The clinical features and immune responses of asymptomatic individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been well described. We studied 37 ...asymptomatic individuals in the Wanzhou District who were diagnosed with RT-PCR-confirmed SARS-CoV-2 infections but without any relevant clinical symptoms in the preceding 14 d and during hospitalization. Asymptomatic individuals were admitted to the government-designated Wanzhou People's Hospital for centralized isolation in accordance with policy
. The median duration of viral shedding in the asymptomatic group was 19 d (interquartile range (IQR), 15-26 d). The asymptomatic group had a significantly longer duration of viral shedding than the symptomatic group (log-rank P = 0.028). The virus-specific IgG levels in the asymptomatic group (median S/CO, 3.4; IQR, 1.6-10.7) were significantly lower (P = 0.005) relative to the symptomatic group (median S/CO, 20.5; IQR, 5.8-38.2) in the acute phase. Of asymptomatic individuals, 93.3% (28/30) and 81.1% (30/37) had reduction in IgG and neutralizing antibody levels, respectively, during the early convalescent phase, as compared to 96.8% (30/31) and 62.2% (23/37) of symptomatic patients. Forty percent of asymptomatic individuals became seronegative and 12.9% of the symptomatic group became negative for IgG in the early convalescent phase. In addition, asymptomatic individuals exhibited lower levels of 18 pro- and anti-inflammatory cytokines. These data suggest that asymptomatic individuals had a weaker immune response to SARS-CoV-2 infection. The reduction in IgG and neutralizing antibody levels in the early convalescent phase might have implications for immunity strategy and serological surveys.
Abstract
Background
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel β-coronavirus, causes severe pneumonia and has spread throughout the globe rapidly. The disease associated ...with SARS-CoV-2 infection is named coronavirus disease 2019 (COVID-19). To date, real-time reverse-transcription polymerase chain reaction (RT-PCR) is the only test able to confirm this infection. However, the accuracy of RT-PCR depends on several factors; variations in these factors might significantly lower the sensitivity of detection.
Methods
In this study, we developed a peptide-based luminescent immunoassay that detected immunoglobulin (Ig)G and IgM. The assay cutoff value was determined by evaluating the sera from healthy and infected patients for pathogens other than SARS-CoV-2.
Results
To evaluate assay performance, we detected IgG and IgM in the sera from confirmed patients. The positive rate of IgG and IgM was 71.4% and 57.2%, respectively.
Conclusions
Therefore, combining our immunoassay with real-time RT-PCR might enhance the diagnostic accuracy of COVID-19.
A peptide-based magnetic chemiluminescence enzyme immunoassay for the detection of SARS-CoV-2 antibodies was developed; 71.4% (197 of 276) and 57.2% (158 of 276) of the COVID-19 inpatients were positive for IgG and IgM against SARS-CoV-2.
The effectiveness of control measures to contain coronavirus disease 2019 (COVID-19) in Wanzhou, China was assessed. Epidemiological data were analyzed for 183 confirmed COVID-19 cases and their ...close contacts from five generations of transmission of severe acute respiratory syndrome coronavirus 2 throughout the entire COVID-19 outbreak in Wanzhou. Approximately 67.2% and 32.8% of cases were symptomatic and asymptomatic, respectively. Asymptomatic and presymptomatic transmission accounted for 75.9% of the total recorded transmission. The reproductive number was 1.64 (95% confidence interval: 1.16-2.40) for G1-to-G2 transmission, decreasing to 0.31-0.39 in later generations, concomitant with implementation of rigorous control measures. Substantially higher infection risk was associated with contact within 5 d after the infectors had been infected, frequent contact and ≥8 h of contact duration. The spread of COVID-19 was effectively controlled in Wanzhou by breaking the transmission chain through social distancing, extensive contact tracing, mass testing and strict quarantine of close contacts.
Abstract
Background
Coronavirus disease 2019 (COVID-19) is a global pandemic with no licensed vaccine or specific antiviral agents for therapy. Little is known about the longitudinal dynamics of ...severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific neutralizing antibodies (NAbs) in patients with COVID-19.
Methods
Blood samples (n = 173) were collected from 30 patients with COVID-19 over a 3-month period after symptom onset and analyzed for SARS-CoV-2–specific NAbs using the lentiviral pseudotype assay, coincident with the levels of IgG and proinflammatory cytokines.
Results
SARS-CoV-2–specific NAb titers were low for the first 7–10 days after symptom onset and increased after 2–3 weeks. The median peak time for NAbs was 33 days (interquartile range IQR, 24–59 days) after symptom onset. NAb titers in 93.3% (28/30) of the patients declined gradually over the 3-month study period, with a median decrease of 34.8% (IQR, 19.6–42.4%). NAb titers increased over time in parallel with the rise in immunoglobulin G (IgG) antibody levels, correlating well at week 3 (r = 0.41, P < .05). The NAb titers also demonstrated a significant positive correlation with levels of plasma proinflammatory cytokines, including stem cell factor (SCF), TNF-related apoptosis-inducing ligand (TRAIL), and macrophage colony-stimulating factor (M-CSF).
Conclusions
These data provide useful information regarding dynamic changes in NAbs in patients with COVID-19 during the acute and convalescent phases.
Background and Aims
The mechanism underlying HCC metastasis remains unclear, many oncogenes are known to regulate this process. However, the role of alternative splicing (AS) in pro‐metastatic HCC is ...poorly understood.
Approach and Results
By performing RNA sequencing on nine pairs of primary HCC tissues with extrahepatic metastasis (EHMH) and nine pairs of metastasis‐free HCC (MFH) tissues, we depicted the AS landscape in HCC and found a higher frequency of AS events in EHMH compared with MFH. Moreover, 28 differentially expressed splicing regulators were identified in EHMH compared with MFH. Among these, DEAD‐box RNA helicase 17 (DDX17) was significantly up‐regulated in EHMH and was strongly associated with patient outcome. Functional studies indicated that DDX17 knockout inhibited the degradation of the extracellular matrix, and diminished the invasive ability of HCC cells. A significant reduction in lung metastasis induced by DDX17 deficiency was also demonstrated in a diethylnitrosamine‐induced DDX17HKO mouse model. Mechanistically, high DDX17 induced intron 3 retention of PXN‐AS1 and produced a transcript (termed PXN‐AS1‐IR3). The transcript PXN‐AS1‐IR3 acted as an important promoter of HCC metastasis by inducing MYC transcription activation via recruiting the complex of testis expressed 10 and p300 to the MYC enhancer region, which led to transcriptional activation of several metastasis‐associated downstream genes. Finally, the PXN‐AS1‐IR3 level was significantly higher in serum and HCC tissues with extrahepatic metastasis.
Conclusions
DDX17 and PXN‐AS1‐IR3 act as important metastatic promoters by modulating MYC signaling, suggesting that DDX17 and PXN‐AS1‐IR3 may be potential prognostic markers for metastatic HCC.
Immune responses elicited by viral infection or vaccination play key roles in the viral elimination and the prevention of reinfection, as well as the protection of healthy persons. As one of the most ...widely used Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccines, there have been increasing concerns about the necessity of additional doses of inactivated vaccines, due to the waning immune response several months after vaccination. To further optimize inactivated SARS‐CoV‐2 vaccines, we compared immune responses to SARS‐CoV‐2 elicited by natural infection and immunization with inactivated vaccines in the early phase. We observed the lower antibody levels against SARS‐CoV‐2 spike (S) and nucleocapsid (N) proteins in the early phase of postvaccination with a slow increase, compared to the acute phase of SARS‐CoV‐2 natural infection. Specifically, IgA antibodies have the most significant differences. Moreover, we further analyzed cytokine expression between these two groups. A wide variety of cytokines presented high expression in the infected individuals, while a few cytokines were elicited by inactivated vaccines. The differences in antibody responses and cytokine levels between natural SARS‐CoV‐2 infection and vaccination with the inactivated vaccines may provide implications for the optimization of inactivated SARS‐CoV‐2 vaccines and the additional application of serological tests.
Objective
Few studies have explored the clinical features in children infected with SARS‐CoV‐2 and other common respiratory viruses, including respiratory syncytial virus (RSV), Influenza virus (IV), ...and adenovirus (ADV). Herein, we reported the clinical characteristics and cytokine profiling in children with COVID‐19 or other acute respiratory tract infections (ARTI).
Methods
We enrolled 20 hospitalized children confirmed as COVID‐19 positive, 58 patients with ARTI, and 20 age and sex‐matched healthy children. The clinical information and blood test results were collected. A total of 27 cytokines and chemokines were measured and analyzed.
Results
The median age in the COVID‐19 positive group was 14.5 years, which was higher than that of the ARTI groups. Around one‐third of patients in the COVID‐19 group experienced moderate fever, with a peak temperature of 38.27°C. None of the patients displayed wheezing or dyspnea. In addition, patients in the COVID‐19 group had lower white blood cells, platelet counts as well as a neutrophil‐lymphocyte ratio. Lower serum concentrations of 14 out of 27 cytokines were observed in the COVID‐19 group than in healthy individuals. Seven cytokines (IL‐1Ra, IL‐1β, IL‐9, IL‐10, TNF‐α, MIP‐1α, and VEGF) changed serum concentration in COVID‐19 compared with other ARTI groups.
Conclusion
Patients with COVID‐19 were older and showed milder symptoms and a favorable prognosis than ARTI caused by RSV, IV, and ADV. There was a low grade or constrained innate immune reaction in children with mild COVID‐19.
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