Immunopathological mechanisms in sepsis of viral etiology in COVID-19.

The article provides information on immunopathology in sepsis and the commonality between immunopathogenetic processes of sepsis and the new coronavirus infection (COVID-19). As a result of the inability of the immune system to cope with aggression of the pathogen, inadequate immune activity occurs manifested by the systemic inflammatory response syndrome, resulting in damage to tissues of the host organism. In response, compensatory anti-inflammatory response syndrome is activated, which is manifested by inhibition of the immune response. One of its main mechanisms is signals produced by membrane receptors and their ligands. Against the background of inability of the host organism to neutralise the pathogen, numerous pathological phenomena and complications occur leading to damage to human tissues.Copyright © 2021, Krasnoyarsk State Medical University. All rights reserved.

COVID-19 and stroke: A review.

COVID-19 patients have presented with a wide range of neurological disorders, among which stroke is the most devastating. We have reviewed current studies, case series, and case reports with a focus on COVID-19 patients complicated with stroke, and presented the current understanding of stroke in this patient population. As evidenced by increased D-dimer, fibrinogen, factor VIII and von Willebrand factor, SARS-CoV-2 infection induces coagulopathy, disrupts endothelial function, and promotes hypercoagulative state. Collectively, it predisposes patients to cerebrovascular events. Additionally, due to the unprecedented strain on the healthcare system, stroke care has been inevitably compromised. The underlying mechanism between COVID-19 and stroke warrants further study, so does the development of an effective therapeutic or preventive intervention.

Plasma Soluble Fibrin Is Useful for the Diagnosis of Thrombotic Diseases.

BACKGROUND: Soluble fibrin (SF) is a form of fibrinogen that is activated by thrombin and is considered to be useful for the diagnosis of the prethrombotic state or thrombosis. METHODS: Plasma levels of fibrin-related markers (FRMs), such as SF, D-dimer, fibrinogen, and fibrin degradation prioduct (FDP) levels in critically ill patients, were examined for the diagnosis of disseminated intravascular coagulation (DIC), venous thromboembolism (VTE), peripheral arterial thromboembolism (PATE), acute myocardial infarction (AMI), and acute cerebral infarction (ACI). RESULTS: FRMs showed the usefulness in diagnosing DIC and VTE and the cutoff values of D-dimer, FDP, and SF for DIC were 7.2-7.8 µg/mL, 10.0 µg/mL, and 9.5 µg/mL, respectively. The cutoff values of D-dimer and FDP for VTE were similar to the 97.5th percentile values of healthy volunteers, while the cutoff value of SF was 6.9 µg/mL. In AMI and ACI, the cutoff values of D-dimer and FDP were lower than the 97.5 percentile values of healthy volunteers. A receiver operating characteristic analysis for all thrombosis cases showed that an adequate cutoff value in only SF among FRMs was higher than the confidence interval of healthy volunteers. Only SF had high sensitivity for thrombosis, as the FDP/SF ratio was markedly low for ACI, AMI and VTE. CONCLUSIONS: FRMs, especially D-dimer and FDP, were useful for diagnosing thrombosis with hyperfibrinolysis (e.g., DIC). As SF showed high sensitivity for predominantly thrombotic diseases, including arterial thrombosis, such as ACI and AMI, a high SF value suggests the possibility of an association with thrombosis. Finally, SF is the most useful marker for raising suspicion of an association with thrombosis, especially arterial thrombosis.

Heat Stroke Leading to a Fatal Outcome.

Heat stroke (HS) can cause several physiological changes in the body. In its most severe form, it can cause multi-organ failure including encephalopathy, circulatory shock, liver failure, renal failure, disseminated intravascular coagulation, and rhabdomyolysis among others. HS is a preventable condition; however, it can be life-threatening in severe forms. We present a case of HS in a 54-year-old male, with rapidly progressive multi-organ failure and a fatal outcome along with a brief literature review.

Acute Pancreatitis and Disseminated Intravascular Coagulopathy in COVID-19 Infection: A Case Report.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and can be a plausible trigger for both disseminated intravascular coagulopathy (DIC) and acute pancreatitis. We present an 85-year-old male patient who presented with altered mental status and tested positive for COVID-19 infection. He was hypoxic with an incremental need for oxygen. He had clinical as well as imaging evidence of acute pancreatitis. Clinical evidence of bleeding was noted and lab findings were suggestive of DIC. Despite aggressive initial management, his clinical status continued to deteriorate and comfort care was sought eventually. This case highlights COVID-19 infection as a possible trigger for acute pancreatitis as well as DIC. It also highlights some of the differences in COVID-19-induced DIC, which fulfills the diagnostic criteria of DIC but has atypical findings.

Inhibition of SARS-CoV-2 nucleocapsid protein-RNA interaction by guanosine oligomeric RNA.

The interaction of the ß-coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) nucleocapsid (N) protein with genomic RNA is initiated by specific RNA regions and subsequently induces the formation of a continuous polymer with characteristic structural units for viral formation. We hypothesized that oligomeric RNAs, whose sequences are absent in the 29.9-kb genome sequence of SARS-CoV-2, might affect RNA-N protein interactions. We identified two such hexameric RNAs, In-1 (CCGGCG) and G6 (GGGGGG), and investigated their effects on the small filamentous/droplet-like structures (< a few µm) of N protein-genomic RNA formed by liquid-liquid phase separation. The small N protein structures were sequence-specifically enhanced by In-1, whereas G6 caused them to coalesce into large droplets. Moreover, we found that a guanosine 12-mer (G12, GGGGGGGGGGGG) expelled preexisting genomic RNA from the small N protein structures. The presence of G12 with the genomic RNA suppressed the formation of the small N protein structures, and alternatively apparently altered phase separation to induce the formation of large droplets with unclear phase boundaries. We showed that the N-terminal RNA-binding domain is required for the stability of the small N protein structures. Our results suggest that G12 may be a strong inhibitor of the RNA-N protein interaction.

Hemophagocytic Lymphohistiocytosis Following COVID-19 Infection.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been associated with multiple inflammatory symptoms involving several organ systems, including hematologic manifestations. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome caused by excessive inflammation in the absence of immune regulation. We present the case of a patient with HLH secondary to dysregulated inflammatory response following COVID-19; we also describe the diagnostic and management challenges associated with the condition.

COVID-19 and Subsequent Development of Pancytopenia With Concurrent Disseminated Intravascular Coagulation.

Complications resulting from coronavirus disease 2019 (COVID-19) sequelae have been well documented. These include blood conditions such as lymphopenia, thrombocytopenia, and hypercoagulability. Less common problems that may arise are disseminated intravascular coagulation (DIC), immune thrombocytopenic purpura (ITP), and pancytopenia. Furthermore, the majority of COVID-19 patients to develop pancytopenia have been immunosuppressed. We present a case of a previously immunocompetent patient who subsequently developed pancytopenia, DIC, as well as symptoms of ITP one month after being diagnosed with COVID-19.

Recurrent upper extremity arterial thrombosis preceding a diagnosis of COVID-19.

Arterial thrombosis occurs when there is endothelial damage in the setting of hypercoagulability and arterial blood stasis. COVID-19 has been theorized to cause both endothelial damage and promote hypercoagulability by causing an imbalance of clotting factors. In many studies, there have been a large proportion of COVID-19 patients that suffered a thromboembolic event, in both the venous and arterial systems. Our patient, who did not have a significant past medical history, presented with a recurrent brachial artery occlusion despite medical and surgical management, and subsequently tested positive for COVID-19 late in his admission. In conclusion, there is high suspicion that there is a relationship between COVID-19 infection and recurrent arterial thrombosis.

Venovenous Extracorporeal Membrane Oxygenation Support in Patients with COVID-19 Respiratory Failure: A Multicenter Study.

Objective: The COVID -19 pandemic presents a high mortality rate amongst patients who develop severe acute respiratory distress syndrome (ARDS). The purpose of this study was to evaluate the outcomes of venovenous ECMO in COVID-19-related ARDS and identify the patients that benefit the most from this procedure. Methods: Adult COVID-19 patients with severe ARDS requiring VV-ECMO support at four academic insititutions between March and October 2020 were included. Data were collected through retrospective chart reviews. Bivariate and multivariable analysis were performed with the primary outcome of in-hospital mortality. Results: Fifty-one consecutive patients underwent VV-ECMO with a mean age of 50.4 years; 64.7% were male. Survival to hospital discharge was 62.8%. Median ICU and hospitalization duration were 27.4 (IQR:17-37) and 34.5 days (IQR:23-43), respectively. Survivors and non-survivors had a median ECMO cannulation time of 11 days (IQR 8-18) and 17 days (IQR: 12-25). The average post decannulation length of stay was 17.5 days (IQR: 12.4-25) for survivors and 0 days for non-survivors (IQR 0-6 days). Only one non-survivor was able to be decannulated. Clinical characteristics associated with mortality between non-surviors and survivors included increasing age (p=0.0048), hemorrhagic stroke (p=0.0014), and post operative dialysis (p=0.0013)were associated with mortality in a bivariate model and retained statistical significance in a multivariable model. Conclusion: This multicenter study confirms the effectiveness of VV-ECMO in selected critically ill patients with COVID-19-related severe ARDS. The survival of these patients is comparable to non-COVID-19-related ARDS.

Cardiovascular Disease in the COVID-19 Era: Myocardial Injury and Thrombosis

COVID-19 is now appreciated as a pandemic, presenting with a wide range of symptoms, mostly respiratory, yet involving other organs massively. Myocardial injury is a crucial complication with significant negative impact on prognosis. Despite all the investigations, exact pathophysiologic mechanisms remain unclear, and so do the appropriate treatments. Thrombosis has been increasingly observed since the first reports, with venous thromboembolism being the major concern. The strategy of thrombosis prophylaxis, though known to be helpful to the clinical scenario, is still a subject of debate. © 2022 Elsevier Inc. All rights reserved.

Effect of Swell-Drying on Mango (Mangifera indica) Drying Kinetics.

Swell-Drying operation (SD) was applied on mangoes to evaluate its effect on drying kinetics: starting accessibility (δW), apparent drying coefficient (Dapp), and time to obtain a final moisture content of 20% d.b (tf = 20% d.b). Swell-drying consisted of (1) submitting fresh mangoes to a first pre-drying stage under Convective Air Drying (CAD) until a moisture content of 37% d.b; (2) applying Instant Controlled Pressure Drop (DIC) treatments on pre-dried mangoes by following a central composite rotatable design (steam pressure: 0.2-0.6 MPa and treatment time: 5 and 55 s); and (3) apply post-drying of mangoes under CAD. In both cases, CAD was performed at 60 °C and airflow of 1 m/s. Results showed that both the treatment time and the steam pressure impacted the Dapp and the δW. By comparing to the control, SD (0.54 MPa and 48 s) increased the Dapp and δW to 12.2 and 2.7 times, respectively. Moreover, SD triggers a significant reduction in post-drying time (tf = 20% d.b), being this of 2.4 h vs. 30.8 h. These results could be linked to the expansion of the internal pores of mangoes generated by the instant autovaporization of residual water triggered by DIC treatment.

Maternal death due to COVID-19, truth or a myth: A narrative review and experience from a teaching hospital in India.

The course of coronavirus disease-2019 (COVID-19) in pregnancy is unpredictable with outcome trends ranging from milder disease with zero mortality to severe forms and deaths in different parts of the world. We did a comprehensive review of the literature to understand maternal deaths due to COVID-19 in detail. The search was conducted in the PubMed, Embase, and Google Scholar databases, using the keywords "maternal mortality", "maternal death", "COVID-19", "septic shock" and "DIC". The search included original articles, review articles, case reports published till date. We found varying case fatality rates ranging from 0.1% to 12.9%. There are various predictors of maternal death, notably the presence of symptoms, comorbidities, severe disease with cytokine storm and multi-organ dysfunction. We also report higher maternal deaths from low-resource regions owing to gaps in expected and delivered maternal care. While reviewing our institutional data, we found 3 maternal deaths related to COVID-19 in pregnancy. We discussed our experience at our institute of three COVID-19 related maternal mortalities to add evidence to the present data. Most maternal deaths occurred in postpartum period. Late referral, loss to follow-up and inadequate care were important determinants of maternal mortality. We concluded that pregnancy cases with or without complications must be considered high risk and addressed judiciously beginning from infection prevention, early diagnosis, disease categorization, and multidisciplinary approach of management to prevent morbidity and mortality. We strongly suggest strengthening the health care delivery system to save pregnant women from dying, particularly in low-resource countries.

COVID-19 Death: Autopsy and Pathological Findings – A Case Report

Corona viruses are a large family of viruses that may cause respiratory illness in animals or humans. The most recently discovered corona virus causes Corona Virus Disease-19 (COVID-19), also known as SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), which became a global pandemic and is persisting. The data on the spectrum of gross and microscopic changes in COVID-19 infections is insufficient to accurately outline the disease process due to its ever-changing viral nature. The current knowledge on this aspect is not comprehensive since limited numbers of autopsies are conducted on such dead bodies because of higher infectivity and increased risk of transmission. We report a case of a 33-year-old male who was admitted to our institute with an alleged history of road traffic accident, later tested positive for COVID-19 and developed Covid-19 Pneumonia and succumbed. The detailed autopsy and histopathological findings are discussed. Performing autopsies on cases of COVID-19 deaths are helpful in understanding the pathology, disease process and variability in clinical presentation of COVID-19. © 2021, Punjab Academy of Forensic Medicine and Toxicology. All rights reserved.

Higher mortality of hospitalized haematologic patients with COVID-19 compared to non-haematologic is driven by thrombotic complications and development of ARDS: An age-matched cohorts study.

BACKGROUND AND OBJECTIVES: The characteristics of COVID-19 in haematologic patients compared to non-haematologic patients have seldom been analyzed. Our aim was to analyze whether there are differences in clinical characteristics and outcome of haematologic patients with COVID-19 as compared to non-haematologic. PATIENTS AND METHODS: Retrospective cohort study in 2 University hospitals of patients admitted with laboratory-confirmed COVID-19 included in the SEMICOVID19 database. The cohort with underlying haematologic disease was compared to a cohort of age and date-of-COVID-19-matched controls without haematologic disease (1:2). RESULTS: 71 cases and 142 controls were included from March-May 2020.Twenty (28.1%) had received recent chemotherapy. Twelve (16.9%) were stem cell transplant recipients (SCT). Eleven (15.5%) were neutropenic concurrently with COVID-19 diagnosis.Haematologic patients presented ARDS (58.5 vs 20.7%, p = 0.0001), thrombotic complications (15.7 vs 2.1%, p = 0.002), DIC (5.7 vs 0.0%, p = 0.011), heart failure (14.3 vs 4.9%, p = 0.029) and required ICU admission (15.5 vs 2.8%, p = 0.001), MV (14.1% vs 2.1%, p 0.001), steroid (64.8 vs 33.1%, p = 0.0001), tocilizumab (33.8 vs 8.5%, p = 0.0001) or anakinra treatment (9.9% vs 0%, p = 0.0001) more often. In-hospital mortality was significantly higher (38.0% vs 18.3%, p = 0.002). CONCLUSIONS: Our results suggest COVID-19 has worse outcomes in haematologic patients than in non-haematologic, independently of age, and that the development of ARDS and thrombotic complications drive the higher in-hospital mortality.

COVID-19 Infection Complicated by Disseminated Intravascular Coagulation during Pregnancy-Two Cases Report.

Coagulopathies are one of the obstetric complications affecting the period of pregnancy, childbirth, and puerperium. One of the more severe and complex disorders of the haemostatic system is the disseminated intravascular coagulation syndrome (DIC), in which generalised activation of the coagulation system and activation of inflammatory cells occurs. DIC syndrome was observed in patients whose pregnancy was complicated by SARS-CoV-2 infection. Both the course of these cases and literature review indicate that particular notice should be paid to laboratory parameters of the coagulation system, closely monitoring the well-being of the foetus and, in the situation of acute DIC development, it is advised to deliver a baby and initiate intensive therapy.

A Case of Low-Flow Priapism as a Complication of COVID-19 Infection.

On 11 March 2020, the World Health Organisation (WHO) declared the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) (COVID-19) a pandemic. With a global incidence of over 414 million cases, as of 16 February 2022, it presents a significant burden on healthcare. COVID-19 is primarily considered a respiratory illness; however, a wide range of presentations have been reported including a tendency for thrombotic complications. We report a case of a 58-year-old man who presented with dyspnoea, pyrexia and dry cough. Upon admission, he was noted to be in a severe type 1 respiratory failure with bilateral pulmonary infiltrates suggestive of COVID-19 infection. Rapid transfer to intensive therapy unit (ITU) ensued with intubation and ventilation. The patient was noted to have developed priapism one day following admission with subsequent aspiration by the Urology team, achieving detumescence. Priapism is a state of persistent penile erection that continues for four hours beyond sexual stimulation. Our case highlights the role of thrombosis, dysregulation of the clotting cascade and acute disseminated intravascular coagulation (DIC) as shared pathologies in priapism and COVID-19 infection. We put forth an example of one of the extra-pulmonary manifestations of the COVID-19 secondary to the pro-thrombotic state associated with the COVID-19 infection.

The Impact of COVID-19 On Comorbidities: A Review Of Recent Updates For Combating It.

Coronavirus disease is caused by the SARS-CoV-2 virus. The virus first appeared in Wuhan (China) in December 2019 and has spread globally. Till now, it affected 269 million people with 5.3 million deaths in 224 countries and territories. With the emergence of variants like Omicron, the COVID-19 cases grew exponentially, with thousands of deaths. The general symptoms of COVID-19 include fever, sore throat, cough, lung infections, and, in severe cases, acute respiratory distress syndrome, sepsis, and death. SARS-CoV-2 predominantly affects the lung, but it can also affect other organs such as the brain, heart, and gastrointestinal system. It is observed that 75 % of hospitalized COVID-19 patients have at least one COVID-19 associated comorbidity. The most common reported comorbidities are hypertension, NDs, diabetes, cancer, endothelial dysfunction, and CVDs. Moreover, older and pre-existing polypharmacy patients have worsened COVID-19 associated complications. SARS-CoV-2 also results in the hypercoagulability issues like gangrene, stroke, pulmonary embolism, and other associated complications. This review aims to provide the latest information on the impact of the COVID-19 on pre-existing comorbidities such as CVDs, NDs, COPD, and other complications. This review will help us to understand the current scenario of COVID-19 and comorbidities; thus, it will play an important role in the management and decision-making efforts to tackle such complications.

Coagulopathy and Fibrinolytic Pathophysiology in COVID-19 and SARS-CoV-2 Vaccination.

Coronavirus Disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is frequently complicated by thrombosis. In some cases of severe COVID-19, fibrinolysis may be markedly enhanced within a few days, resulting in fatal bleeding. In the treatment of COVID-19, attention should be paid to both coagulation activation and fibrinolytic activation. Various thromboses are known to occur after vaccination with SARS-CoV-2 vaccines. Vaccine-induced immune thrombotic thrombocytopenia (VITT) can occur after adenovirus-vectored vaccination, and is characterized by the detection of anti-platelet factor 4 antibodies by enzyme-linked immunosorbent assay and thrombosis in unusual locations such as cerebral venous sinuses and visceral veins. Treatment comprises high-dose immunoglobulin, argatroban, and fondaparinux. Some VITT cases show marked decreases in fibrinogen and platelets and marked increases in D-dimer, suggesting the presence of enhanced-fibrinolytic-type disseminated intravascular coagulation with a high risk of bleeding. In the treatment of VITT, evaluation of both coagulation activation and fibrinolytic activation is important, adjusting treatments accordingly to improve outcomes.