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High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study.

ABSTRACT: PURPOSE:Little evidence of increased thrombotic risk is available in COVID-19 patients. Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection. METHODS:All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included. Medical history, symptoms, biological data and imaging were prospectively collected. Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients. RESULTS:150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points). Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting. Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO. Most patients (>?95%) had elevated D-dimer and fibrinogen. No patient developed disseminated intravascular coagulation. Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant. Comparison with non-COVID-19 ARDS patients (n?=?145) confirmed that COVID-19 ARDS patients (n?=?77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs. 2.1%, p?

SUBMITTER: Helms J

PROVIDER: S-EPMC7197634 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study.

Helms Julie J Tacquard Charles C Severac François F Leonard-Lorant Ian I Ohana Mickaël M Delabranche Xavier X Merdji Hamid H Clere-Jehl Raphaël R Schenck Malika M Fagot Gandet Florence F Fafi-Kremer Samira S Castelain Vincent V Schneider Francis F Grunebaum Lélia L Anglés-Cano Eduardo E Sattler Laurent L Mertes Paul-Michel PM Meziani Ferhat F

Intensive care medicine 20200504 6

<h4>Purpose</h4>Little evidence of increased thrombotic risk is available in COVID-19 patients. Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection.<h4>Methods</h4>All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included. Medical history, symptoms, biological data and imaging were prospectively collected. Propensit ...[more]

PMID: 32367170

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Project description:BackgroundWhether young adults who are infected with SARS-CoV-2 are at risk of subsequent infection is uncertain. We investigated the risk of subsequent SARS-CoV-2 infection among young adults seropositive for a previous infection.MethodsThis analysis was performed as part of the prospective COVID-19 Health Action Response for Marines study (CHARM). CHARM included predominantly male US Marine recruits, aged 18-20 years, following a 2-week unsupervised quarantine at home. After the home quarantine period, upon arrival at a Marine-supervised 2-week quarantine facility (college campus or hotel), participants were enrolled and were assessed for baseline SARS-CoV-2 IgG seropositivity, defined as a dilution of 1:150 or more on receptor-binding domain and full-length spike protein ELISA. Participants also completed a questionnaire consisting of demographic information, risk factors, reporting of 14 specific COVID-19-related symptoms or any other unspecified symptom, and brief medical history. SARS-CoV-2 infection was assessed by PCR at weeks 0, 1, and 2 of quarantine and participants completed a follow-up questionnaire, which included questions about the same COVID-19-related symptoms since the last study visit. Participants were excluded at this stage if they had a positive PCR test during quarantine. Participants who had three negative swab PCR results during quarantine and a baseline serum serology test at the beginning of the supervised quarantine that identified them as seronegative or seropositive for SARS-CoV-2 then went on to basic training at Marine Corps Recruit Depot-Parris Island. Three PCR tests were done at weeks 2, 4, and 6 in both seropositive and seronegative groups, along with the follow-up symptom questionnaire and baseline neutralising antibody titres on all subsequently infected seropositive and selected seropositive uninfected participants (prospective study period).FindingsBetween May 11, 2020, and Nov 2, 2020, we enrolled 3249 participants, of whom 3168 (98%) continued into the 2-week quarantine period. 3076 (95%) participants, 2825 (92%) of whom were men, were then followed up during the prospective study period after quarantine for 6 weeks. Among 189 seropositive participants, 19 (10%) had at least one positive PCR test for SARS-CoV-2 during the 6-week follow-up (1·1 cases per person-year). In contrast, 1079 (48%) of 2247 seronegative participants tested positive (6·2 cases per person-year). The incidence rate ratio was 0·18 (95% CI 0·11-0·28; p<0·001). Among seropositive recruits, infection was more likely with lower baseline full-length spike protein IgG titres than in those with higher baseline full-length spike protein IgG titres (hazard ratio 0·45 [95% CI 0·32-0·65]; p<0·001). Infected seropositive participants had viral loads that were about 10-times lower than those of infected seronegative participants (ORF1ab gene cycle threshold difference 3·95 [95% CI 1·23-6·67]; p=0·004). Among seropositive participants, baseline neutralising titres were detected in 45 (83%) of 54 uninfected and in six (32%) of 19 infected participants during the 6 weeks of observation (ID50 difference p<0·0001).InterpretationSeropositive young adults had about one-fifth the risk of subsequent infection compared with seronegative individuals. Although antibodies induced by initial infection are largely protective, they do not guarantee effective SARS-CoV-2 neutralisation activity or immunity against subsequent infection. These findings might be relevant for optimisation of mass vaccination strategies.FundingDefense Health Agency and Defense Advanced Research Projects Agency.

Project description:The presence of antiphospholipid antibodies was shown to be associated with thrombosis in coronavirus disease 2019 (COVID-19) patients. Recently, according to reports from several studies, the vaccine-induced immune thrombotic thrombocytopenia is mediated by anti-platelet factor 4 (PF4)-polyanion complex in adenovirus-vectored COVID-19 vaccine recipients. It is impendent to explore whether inactivated COVID-19 vaccine widely used in China influences prothrombotic autoantibody production and induces thrombosis. In this prospective study, we recruited 406 healthcare workers who received two doses, 21 days apart, of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (BBIBP-CorV, Sinopharm). Paired blood samples taken before vaccination and four weeks after the second vaccination were used in detecting prothrombotic autoantibodies, including anticardiolipin (aCL), anti-β2 glycoprotein I (aβ2GP1), anti-phosphatidylserine/prothrombin (aPS/PT), and anti-PF4-heparin. The seroconversion rate of SARS-CoV-2 specific antibodies was 95.81% (389/406) four weeks after vaccination. None of the subjects had spontaneous thrombosis or thrombocytopenia over a minimum follow-up period of eight weeks. There was no significant difference in the presence of all ten autoantibodies between samples collected before and after vaccination: for aCL, IgG (7 vs. 8, P = 0.76), IgM (41 vs. 44, P = 0.73), IgA (4 vs. 4, P = 1.00); anti-β2GP1, IgG (7 vs. 6, P = 0.78), IgM (6 vs. 5, P = 0.76), IgA (3 vs. 5, P = 0.72); aPS/PT IgG (0 vs. 0, P = 1.00), IgM (6 vs. 5, P = 0.76); aPF4-heparin (2 vs. 7, P = 0.18), and antinuclear antibody (ANA) (18 vs. 21, P = 0.62). Notably, seven cases presented with anti-PF4-heparin antibodies (range: 1.18-1.79 U/mL) after vaccination, and none of them exhibited any sign of thrombotic disorder. In conclusion, inactivated SARS-CoV-2 vaccine does not influence the profile of antiphospholipid antibody and anti-PF4-heparin antibody nor increase the risk of thrombosis.

Project description:The nutritional sequelae of COVID-19 have not been explored in a large cohort study.ObjectivesTo identify factors associated with the change in nutritional status between discharge and 30 days post-discharge (D30). Secondary objectives were to determine the prevalence of subjective functional loss and severe disability at D30 and their associated factors.MethodsCollected data included symptoms, nutritional status, self-evaluation of food intake, Performance Status (PS) Scale, Asthenia Scale, self-evaluation of strength (SES) for arms and legs at discharge and at D30. An SES <7 was used to determine subjective functional loss. A composite criteria for severe disability was elaborated combining malnutrition, subjective functional loss and PS >2. Patients were classified into three groups according to change in nutritional status between discharge and D30 (persistent malnutrition, correction of malnutrition and the absence of malnutrition).ResultsOf 549 consecutive patients hospitalised for COVID-19 between 1 March and 29 April 2020, 130 died including 17 after discharge (23.7%). At D30, 312 patients were at home, 288 (92.3%) of whom were interviewed. Of the latter, 33.3% were malnourished at discharge and still malnourished at D30, while 23.2% were malnourished at discharge but no longer malnourished at D30. The highest predictive factors of persistent malnutrition were intensive care unit (ICU) stay (OR=3.42, 95% CI: 2.04 to 5.75), subjective functional loss at discharge (OR=3.26, 95% CI: 1.75 to 6.08) and male sex (OR=2.39, 95% CI: 1.44 to 3.97). Subjective functional loss at discharge (76.8%) was the main predictive factor of subjective functional loss at D30 (26.3%) (OR=32.6, 95% CI: 4.36 to 244.0). Lastly, 8.3% had a severe disability, with a higher risk in patients requiring an ICU stay (OR=3.39, 95% CI: 1.43 to 8.06).ConclusionPatients who survived a severe form of COVID-19 had a high risk of persistent malnutrition, functional loss and severe disability at D30. We believe that nutritional support and rehabilitation should be strengthened, particularly for male patients who were admitted in ICU and had subjective functional loss at discharge.Trial registration numberNCT04451694.

Dataset Information

High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study.

Publications

High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study.

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