Prognostic Significance of the Coagulation and Complement Systems in Critical COVID-19 Infection.

Infection with the SARS-CoV-2 virus (COVID-19 disease) can cause a wide range of clinical situations - from an asymptomatic state to fatal outcomes. In cases of serious clinical manifestations, the underlying mechanisms involve a number of immune cells and stromal cells as well as their products such as pro-inflammatory interleukin-6 and tumour necrosis factor-alpha that ultimately cause the cytokine storm. The situation of overproduction of pro-inflammatory cytokines is somewhat similar to, though in a mild form, health conditions in obesity and related metabolic disorders like type-2 diabetes, which are also considered important risk factors for severe illness in COVID-19. Interestingly, neutrophils perhaps play a significant role in this pathogenesis. On the other hand, it is thought that COVID-19-related critical illness is associated with pathological hyperactivity of the complement system and coagulopathy. Although the precise molecular interactions between the complement and coagulation systems are not clear, we observe an intimate cross-talk between these two systems in critically ill COVID-19 patients. It is believed that both of these biological systems are connected with the cytokine storm in severe COVID-19 disease and actively participate in this vicious cycle. In order to hinder the pathological progression of COVID-19, a number of anticoagulation agents and complement inhibitors have been used with varying success. Among these drugs, low molecular weight heparin enoxaparin, factor Xa inhibitor apixaban, and complement C5 inhibitor eculizumab have been commonly used in patients with COVID-19. Our overall experience might help us in the future to tackle any such conditions.

Update on Innate Immunity in Acute Kidney Injury-Lessons Taken from COVID-19.

The serious clinical course of SARS-CoV-2 infection is usually accompanied by acute kidney injury (AKI), worsening prognosis and increasing mortality. AKI in COVID-19 is above all a consequence of systemic dysregulations leading to inflammation, thrombosis, vascular endothelial damage and necrosis. All these processes rely on the interactions between innate immunity elements, including circulating blood cells, resident renal cells, their cytokine products, complement systems, coagulation cascades and contact systems. Numerous simultaneous pathways of innate immunity should secure an effective host defense. Since they all form a network of cross-linked auto-amplification loops, uncontrolled activation is possible. When the actions of selected pathways amplify, cascade activation evades control and the propagation of inflammation and necrosis worsens, accompanied by complement overactivity and immunothrombosis. The systemic activation of innate immunity reaches the kidney, where the damage affecting single tubular cells spreads through tissue collateral damage and triggers AKI. This review is an attempt to synthetize the connections between innate immunity components engaged in COVID-19-related AKI and to summarize the knowledge on the pathophysiological background of processes responsible for renal damage.

D-Dimer Level Among COVID-19 Patients as Biological Mediator for Hyper Coagulation State.

<b>Background and Objective:</b> Viremia due to SARS-CoV-2 lead variety of biochemical change in the human body, which play a crucial role in the activation of the coagulation cascade causing thrombotic complications and coagulopathies. The study aimed<i> </i>to ascertain the D-dimer level as a biological mediator in COVID-19 patients in Khartoum state and compare the results to the control group. <b>Materials and Methods:</b> A cross-sectional study was conducted during the period of August to December, 2021, including 50 healthy patients and 50 COVID-19 patients, blood samples were collected from study groups for measurement of D-dimer level using an I Chroma device. Statistical analysis was conducted using SSPS version 21. <b>Results:</b> This study revealed a statistically increased D-dimer level among COVID-19 patients compared with the control group (2000-10000 vs. up to 500 ng mL¹), respectively. <b>Conclusion:</b> Viremia induced by COVID-19 infection can cause a high D-dimer level which can lead to thrombosis event or bleeding tendency.

Prognostic factors for predicting severity and mortality in hospitalized COVID-19 patients.

BACKGROUND: Coronavirus disease 2019, COVID-19, has reached all the corners of the world and was declared by the WHO as a global pandemic and public health emergency of international concern on the January 31, 2020. Allocating quick and specific biomarkers to predict the disease severity upon admission to hospital became a crucial need. This study, therefore, aimed at exploring the relationship between laboratory results in COVID-19 patients admitted to hospital and the final outcome in these patients. METHODS: Retrospective analysis was performed on the medical records of 310 COVID-19-positive patients admitted to Uhod Hospital, the referral hospital in the area of Madinah, Kingdom of Saudi Arabia, between the April 13 and the July 29, 2020. The association of laboratory results with the survival/mortality outcomes was studied. RESULTS: It was demonstrated that lymphopenia, prolonged aPTT, high INR, high D. dimer and high CK are valuable prognostic predictors of the severity of the disease at early stages that can determine the outcome. Based on the results of the multiple logistic regression, the variables that are associated with death outcome are aPTT, HR, RR, ALT and CK level CONCLUSION: It is proposed to perform these tests on admission to hospital for moderate to severe COVID-19 patients to improve the management of those cases and reduce mortality.

Case reports of cerebral sinus venous thrombosis in COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic has started in December 2019 and still ongoing. The disease has been expanding rapidly with a high variety of phenotypes from asymptomatic, mild respiratory tract infection, multiple organ system dysfunction, and death. Neurological manifestations also appear in patients with COVID-19, such as headache, seizures, a decrease of consciousness, and paralysis. The hypercoagulable state in patients with COVID-19 is associated with the thromboembolic incident including ischemic strokes, venous thromboembolism, pulmonary artery embolism, and many further. Cerebral sinus venous thrombosis (CSVT) is a rare neurovascular emergency that is often found in critically ill patients. We report two cases of CSVT with different onsets, neurologic manifestations, and prognoses. CASE PRESENTATION: Two cases of cerebral sinus venous thrombosis in COVID-19 patients were reported, following respiratory, hematology, and coagulation disarrangements, which was triggered by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The first patient, which was presented with a seizure, had hypertension and diabetes mellitus as comorbidities. The latter case had no comorbidity but showed more severe presentations of COVID-19 such as brain and lung thrombosis, although already had several days of intravenous anticoagulant administrations. These two cases also have a different course of disease and outcomes, which were interesting topics to study. CONCLUSIONS: CSVT is one of the neurological complications of the COVID-19 when the brainstem venous drainage is involved. Despite successful alteration to the negative result of SARS-CoV-2 through the rt-PCR test, thrombogenesis and coagulation cascade continuing. Therefore, a high level of neutrophil to lymphocyte ratio (NLR), D-dimer, fibrinogen, and C-reactive protein (CRP) are paramount indicators of poor prognosis.

Lung Epithelial Cell Transcriptional Regulation as a Factor in COVID-19-associated Coagulopathies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become a global pandemic. In addition to the acute pulmonary symptoms of coronavirus disease (COVID-19) (the disease associated with SARS-CoV-2 infection), pulmonary and distal coagulopathies have caused morbidity and mortality in many patients. Currently, the molecular pathogenesis underlying COVID-19-associated coagulopathies are unknown. Identifying the molecular basis of how SARS-CoV-2 drives coagulation is essential to mitigating short- and long-term thrombotic risks of sick and recovered patients with COVID-19. We aimed to perform coagulation-focused transcriptome analysis of in vitro infected primary respiratory epithelial cells, patient-derived bronchial alveolar lavage cells, and circulating immune cells during SARS-CoV-2 infection. Our objective was to identify transcription-mediated signaling networks driving coagulopathies associated with COVID-19. We analyzed recently published experimentally and clinically derived bulk or single-cell RNA sequencing datasets of SARS-CoV-2 infection to identify changes in transcriptional regulation of blood coagulation. We also confirmed that the transcriptional expression of a key coagulation regulator was recapitulated at the protein level. We specifically focused our analysis on lung tissue-expressed genes regulating the extrinsic coagulation cascade and the plasminogen activation system. Analyzing transcriptomic data of in vitro infected normal human bronchial epithelial cells and patient-derived bronchial alveolar lavage samples revealed that SARS-CoV-2 infection induces the extrinsic blood coagulation cascade and suppresses the plasminogen activation system. We also performed in vitro SARS-CoV-2 infection experiments on primary human lung epithelial cells to confirm that transcriptional upregulation of tissue factor, the extrinsic coagulation cascade master regulator, manifested at the protein level. Furthermore, infection of normal human bronchial epithelial cells with influenza A virus did not drive key regulators of blood coagulation in a similar manner as SARS-CoV-2. In addition, peripheral blood mononuclear cells did not differentially express genes regulating the extrinsic coagulation cascade or plasminogen activation system during SARS-CoV-2 infection, suggesting that they are not directly inducing coagulopathy through these pathways. The hyperactivation of the extrinsic blood coagulation cascade and the suppression of the plasminogen activation system in SARS-CoV-2-infected epithelial cells may drive diverse coagulopathies in the lung and distal organ systems. Understanding how hosts drive such transcriptional changes with SARS-CoV-2 infection may enable the design of host-directed therapeutic strategies to treat COVID-19 and other coronaviruses inducing hypercoagulation.