Evaluating SARS-CoV-2 antibody reactivity to natural exposure and inactivated vaccination with peptide microarrays.

Objective: Vaccination is effective tool for preventing and controlling SARS-CoV-2 infections, and inactivated vaccines are the most widely used type of vaccine. In order to identify antibody-binding peptide epitopes that can distinguish between individuals who have been vaccinated and those who have been infected, this study aimed to compare the immune responses of vaccinated and infected individuals. Methods: SARS-CoV-2 peptide microarrays were used to assess the differences between 44 volunteers inoculated with the inactivated virus vaccine BBIBP-CorV and 61 patients who were infected with SARS-CoV-2. Clustered heatmaps were used to identify differences between the two groups in antibody responses to peptides such as M1, N24, S15, S64, S82, S104, and S115. Receiver operating characteristic curve analysis was used to determine whether a combined diagnosis with S15, S64, and S104 could effectively distinguish infected patients from vaccinated individuals. Results: Our findings showed that the specific antibody responses against S15, S64, and S104 peptides were stronger in vaccinators than in infected persons, while responses to M1, N24, S82, and S115 were weaker in asymptomatic patients than in symptomatic patients. Additionally, two peptides (N24 and S115) were found to correlate with the levels of neutralizing antibodies. Conclusion: Our results suggest that antibody profiles specific to SARS-CoV-2 can be used to distinguish between vaccinated individuals and those who are infected. The combined diagnosis with S15, S64, and S104 was found to be more effective in distinguishing infected patients from those who have been vaccinated than the diagnosis using individual peptides. Moreover, the specific antibody responses against the N24 and S115 peptides were found to be consistent with the changing trend of neutralizing antibodies.

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.

Detection of Anti-SARS-CoV-2-S2 IgG Is More Sensitive Than Anti-RBD IgG in Identifying Asymptomatic COVID-19 Patients.

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.

Author Correction: Temporal dynamics in viral shedding and transmissibility of COVID-19.

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

Clinical Characteristics of Patients Infected With the Novel 2019 Coronavirus (SARS-Cov-2) in Guangzhou, China.

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.

Longitudinal clinical and radiographic evaluation reveals interleukin-6 as an indicator of persistent pulmonary injury in COVID-19.

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.

Temporal dynamics in viral shedding and transmissibility of COVID-19.

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.