Prospective Study of Sars-cov2 Associated Coagulopathy and Role of Complement Activation (preprint)

Sars-CoV2 associated coagulopathy is a complex entity. Platelets, coagulation factors, fibrinolysis, inflammatory cytokines, immunothrombosis, antiphospholipd antibodies, von Willebrand factor/ADAMTS13 axis, complement system have all been demonstrated to be actively involved in the determination of thrombotic events. Til now retrospective studies have analyzed the activaction of vWF/ADAMTS13 axis and complement involvement. We performed a prospective study with the aim of describing clinical and laboratoristic features of Sars-CoV2 associated coagulopathy and its relationship with complement activation. Biochemical variables, vWF/ADAMTS13 axis, complement factors of the enrolled patients have been analyzed. These variables have been correlated to clinical outcome of the disease. Covid associated coagulopathy is neither a Trombotic Trombocitopenc Purpura (TTP) nor and atypical hemolytic uremic syndrome (aSEU). Nevertheless, imbalance of vWF/Adamts13 axis and complement activation simultaneously occurre and are significantly higher in the severe form of disease.

Thrombotic microangiopathy with kidney involvement in a patient with coronavirus disease 2019: A case report and literature review (preprint)

Background and aim: Millions of people worldwide have suffered from coronavirus disease 2019 (COVID-19). COVID-19 can lead to coagulopathy and thrombosis, presenting as pulmonary artery thromboembolism, deep vein thrombosis, and thrombotic microangiopathy (TMA), the latter being a rare finding in affected patients’ kidneys. Prior reports have rarely addressed the pathophysiology, clinical presentations, and therapeutic options in patients with COVID-19-associated TMA. Case presentation: We herein described a case of renal biopsy-proven TMA after COVID-19 in a 36-year-old woman. Initial examination revealed inflammation, acute kidney injury (AKI), anemia, and thrombocytopenia. She was diagnosed with hemolytic uremic syndrome, pulmonary infection, and COVID-19. After treatment, her condition stabilized but remained hemodialysis-dependent after discharge. One week later, she was re-hospitalized, and physical examination showed anemia and bilateral lower extremity edema. Abdominal ultrasound showed increased bilateral kidney echogenicity. Whole-exome sequencing detected an unknown variant of the C3 gene associated with hemolytic uremic syndrome susceptibility type 5/complement C3 deficiency. Kidney biopsy showed renal artery lesions, including small arteriole endothelial swelling, intimal thickening, mucinous degeneration, luminal occlusion, and small arterial wall necrosis. She received plasma exchange and steroids with significant renal function recovery. Conclusion: TMA likely contributed to AKI after COVID-19,thus supporting the notion that TMA plays an important role in the pathogenesis of COVID-19-related kidney injury. When diagnosing and treating COVID-19 patients with abnormal renal function, clinicians should incorporate kidney biopsy and genetic testing for the complement system, identify renal-limited and systemic TMA, and treat accordingly, which can improve patient outcomes.

AHUS mistaken for TTP associated with COVID-19: a case report (preprint)

Thrombotic thrombocytopenic purpura (TTP) and atypical hemolytic uremic syndrome (aHUS) are both thrombotic microangiopathies that share several clinical traits including microangiopathic hemolytic anemia, thrombocytopenia, and organic damage. There is inherent opportunity for misdiagnosis. As thrombocytopenia and thrombus are strongly related to COVID-19, it may be more difficult to tell an aHUS from a TTP when COVID-19 is present. Thus, we describe a patient presenting with severe COVID-19 who was misdiagnosed with TTP but in the end corrected to aHUS. We suggest that perform detection to ADAMTS-13 activity and complement gene mutation as soon as possible is necessary.

Thrombotic microangiopathy in children.

The syndrome of thrombotic microangiopathy (TMA) is a clinical-pathological entity characterized by microangiopathic hemolytic anemia, thrombocytopenia, and end organ involvement. It comprises a spectrum of underlying etiologies that may differ in children and adults. In children, apart from ruling out shigatoxin-associated hemolytic uremic syndrome (HUS) and other infection-associated TMA like Streptococcus pneumoniae-HUS, rare inherited causes including complement-associated HUS, cobalamin defects, and mutations in diacylglycerol kinase epsilon gene must be investigated. TMA should also be considered in the setting of solid organ or hematopoietic stem cell transplantation. In this review, acquired and inherited causes of TMA are described with a focus on particularities of the main causes of TMA in children. A pragmatic approach that may help the clinician tailor evaluation and management is provided. The described approach will allow for early initiation of treatment while waiting for the definitive diagnosis of the underlying TMA.

Hemolytic Uremic Syndrome: A Covid-19 Vaccine Reaction Case Report (preprint)

Hemolytic uremic syndrome (HUS) is associated with microthrombi ,mainly in the kidneys. It may be classified as typical HUS or atypical HUS (aHUS) .Majority of HUS occur in children (usually at 6 months of age), as a sequela of shigella infection. In aHUS, a genetic or sporadic insult causes dysfunction in the complement cascade, leading to complement deposition on endothelial cells, thickening of arterioles and capillaries, and endothelial swelling and detachment. Consequently, there is formation of obstructive thrombi in the vessel lumina and shearing of red blood cells, creating schistiocytes, that results in the triad of Coombs negative hemolytic anemia, renal impairment, and thrombocytopenia. We report a rare case of a 43-year-old black male who reacted to the 2nd booster dose (some 7 months after the 1st) of Astra Zeneca Covid-19 vaccine with aHUS. He had ophthalmoplegia, occipital headaches and suicidal ideation which all resolved on high dose oral prednisolone. The Astra Zeneca vaccine which uses a chimpanzee platform is the only one reported to have similar reactions and this is important to note and manage such potentially life threatening rare adverse event.

Coronavirus Disease-2019 in Children with Primary Kidney Disease: A Case series.

Underlying comorbid illness is a known risk factor for severe coronavirus disease-2019 (COVID-19). Clinical course of COVID-19 in children with primary kidney disease is not well understood. We present the clinical profile and management of COVID-19 in three children at a COVID hospital in India. These children had nephrotic syndrome, hemolytic uremic syndrome, and chronic kidney disease, respectively. The first two were immunosuppressed, mandating to stop their immunosuppressive medications temporarily. Both had mild course of illness. Third child presented with respiratory distress requiring oxygen support, falling into moderate disease. Renal functions were normal in all of them. They all responded well to oral azithromycin and supportive management. None of them received chloroquine, corticosteroids, or monoclonal antibodies. All three recovered without complications.

Personnel Well-being in the Helsinki University Hospital During the COVID-19 Pandemic – A Prospective Cohort Study (preprint)

On March 2020 strict measures took place in Finland to limit the COVID -19 pandemic. A majority of the Finnish COVID -19 –patients have been located in the southern Finland and consequently cared for in the HUS Helsinki University Hospital. During the ongoing pandemic, HUS personnel’s psychological symptoms are followed via an electronic survey, which also delivers information on psychosocial support services. The baseline survey in June 2020 was sent to 25494 HUS employees out of whom 4804 (19%) answered; altogether 62.4% of the respondents were nursing staff and 8.9% medical doctors. While the follow-up continues for a year and a half, this report shares the sociodemographic characteristics of the respondents and the first results of psychological symptoms from the baseline survey. Out of those who were directly involved in pandemic patients` care, 43.4% reported potentially traumatic COVID-19 pandemic-related experiences vs. 21.8% among the other (p < 0.001). While over a half of the personnel was symptomless, a group of respondents reported pandemic work –related traumatic events and concurrent depressive, insomnia and anxiety symptoms. This highlights the need to ensure appropriate psychosocial support services to all traumatized personnel and PTEs were present especially among nursing staff.