Phospholipid remodeling and its derivatives are associated with COVID-19 severity.

BACKGROUND: Timely medical intervention in severe cases of coronavirus disease 2019 (COVID-19) and better understanding of the disease's pathogenesis are essential for reducing mortality, but early classification of severe cases and its progression is challenging. OBJECTIVE: We investigated the levels of circulating phospholipid metabolites and their relationship with COVID-19 severity, as well as the potential role of phospholipids in disease progression. METHODS: We performed nontargeted lipidomic analysis of plasma samples (n = 150) collected from COVID-19 patients (n = 46) with 3 levels of disease severity, healthy individuals, and subjects with metabolic disease. RESULTS: Phospholipid metabolism was significantly altered in COVID-19 patients. Results of a panel of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) and of phosphatidylethanolamine and lysophosphatidylethanolamine (LPE) ratios were significantly correlated with COVID-19 severity, in which 16 phospholipid ratios were shown to distinguish between patients with severe disease, mild disease, and healthy controls, 9 of which were at variance with those in subjects with metabolic disease. In particular, relatively lower ratios of circulating (PC16:1/22:6)/LPC 16:1 and (PE18:1/22:6)/LPE 18:1 were the most indicative of severe COVID-19. The elevation of levels of LPC 16:1 and LPE 18:1 contributed to the changes of related lipid ratios. An exploratory functional study of LPC 16:1 and LPE 18:1 demonstrated their ability in causing membrane perturbation, increased intracellular calcium, cytokines, and apoptosis in cellular models. CONCLUSION: Significant Lands cycle remodeling is present in patients with severe COVID-19, suggesting a potential utility of selective phospholipids with functional consequences in evaluating COVID-19's severity and pathogenesis.

Phospholipid remodeling and its derivatives are associated with the severity of COVID-19

Graphical Background Timely medical interventions in severe cases of COVID-19 and better understanding of the pathogenesis are essential for reducing the mortality, but early classification of severe cases and its progression is challenging. Objective To investigate the levels of circulating phospholipid metabolites and their relationship with the severity of COVID-19 and the potential role of phospholipids in the progression of the disease. Methods In this study, we performed non-targeted lipidomic analysis of plasma samples (n=150) collected from COVID-19 patients (N=46) with three levels of severity, healthy individuals and subjects with metabolic diseases. Results Results showed that phospholipid metabolism was significantly altered in COVID-19 patients. A panel of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) and of phosphatidylethanolamine (PE) and lysophosphatidylethanolamine (LPE) ratios were significantly correlated with the severity of COVID-19, in which 16 phospholipid ratios were shown to distinguish severe patients from mild cases and healthy controls, and 9 of which were at variance with those in subjects with metabolic diseases. In particular, relatively lower ratios of circulating (PC16:1/22:6)/LPC16:1 and (PE18:1/22:6)/LPE18:1 were the most indicative of severe COVID-19. The elevation of levels of LPC16:1 and LPE18:1 contributed to the changes of related lipid ratios. An exploratory functional study of LPC16:1 and LPE18:1 demonstrated their ability in causing membrane perturbation, increased intracellular calcium, cytokines, and apoptosis in cellular models. Conclusion These results demonstrate significant Lands cycle remodeling in patients with severe COVID-19, and suggest the potential utility of selective phospholipids with functional consequences in evaluating COVID-19 severity and its pathogenesis. Phospholipid ratio correlated with the severity of COVID-19, and the biological functions of phospholipid derivatives may be associated with exacerbation of the disease

3- to 24-month Follow-up on COVID-19 with Pulmonary Tuberculosis Survivors after Discharge: Results from a Prospective, Multicenter Study.

Objective: Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors. Methods: From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13 hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collected via telephone and face-to-face interviews at 3, 12, and 24 months after discharge. Results: Thirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9%) were men. Among them, nearly two-thirds (62.5%) of the survivors were moderate, three (9.4%) were severe, and more than half (59.4%) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6% at 3 months to 15.8% at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1%) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period. Conclusion: The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

ACE2 expression in adipose tissue is associated with cardio-metabolic risk factors and cell type composition-implications for COVID-19.

BACKGROUND: COVID-19 severity varies widely. Although some demographic and cardio-metabolic factors, including age and obesity, are associated with increasing risk of severe illness, the underlying mechanism(s) are uncertain. SUBJECTS/METHODS: In a meta-analysis of three independent studies of 1471 participants in total, we investigated phenotypic and genetic factors associated with subcutaneous adipose tissue expression of Angiotensin I Converting Enzyme 2 (ACE2), measured by RNA-Seq, which acts as a receptor for SARS-CoV-2 cellular entry. RESULTS: Lower adipose tissue ACE2 expression was associated with multiple adverse cardio-metabolic health indices, including type 2 diabetes (T2D) (P = 9.14 × 10-6), obesity status (P = 4.81 × 10-5), higher serum fasting insulin (P = 5.32 × 10-4), BMI (P = 3.94 × 10-4), and lower serum HDL levels (P = 1.92 × 10-7). ACE2 expression was also associated with estimated proportions of cell types in adipose tissue: lower expression was associated with a lower proportion of microvascular endothelial cells (P = 4.25 × 10-4) and higher proportion of macrophages (P = 2.74 × 10-5). Despite an estimated heritability of 32%, we did not identify any proximal or distal expression quantitative trait loci (eQTLs) associated with adipose tissue ACE2 expression. CONCLUSIONS: Our results demonstrate that individuals with cardio-metabolic features known to increase risk of severe COVID-19 have lower background ACE2 levels in this highly relevant tissue. Reduced adipose tissue ACE2 expression may contribute to the pathophysiology of cardio-metabolic diseases, as well as the associated increased risk of severe COVID-19.

Migrasomes: From Biogenesis, Release, Uptake, Rupture to Homeostasis and Diseases.

Migrasomes are migration-dependent membrane-bound vesicular structures that contain cellular contents and small vesicles. Migrasomes grow on the tips or intersections of the retraction fibers after cells migrate away. The process of releasing migrasomes into the extracellular space is named as "migracytosis". After releasing, they can be taken up by the surrounding cells, or rupture and further release their contents into the extracellular environment. Physiologically, migrasomes provide regional cues for organ morphogenesis during zebrafish gastrulation and discard the damaged mitochondria in response to mild mitochondrial stresses. Pathologically, migrasomes are released from podocyte during early podocyte stress and/or damage, from platelets after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), from microglia/macrophages of the ischemic brain, and from tumor necrosis factor α (TNFα)-activated endothelial cells (ECs); thus, this newly discovered extracellular vesicle is involved in all these pathological processes. Moreover, migrasomes can modulate the proliferation of cancer cell via lateral transferring mRNA and protein. In this review, we will summarize the biogenesis, release, uptake, and rupture of migrasomes and discuss its biological roles in development, redox signalling, innate immunity and COVID-19, cardio-cerebrovascular diseases, renal diseases, and cancer biology, all of these highlight the importance of migrasomes in modulating body homeostasis and diseases.

Potent Anti-SARS-CoV-2 Efficacy of COVID-19 Hyperimmune Globulin from Vaccine-Immunized Plasma.

Coronavirus disease 2019 (COVID-19) remains a global public health threat. Hence, more effective and specific antivirals are urgently needed. Here, COVID-19 hyperimmune globulin (COVID-HIG), a passive immunotherapy, is prepared from the plasma of healthy donors vaccinated with BBIBP-CorV (Sinopharm COVID-19 vaccine). COVID-HIG shows high-affinity binding to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein, the receptor-binding domain (RBD), the N-terminal domain of the S protein, and the nucleocapsid protein; and blocks RBD binding to human angiotensin-converting enzyme 2 (hACE2). Pseudotyped and authentic virus-based assays show that COVID-HIG displays broad-spectrum neutralization effects on a wide variety of SARS-CoV-2 variants, including D614G, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Kappa (B.1.617.1), Delta (B.1.617.2), and Omicron (B.1.1.529) in vitro. However, a significant reduction in the neutralization titer is detected against Beta, Delta, and Omicron variants. Additionally, assessments of the prophylactic and treatment efficacy of COVID-HIG in an Adv5-hACE2-transduced IFNAR-/- mouse model of SARS-CoV-2 infection show significantly reduced weight loss, lung viral loads, and lung pathological injury. Moreover, COVID-HIG exhibits neutralization potency similar to that of anti-SARS-CoV-2 hyperimmune globulin from pooled convalescent plasma. Overall, the results demonstrate the potential of COVID-HIG against SARS-CoV-2 infection and provide reference for subsequent clinical trials.

Correlation Study of Chest CT Features of Severe/Critical type COVID-19 with Early Renal Damage and Clinical Prognosis (preprint)

Background: Among patients with confirmed severe/critical type COVID-19, we found that although the seurm creatinine (Cr) value is in normal range, patients might have occured early renal damage. For severe/critical type COVID-19 patients, whether some chest CT features can be used to predict the early renal damage or clinical prognosis.Methods: 162 patients with severe/critical type COVID-19 were reviewed retrospectively in 13 medical centers from China. According to the level of eGFR, 162 patients were divided into three groups, group A (eGFR < 60 ml/min/1.73m2), group B (60 ml/min/1.73m2 ≤ eGFR < 90 ml/min/1.73m2 group) and group C (eGFR ≥ 90 ml/min/1.73m2). All patients’ baseline clinical characteristics, laboratory data, CT features and clinical outcomes were collected and compared. The eGFR and CT features was assessed using univariate and multivariate Cox regression.Results: Baseline clinical characteristics showed that there were significant differences in age, hypertension, cough and fatigue among groups A, B and C. Laboratory data analysis revealed significant differences between the three groups of leukocyte count, platelet count, C-reactive protein, aspartate aminotransferase, creatine kinase. Chest CT features analysis indicated that crazy-paving pattern has significant statistical difference in groups A and B compared with group C. The eGFR of patients with crazy-paving pattern was significant lower than those without crazy-paving pattern (76.73 ± 30.50 vs. 101.69 ± 18.24 ml/min/1.73m2, p < 0.001), and eGFR (OR = 0.962, 95% CI = 0.940-0.985) was the independent risk factor of crazy-paving pattern. The eGFR (HR = 0.549, 95% CI = 0.331-0.909, p = 0.020) and crazy-paving pattern (HR = 2.996, 95% CI = 1.010-8.714, p = 0.048) were independent risk factors of mortality.Conclusions: In patients with severe/critical type COVID-19, the presence of crazy-paving pattern on chest CT are more likely occured the decline of eGFR and poor clinical prognosis. The crazy-paving pattern appeared could be used as an early warning indicator of renal damage and to guide clinicians to use drugs reasonably.

CT Findings in a Novel Coronavirus Disease (COVID-19) Pneumonia at Initial Presentation.

BACKGROUND: COVID-19 first broke out in China and spread rapidly over the world. OBJECTIVES: To describe the CT features of COVID-19 pneumonia and to share our experience at initial diagnoses. Patients and Methods. Data from 53 patients (31 men, 22 women; mean age, 53 years; age range, 16-83 years) with confirmed COVID-19 pneumonia were collected. Their complete clinical data was reviewed, and their CT features were recorded and analyzed. RESULTS: The average time between onset of illness and the initial CT scan was six days (range, 1-42 days). A total of 399 segments were involved and distributed bilaterally (left lung: 186 segments [46.6%], right lung: 213 segments [53.4%]) and peripherally (38 [71.7%] patients). Multiple lobes (45 [84.9%]) and bilateral lower lobes (left lower lobe: 104 [26.1%], right lower lobe: 107 [26.8%], and total: 211 [52.9%]) were the most commonly involved. Ground-glass opacity with consolidation (24 [45.3%]) and pure ground-glass opacity (28 [52.8%]) were the main findings. The other findings were crazy-paving (14 [26.4%]), bronchiectasis (12 [22.6%]), atelectasis (7 [13.2%]), parenchymal bands (6 [11.3%]), air bronchogram (6 [11.3%]), interlobular thickening (5 [9.4%]), reticular pattern (1 [1.9%]), and pleural effusion (1 [1.9%]). CONCLUSIONS: Most COVID-19 pneumonia patients had abnormalities on chest CT images at initial presentation. Imaging features combined with patient's exposure history and onset symptoms could facilitate the identification of the suspected patient for further examinations.

Effects of methylprednisolone use on viral genomic nucleic acid negative conversion and CT imaging lesion absorption in COVID-19 patients under 50 years old.

The use of corticosteroids has been controversial in viral pneumonia. In most cases, application of methylprednisolone in severe and critical viral pneumonia patients can quickly alleviate the symptoms of dyspnea and prevent disease progression. However, some scholars have confirmed that corticosteroids delayed the body's clearance of the virus. In our retrospective non-randomized study, 34 patients under 50 years old and diagnosed with coronavirus disease 2019 (COVID-19) were included. According to the given methylprednisolone treatment (n = 18) or not (n = 16), they were separated into two groups. By comparing the clinical data we concluded that corticosteroids therapy can effectively release COVID-19 symptoms such as persistent fever and difficult in breathing, improve oxygenation, and prevent disease progression. However, it can prolong the negative conversion of nucleic acids.