Background: Critically ill patients with coronavirus disease 2019 (COVID-19) have a profound hypercoagulable state and often develop coagulopathy which leads to organ failure and death. Because of a prolonged activated partial-thromboplastin time (aPTT), a relationship with anti-phospholipid antibodies (aPLs) has been proposed, but results are controversial. Functional assays for aPL (i.e., lupus anticoagulant) can be influenced by concomitant anticoagulation and/or high levels of C reactive protein. The presence of anticardiolipin (aCL), anti-beta2-glycoprotein I (anti-b 2 GPI), and anti-phosphatidylserine/ prothrombin (aPS/PT) antibodies was not investigated systematically. Epitope specificity of anti-b 2 GPI antibodies was not reported. Objective: To evaluate the prevalence and the clinical association of aPL in a large cohort of COVID-19 patients, and to characterize the epitope specificity of anti-b 2 GPI antibodies. Methods: ELISA and chemiluminescence assays were used to test 122 sera of patients suffering from severe COVID-19. Of them, 16 displayed major thrombotic events.

Background The highest number of COVID-19 cases in Italy have been reported in Lombardy, a region in northern Italy. We aimed to analyse the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with rheumatic and musculoskeletal diseases living in a district of Lombardy with a high prevalence of COVID-19. MethodsWe did a single-centre observational study at the Azienda Socio Sanitaria Territoriale (ASST) Spedali Civili of Brescia, Italy. We collected data from patients with rheumatic and musculoskeletal diseases enrolled in our outpatient clinic to identify confirmed or possible cases of SARS-CoV-2 infection. Data were collected through a survey that was administered via telephone or in the outpatient clinic by rheumatologists. We also did a case-control study of all patients with confirmed COVID-19 pneumonia and rheumatic and musculoskeletal diseases who were admitted to the ASST Spedali Civili of Brescia during the study period. Cases were matched by age, sex, and month of hospital admission to at least two controls admitted to the same hospital for COVID-19 pneumonia during the study period. Findings Between Feb 24 and May 1, 2020, we collected data from 1525 patients with rheumatic and musculoskeletal diseases: 117 (8%) presented with symptoms that were compatible with COVID-19. 65 patients had a swab confirmation of SARS-CoV-2 infection, whereas 52 presented with a spectrum of symptoms indicative of COVID-19 but were not swab tested. Patients with confirmed COVID-19 were older than those with suspected COVID-19 (median age 68 [IQR 55-76] years vs 57 [49-67] years; p=0•0010) and more likely to have arterial hypertension (33 [51%] vs 14 [27%] patients; odds ratio [OR] 2•8 [95% CI 1•3-6•1]; p=0•031) and obesity (11 [17%] vs 1 [2%]; OR 11•0 [1•3-83•4]; p=0•0059). We found no differences in rheumatological disease or background therapy between confirmed and suspected COVID-19 cases. 47 (72%) of the 65 patients with confirmed COVID-19 developed pneumonia that required admission to hospital. 12 (10%) deaths occurred among the 117 patients with confirmed or suspected COVID-19 (ten in those with confirmed COVID-19 and two in those with suspected COVID-19). Deceased patients with confirmed COVID-19 were older than survivors (median age 78•8 years [IQR 75•3-81•3] vs 65•5 years [53•3-74•0]; p=0•0002). We observed no differences in sex, comorbidities, or therapies between the deceased patients and survivors. The case-control study comprised 26 patients with rheumatic and musculoskeletal diseases and COVID-19 pneumonia and 62 matched controls. We found no significant differences between cases and controls in duration of COVID-19 symptoms before admission, duration of stay in hospital, or the local chest X-ray scoring system. Glucocorticoids were used for severe respiratory manifestations related to lung involvement in 17 (65%) of 26 cases and tocilizumab in six (23%) of 26; thrombotic events occurred in four (15%) of 26 cases. Four (15%) of 26 cases and six (10%) of 62 controls died...

Background. Critically ill patients with coronavirus disease 2019 (COVID-19) have a profound hypercoagulable state and often develop coagulopathy which leads to organ failure and death. Because of a prolonged activated partial-thromboplastin time (aPTT), a relationship with anti-phospholipid antibodies (aPL) has been proposed, but results are controversial. Functional assays for aPL (i.e., lupus anticoagulant) can be influenced by concomitant anticoagulation and/or high levels of C reactive protein. The presence of anti-cardiolipin (aCL), anti-beta2-glycoprotein I (anti-β2GPI) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies was not investigated systematically. Epitope specificity of anti-β2GPI antibodies was not reported. Objective. To evaluate the prevalence and the clinical association of aPL in a large cohort of COVID-19 patients, and to characterize the epitope specificity of anti-β2GPI antibodies. Methods. ELISA and chemiluminescence assays were used to test 122 sera of patients suffering from severe COVID-19. Of them, 16 displayed major thrombotic events. Results. Anti-β2GPI IgG/IgA/IgM were the most frequent in 15.6/6.6/9.0% of patients, while aCL IgG/IgM were detected in 5.7/6.6% by ELISA. Comparable values were found by chemiluminescence. aPS/PT IgG/IgM were detectable in 2.5 and 9.8% by ELISA. No association between thrombosis and aPL was found. Reactivity against domain 1 and 4-5 of β2GPI was limited to 3/58 (5.2%) tested sera for each domain and did not correlate with aCL/anti-β2GPI nor with thrombosis. Conclusions. aPL show a low prevalence in COVID-19 patients and are not associated with major thrombotic events. aPL in COVID-19 patients are mainly directed against β2GPI but display an epitope specificity different from antibodies in antiphospholipid syndrome.

Objectives To investigate fetal/perinatal and maternal outcomes from a large multicentre cohort of women diagnosed with UCTD. Methods This multicentre retrospective cohort study describes the outcomes of 224 pregnancies in 133 consecutive women with a diagnosis of UCTD, positive for ANA and aged <45 years old at study inclusion. Results Of the 224 pregnancies analysed, 177 (79%) resulted in live births, 45 (20.1%) in miscarriages (defined as pregnancy loss before 12 weeks’ gestation), 2 (0.9%) in stillbirths (pregnancy loss after 20 weeks’ gestation) and 6 (2.7%) cases showed intrauterine growth restriction. Miscarriages and stillbirths were strongly associated with the presence of aPL and ENA antibodies (P < 0.05). Maternal pregnancy complications were as follows: 5 (2.2%) cases developed pre-eclampsia, 11 (4.9%) cases gestational hypertension and 12 (5.4%) cases gestational diabetes. Joint involvement represented the most frequent clinical manifestation of the cohort (57.9%), followed by RP (40.6%), photosensitivity (32.3%) and haematological manifestations (27.1%). The rate of disease evolution of our cohort from a diagnosis of UCTD to a diagnosis of definite CTD was 12% within a mean time of 5.3 ± 2.8 years. With a total follow-up after first pregnancy of 1417 patient-years, we observed the evolution to a defined CTD in one out of every 88 patient- years. Conclusion In our multicentre cohort, women with UCTD had a live birth rate of 79%. Women with UCTD should be referred to specialist follow-up when planning a pregnancy. ENA profiling and aPL testing should be mandatory in this setting, and further therapeutic approaches and management should be planned accordingly.

Women with SLE should be timely and periodically counselled on family planning. Preconception counselling and risk stratification (based on disease activity and serological profile) are key points for having successful pregnancies thanks to individualized treatments and close monitoring for maternal and foetal complications. Contraception and assisted reproduction techniques are feasible in women with SLE, provided that potential risks are minimized by individualized management and appropriate prophylaxis.

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Antiphospholipid antibodies (aPL) can induce fetal loss in experimental animal models. Human studies did find hypocomplementemia associated with pregnancy complications in patients with antiphospholipid syndrome (APS), but these results are not unanimously confirmed. To investigate if the detection of low C3/C4 could be considered a risk factor for adverse pregnancy outcomes (APO) in APS and aPL carriers’ pregnancies we performed a multicenter study including 503 pregnancies from 11 Italian and 1 Russian centers. Data in women with APS and asymptomatic carriers with persistently positive aPL and preconception complement levels were available for 260 pregnancies. In pregnancies with low preconception C3/C4, a significantly higher prevalence of pregnancy losses was observed (p = 0.008). A subgroup analysis focusing on triple aPL-positive patients found that preconception low C3 and/or C4 levels were associated with an increased rate of pregnancy loss (p = 0.05). Our findings confirm that decreased complement levels before pregnancy are associated with increased risk of APO. This has been seen only in women with triple aPL positivity, indeed single or double positivity does not show this trend. Complement levels are cheap and easy to be measured therefore they could represent a useful aid to identify patients at increased risk of pregnancy loss.