Idiopathic systemic capillary leak syndrome: a case report.

BACKGROUND: Idiopathic systemic capillary leak syndrome (ISCLS) is a rare disease characterized by recurrent episodes of acute life-threatening attacks of shock, hemoconcentration, and hypoalbuminemia. Increase in capillary permeability results in reversible plasma movement into the interstitial spaces followed by appearance of related symptoms or complications, including renal failure. This condition can be potentially life-threatening; however, it is easily misdiagnosed. CASE PRESENTATION: A 47-year-old man with no previous medical history presented to the emergency department after experiencing general weakness and abdominal pain. He developed hypovolemic shock within 3 h of presentation and initial laboratory tests showed hemoconcentration, hypoalbuminemia and acute kidney injury. Following vigorous fluid therapy and supportive care, the patient recovered, but a similar episode recurred after 4 months without any specific trigger. Based on the combined clinical manifestations and laboratory findings of both the attacks, he was diagnosed with ISCLS. Symptomatic relief was achieved via oxygen supplementation and massive volume replacement using normal saline and the patient was prescribed bambuterol 10 mg and theophylline 400 mg once-a-day. He was discharged from the hospital on day 5 of hospitalization. Thereafter, the patient has been followed for 5 years without any symptoms or recurrence of ISCLS even in the situation of COVID-19 infection. CONCLUSIONS: ISCLS is an extremely infrequent and commonly misdiagnosed disease. However, early diagnosis, treatment and prophylaxis through accumulated clinical data can prevent ISCLS recurrence and the development of related fatal complications. Therefore, clinicians need to be well aware of the variety of clinical characteristics and treatment options of this disease.

Minimal change disease following the Moderna COVID-19 vaccine: first case report.

BACKGROUND: There have been cases of minimal change disease (MCD) reported following previous vaccines. During the COVID-19 era, only 3 cases of new-onset MCD and a case of MCD relapse were reported following the Pfizer-BioNTech COVID-19 vaccine. We herein report the first case of MCD after receiving the Moderna COVID-19 vaccine. CASE PRESENTATION: A 43-year-old man presented to hospital 3 weeks after receiving the first dose of the Moderna vaccine, with both bilateral lower extremities and scrotal edema. He initially developed a sudden-onset bilateral lower extremities swelling on day 7 post-vaccine. He, then, developed dyspnea and scrotal swelling over a time span of 2 weeks. On physical examination, his blood pressure was 150/92 mmHg. There was a decreased air entry at lung bases, bilateral lower extremities and scrotal edema. Labs revealed hypoalbuminemia, hyperlipidemia and 15 g of proteinuria. His immunologic and serologic work up was negative. Renal biopsy showed concomitant MCD and IgA nephropathy. Patient was treated with oral steroids and had a good response; his edema resolved, serum albumin improved, and proteinuria decreased to 1 g within 2 weeks of treatment. CONCLUSIONS: To the best of our knowledge, MCD has not been previously reported after receiving the Moderna COVID-19 vaccine. It remains unclear whether the COVID-19 mRNA vaccines are associated with the development of MCD, or it coincided with the mass vaccination. Further studies are needed to determine the incidence of MCD post COVID-19 vaccines and the underlying pathophysiology of glomerular injury post vaccination.

Pediatric Multisystemic Inflammatory Syndrome Temporarily associated with COVID-19: Clinical characteristics and management in a Pediatric Critical Care Unit. / Síndrome Inflamatorio Multisistémico Pediátrico asociado a COVID-19: Características clínicas y manejo en una Unidad de Paciente Crítico Pediátrico.

INTRODUCTION: In April 2020, the pediatric multisystem inflammatory syndrome temporarily associated with COVID-19 (MIS-C) was described for the first time. MIS-C could have a severe course and may require critical care support. OBJECTIVE: To describe the clinical, laboratory, and management characteristics of hospitalized children who meet MIS-C criteria with severe presentation in a pediatric critical pa tient unit. PATIENTS AND METHOD: Descriptive prospective study of children with severe MIS-C mana ged by treatment phases with immunoglobulin and methylprednisolone, according to their clinical response. Epidemiological, clinical, laboratory and imaging data were obtained. Phenotypes were classified into Kawasaki and not Kawasaki, comparing their findings. RESULTS: 20 patients were analy zed, the median age was 6 years, 60% were female, and 40% presented comorbidity. SARS-CoV-2 was detected in 90% of the patients. They presented fever as the first symptom, followed by brief and early gastrointestinal symptoms (70%). 75% presented the Kawasaki phenotype. They evolved with lymphopenia, hypoalbuminemia, coagulation alterations, and elevated systemic and cardiac in flammatory parameters. 80% of the cases presented echocardiographic alterations and 90% shock that required critical care support. All the patients had a short and favorable evolution. All patients responded to the established therapy, but 40% required a second phase of treatment. There were no differences when comparing phenotypes. No deaths were reported. CONCLUSION: MIS-C is a new childhood disease whose presentation could be life-threatening. It requires early suspicion, immuno modulatory management, critical care support, and a multidisciplinary approach to obtain the best results and optimize its prognosis.

Hypoalbuminemia as Surrogate and Culprit of Infections.

Hypoalbuminemia is associated with the acquisition and severity of infectious diseases, and intact innate and adaptive immune responses depend on albumin. Albumin oxidation and breakdown affect interactions with bioactive lipid mediators that play important roles in antimicrobial defense and repair. There is bio-mechanistic plausibility for a causal link between hypoalbuminemia and increased risks of primary and secondary infections. Serum albumin levels have prognostic value for complications in viral, bacterial and fungal infections, and for infectious complications of non-infective chronic conditions. Hypoalbuminemia predicts the development of healthcare-associated infections, particularly with Clostridium difficile. In coronavirus disease 2019, hypoalbuminemia correlates with viral load and degree of acute lung injury and organ dysfunction. Non-oncotic properties of albumin affect the pharmacokinetics and pharmacodynamics of antimicrobials. Low serum albumin is associated with inadequate antimicrobial treatment. Infusion of human albumin solution (HAS) supplements endogenous albumin in patients with cirrhosis of the liver and effectively supported antimicrobial therapy in randomized controlled trials (RCTs). Evidence of the beneficial effects of HAS on infections in hypoalbuminemic patients without cirrhosis is largely observational. Prospective RCTs are underway and, if hypotheses are confirmed, could lead to changes in clinical practice for the management of hypoalbuminemic patients with infections or at risk of infectious complications.

Hypoalbuminemia in COVID-19: assessing the hypothesis for underlying pulmonary capillary leakage.

BACKGROUND: Since the first observations of patients with COVID-19, significant hypoalbuminaemia was detected. Its causes have not been investigated yet. OBJECTIVE: We hypothesized that pulmonary capillary leakage affects the severity of respiratory failure, causing a shift of fluids and proteins through the epithelial-endothelial barrier. METHODS: One hundred seventy-four COVID-19 patients with respiratory symptoms, 92 admitted to the intermediate medicine ward (IMW) and 82 to the intensive care unit (ICU) at Luigi Sacco Hospital in Milan, were studied. RESULTS: Baseline characteristics at admission were considered. Proteins, interleukin 8 (IL-8) and interleukin 10 (IL-10) in bronchoalveolar lavage fluid (BALF) were analysed in 26 ICU patients. In addition, ten autopsy ultrastructural lung studies were performed in patients with COVID-19 and compared with postmortem findings in a control group (bacterial pneumonia-ARDS and H1N1-ARDS). ICU patients had lower serum albumin than IMW patients [20 (18-23) vs 28 (24-33) g L-1 , P < 0.001]. Serum albumin was lower in more compromised groups (lower PaO2 -to-FiO2 ratio and worst chest X-ray findings) and was associated with 30 days of probability of survival. Protein concentration was correlated with IL-8 and IL-10 levels in BALF. Electron microscopy examinations of eight out of ten COVID-19 lung tissues showed loosening of junctional complexes, quantitatively more pronounced than in controls, and direct viral infection of type 2 pneumocytes and endothelial cells. CONCLUSION: Hypoalbuminaemia may serve as severity marker of epithelial-endothelial damage in patients with COVID-19. There are clues that pulmonary capillary leak syndrome plays a key role in the pathogenesis of COVID-19 and might be a potential therapeutic target.

Hematological changes in patients with COVID­19 (Review).

In December 2019, an emergence of pneumonia was detected in patients infected with a novel coronavirus (CoV) in Wuhan (Hubei, China). The International Committee on Taxonomy of Viruses named the virus severe acute respiratory syndrome­CoV­2 and the disease CoV disease­19 (COVID­19). Patients with COVID­19 present with symptoms associated with respiratory system dysfunction and hematological changes, including lymphopenia, thrombocytopenia and coagulation disorders. However, to the best of our knowledge, the pathogenesis of COVID­19 remains unclear. Therefore, understanding the mechanisms underlying the hematological changes that manifest during COVID­19 may aid in the development of treatments and may improve patient prognosis.

Systemic Capillary Leak Syndrome Secondary to Coronavirus Disease 2019.

Systemic capillary leak syndrome is a rare disorder characterized by dysfunctional inflammatory response, endothelial dysfunction, and extravasation of fluid from the vascular space to the interstitial space leading to shock, hemoconcentration, hypoalbuminemia, and subsequent organ failure. The condition may be idiopathic or secondary to an underlying cause, which can include viral infections. Here we describe a patient with acute coronavirus disease 2019 (COVID-19) infection who presented with hemoconcentration, shock, and hypoalbuminemia. The patient subsequently developed rhabdomyolysis and compartment syndrome of all four extremities, requiring fasciotomies. This is the first reported case of systemic capillary leak syndrome associated with COVID-19 infection. This case adds to the evolving spectrum of inflammatory effects associated with this viral infection.

DVT incidence and risk factors in critically ill patients with COVID-19.

Few data are available on the incidence of deep vein thrombosis (DVT) in critically ill COVID-19 with thrombosis prophylaxis. This study retrospectively included 88 patients in the ICU with critically ill COVID-19 at Jinyintan Hospital in Wuhan, China. All patients underwent compression ultrasonography for identifying DVT. Firth logistic regression was used to examine the association of DVT with sex, age, hypoalbuminemia, D-dimer, and SOFA score. The median (interquartile range [IQR]) age and SOFA score of 88 patients were 63 (55-71) years old and 5 (4-6), respectively. Despite all patients receiving guideline-recommended low-molecular-weight heparin (LMWH) thromboprophylaxis, the incidence of DVT was 46% (95% CI 35-56%). Proximal DVT was recognized in 9% (95% CI 3-15%) of the patients, while 46% (95% CI 35-56%) of patients had distal DVT. All of the proximal DVT combined with distal DVT. Risk factors of DVT extension occurred in all distal DVT patients. As Padua score ≥ 4 or IMPROVE score ≥ 2, 53% and 46% of patients had DVT, respectively. Mortality was higher in patients with acute DVT (30%) compared with non-DVT (17%), but did not reach statistical significance. Hypoalbuminemia (odds ratio [OR], 0.17; 95% CI 0.06-0.05, P = 0.001), higher SOFA score (OR per IQR, 2.07; 95% CI 1.38-3.39, P = 0.001), and elevated D-dimer (OR per IQR, 1.04; 95% CI 1.03-1.84, P = 0.029) were significant DVT risk factors in multivariable analyses. High incidence of DVT was identified in patients with critically ill COVID-19, despite the use of guideline-recommended pharmacologic thromboprophylaxis. The presence of hypoalbuminemia, higher SOFA score, and elevated D-dimer were significantly independent risk factors of DVT. More effective VTE prevention and management strategies may need to be addressed.