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.

As a link between exercise and metabolism, irisin is assumed to be involved in increased total body energy expenditure, reduced body weight, and increased insulin sensitivity. Although our recent evidence supported the contribution of irisin to vascular endothelial cell (ECs) proliferation and apoptosis, further research of irisin involvement in the angiogenesis of ECs was not conclusive. In the current study, it was found that irisin promoted Human Umbilical Vein Endothelial Cell (HUVEC) angiogenesis via increasing migration and tube formation, and attenuated chemically-induced intersegmental vessel (ISV) angiogenic impairment in transgenic TG (fli1: GFP) zebrafish. It was further demonstrated that expression of matrix metalloproteinase (MMP) 2 and 9 were also up-regulated in endothelial cells. We also found that irisin activated extracellular signal–related kinase (ERK) signaling pathways. Inhibition of ERK signaling by using U0126 decreased the pro-migration and pro-angiogenic effect of irisin on HUVEC. Also, U0126 inhibited the elevated expression of MMP-2 and MMP-9 when they were treated with irisin. In summary, these findings provided direct evidence that irisin may play a pivotal role in maintaining endothelium homeostasis by promoting endothelial cell angiogenesis via the ERK signaling pathway.

Detection of circulating tumor cells remains a significant challenge due to their vast physical and biological heterogeneity. We developed a cell-surface-marker-independent technology based on telomerase-specific, replication-selective oncolytic herpes-simplex-virus-1 that targets telomerase-reverse-transcriptase-positive cancer cells and expresses green-fluorescent-protein that identifies viable CTCs from a broad spectrum of malignancies. Our method recovered 75.5–87.2% of tumor cells spiked into healthy donor blood, as validated by different methods, including single cell sequencing. CTCs were detected in 59–100% of 326 blood samples from patients with 6 different solid organ carcinomas and lymphomas. Significantly, CTC-positive rates increased remarkably with tumor progression from N0M0, N+M0 to M1 in each of 5 tested cancers (lung, colon, liver, gastric and pancreatic cancer, and glioma). Among 21 non-small cell lung cancer cases in which CTC values were consecutively monitored, 81% showed treatment-related decreases, which was also found after treatments in the other solid tumors. Moreover, monitoring CTC values provided an efficient treatment response indicator in hematological malignancies. Compared to CellSearch, our method detected significantly higher positive rates in 40 NSCLC in all stages, including N0M0, N+M0 and M1, and was less affected by chemotherapy. This simple, robust and clinically-applicable technology detects viable CTCs from solid and hematopoietic malignancies in early to late stages, and significantly improves clinical detection and treatment prognostication.

The TLR5 signaling pathway plays an important role in T cell-mediated hepatic injury and may be exploited for therapeutic treatment of inflammatory liver diseases. (Hepatology 2017;65:2059-2073).