A robust serological test to detect neutralizing antibodies to SARS-CoV-2 is urgently needed to determine not only the infection rate, herd immunity and predicted humoral protection, but also vaccine ...efficacy during clinical trials and after large-scale vaccination. The current gold standard is the conventional virus neutralization test requiring live pathogen and a biosafety level 3 laboratory. Here, we report a SARS-CoV-2 surrogate virus neutralization test that detects total immunodominant neutralizing antibodies targeting the viral spike (S) protein receptor-binding domain in an isotype- and species-independent manner. Our simple and rapid test is based on antibody-mediated blockage of the interaction between the angiotensin-converting enzyme 2 (ACE2) receptor protein and the receptor-binding domain. The test, which has been validated with two cohorts of patients with COVID-19 in two different countries, achieves 99.93% specificity and 95-100% sensitivity, and differentiates antibody responses to several human coronaviruses. The surrogate virus neutralization test does not require biosafety level 3 containment, making it broadly accessible to the wider community for both research and clinical applications.
•The largest study of inactive COVID-19 vaccine in preventing severe illness in China.•Those who received 2 doses of inactivated vaccine had an 88% reduced risk in severe illness.•The full ...immunization offered 100% protection from severe illness among women.•The effect of the vaccine was potentially affected by underlying medical conditions.
The SARS-CoV-2 B.1.617.2 (Delta) variant has caused a new surge in the number of COVID-19 cases. The effectiveness of inactivated vaccines against this variant is not fully understood.
Using data from a recent large-scale outbreak of B.1.617.2 SARS-CoV-2 infection in Jiangsu, China, we conducted a real-world study to explore the effect of inactivated vaccine immunization on the course of disease in patients infected with the Delta variant.
Of 476 patients with B.1.617.2 infection, 184 were unvaccinated, 105 were partially vaccinated, and 187 were fully vaccinated. A total of 42 (8.8%) patients developed severe illness, of whom, 27 (14.7%), 13 (12.4%), and 2 (1.1%) were unvaccinated, partially vaccinated, and fully vaccinated, respectively (P <0.001). All 15 (3.2%) patients who required mechanical ventilation were unvaccinated. After adjusting for age, sex, and comorbidities, fully vaccinated patients had an 88% reduced risk of progressing to severe illness (ORadjusted: 0.12, 95% CI: 0.02-0.45). However, this protective effect was not observed in partially vaccinated patients (ORadjusted: 1.11, 95% CI: 0.51-2.36). Full immunization offered 100% protection from severe illness among women. The effect of the vaccine was potentially affected by underlying medical conditions (ORadjusted: 0.26, 95% CI: 0.03-1.23).
Full vaccination with inactivated vaccines is highly effective in preventing severe illness in Delta variant–infected patients. However, partial vaccination does not offer clinically meaningful protection against severe disease.
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•Neutralizing antibody evaluation helps to assess the risk of re-infection.•Some COVID-19 patients may not develop neutralizing antibody after recovery.•SARS-CoV-2 neutralizing antibody levels are ...correlated with COVID-19 disease severity.
The emerging coronavirus disease 2019 (COVID-19) has become a serious global public health threat. With more and more recovered patients, it is urgently needed for evaluation of the neutralizing antibody (NAb) in these patients. In this study, we collected blood samples from 49 patients recently recovered from COVID-19. Serum NAbs were measured using a novel surrogate virus neutralization test (sVNT). Factors associated with NAb titers were analyzed using Ordinary Least Squares regression model. The median age of the study participants was 37 years (IQR, 30.0–54.5) and 55.1 % (27/49) of which were male. The median time to blood collection (for NAb analysis) from illness onset, viral clearance and discharge were 43.0 days (IQR, 36.0–50.0), 27.0 days (IQR, 20.5–37) and 17.0 days (IQR, 15.0–33.0), respectively. Patients had a median NAb titer of 1: 40 (IQR, 1:15–1:120). NAbs were not detected in two asymptomatic children who quickly cleared the virus. NAb titers were higher in patients with older age (p = 0.020), symptomatic infection (p = 0.044), more profound lung involvement (p＜0.001), abnormal C-reactive protein level (p＜0.01) and elevated lactate dehydrogenase (p = 0.019). Multivariable analysis revealed that severity of pneumonia and having comorbidity positively correlated with NAb titers in recovered patients (p = 0.02), while use of corticosteroids negatively impacted NAb titers (p = 0.01). Our study suggests that some COVID-19 patients may not have detectable NAb after recovery. SARS-CoV-2 NAb titers are positively correlated with severity of COVID-19 pneumonia.
Varicella-zoster virus (VZV) infection can be diagnosed clinically once classical rash occurs but the diagnosis is challenging when typical rash is absent. We reported a case of fulminant central ...nervous system (CNS) VZV infection in a human immunodeficiency virus (HIV)-infected patient without typical VZV-related rash. CNS VZV infection was unexpected identified by metagenomic next-generation sequencing (mNGS).
A 28-year-old HIV-infected patient presented with neurological symptoms for 3 days. The patient, who was not suspected of VZV infection at admission, quickly progressed to deep coma during the first 24 h of hospitalization. An unbiased mNGS was performed on DNA extract from 300 μL cerebrospinal fluid (CSF) with the BGISEQ-50 platform. The sequencing detection identified 97,248 (out of 38,561,967) sequence reads uniquely aligned to the VZV genome, and these reads covered a high percentage (99.91%) of the VZV. Presence of VZV DNA in CSF was further verified by VZV-specific polymerase chain reaction and Sanger sequencing. Altogether, those results confirmed CNS VZV infection.
This study suggests that mNGS may be a useful diagnostic tool for CNS VZV infection. As mNGS could identify all pathogens directly from CSF sample in a single run, it has the promise of strengthening our ability to diagnose CNS infections in HIV-infected patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
More than 100 different pathogens can cause encephalitis. Testing of all the neurological pathogens by conventional methods can be difficult. Metagenomic next-generation sequencing (NGS) could ...identify the infectious agents in a target-independent manner. The role of this novel method in clinical diagnostic microbiology still needs to be evaluated. In present study, we used metagenomic NGS to search for an infectious etiology in a human immunodeficiency virus (HIV)-infected patient with lethally diffuse brain lesions. Sequences mapping to Toxoplasma gondii were unexpectedly detected.
A 31-year-old HIV-infected patient presented to hospital in a critical ill condition with a Glasgow coma scale score of 3. Brain magnetic resonance imaging showed diffuse brain abnormalities with contrast enhancement. Metagenomic NGS was performed on DNA extract from 300 μL patient's cerebrospinal fluid (CSF) with the BGISEQ-50 platform. The sequencing detection identified 65,357 sequence reads uniquely aligned to the Toxoplasma gondii genome. Presence of Toxoplasma gondii genome in CSF was further verified by Toxoplasma gondii-specific polymerase chain reaction and Sanger sequencing. Altogether, those results confirmed the diagnosis of toxoplasmic encephalitis.
This study suggests that metagenomic NGS may be a useful diagnostic tool for toxoplasmic encephalitis. As metagenomic NGS is able to identify all pathogens in a single run, it may be a promising strategy to explore the clinical causative pathogens in central nervous system infections with atypical features.
The role of natural killer (NK) cell function in HIV disease especially in the setting of long-term antiretroviral therapy (ART) and viral suppression is not fully understood. In the current study, ...we have investigated NK cell activation in healthy controls and aviremic ART-treated HIV+ subjects with different degrees of immune restoration. We performed a cross sectional study in 12 healthy controls and 24 aviremic ART-treated HIV-infected subjects including 13 HIV+ subjects with CD4+ T cells above 500 cells/μL defined as "immunologic responders" and 11 HIV+ subjects with CD4+ T cells below 350 cells/μL defined as "immunologic non-responders". We analyzed NK cell number, subset, and activation by expression of CD107a and NKG2D and co-expression of CD38 and HLA-DR. NK cell-mediated cytotoxicity against uninfected CD4+ T cells was tested in vitro. We found that NK cell absolute number, percentage of NK cells, and percentage of NK cell subsets were similar in the three study groups. The increased NK cell activation was found predominantly in CD56dimCD16+ subset of immunologic non-responders but not immunologic responders compared to healthy controls. The activation of NK cells was inversely correlated with the peripheral CD4+ T cell count in HIV+ subjects, even after controlling for chronic T cell activation, sex, and age, potential contributors for CD4+ T cell counts in HIV disease. Interestingly, NK cells from immunologic non-responders mediated cytotoxicity against uninfected CD4+ T cells ex vivo. NK cells may play a role in blunted CD4+ T cell recovery in ART-treated HIV disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Although considerable interest in metagenomic next-generation sequencing (mNGS) has been attracted in recent years, limited data are available regarding the performance of mNGS in HIV-associated ...central nervous system (CNS) infection. Here, we conducted a retrospectively analyzing of the cerebrospinal fluid (CSF) mNGS reports and other clinical data from 80 HIV-infected patients admitted to the Second Hospital of Nanjing, China from March, 2018 to March, 2022. In our study, CSF mNGS reported negative result, mono-infection, and mixed infection in 8.8, 36.2, and 55% of the patients, respectively.
Epstein–Barr virus
(EBV), positive in 52.5% of samples, was the most commonly reported pathogen, followed by
cytomegalovirus
(CMV),
John Cunningham virus
(JCV),
torque teno virus
(TTV),
cryptococcus neoformans
(CN),
toxoplasma Gondii
(TE), and
mycobacterium tuberculosis
(MTB). 76.2% of the EBV identification and 54.2% of the CMV identification were not considered clinically important, and relative less sequence reads were reported in the clinical unimportant identifications. The clinical importance of the presence of TTV in CSF was not clear. Detection of JCV, CN, or TE was 100% suggestive of specific CNS infection, however, 60% of the MTB reports were considered contamination. Moreover, of the 44 (55%) mixed infections reported by mNGS, only 4 (5%) were considered clinical important, and mNGS failed to identify one mixed infection. Additionally, except for MTB, CSF mNGS tended to have high sensitivity to identify the above-mentioned pathogens (almost with 100% sensitivity). Even all the diagnostic strategies were evaluated, the cause of neurological symptoms remained undetermined in 6 (7.5%) patients. Overall, our results suggest that mNGS is a very sensitive tool for detecting common opportunistic CNS pathogen in HIV-infected patients, although its performance in CNS tuberculosis is unsatisfactory. EBV and CMV are commonly detected by CSF mNGS, however, the threshold of a clinical important detection remains to be defined.
Chest computerized tomography (CT) scan is an important strategy that quantifies the severity of COVID-19 pneumonia. To what extent inactivated COVID-19 vaccines could impact the COVID-19 pneumonia ...on chest CT is not clear.
This study recruited 357 SARS-COV-2 B.1.617.2 (Delta) variant-infected patients admitted to the Second Hospital of Nanjing from July to August 2021. An artificial intelligence-assisted CT imaging system was used to quantify the severity of COVID-19 pneumonia. We compared the volume of infection (VOI), percentage of infection (POI) and chest CT scores among patients with different vaccination statuses.
Of the 357 Delta variant-infected patients included for analysis, 105 were unvaccinated, 72 were partially vaccinated and 180 were fully vaccinated. Fully vaccination had the least lung injuries when quantified by VOI (median VOI of 222.4 cm
, 126.6 cm
and 39.9 cm
in unvaccinated, partially vaccinated and fully vaccinated, respectively; p < 0.001), POI (median POI of 7.60%, 3.55% and 1.20% in unvaccinated, partially vaccinated and fully vaccinated, respectively; p < 0.001) and chest CT scores (median CT score of 8.00, 6.00 and 4.00 in unvaccinated, partially vaccinated and fully vaccinated, respectively; p < 0.001). After adjustment for age, sex, comorbidity, time from illness onset to hospitalization and viral load, fully vaccination but not partial vaccination was significantly associated with less lung injuries quantified by VOI {adjust coefficient95%CI for "full vaccination": - 106.10(- 167.30,44.89); p < 0.001}, POI {adjust coefficient95%CI for "full vaccination": - 3.88(- 5.96, - 1.79); p = 0.001} and chest CT scores {adjust coefficient95%CI for "full vaccination": - 1.81(- 2.72, - 0.91); p < 0.001}. The extent of reduction of pulmonary injuries was more profound in fully vaccinated patients with older age, having underlying diseases, and being female sex, as demonstrated by relatively larger absolute values of adjusted coefficients. Finally, even within the non-severe COVID-19 population, fully vaccinated patients were found to have less lung injuries.
Fully vaccination but not partially vaccination could significantly protect lung injury manifested on chest CT. Our study provides additional evidence to encourage a full course of vaccination.
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