Complementary Sets of Autoantibodies Induced by SARS-CoV-2, Adenovirus and Bacterial Antigens Cross-React with Human Blood Protein Antigens in COVID-19 Coagulopathies

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Abstract

COVID-19 patients often develop coagulopathies including microclotting, thrombotic strokes or thrombocytopenia. Autoantibodies are present against blood-related proteins including cardiolipin (CL), serum albumin (SA), platelet factor 4 (PF4), beta 2 glycoprotein 1 (β2GPI), phosphodiesterases (PDE), and coagulation factors such as Factor II, IX, X and von Willebrand factor (vWF). Different combinations of autoantibodies associate with different coagulopathies. Previous research revealed similarities between proteins with blood clotting functions and SARS-CoV-2 proteins, adenovirus, and bacterial proteins associated with moderate-to-severe COVID-19 infections. This study investigated whether polyclonal antibodies (mainly goat and rabbit) against these viruses and bacteria recognize human blood-related proteins. Antibodies against SARS-CoV-2 and adenovirus recognized vWF, PDE and PF4 and SARS-CoV-2 antibodies also recognized additional antigens. Most bacterial antibodies tested (group A streptococci [GAS], staphylococci, Escherichia coli [E. coli], Klebsiella pneumoniae, Clostridia, and Mycobacterium tuberculosis) cross-reacted with CL and PF4. while GAS antibodies also bound to F2, Factor VIII, Factor IX, and vWF, and E. coli antibodies to PDE. All cross-reactive interactions involved antibody-antigen binding constants smaller than 100 nM. Since most COVID-19 coagulopathy patients display autoantibodies against vWF, PDE and PF4 along with CL, combinations of viral and bacterial infections appear to be necessary to initiate their autoimmune coagulopathies.

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Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Fei Zhou, Ting Yu, Ronghui Du … (2020)

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

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Clinical characteristics of 140 patients infected by SARS‐CoV‐2 in Wuhan, China

Jin-jin Zhang, Xiang Dong, Yi‐Yuan Cao … (2020)

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been widely spread. We aim to investigate the clinical characteristic and allergy status of patients infected with SARS-CoV-2.

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COVID-19 and its implications for thrombosis and anticoagulation

Jean M Connors, Jerrold Levy (2020)

Severe acute respiratory syndrome coronavirus 2, coronavirus disease 2019 (COVID-19)-induced infection can be associated with a coagulopathy, findings consistent with infection-induced inflammatory changes as observed in patients with disseminated intravascular coagulopathy (DIC). The lack of prior immunity to COVID-19 has resulted in large numbers of infected patients across the globe and uncertainty regarding management of the complications that arise in the course of this viral illness. The lungs are the target organ for COVID-19; patients develop acute lung injury that can progress to respiratory failure, although multiorgan failure can also occur. The initial coagulopathy of COVID-19 presents with prominent elevation of D-dimer and fibrin/fibrinogen-degradation products, whereas abnormalities in prothrombin time, partial thromboplastin time, and platelet counts are relatively uncommon in initial presentations. Coagulation test screening, including the measurement of D-dimer and fibrinogen levels, is suggested. COVID-19–associated coagulopathy should be managed as it would be for any critically ill patient, following the established practice of using thromboembolic prophylaxis for critically ill hospitalized patients, and standard supportive care measures for those with sepsis-induced coagulopathy or DIC. Although D-dimer, sepsis physiology, and consumptive coagulopathy are indicators of mortality, current data do not suggest the use of full-intensity anticoagulation doses unless otherwise clinically indicated. Even though there is an associated coagulopathy with COVID-19, bleeding manifestations, even in those with DIC, have not been reported. If bleeding does occur, standard guidelines for the management of DIC and bleeding should be followed.