key: cord-0967845-zmjmlc2a authors: Mendoza‐Pinto, Claudia; Escárcega, Ricardo O.; García‐Carrasco, Mario; Bailey, David J.O.; Gálvez‐Romero, Jose Luis; Cervera, Ricard title: Viral Infections and Their Relationship with Catastrophic Antiphospholipid Syndrome: A Possible Pathogenic Mechanism of Severe COVID‐19 Thrombotic Complications date: 2020-06-07 journal: J Intern Med DOI: 10.1111/joim.13123 sha: 3c26c921c42bb4b2c2dcd0e513bf0ef45aa6a25e doc_id: 967845 cord_uid: zmjmlc2a The disease caused by SARS‐CoV‐2 (COVID‐19) has different presentations and outcomes. Severe COVID‐19 is commonly complicated by markedly elevated D‐dimer, thrombocytopenia and coagulation abnormalities that are considered to be regulated by various pro‐inflammatory cytokines and similar to pneumonia induced by other pathogens(1), and are correlated with mortality. Recently, a small case series described aPL antibodies in patients with COVID‐19 (2). About 1% of APS patients develop a severe life‐threatening clinical condition characterized by multiple thrombosis involving mainly small vessels, which has been described as catastrophic APS (CAPS). Patients with CAPS have in common: 1) clinical evidence of multiple organ involvement developing over a very short period of time; 2) histopathological findings of multiple small vessel occlusions, and 3) laboratory confirmation of the presence of aPL, usually in high titres. This article is protected by copyright. All rights reserved The disease caused by SARS-CoV-2 (COVID-19) has different presentations and outcomes. Severe COVID-19 is commonly complicated by markedly elevated D-dimer, thrombocytopenia and coagulation abnormalities that are considered to be regulated by various pro-inflammatory cytokines and similar to pneumonia induced by other pathogens (1) , and are correlated with mortality. Recently, a small case series described aPL antibodies in patients with COVID-19 (2) . About 1% of APS patients develop a severe life-threatening clinical condition characterized by multiple thrombosis involving mainly small vessels, which has been described as catastrophic APS (CAPS). Patients with CAPS have in common: 1) clinical evidence of multiple organ involvement developing over a very short period of time; 2) histopathological findings of multiple small vessel occlusions, and 3) laboratory confirmation of the presence of aPL, usually in high titres. Although, it is an uncommon disorder, its potentially lethal outcome emphasizes its relevance in clinical practice today. Most patients with CAPS are admitted in intensive care units with multiorgan system failure. The pathogenesis not completely understood. Precipitating factors have been identified in more than 50% of patients, and include, by frequency, infections (49%), surgical procedures (17%), malignancies (16%), anticoagulation withdrawal (8%), pregnancy complications (8%), drugs (5%), and disease activity of systemic lupus erythematosus (SLE)(3). Moreover, emerging infectious diseases (influenza A virus subtype H1N1) have recently been related to the presence of CAPS. CAPS has been recently included in the "thrombotic storm" conditions together with purpura fulminans or hemolysis, elevated liver enzyme levels, and low platelet count (HELLP) syndrome. This new concept defines a group of entities defined by an extreme prothrombotic phenotype and some patients with thrombotic storm presented high levels of acute phase reactants such as erythrocyte sedimentation rate, C-reactive protein, fibrinogen, ferritin and/or factor-VIII levels suggesting the evidence of an acute inflammatory states. Moreover, in sepsis, SIRS affect coagulation, particularly, pro-inflammatory cytokines (TNF-, IFN- and IL-1] which induce tissue factor expression on monocytes and endothelial cells, downregulate physiological anticoagulant pathways, and inhibit fibrinolysis leading to microvascular thrombosis and influences and modulates the inflammatory response. Immune mediated damage may be the predominant feature in severe COVID-19 and may resemble CAPS (Table 1) . Initial reports from China(4) suggest that the abnormalities seen in COVID-19 may be associated with cellular immune deficiency, coagulation activation, myocardial This article is protected by copyright. All rights reserved This article is protected by copyright. All rights reserved benefit was seen in subgroup analysis in those with D-dimer > 6-fold the upper limit of normal (32.8% vs 52.4%, p=0.01) and in those with increased sepsis-induced coagulopathy score (40% vs 64%, p=0.02). More recent case series (2) , suggest the presence of aPL antibodies (aCL and aß2GPI) in COVID-19 patients, therefore a possible underrecognized mechanism of thrombosis in patients with severe COVID-19 may be the production of aPL antibodies and development of its potential catastrophic variant. In conclusion, although thrombotic events in critically ill patients can occur due to a number of mechanisms, in clinical practice these are challenging scenarios to differentiate. We believe it is plausible that in at least a subset of patients with severe COVID-19, aPL antibodies may play a role leading to CAPS. Prospective studies are needed in this field to evaluate the prevalence of aPL antibodies and CAPS. Dr. Difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2 Coagulopathy and Antiphospholipid Antibodies in Patients with Covid-19 Catastrophic antiphospholipid syndrome (CAPS): descriptive analysis of a series of 280 patients from the "CAPS Registry Clinical Characteristics of 138 Hospitalized Patients With Novel Coronavirus-Infected Pneumonia in Wuhan, China Clinical Characteristics of Coronavirus Disease 2019 in China Will Complement Inhibition be the New Target in Treating COVID-19 Related Systemic Thrombosis? Circulation Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy Accepted Article This article is protected by copyright. All rights reserved