Paradoxical Immune Reconstitution Inflammatory Syndrome in SARS-CoV-2 Infection After Improvement of Chemotherapy-Induced Aplasia.

Severe coronavirus disease 2019 (COVID-19) is known to manifest in two phases, with a potential worsening in the second week. The pathophysiology of the first phase is expected to be heavily influenced by viral replication while the second phase is thought to be primarily characterized by systemic inflammation. We present the case of a 42-year-old man hospitalized for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with a history of Philadelphia-positive chronic myeloid leukemia, diagnosed seven months earlier, proposed to bone marrow allotransplantation after refractory imatinib and dasatinib treatment. After an initial clinical and laboratory improvement, the patient got worse. A pulmonary CT scan showed worsening ground-glass opacities and multiple bilateral consolidations. Neutropenia was resolved, and on the same day, the patient developed progressive respiratory failure with rapidly increasing oxygen demand and distributive shock, requiring mechanical ventilation. Acute respiratory distress syndrome (ARDS) induced by paradoxical COVID-19 immune reconstitution inflammatory syndrome (IRIS) following chemotherapy-induced aplasia was equated. High-dose corticosteroid therapy was rapidly effective. IRIS occurs in patients with severe immunosuppression in response to rapid immune reconstitution and results in an uncontrolled inflammatory response to infectious agents that cause tissue damage. The inflammation associated with both IRIS and COVID-19 shares a common path in terms of immunological response. We hypothesize that in our patient, a hyperinflammation overlap exerted a synergistic effect, leading to the worsening of the disease.

SPONTANEOUS RENAL HAEMORRHAGE.

Introduction: Spontaneous renal haemorrhage is a rare condition with potentially serious complications. Case description: We describe a 76-year-old woman with a 3-day history of fever and malaise, with no associated trauma. She was admitted to our emergency room with signs of shock. A contrast-enhanced computed tomography scan revealed an extensive right kidney haematoma. Despite fast surgical management, the patient died less than 24 h after admission. Conclusion: Spontaneous renal haemorrhage should be quickly identified due to its fatal complications. Early diagnosis leads to a better prognosis. LEARNING POINTS: Spontaneous renal haemorrhage is a severe and rare condition in the absence of trauma and antithrombotic therapy.Contrast-enhanced abdominal CT scan is the gold standard for diagnosis.Surgical nephrectomy should be considered in haemodynamically unstable patients.Conservative therapy with intravenous resuscitation and blood products should be considered in stable patients.

ANTERIOR THALAMIC ISCHAEMIC STROKE SECONDARY TO CARDIOPULMONARY ARREST.

Introduction: Ischaemic anterior thalamic lesions are rare and can present with disturbances of behaviour and memory. We describe a patient with post-cardiac arrest thalamic stroke. Case description: A 63-year-old man presented with cardiac arrest, was resuscitated after receiving life support, and showed no lesions on computed tomography. Three days later, he presented with short-term memory disturbance and disorientation, with a de novo anterior thalamic lesion. Conclusion: The anterior thalamic nucleus, supplied by the posterior communicating artery, is part of the Papez circuit and has a role in modulating behaviour and memory. An anterior thalamic syndrome presents with no sensory-motor deficits. LEARNING POINTS: Anterior thalamic stroke is a rare condition and can present with disturbances of short-term memory and behaviour; it usually does not include any motor or sensory deficits.Thalamic stroke can occur due to global hypoxia, such as during cardiopulmonary arrest.

COVID-19 Myopericarditis in a Young Healthy Male.

SARS-CoV-2 infection can present in different clinical forms, most commonly as bilateral pneumonia, but also with pericardial/myocardial involvement. Cardiac involvement in COVID-19 is associated with worse outcomes. The authors report a case of myopericarditis as the primary manifestation of SARS-CoV-2 infection in a 20-year-old male patient with no known cardiovascular (CV) disorders or risk factors. The patient presented with pleuritic chest pain and high fever, with no respiratory symptoms. Electrocardiogram (ECG) and echocardiogram changes were consistent with pericarditis; concomitant elevation of cardiac enzymes revealed myocardial involvement. The patient had a slow but favourable evolution with no apparent impact on cardiac function. Other causes of myopericarditis were excluded and SARS-CoV-2 admitted as the most likely aetiological agent. This case highlights possible cardiac involvement in SARS-CoV-2 infection with little or no pulmonary disease in a young healthy patient. Such systemic and potentially troublesome manifestations of COVID-19 are increasingly being described. LEARNING POINTS: Acute myopericarditis is a possible manifestation of SARS-CoV-2 infection.SARS-CoV-2 cardiac involvement may occur both in older and in younger previously healthy subjects, and could be more frequent than expected.Further investigation should address the prevalence of myocardium and pericardium involvement in COVID-19 patients, as well as its complications, sequelae and prognostic value for both older and young patients.

Humoral Immune Response of SARS-CoV-2-Infected Patients with Cancer: Influencing Factors and Mechanisms.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients with cancer show worse outcomes compared with patients without cancer. The humoral immune response (HIR) of patients with cancer against SARS-CoV-2 is not well characterized. To better understand it, we conducted a serological study of hospitalized patients with cancer infected with SARS-CoV-2. MATERIALS AND METHODS: This was a unicentric, retrospective study enrolling adult patients with SARS-CoV-2 admitted to a central hospital from March 15 to June 17, 2020, whose serum samples were quantified for anti-SARS-CoV-2 receptor-binding domain or spike protein IgM, IgG, and IgA antibodies. The aims of the study were to assess the HIR to SARS-CoV-2; correlate it with different cancer types, stages, and treatments; clarify the interplay between the HIR and clinical outcomes of patients with cancer; and compare the HIR of SARS-CoV-2-infected patients with and without cancer. RESULTS: We included 72 SARS-CoV-2-positive subjects (19 with cancer, 53 controls). About 90% of controls revealed a robust serological response. Among patients with cancer, a strong response was verified in 57.9%, with 42.1% showing a persistently weak response. Treatment with chemotherapy within 14 days before positivity was the only factor statistically shown to be associated with persistently weak serological responses among patients with cancer. No significant differences in outcomes were observed between patients with strong and weak responses. All IgG, IgM, IgA, and total Ig antibody titers were significantly lower in patients with cancer compared with those without. CONCLUSION: A significant portion of patients with cancer develop a proper HIR. Recent chemotherapy treatment may be associated with weak serological responses among patients with cancer. Patients with cancer have a weaker SARS-CoV-2 antibody response compared with those without cancer. IMPLICATIONS FOR PRACTICE: These results place the spotlight on patients with cancer, particularly those actively treated with chemotherapy. These patients may potentially be more vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, so it is important to provide oncologists further theoretical support (with concrete examples and respective mechanistic correlations) for the decision of starting, maintaining, or stopping antineoplastic treatments (particularly chemotherapy) not only on noninfected but also on infected patients with cancer in accordance with cancer type, stage and prognosis, treatment agents, treatment setting, and SARS-CoV-2 infection risks.

The Effect of Chronic and Inhospital Exposure to Renin-Angiotensin System Inhibitors on the Outcome and Inflammatory State of Coronavirus Disease 2019 Adult Inpatients.

BACKGROUND: Controversies exist about the effect of renin-angiotensin system inhibitors (RASi) on coronavirus disease 2019 (COVID-19) outcome. The inhospital use of RASi and its effect on inflammatory sate are still poorly studied during the COVID-19 pandemic. OBJECTIVES: We aimed to compare the impact of previous and inhospital RASi exposure on the outcome and inflammatory response of COVID-19 patients. METHODS: Single-centre, ambispective analysis of hospitalized adult COVID-19 patients at Hospital de Santa Maria, Lisbon, between March and August 2020 was performed. We excluded asymptomatic patients and those admitted due to another disease. The primary outcome was inhospital all-cause mortality. Illness severity was assessed based on the development of acute respiratory distress syndrome/acute lung injury (ARDS/ALI), intensive care unit (ICU) admission, and need for invasive mechanical ventilation (IMV). We used C-reactive protein (CRP), ferritin, and interleukin 6 (IL-6) as surrogate markers of the inflammatory response. RESULTS: From a total of 432 patients, 279 were selected, among whom 133 (47.7%) were receiving a RASi. Chronic treatment with RASi was not associated with the risk of death (OR 1.24, 95% CI 0.66-2.31, p=0.500), ARDS/ALI development (OR 1.12, 95% CI 0.67-1.86, p=0.676), ICU admission (OR 1.11, 95% CI 0.67-1.84, p = 0.686), and IMV need (OR 1.03, 95% CI 0.58-1.84, p=0.917) in a univariable and multivariable analysis. Inhospital RASi withdrawing was associated with the risk of death (OR 4.38, 95% CI 1.11-17.21, p=0.035) and ARDS/ALI development (OR 4.33, 95% CI 1.49-12.6, p=0.007), the latter remaining significant after adjustment. Previous exposure to RASi was associated with lower CRP levels at admission (p=0.018). IL-6 levels were significantly higher in those patients whose RASi were stopped (p=0.024). CONCLUSION: Previous and inhospital exposure to RASi was not associated with mortality nor severity of COVID-19. This study supports current guidance on RASi management during the COVID-19 pandemic.

Organizing pneumonia and COVID-19: A report of two cases.

Organizing pneumonia (OP) is a sub-acute process of pulmonary tissue repair secondary to lung injury, defined histopathologically by intra-alveolar buds of granulation tissue within the lumen of distal pulmonary airspaces. It can be either cryptogenic or secondary (SOP) to different clinical conditions, namely infections. Despite being nonspecific, its diagnosis can be made by the association of clinical and imaging criteria. We report two cases of OP associated to SARS-CoV-2 pneumonia, admitted at a Portuguese tertiary hospital unit dedicated to COVID-19. Both patients presented with severe respiratory failure with need of invasive mechanical ventilation. After initial recovery, there was worsening of dyspnea and hypoxemic respiratory failure with increase in inflammatory markers. Chest CT revealed an OP pattern. Other conditions such as superinfection, auto-immune disease and iatrogenic etiology, were excluded and corticotherapy at a dose of 1 mg/kg/day was administered. Chest CT follow up of both our patients showed complete resolution of OP pattern, with mild to moderate residual pulmonary fibrosis without honeycombing. There is no OP to SARS-CoV-2 case series yet published describing the progress of patients after corticotherapy, although the association between systemic corticosteroids and lower all-cause mortality in patients with COVID-19 has been recently established. It is possible that, as has been described with other viruses, OP secondary to SARS-CoV-2 represents an immunological process after initial infection, presenting with elevation of inflammatory markers and cytokines storm in the bloodstream and lung tissue, which may explain the favorable response to corticosteroids.

Immunosuppression Therapy in Acquired Hemophilia A: Pursuing an Optimal Regimen.

Acquired hemophilia A (AHA) is a rare bleeding disorder occurring mostly in elderly persons, caused by inhibition of factor VIII (FVIII). It is generally detected prior to surgery by an isolated prolonged activated partial thromboplastin time (aPTT) not correcting on mixing studies, with subsequent identification of reduced FVIII levels and presence of FVIII inhibitor. It is treated with hemostatics and immunosuppressants, which may increase the risk for life-threatening opportunistic infections. A 79-year-old woman with idiopathic acquired FVIII inhibition and severe bleeding presented with anemia, isolated and prolonged aPTT, low FVIII activity (<1%), and elevated FVIII inhibitor titer (471 Bethesda units per milliliter [BU/mL]). Initially, she was treated with recombinant activated factor VII and steroids. However, several hematomas appeared, one of which caused airway compression that required orotracheal intubation. Cyclophosphamide, rituximab (RTX), and activated prothrombin complex concentrate were initiated, resulting in clinical and laboratory resolution after five weeks. Cyclophosphamide and RTX were maintained for six and four weeks more, respectively. After 12 weeks of oral immunosuppression, the patient was readmitted due to antibiotic-resistant Pseudomonas aeruginosa sepsis, which resulted in death. Infection secondary to immunosuppression is the leading cause of death of patients with AHA. In AHA, combination therapy was shown to be more effective than monotherapy, but it was also identified to increase the risk of infection. Age, FVIII activity <1%, and FVIII inhibitor titers >20 BU are predictors of adverse events and poor prognosis in AHA patients. Additional studies are needed to clarify the ideal drug regimens and the need for prophylactic antibiotics in this population.

[High-sensitivity C-reactive protein as a biomarker of risk in coronary artery disease]. / Proteína C reativa de alta sensibilidade como biomarcador de risco na doença coronária.

Vascular inflammation plays a crucial role in the pathogenesis of atherosclerosis and mediates various stages of atherosclerotic plaque development, from lipid streak formation to the plaque rupture and destabilization that precedes the clinical syndromes of cardiovascular disease. Inflammatory biomarkers constitute valuable tools to study this process, enabling the effects of different therapeutic interventions to be assessed. Currently, C-reactive protein (CRP) determined by high-sensitivity methods (hs-CRP) is the most extensively studied biomarker. Data regarding hs-CRP and cardiovascular risk, though largely consistent, are of unclear clinical relevance. This article provides a comprehensive review of current knowledge concerning cardiovascular risk and hs-CRP, and concludes with an evidence-based analysis of the current role of hs-CRP in cardiovascular risk assessment.