52 mg/L FEU}), but the patient had no clinical signs and symptoms of DVT. Ultrasound of the bilateral legs was not performed due to low clinical suspicion. The patient received an enoxaparin DVT prophylaxis dose during the quarantine period. Follow-up D-dimer levels were done at frequent intervals after recovery, but D-dimer levels continued to remain elevated up till six weeks after her 10-day quarantine period ended. Based on previous experience with other long-term care residents who suffered from COVID-19, bilateral lower extremity ultrasound was performed, which showed bilateral DVT. Elevated D-dimer levels are a predictor of hypercoagulation complications in COVID-19. Patients with persistently elevated D-dimer levels after recovery from COVID-19 should be screened for thromboembolic complications, even if they are asymptomatic. DVT can occur up to three months post-recovery from COVID-19 infection.

Acquired antibodies against factor II (prothrombin) are rare and most commonly associated with severe liver disease or vitamin K antagonist treatment. In very rare cases, these antibodies and associated hypoprothrombinemia are found in patients with lupus anticoagulant (LAC), an antiphospholipid antibody that inhibits phospholipid-dependent coagulation tests. This uncommon entity, called lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS), may cause both severe, life-threatening bleeding and a predisposition to thrombosis. Coronavirus disease 2019 (COVID-19) is associated with a variety of coagulation abnormalities and an increased risk of thrombosis. Bleeding may occur, but it is less common than thromboembolism and has mostly been described in association with the severity of the disease and anticoagulation treatment in hospitalized patients, rarely in the post-acute phase of the disease. We report on a case of an 80-year-old man who developed LAHPS with prothrombin antibodies and severe bleeding after COVID-19.