More attention should be paid to Omicron-associated sepsis: a multicenter retrospective study in south China.

Background: The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly transmissible but causes less severe disease compared to other variants. However, its association with sepsis incidence and outcomes is unclear. This study aimed to investigate the incidence of Omicron-associated sepsis, as per the Sepsis 3.0 definition, in hospitalized patients, and to explore its relationship with clinical characteristics and prognosis. Methods: This multicenter retrospective study included adults hospitalized with confirmed SARS-CoV-2 infection across six tertiary hospitals in Guangzhou, China from November 2022 to January 2023. The Sequential Organ Failure Assessment (SOFA) score and its components were calculated at hospital admission to identify sepsis. Outcomes assessed were need for intensive care unit (ICU) transfer and mortality. Receiver operating characteristic curves evaluated the predictive value of sepsis versus other biomarkers for outcomes. Results: A total of 299 patients (mean age: 70.1±14.4 years, 42.14% female) with SOFA score were enrolled. Among them, 152 were categorized as non-serious cases while the others were assigned as the serious group. The proportion of male patients, unvaccinated patients, patients with comorbidity such as diabetes, chronic cardiovascular disease, and chronic lung disease was significantly higher in the serious than non-serious group. The median SOFA score of all enrolled patients was 1 (interquartile range, 0-18). In our study, 147 patients (64.19%) were identified as having sepsis upon hospital admission, with the majority of these septic patients (113, representing 76.87%) being in the serious group, the respiratory, coagulation, cardiovascular, central nervous, and renal organ SOFA scores were all significantly higher in the serious compared to the non-serious group. Among septic patients, 20 out of 49 (40.81%) had septic shock as indicated by lactate measurement within 24 hours of admission, and the majority of septic patients were in the serious group (17/20, 76.87%). Sepsis was present in 118 out of 269 (43.9%) patients in the general ward, and among those with sepsis, 34 out of 118 (28.8%) later required ICU care during hospitalization. By contrast, none of the patients without sepsis required ICU care. Moreover, the mortality rate was significantly higher in patients with than without sepsis. Conclusions: A considerable proportion of patients infected with Omicron present with sepsis upon hospital admission, which is associated with a poorer prognosis. Therefore, early recognition of viral sepsis by evaluation of the SOFA score in hospitalized coronavirus disease 2019 patients is crucial.

Gut microbial co-metabolite 2-methylbutyrylcarnitine exacerbates thrombosis via binding to and activating integrin α2ß1.

Thrombosis represents the leading cause of death and disability upon major adverse cardiovascular events (MACEs). Numerous pathological conditions such as COVID-19 and metabolic disorders can lead to a heightened thrombotic risk; however, the underlying mechanisms remain poorly understood. Our study illustrates that 2-methylbutyrylcarnitine (2MBC), a branched-chain acylcarnitine, is accumulated in patients with COVID-19 and in patients with MACEs. 2MBC enhances platelet hyperreactivity and thrombus formation in mice. Mechanistically, 2MBC binds to integrin α2ß1 in platelets, potentiating cytosolic phospholipase A2 (cPLA2) activation and platelet hyperresponsiveness. Genetic depletion or pharmacological inhibition of integrin α2ß1 largely reverses the pro-thrombotic effects of 2MBC. Notably, 2MBC can be generated in a gut-microbiota-dependent manner, whereas the accumulation of plasma 2MBC and its thrombosis-aggravating effect are largely ameliorated following antibiotic-induced microbial depletion. Our study implicates 2MBC as a metabolite that links gut microbiota dysbiosis to elevated thrombotic risk, providing mechanistic insight and a potential therapeutic strategy for thrombosis.

Diverse immune responses in vaccinated individuals with and without symptoms after omicron exposure during the recent outbreak in Guangzhou, China.

Objectives: During the recent wave of coronavirus disease 2019 (COVID-19) infections in China, most individuals have been vaccinated and exposed to the omicron variant. In the present study, two cohorts were observed in the vaccinated population: vaccinated individuals with symptoms (VIWS) and those without symptoms (VIWOS). Our study aimed to characterize the antibody response in two cohorts: VIWS and VIWOS. Methods: A questionnaire survey was conducted in the community. Blood and saliva samples were collected from 124 individuals in the VIWS and VIWOS cohorts. Capture enzyme-linked immunosorbent assay (ELISA) was performed to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibodies. Results: The questionnaire survey revealed that 30.0 % (302/1005) of individuals in the older adult group (≥65 years) experienced no symptoms, whereas the rate of individuals without symptoms in the younger group (<65 years) was 17.8 % (166/932). Nucleocapsid (N)-specific IgM (N-IgM) was detected in the blood samples at a rate of 69.2 % (54/78) in the VIWS cohort. The positivity rate for N-specific IgA (N-IgA) was 93.6 % (73/78). In addition, the positivity rates of spike (S)-specific IgA (S-IgA) and N-IgA detected in saliva samples were 42 % (21/50) and 54 % (27/50), respectively. Both N-IgA positivity and negativity were observed in the VIWOS cohort. The detection rate of N-IgM positivity was 57.1 % (12/21) in the N-IgA-positive group. In addition, 54.3 % (25/46) of the vaccinated individuals without symptoms were IgA-negative. Conclusions: Our study indicates that substantial N-specific antibodies were induced during omicron infection and that testing for N-IgA in both blood and saliva may aid in the diagnosis of SARS-CoV-2 infection in vaccinated populations.

Venovenous extracorporeal membrane oxygenation for COVID-19 and influenza H1N1 associated acute respiratory distress syndrome: A comparative cohort study in China.

Background: Venovenous extracorporeal membrane oxygenation (VV-ECMO) has been demonstrated to be effective in treating patients with virus-induced acute respiratory distress syndrome (ARDS). However, whether the management of ECMO is different in treating H1N1 influenza and coronavirus disease 2019 (COVID-19)-associated ARDS patients remains unknown. Methods: This is a retrospective cohort study. We included 12 VV-ECMO-supported COVID-19 patients admitted to The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Eighth People's Hospital, and Wuhan Union Hospital West Campus between January 23 and March 31, 2020. We retrospectively included VV-ECMO-supported patients with COVID-19 and H1N1 influenza-associated ARDS. Clinical characteristics, respiratory mechanics including plateau pressure, driving pressure, mechanical power, ventilatory ratio (VR) and lung compliance, and outcomes were compared. Results: Data from 25 patients with COVID-19 (n=12) and H1N1 (n=13) associated ARDS who had received ECMO support were analyzed. COVID-19 patients were older than H1N1 influenza patients (P=0.004). The partial pressure of arterial carbon dioxide (PaCO2) and VR before ECMO initiation were significantly higher in COVID-19 patients than in H1N1 influenza patients (P <0.001 and P=0.004, respectively). COVID-19 patients showed increased plateau and driving pressure compared with H1N1 subjects (P=0.013 and P=0.018, respectively). Patients with COVID-19 remained longer on ECMO support than did H1N1 influenza patients (P=0.015). COVID-19 patients who required ECMO support also had fewer intensive care unit and ventilator-free days than H1N1. Conclusions: Compared with H1N1 influenza patients, COVID-19 patients were older and presented with increased PaCO2 and VR values before ECMO initiation. The differences between ARDS patients with COVID-19 and influenza on VV-ECMO detailed herein could be helpful for obtaining a better understanding of COVID-19 and for better clinical management.

Effect of the Timing of Amubarvimab/Romlusevimab (BRII-196/198) Administration on Progression to Severe Disease in Elderly Patients with COVID-19 Infection: A Retrospective Cohort Study.

Objective: Early intervention with neutralizing antibodies is considered to be effective in preventing disease progression in patients with mild to moderate COVID-19 infection. Elderly patients are the most susceptible and at a higher risk of COVID-19 infection. The present study aimed to assess the necessity and possible clinical benefits of the early administration of Amubarvimab/Romlusevimab (BRII-196/198) in the elderly population. Methods: The present study was designed as a retrospective, multi-center cohort study conducted with 90 COVID-19 patients aged over 60, who were divided into two groups based on the timing of the administration of BRII-196/198 (administration at ≤ 3 days or > 3 days from the onset of infection symptoms). Results: The ≤ 3 days group exhibited a greater positive effect (HR 5.94, 95% CI, 1.42-24.83; P < 0.01), with only 2 patients among 21 patients (9.52%) exhibiting disease progression, compared to the 31 patients among the 69 patients (44.93%) of the > 3 days group who exhibited disease progression. The multivariate Cox regression analysis revealed low flow oxygen support prior to BRII-196/198 administration (HR 3.53, 95% CI 1.42-8.77, P < 0.01) and PLT class (HR 3.68, 95% CI 1.37-9.91, P < 0.01) as independent predictors of disease progression. Conclusions: In elderly patients with mild or moderate COVID-19 disease, who do not require oxygen support and had the risk factors for disease progression to severe COVID-19 disease, the administration of BRII-196/198 within 3 days resulted in a beneficial trend in terms of preventing disease progression.

High titers of neutralizing antibodies in the blood fail to eliminate SARS-CoV-2 viral RNA in the upper respiratory tract.

Retest-positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA, as a unique phenomenon among discharged individuals, has been demonstrated to be safe in the community. Still, the underlying mechanism of viral lingering is less investigated. In this study, first, we find that the frequency of viral RNA-positive retesting differs among variants. Higher ratios of viral RNA-positive retest were more frequently observed among Delta (61.41%, 514 of 837 cases) and Omicron (39.53%, 119 of 301 cases) infections than among ancestral viral infection (7.27%, 21 of 289 cases). Second, the tissues where viral RNA reoccurred were altered. Delta RNA reoccurred mainly in the upper respiratory tract (90%), but ancestral virus RNA reoccurred mainly in the gastrointestinal tract (71%). Third, vaccination did not reduce the frequency of viral RNA-positive retests, despite high concentrations of viral-specific antibodies in the blood. Finally, 37 of 55 (67.27%) Delta-infected patients receiving neutralizing antibody therapy become viral RNA retest positive when high concentrations of neutralizing antibodies still patrol in the blood. Altogether, our findings suggest that the presentence of high titers of neutralizing antibodies in the blood is incompetent in clearing residual viral RNA in the upper respiratory tract.

Clinical characteristics and severe risk factors of tsutsugamushi disease / 中国热带医学

@#Abstract: Objective To investigate the clinical features and risk factors for severe tsutsugamushi disease, so as to provide reference for diagnosis and differentiation of severe tsutsugamushi disease as soon as possible. Methods The clinical data of 178 cases of inpatients with tsutsugamushi disease admitted to the Guangzhou Eighth People's Hospital, Guangzhou Medical University from January 2016 to September 2021 were collected and analyzed according to their gender, age, underlying diseases, clinical characteristics at admission, laboratory examination results within 24 hours of admission and epidemiological history. The patients were divided into the severe group and the non-severe group according to the diagnostic criteria. The data of clinical characteristics, laboratory examination and prognosis of the two groups were compared. Multivariate logistic regression analysis was performed on the variables with statistical significance and the receiver operating characteristic curve (ROC) was drawn. Results A total of 178 patients were included in this study, with 37 in the severe group and 141 in the non-severe group. Compared with the non-severe group, the age of the severe group was older, the underlying diseases were more, the incidence of dyspnea and the levels of white blood cell, total bilirubin, aspartate aminotransferase, lactate dehydrogenase, cystatin C, uric acid and serum creatinine were significantly increased, the levels of platelet and albumin were significantly decreased (all P<0.05). The dyspnea [odds ratio (OR value)=8.93, 95% confidence interval (CI): 1.200-66.424; P=0.032], total bilirubin (OR=1.091, 95%CI: 1.028-1.159; P=0.004) and serum creatinine (OR=1.052, 95%CI: 1.004-1.102; P=0.033) were independent risk factors for severe tsutsugamushi disease. The area under ROC curve of total bilirubin and serum creatinine were 0.777 and 0.764, respectively (both P<0.01), indicating high predictive value for severe tsutsugamushi disease. The optimal cut-off value for total bilirubin was 23.01 µmol/L, with a sensitivity of 54.10% and a specificity of 90.60%; the optimal cut-off value for creatinine was 126.45 µmol/L, with a sensitivity of 43.20% and a specificity of 100.00%. The case fatality rate of severe tsutsugamushi disease was 2.70%. Conclusions The patients with severe tsutsugamushi disease are older, and have more underlying diseases. Dyspnea, increased total bilirubin and elevated serum creatinine are independent risk factors for severe tsutsugamushi disease, which can help in the early identification of severe tsutsugamushi disease early.

Immune response and severity of Omicron BA.5 reinfection among individuals previously infected with different SARS-CoV-2 variants.

Introduction: COVID-19 continues to spread worldwide, with an increasing number of individuals experiencing reinfection after recovering from their primary infection. However, the nature and progression of this infection remain poorly understood. We aimed to investigate the immune response, severity and outcomes of Omicron BA.5 reinfection among individuals previously infected with different SARS-CoV-2 variants. Methods: We enrolled 432 COVID-19 cases who had experienced prior infection with the ancestral SARS-CoV-2 virus, Delta variant or Omicron BA.2 variant between January 2020 and May 2022 in Guangzhou, China. All cases underwent follow-up from March to April, 2023 through telephone questionnaires and clinical visits. Nasal lavage fluid and peripheral blood were collected to assess anti-RBD IgA, anti-RBD IgG and virus-specific IFN-γ secreting T cells. Results: Our study shows that 73.1%, 56.7% and 12.5% of individuals with a prior infection of the ancestral virus, Delta or Omicron BA.2 variant experienced reinfection with the BA.5 variant, respectively. Fever, cough and sore throat were the most common symptoms of BA.5 reinfection, with most improving within one week and none progressing to a critical condition. Compared with individuals without reinfection, reinfected patients with a prior Delta infection exhibited elevated levels of nasal anti-RBD IgA, serum anti-RBD IgG and IFN-γ secreting T cells, whereas there was no noticeable change in reinfected individuals with a prior BA.2 infection. Conclusion: These results suggest that BA.5 reinfection is common but severe outcomes are relatively rare. Reinfection with a novel SARS-CoV-2 variant different from the prior infection may induce a more robust immune protection, which should be taken into account during vaccine development.

Clinical characteristics and immune profile alterations in vaccinated individuals with breakthrough Delta SARS-CoV-2 infections.

Despite timely immunization programs, and efficacious vaccines conveying protection against SARS-CoV-2 infection, breakthrough infections in vaccinated individuals have been reported. The Delta variant of concern (VOC) outbreak in Guangzhou resulted in local transmission in vaccinated and non-vaccinated residents, providing a unique opportunity to study the protective effects of the inactivated vaccines in breakthrough infection. Here, we find that the 2-dose vaccinated group has similar peak viral titers and comparable speeds of viral RNA clearance to the non-vaccinated group but accelerated viral suppression in the middle course of the disease. We quantitatively demonstrate that peak viral pneumonia is significantly mitigated in the 2-dose vaccine group (median 0.298%) compared with the non-vaccinated (5.77%) and 1-dose vaccine (3.34%) groups. Pneumonia absorbance is approximately 6 days ahead in the 2-dose group (median 10 days) than in the non-vaccinated group (16 days) (p = 0.003). We also observe reduced cytokine inflammation and markedly undisturbed gene transcription profiles of peripheral blood mononuclear cells (PBMCs) in the 2-dose group. In short, our study demonstrates that prior vaccination substantially restrains pneumonia development, reduces cytokine storms, and facilitates clinical recovery.

Risk factors for impaired pulmonary diffusion function in convalescent COVID-19 patients: A systematic review and meta-analysis.

Background: The long-term prognosis of COVID-19 survivors remains poorly understood. It is evidenced that the lung is the main damaged organ in COVID-19 survivors, most notably in impairment of pulmonary diffusion function. Hence, we conducted a meta-analysis of the potential risk factors for impaired diffusing capacity for carbon monoxide (DLCO) in convalescent COVID-19 patients. Methods: We performed a systematic search of PubMed, Web of Science, Embase, and Ovid databases for relevant studies from inception until January 7, 2022, limited to papers involving human subjects. Studies were reviewed for methodological quality. Fix-effects and random-effects models were used to pool results. Heterogeneity was assessed using I2. The publication bias was assessed using the Egger's test. PROSPERO registration: CRD42021265377. Findings: A total of eighteen qualified articles were identified and included in the systematic review, and twelve studies were included in the meta-analysis. Our results showed that female (OR: 4.011; 95% CI: 2.928-5.495), altered chest computerized tomography (CT) (OR: 3.002; 95% CI: 1.319-6.835), age (OR: 1.018; 95% CI: 1.007-1.030), higher D-dimer levels (OR: 1.012; 95% CI: 1.001-1.023) and urea nitrogen (OR: 1.004;95% CI: 1.002-1.007) were identified as risk factors for impaired DLCO. Interpretation: Pulmonary diffusion capacity was the most common impaired lung function in recovered patients with COVID-19. Several risk factors, such as female, altered chest CT, older age, higher D-dimer levels and urea nitrogen are associated with impairment of DLCO. Raising awareness and implementing interventions for possible modifiable risk factors may be valuable for pulmonary rehabilitation. Funding: This work was financially supported by Emergency Key Program of Guangzhou Laboratory (EKPG21-29, EKPG21-31), Incubation Program of National Science Foundation for Distinguished Young Scholars by Guangzhou Medical University (GMU2020-207).

Follow-up of patients with COVID-19 by the Delta variant after hospital discharge in Guangzhou, Guandong, China.

The B.1.617.2 (Delta) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has contributed to a new increment in cases across the globe. We conducted a prospective follow-up of COVID-19 cases to explore the recurrence and potential propagation risk of the Delta variant and discuss potential explanations for the infection recurrence. A prospective, non-interventional follow-up of discharged patients who had SARS-CoV-2 infections by the Delta variant in Guangdong, China, from May 2021 to June 2021 was conducted. The subjects were asked to complete a physical health examination and undergo nucleic acid testing and antibody detection for the laboratory diagnosis of COVID-19. In total, 20.33% (25/123) of patients exhibited recurrent positive results after discharge. All patients with infection recurrence were asymptomatic and showed no abnormalities in the pulmonary computed tomography. The time from discharge to the recurrent positive testing was usually between 1-33 days, with a mean time of 9.36 days. The cycle threshold from the real-time polymerase chain reaction assay that detected the recurrence of positivity ranged from 27.48 to 39.00, with an average of 35.30. The proportion of vaccination in the non-recurrent group was higher than that in the recurrently positive group (26% vs. 4%; χ2 = 7.902; P < 0.05). Two months after discharge, the most common symptom was hair loss and 59.6% of patients had no long-term symptoms at all. It is possible for the Delta variant SARS-CoV-2 patients after discharge to show recurrent positive results of nucleic acid detection; however, there is a low risk of continuous community transmission. Both, the physical and mental quality of life of discharged patients were significantly affected. Our results suggest that it makes sense to implement mass vaccination against the Delta variant of SARS-CoV-2.

Kinetics of Severity Biomarkers and Immunological Features of Methylprednisolone Therapy for Severe COVID-19 Patients.

In contrast to dexamethasone, the clinical efficacy of methylprednisolone (MP) remains controversial, and a systems biology study on its mechanism is lacking. In this study, a total of 38 severe COVID-19 patients were included. The demographics, clinical characteristics, and severity biomarkers including C-reactive protein (CRP), d-dimer, albumin, and Krebs von den Lungen 6 of patients receiving MP (n=26, 40 mg or 80 mg daily for 3-5 days) and supportive therapy (n=12) were compared. Longitudinal measurements of 92 cytokines in MP group from admission to over six months after discharge were performed by multiplex Proximity Extension Assay. The results showed that demographics, baseline clinical characteristics were similar in MP and non-MP groups. No death occurred and the hospital stays between the two groups were similar. Kinetics studies showed that MP was not better than supportive therapy at improving the four severity biomarkers. Cytokines in MP group were characterized by five clusters according to their baseline levels and responses to MP. The immunological feature of severe COVID-19 could be defined by the "core signature" cytokines in cluster 2: MCP-3, IL-6, IFN-γ, and CXCL10, which strongly correlated with each other and CRP, and are involved in cytokine release storm. The "core signature" cytokines were significantly upregulated at baseline and remained markedly elevated after MP treatment. Our work showed a short course of MP therapy could not rapidly improve the immune disorders among severe COVID-19 patients or clinical outcomes, also confirmed "core signature" cytokines, as severity biomarkers similar to CRP, could be applied to evaluate clinical treatment effect.

Dynamic changes of pulmonary diffusion capacity in survivors of non-critical COVID-19 during the first six months.

BACKGROUND: The dynamic trends of pulmonary function in coronavirus disease 2019 (COVID-19) survivors since discharge have been rarely described. We aimed to describe the changes of lung function and identify risk factors for impaired diffusion capacity. METHODS: Non-critical COVID-19 patients admitted to the Guangzhou Eighth People's Hospital, China, were enrolled from March to June 2020. Subjects were prospectively followed up with pulmonary function tests at discharge, three and six months after discharge. FINDINGS: Eighty-six patients completed diffusion capacity tests at three timepoints. The mean diffusion capacity for carbon monoxide (DLCO)% pred was 79.8% at discharge and significantly improved to 84.9% at Month-3. The transfer coefficient of the lung for carbon monoxide (KCO)% pred significantly increased from 91.7% at discharge to 95.7% at Month-3. Both of them showed no further improvement at Month-6. The change rates of DLCO% pred and KCO% pred were significantly higher in 0-3 months than in 3-6 months. The alveolar ventilation (VA) improved continuously during the follow-ups. At Month-6, impaired DLCO% pred was associated with being female (OR 5.2 [1.7-15.8]; p = 0.004) and peak total lesion score (TLS) of chest CT > 8.5 (OR 6.6 [1.7-26.5]; p = 0.007). DLCO% pred and KCO% pred were worse in females at discharge. And in patients with impaired diffusion capacity, females' DLCO% pred recovered slower than males. INTERPRETATION: The first three months is the critical recovery period for diffusion capacity. The impaired diffusion capacity was more severe and recovered slower in females than in males. Early pulmonary rehabilitation and individualized interventions for recovery are worthy of further investigations.

Metabolomic analyses reveal new stage-specific features of COVID-19.

The current pandemic of coronavirus disease 2019 (COVID-19) has affected >160 million individuals to date, and has caused millions of deaths worldwide, at least in part due to the unclarified pathophysiology of this disease. Identifying the underlying molecular mechanisms of COVID-19 is critical to overcome this pandemic. Metabolites mirror the disease progression of an individual and can provide extensive insights into their pathophysiological significance at each stage of disease. We provide a comprehensive view of metabolic characterisation of sera from COVID-19 patients at all stages using untargeted and targeted metabolomic analysis. As compared with the healthy controls, we observed different alteration patterns of circulating metabolites from the mild, severe and recovery stages, in both the discovery cohort and the validation cohort, which suggests that metabolic reprogramming of glucose metabolism and the urea cycle are potential pathological mechanisms for COVID-19 progression. Our findings suggest that targeting glucose metabolism and the urea cycle may be a viable approach to fight COVID-19 at various stages along the disease course.

Follow-up of patients with COVID-19 by the Delta variant after hospital discharge in Guangzhou, Guandong, China

ABSTRACT The B.1.617.2 (Delta) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has contributed to a new increment in cases across the globe. We conducted a prospective follow-up of COVID-19 cases to explore the recurrence and potential propagation risk of the Delta variant and discuss potential explanations for the infection recurrence. A prospective, non-interventional follow-up of discharged patients who had SARS-CoV-2 infections by the Delta variant in Guangdong, China, from May 2021 to June 2021 was conducted. The subjects were asked to complete a physical health examination and undergo nucleic acid testing and antibody detection for the laboratory diagnosis of COVID-19. In total, 20.33% (25/123) of patients exhibited recurrent positive results after discharge. All patients with infection recurrence were asymptomatic and showed no abnormalities in the pulmonary computed tomography. The time from discharge to the recurrent positive testing was usually between 1-33 days, with a mean time of 9.36 days. The cycle threshold from the real-time polymerase chain reaction assay that detected the recurrence of positivity ranged from 27.48 to 39.00, with an average of 35.30. The proportion of vaccination in the non-recurrent group was higher than that in the recurrently positive group (26% vs. 4%; χ2 = 7.902; P < 0.05). Two months after discharge, the most common symptom was hair loss and 59.6% of patients had no long-term symptoms at all. It is possible for the Delta variant SARS-CoV-2 patients after discharge to show recurrent positive results of nucleic acid detection; however, there is a low risk of continuous community transmission. Both, the physical and mental quality of life of discharged patients were significantly affected. Our results suggest that it makes sense to implement mass vaccination against the Delta variant of SARS-CoV-2.

COVID-19 induces new-onset insulin resistance and lipid metabolic dysregulation via regulation of secreted metabolic factors.

Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism. In this study, we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases, and found new-onset insulin resistance, hyperglycemia, and decreased HDL-C in these patients. Mechanistically, SARS-CoV-2 infection increased the expression of RE1-silencing transcription factor (REST), which modulated the expression of secreted metabolic factors including myeloperoxidase, apelin, and myostatin at the transcriptional level, resulting in the perturbation of glucose and lipid metabolism. Furthermore, several lipids, including (±)5-HETE, (±)12-HETE, propionic acid, and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation, especially in insulin resistance. Taken together, our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19, and further illustrated the underlying mechanisms, providing potential therapeutic targets for COVID-19-induced metabolic complications.

Transmission, viral kinetics and clinical characteristics of the emergent SARS-CoV-2 Delta VOC in Guangzhou, China.

BACKGROUND: A novel variant of SARS-CoV-2, the Delta variant of concern (VOC, also known as lineage B.1.617.2), is fast becoming the dominant strain globally. We reported the epidemiological, viral, and clinical characteristics of hospitalized patients infected with the Delta VOC during the local outbreak in Guangzhou, China. METHODS: We extracted the epidemiological and clinical information pertaining to the 159 cases infected with the Delta VOC across seven transmission generations between May 21 and June 18, 2021. The whole chain of the Delta VOC transmission was described. Kinetics of viral load and clinical characteristics were compared with a cohort of wild-type infection in 2020 admitted to the Guangzhou Eighth People's Hospital. FINDINGS: There were four transmission generations within the first ten days. The Delta VOC yielded a significantly shorter incubation period (4.0 vs. 6.0 days), higher viral load (20.6 vs. 34.0, cycle threshold of the ORF1a/b gene), and a longer duration of viral shedding in pharyngeal swab samples (14.0 vs. 8.0 days) compared with the wild-type strain. In cases with critical illness, the proportion of patients over the age of 60 was higher in the Delta VOC group than in the wild-type strain (100.0% vs. 69.2%, p = 0.03). The Delta VOC had a higher risk than wild-type infection in deterioration to critical status (hazards ratio 2.98 [95%CI 1.29-6.86]; p = 0.01). INTERPRETATION: Infection with the Delta VOC is characterized by markedly increased transmissibility, viral loads and risk of disease progression compared with the wild-type strain, calling for more intensive prevention and control measures to contain future outbreaks. FUNDING: National Grand Program, National Natural Science Foundation of China, Guangdong Provincial Department of Science and Technology, Guangzhou Laboratory.