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.

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.

Objective The coronavirus disease 2019 (COVID‐19) has rapidly developed into a pandemic. Increased levels of ferritin due to cytokine storm and secondary hemophagocytic lymphohistiocytosis were found in severe COVID‐19 patients. Therefore, the aim of this study was to determine the role of ferritin in COVID‐19. Methods Studies investigating ferritin in COVID‐19 were collected from PubMed, EMBASE, CNKI, SinoMed, and WANFANG. A meta‐analysis was performed to compare the ferritin level between different patient groups: non‐survivors versus survivors; more severe versus less severe; with comorbidity versus without comorbidity; ICU versus non‐ICU; with mechanical ventilation versus without mechanical ventilation. Results A total of 52 records involving 10 614 COVID‐19‐confirmed patients between December 25, 2019, and June 1, 2020, were included in this meta‐analysis, and 18 studies were included in the qualitative synthesis. The ferritin level was significantly increased in severe patients compared with the level in non‐severe patients [WMD 397.77 (95% CI 306.51‐489.02), P < .001]. Non‐survivors had a significantly higher ferritin level compared with the one in survivors [WMD 677.17 (95% CI 391.01‐963.33), P < .001]. Patients with one or more comorbidities including diabetes, thrombotic complication, and cancer had significantly higher levels of ferritin than those without (P < .01). Severe acute liver injury was significantly associated with high levels of ferritin, and its level was associated with intensive supportive care, including ICU transfer and mechanical ventilation. Conclusions Ferritin was associated with poor prognosis and could predict the worsening of COVID‐19 patients.

Comprehensive profiling of humoral antibody response to severe acute respiratory syndrome (SARS) coronavirus-2 (CoV-2) proteins is essential in understanding the host immunity and in developing diagnostic tests and vaccines. To address this concern, we developed a SARS-CoV-2 proteome peptide microarray to analyze antibody interactions at the amino acid resolution. With the array, we demonstrate the feasibility of employing SARS-CoV-1 antibodies to detect the SARS-CoV-2 nucleocapsid phosphoprotein. The first landscape of B-cell epitopes for SARS-CoV-2 IgM and IgG antibodies in the serum of 10 coronavirus disease of 2019 (COVID-19) patients with early infection is also constructed. With array data and structural analysis, a peptide epitope for neutralizing antibodies within the SARS-CoV-2 spike receptor-binding domain’s interaction interface with the angiotensin-converting enzyme 2 receptor was predicted. All the results demonstrate the utility of our microarray as a platform to determine the changes of antibody responses in COVID-19 patients and animal models as well as to identify potential targets for diagnosis and treatment.

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.

Background COVID-19 is a viral respiratory disease caused by the severe acute respiratory syndrome-Coronavirus type 2 (SARS-CoV-2). Patients with this disease may be more prone to venous or arterial thrombosis because of the activation of many factors involved in it, including inflammation, platelet activation and endothelial dysfunction. Interferon gamma inducible protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein 1-alpha (MIP1α) are cytokines related to thrombosis. Therefore, this study focused on these three indicators in COVID-19, with the hope to find biomarkers that are associated with patients’ outcome. Methods This is a retrospective single-center study involving 74 severe and critically ill COVID-19 patients recruited from the ICU department of the Tongji Hospital in Wuhan, China. The patients were divided into two groups: severe patients and critically ill patients. The serum IP-10, MCP-1 and MIP1α level in both groups was detected using the enzyme-linked immunosorbent assay (ELISA) kit. The clinical symptoms, laboratory test results, and the outcome of COVID-19 patients were retrospectively analyzed. Results The serum IP-10 and MCP-1 level in critically ill patients was significantly higher than that in severe patients (P < 0.001). However, no statistical difference in MIP1α between the two groups was found. The analysis of dynamic changes showed that these indicators remarkably increased in patients with poor prognosis. Since the selected patients were severe or critically ill, no significant difference was observed between survival and death. Conclusions IP-10 and MCP-1 are biomarkers associated with the severity of COVID-19 disease and can be related to the risk of death in COVID-19 patients.

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.

The outbreak of novel coronavirus disease 2019 (COVID-19) has now become a global pandemic. Coagulopathy has been reported widely in critically ill COVID-19 patients and was related to high mortality. However, the comprehensive coagulation profiles have not been examined and the underlying mechanism of the coagulopathy in COVID-19 patients is unclear. To study the coagulation profiles of routine hemostasis tests, natural anticoagulants, coagulant factors and antiphospholipid antibodies in critically ill COVID-19 patients. This single-center and cross-section study included 19 patients with COVID-19, who were admitted to intensive care unit (ICU) at Tongji hospital in Wuhan, China, from Feb 23 to Mar 3, 2020. Demographic data, laboratory parameters, treatments and clinical outcomes of the patients were collected and analyzed. The final date of follow-up was Mar 31, 2020. In this study, 12 thrombotic events occurred in 9 patients, including 4 cerebral infarctions, 7 acro-ischemia and 1 internal jugular vein thrombosis. The common abnormalities of routine coagulation tests included evelated D-Dimer level (100%), prolonged prothrombin time (73.7%) and hyperfibrinogenemia (73.7%). The median activities of natural anticoagulants including protein C, protein S and antithrombin were all below the normal range. Factor VIII activities were significantly above normal range (median value 307%, IQR 198-441) in all patients. Factor V and factor VII activities were significantly lower in near-terminal stage patients. Anti-phospholipid antibodies were present in 10 patients. Strikingly, 4 cerebral infarction events were in patients had anti-phospholipid antibodies of multiple isotypes. Sustained hypercoagulable status and thrombotic events were common in critically ill patients with COVID-19. The low activities of natural anticoagulants, elevated factor VIII level and the presence of antiphospholipid antibodies, together, may contribute to the etiopathology of coagulopathy in COVID-19 patients.