Covid-19 CasesTo rapidly communicate information on the global clinical effort against Covid-19, the Journal has initiated a series of case reports that offer important teaching points or novel findings. The case reports should be viewed as observations rather than as recommendations for evaluation or treatment. In the interest of timeliness, these reports are evaluated by in-house editors, with peer review reserved for key points as needed. Coagulopathy and Antiphospholipid Antibodies in Patients with Covid-19We describe a patient with Covid-19 and clinically significant coagulopathy, antiphospholipid antibodies, and multiple infarcts. He was one of three patients with these findings in an intensive care unit designated for patients with Covid-19. This unit, which was managed by a multidisciplinary team from Peking Union Medical College Hospital in the Sino-French New City Branch of Tongji Hospital in Wuhan, China, was set up on an emergency basis to accept the most critically ill patients during the outbreak of Covid-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was confirmed in all the patients by reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay or serologic testing.A 69-year-old man with a history of hypertension, diabetes, and stroke presented with fever, cough, dyspnea, diarrhea, and headache. Covid-19 was diagnosed in the patient on January 25, 2020, on the basis of RT-PCR testing that detected SARS-CoV-2. The initial treatment was supportive; however, the illness subsequently progressed to hypoxemic respiratory failure warranting the initiation of invasive mechanical ventilation.

A coronavirus (HCoV-19) has caused the novel coronavirus disease (COVID-19) outbreak in Wuhan, China. Preventing and reversing the cytokine storm may be the key to save the patients with severe COVID-19 pneumonia. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. This study aims to investigate whether MSC transplantation improves the outcome of 7 enrolled patients with COVID-19 pneumonia in 217 16, 2020. The clinical outcomes, as well as changes of inflammatory and immune function levels and adverse effects of 7 enrolled patients were assessed for 14 days after MSC injection. MSCs could cure or significantly improve the functional outcomes of seven patients without observed adverse effects. The pulmonary function and symptoms of these seven patients were significantly improved in 2 days after MSC transplantation. Among them, two common and one severe patient were recovered and discharged in 10 days after treatment. After treatment, the peripheral lymphocytes were increased, the C-reactive protein decreased, and the overactivated cytokinesecreting immune cells CXCR3+CD4+ T cells, CXCR3+CD8+ T cells, and CXCR3+ NK cells disappeared in 3-6 days. In addition, a group of CD14+CD11c+CD11b mid regulatory DC cell population dramatically increased. Meanwhile, the level of TNF-α was significantly decreased, while IL-10 increased in MSC treatment group compared to the placebo control group. Furthermore, the gene expression profile showed MSCs were ACE2and TMPRSS2which indicated MSCs are free from COVID-19 infection. Thus, the intravenous transplantation of MSCs was safe and effective for treatment in patients with COVID-19 pneumonia, especially for the patients in critically severe condition.

The pandemic outbreak of coronavirus disease 2019 is rap idly spreading all over the world. Reports from China showed that about 20% of patients developed severe disease, resulting in a fatality of 4%. In the past two months, we clinical immunologists participated in mu lti-rounds of MDT (mult idiscipline team) discussion on the anti-inflammat ion management of critical ill COVID-19 patients, with our colleagues dispatched from Ch inese leading PUM C Hospital to Wuhan to admit and treat the most severe patients . Here, fro m the perspective of clinical immunologists, we will discuss the clin ical and immunological characteristics of severe patients, and summarize the current evidence and share our experience in anti-inflammat ion treatment, including glucocorticoids, IL-6 antagonist, JAK inhibitors and choloroquine/hydrocholoroquine, of patients with severe COVID-19 that may have an impaired immune system.

We carried out metagenomic shotgun sequencing and a metagenome-wide association study (MGWAS) of fecal, dental and salivary samples from a cohort of individuals with rheumatoid arthritis (RA) and healthy controls. Concordance was observed between the gut and oral microbiomes, suggesting overlap in the abundance and function of species at different body sites. Dysbiosis was detected in the gut and oral microbiomes of RA patients, but it was partially resolved after RA treatment. Alterations in the gut, dental or saliva microbiome distinguished individuals with RA from healthy controls, were correlated with clinical measures and could be used to stratify individuals on the basis of their response to therapy. In particular, Haemophilus spp. were depleted in individuals with RA at all three sites and negatively correlated with levels of serum autoantibodies, whereas Lactobacillus salivarius was over-represented in individuals with RA at all three sites and was present in increased amounts in cases of very active RA. Functionally, the redox environment, transport and metabolism of iron, sulfur, zinc and arginine were altered in the microbiota of individuals with RA. Molecular mimicry of human antigens related to RA was also detectable. Our results establish specific alterations in the gut and oral microbiomes in individuals with RA and suggest potential ways of using microbiome composition for prognosis and diagnosis.

BackgroundIntravenous belimumab plus standard of care (SoC) is approved in the USA and Europe for treatment of active, autoantibody-positive systemic lupus erythematosus (SLE).MethodsThis phase III, multicentre, randomised, double-blind, placebo-controlled study (BEL113750; NCT01345253) was conducted in 49 centres across China, Japan and South Korea (May 2011–September 2015). Patients with SLE were randomised 2:1 to intravenous belimumab 10 mg/kg or placebo, plus SoC, every 4 weeks until Week 48. The primary endpoint was the SLE Responder Index (SRI) 4 response rate at Week 52. Secondary endpoints were the percentage of patients with ≥4 point reduction in Safety of Oestrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI), SRI7, time to first severe flare and number of days prednisone (or equivalent) dose ≤7.5 mg/day and/or reduced by 50% from baseline. Safety was assessed.ResultsThe modified intent-to-treat population included 677 patients (belimumab n=451, placebo n=226). At Week 52, the SRI4 response rate was higher with belimumab versus placebo (53.8% vs 40.1%; OR: 1.99 (95% CI: 1.40, 2.82; P=0.0001)). The percentages of patients with a ≥4 point reduction in SELENA-SLEDAI and an SRI7 response were significantly greater for belimumab versus placebo. Patients in the belimumab group had a 50% lower risk of experiencing a severe flare than those receiving placebo (P=0.0004). In patients with baseline prednisone dose >7.5 mg/day, there was a significant reduction in steroid use favouring belimumab (P=0.0228). The incidence of adverse events was similar between groups.ConclusionsIn patients with SLE from North East Asia, belimumab significantly improved disease activity, while reducing prednisone use, with no new safety issues.

IgG4-RD is a systemic inflammatory and sclerosing disease. Parotid and lacrimal involvement (formerly called Mikulicz's disease), lymphadenopathy and pancreatitis are the most common manifestations. Patients with IgG4-RD showed favourable responses to treatment with glucocorticoids and immunosuppressive agents.

PurposeIgG4-related disease (IgG4-RD) is an increasingly recognized clinicopathological disorder with immune-mediated inflammatory lesions mimicking malignancies. A cohort study was prospectively designed to investigate the value of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in characterizing IgG4-RD.MethodsThirty-five patients diagnosed with IgG4-RD according to the consensus criteria were enrolled with informed consent. All patients underwent baseline 18F-FDG PET/CT evaluation. Among them, 29 patients underwent a second 18F-FDG PET/CT scan after 2 to 4 weeks of steroid-based therapy.ResultsAll 35 patients were found with 18F-FDG-avid hypermetabolic lesion(s); 97.1 % (34/35) of these patients showed multi-organ involvement. Among the 35 patients, 71.4 % (25/35) patients were found with more organ involvement on 18F-FDG PET/CT than conventional evaluations including physical examination, ultrasonography, and computed tomography (CT). 18F-FDG PET/CT demonstrated specific image characteristics and pattern of IgG4-RD, including diffusely elevated 18F-FDG uptake in the pancreas and salivary glands, patchy lesions in the retroperitoneal region and vascular wall, and multi-organ involvement that cannot be interpreted as metastasis. Comprehensive understanding of all involvement aided the biopsy-site selection in seven patients and the recanalization of ureteral obstruction in five patients. After 2 to 4 weeks of steroid-based therapy at 40 mg to 50 mg prednisone per day, 72.4 % (21/29) of the patients showed complete remission, whereas the others exhibited > 81.8 % decrease in 18F-FDG uptake.ConclusionF-FDG PET/CT is a useful tool for assessing organ involvement, monitoring therapeutic response, and guiding interventional treatment of IgG4-RD. The image pattern is suggested to be updated into the consensus diagnostic criteria for IgG4-RD.

Objective Coagulopathy is one of the characteristics observed in critically ill patients with coronavirus disease 2019 (COVID‐19). Antiphospholipid antibodies (aPLs) contribute to coagulopathy, though their role in COVID‐19 remains unclear. This study was undertaken to determine the prevalence and characteristics of aPLs in patients with COVID‐19. Methods Sera collected from 66 COVID‐19 patients who were critically ill and 13 COVID‐19 patients who were not critically ill were tested by chemiluminescence immunoassay for anticardiolipin antibodies (aCLs), anti–β2‐glycoprotein I (anti‐β2GPI) (IgG, IgM, and IgA), and IgG anti‐β2GPI–domain 1 (anti‐β2GPI–D1) and IgM and IgG anti–phosphatidylserine/prothrombin (anti‐PS/PT) antibodies were detected in the serum by enzyme‐linked immunosorbent assay. Results Of the 66 COVID‐19 patients in critical condition, aPLs were detected in 31 (47% ). Antiphospholipid antibodies were not present among COVID‐19 patients who were not in critical condition. The IgA anti‐β2GPI antibody was the most commonly observed aPL in patients with COVID‐19 and was present in 28.8% (19 of 66) of the critically ill patients, followed by IgA aCLs (17 of 66, or 25.8%) and IgG anti‐β2GPI (12 of 66, or 18.2%). For multiple aPLs, IgA anti‐β2GPI + IgA aCLs was the most common antibody profile observed (15 of 66, or 22.7%), followed by IgA anti‐β2GPI + IgA aCL + IgG anti‐β2GPI (10 of 66, or 15.2%). Antiphospholipid antibodies emerge ~35–39 days after disease onset. A dynamic analysis of aPLs revealed 4 patterns based on the persistence or transient appearance of the aPLs. Patients with multiple aPLs had a significantly higher incidence of cerebral infarction compared to patients who were negative for aPLs (P = 0.023). Conclusion Antiphospholipid antibodies were common in critically ill patients with COVID‐19. Repeated testing demonstrating medium to high titers of aPLs and the number of aPL types a patient is positive for may help in identifying patients who are at risk of developing cerebral infarction. Antiphospholipid antibodies may be transient and disappear within a few weeks, but in genetically predisposed patients, COVID‐19 may trigger the development of an autoimmune condition similar to the antiphospholipid syndrome (APS), referred to as “COVID‐19–induced APS‐like syndrome.” Long‐term follow‐up of COVID‐19 patients who are positive for aPLs would be of great importance in understanding the pathogenesis of this novel coronavirus.