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1.
Signal Transduct Target Ther ; 6(1): 427, 2021 12 16.
Article in English | MEDLINE | ID: covidwho-1795805

ABSTRACT

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.


Subject(s)
COVID-19/blood , Hyperglycemia/blood , Insulin Resistance , Lipid Metabolism , Lipids/blood , SARS-CoV-2/metabolism , Adult , Aged , Biomarkers/blood , COVID-19/complications , Female , Humans , Hyperglycemia/etiology , Male , Middle Aged , Retrospective Studies
2.
EClinicalMedicine ; 40: 101129, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1401440

ABSTRACT

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.

3.
Front Immunol ; 12: 724763, 2021.
Article in English | MEDLINE | ID: covidwho-1399141

ABSTRACT

Characterizing the serologic features of asymptomatic SARS-CoV-2 infection is imperative to improve diagnostics and control of SARS-CoV-2 transmission. In this study, we evaluated the antibody profiles in 272 plasma samples collected from 59 COVID-19 patients, consisting of 18 asymptomatic patients, 33 mildly ill patients and 8 severely ill patients. We measured the IgG against five viral structural proteins, different isotypes of immunoglobulins against the Receptor Binding Domain (RBD) protein, and neutralizing antibodies. The results showed that the overall antibody response was lower in asymptomatic infections than in symptomatic infections throughout the disease course. In contrast to symptomatic patients, asymptomatic patients showed a dominant IgG-response towards the RBD protein, but not IgM and IgA. Neutralizing antibody titers had linear correlations with IgA/IgM/IgG levels against SARS-CoV-2-RBD, as well as with IgG levels against multiple SARS-CoV-2 structural proteins, especially with anti-RBD or anti-S2 IgG. In addition, the sensitivity of anti-S2-IgG is better in identifying asymptomatic infections at early time post infection compared to anti-RBD-IgG. These data suggest that asymptomatic infections elicit weaker antibody responses, and primarily induce IgG antibody responses rather than IgA or IgM antibody responses. Detection of IgG against the S2 protein could supplement nucleic acid testing to identify asymptomatic patients. This study provides an antibody detection scheme for asymptomatic infections, which may contribute to epidemic prevention and control.


Subject(s)
Antibodies, Viral/blood , Asymptomatic Infections , Immunoglobulin G/blood , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Viral Structural Proteins/immunology , Adolescent , Adult , Antibodies, Neutralizing/immunology , Antibodies, Viral/physiology , Binding Sites, Antibody , Female , Humans , Immunoglobulin G/classification , Immunoglobulin M/immunology , Kinetics , Male , Middle Aged , Neutralization Tests/statistics & numerical data , SARS-CoV-2/chemistry , Young Adult
4.
Nat Med ; 26(9): 1491-1493, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1286464

ABSTRACT

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

5.
Open Forum Infect Dis ; 7(6): ofaa187, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-1109308

ABSTRACT

BACKGROUND: The clinical manifestations and factors associated with the severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections outside of Wuhan are not clearly understood. METHODS: All laboratory-confirmed cases with SARS-Cov-2 infection who were hospitalized and monitored in Guangzhou Eighth People's Hospital were recruited from January 20 to February 10. RESULTS: A total of 275 patients were included in this study. The median patient age was 49 years, and 63.6% had exposure to Wuhan. The median virus incubation period was 6 days. Fever (70.5%) and dry cough (56.0%) were the most common symptoms. A decreased albumin level was found in 51.3% of patients, lymphopenia in 33.5%, and pneumonia based on chest computed tomography in 86%. Approximately 16% of patients (n = 45) had severe disease, and there were no deaths. Compared with patients with nonsevere disease, those with severe disease were older, had a higher frequency of coexisting conditions and pneumonia, and had a shorter incubation period (all P < .05). There were no differences between patients who likely contacted the virus in Wuhan and those who had no exposure to Wuhan. Multivariate logistic regression analysis indicated that older age, male sex, and decreased albumin level were independently associated with disease severity. CONCLUSIONS: Most of the patients infected with SARS-CoV-2 in Guangzhou, China are not severe cases and patients with older age, male, and decreased albumin level were more likely to develop into severe ones.

6.
Int J Med Sci ; 18(1): 29-41, 2021.
Article in English | MEDLINE | ID: covidwho-994132

ABSTRACT

Rationale: Previous studies of coronavirus disease 2019 (COVID-19) were mainly focused on cross-sectional analysis. In this study, we sought to evaluate the dynamic changes of immunological and radiographic features, and the association with the outcome of pulmonary lesions in COVID-19 patients. Methods: Peripheral blood samples and radiographic data were collected longitudinally for up to 8 weeks from 158 laboratory-confirmed COVID-19 patients. The chest computed tomography (CT) scans were scored based on a semi-quantification assessment according to the extent of pulmonary abnormalities; the temporal change of the immunological and radiographic features was analyzed. Results: Compared with mild and moderate patients, severe patients had significantly decreased counts of lymphocytes, CD4+ T cells, CD8+ T cells, and CD19+ B cells but dramatically elevated counts of neutrophils and levels of interleukin (IL)-6. Sequential monitoring showed a sustained increase in lymphocytes counts and significantly decreased levels of IL-6 in severe patients during the disease course. Notably, patients with persistent pulmonary lesions (CT score ≥ 5 in week 8) showed high levels of IL-6 during the follow-up period, compared with those with recovery lesions (CT score < 5 in week 8). More importantly, the peak expression of IL-6 prior to the aggravated lung injury was mainly found in patients with persistent lesions, and multivariate analysis showed that IL-6 level upon admission was an independent factor associated with the persistent pulmonary injury. Conclusion: Prolonged elevation of IL-6 is associated with persistent pulmonary lesions in COVID-19 patients. Sequential monitoring and timely intervention of IL-6 may favor the clinical management of COVID-19.


Subject(s)
COVID-19/immunology , Interleukin-6/blood , Lung Injury/blood , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/blood , COVID-19/complications , COVID-19/diagnostic imaging , Female , Humans , Longitudinal Studies , Lung Injury/diagnostic imaging , Lung Injury/virology , Lymphocyte Count , Male , Middle Aged , Radiography, Thoracic , Retrospective Studies , SARS-CoV-2 , Tomography, X-Ray Computed , Young Adult
7.
Nat Med ; 26(5): 672-675, 2020 05.
Article in English | MEDLINE | ID: covidwho-65153

ABSTRACT

We report temporal patterns of viral shedding in 94 patients with laboratory-confirmed COVID-19 and modeled COVID-19 infectiousness profiles from a separate sample of 77 infector-infectee transmission pairs. We observed the highest viral load in throat swabs at the time of symptom onset, and inferred that infectiousness peaked on or before symptom onset. We estimated that 44% (95% confidence interval, 25-69%) of secondary cases were infected during the index cases' presymptomatic stage, in settings with substantial household clustering, active case finding and quarantine outside the home. Disease control measures should be adjusted to account for probable substantial presymptomatic transmission.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/transmission , Pneumonia, Viral/transmission , Virus Shedding , COVID-19 , Coronavirus Infections/epidemiology , Humans , Pandemics , Pneumonia, Viral/epidemiology , SARS-CoV-2
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