Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 6 de 6
Filter
1.
Jci Insight ; 8(1):10, 2023.
Article in English | MEDLINE | ID: covidwho-2194475

ABSTRACT

BACKGROUND: To minimize COVID-19 pandemic burden and spread, 3-dose vaccination campaigns commenced worldwide. Since patients who are pregnant are at increased risk for severe disease, they were recently included in that policy, despite the lack of available evidence regarding the impact of a third boosting dose during pregnancy, underscoring the urgent need for relevant data. We aimed to characterize the effect of the third boosting dose of mRNA Pfizer BNT162b2 vaccine in pregnancy.

2.
Journal of Virology ; 95(14):16, 2021.
Article in English | Web of Science | ID: covidwho-1501538

ABSTRACT

The nasal mucosa constitutes the primary entry site for respiratory viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While the imbalanced innate immune response of end-stage coronavirus disease 2019 (COVID-19) has been extensively studied, the earliest stages of SARS-CoV-2 infection at the mucosal entry site have remained unexplored. Here, we employed SARS-CoV-2 and influenza virus infection in native multi-cell-type human nasal turbinate and lung tissues ex vivo, coupled with genome-wide transcriptional analysis, to investigate viral susceptibility and early patterns of local mucosal innate immune response in the authentic milieu of the human respiratory tract. SARS-CoV-2 productively infected the nasal turbinate tissues, predominantly targeting respiratory epithelial cells, with a rapid increase in tissue-associated viral subgenomic mRNA and secretion of infectious viral progeny. Importantly, SARS-CoV-2 infection triggered robust antiviral and inflammatory innate immune responses in the nasal mucosa. The upregulation of interferon -stimulated genes, cytokines, and chemokines, related to interferon signaling and immune cell activation pathways, was broader than that triggered by influenza virus infection. Conversely, lung tissues exhibited a restricted innate immune response to SARS-CoV-2, with a conspicuous lack of type I and III interferon upregulation, contrasting with their vigorous innate immune response to influenza virus. Our findings reveal differential tissue-specific innate immune responses in the upper and lower respiratory tracts that are specific to SARS-CoV-2. The studies shed light on the role of the nasal mucosa in active viral transmission and immune defense, implying a window of opportunity for early interventions, whereas the restricted innate immune response in early-SARS-CoV2-infected lung tissues could underlie the unique uncontrolled late-phase lung damage of advanced COVID-19. IMPORTANCE In order to reduce the late-phase morbidity and mortality of COVID-19, there is a need to better understand and target the earliest stages of SARS-CoV-2 infection in the human respiratory tract. Here, we have studied the initial steps of SARS-CoV-2 infection and the consequent innate immune responses within the natural multicellular complexity of human nasal mucosal and lung tissues. Comparing the global innate response patterns of nasal and lung tissues infected in parallel with SARS-CoV-2 and influenza virus, we found distinct virus-host interactions in the upper and lower respiratory tract, which could determine the outcome and unique pathogenesis of SARS-CoV-2 infection. Studies in the nasal mucosal infection model can be employed to assess the impact of viral evolutionary changes and evaluate new therapeutic and preventive measures against SARS-CoV-2 and other human respiratory pathogens.

3.
Journal of the American Society of Nephrology ; 32:101, 2021.
Article in English | EMBASE | ID: covidwho-1489560

ABSTRACT

Background: Dialysis-treated (DT) and kidney transplant (TX) patients face higher morbidly and mortality risks than the general population during COVID-19 pandemic. Determining humoral response and associated COVID-19 morbidity after vaccination will guide risk assessment and changes in vaccination policy in this vulnerable population. Methods: Prospective cohort study up to 5 months follow-up after Tozinameran or SARS-CoV-2 infection. Primary outcomes: qualitative and quantitative anti S1/ S2 antibody (ABs) and disease rates during follow up. Anti-SARS-2 IgG ABs were quantified using LIAISON SARS-CoV-2 S1/S2 IgG (DiaSorin) immunoassay in serum of TX, DT and treating team at our hospital. Demographics and clinical data were collected from participants files. Results: 174 DT patients (40% women, age 65±15 years) 253 TX patients (33%, 53±14 years) and 71 control participants (65%, 44±14 years) were recruited. 3 months or more after vaccination we detected anti S1/S2 ABs in 81% of DT (95%CI, 72-90%), 43% of TX (95%CI, 29-57%) and 100% of controls. After COVID-19 respective rates were 94% (95%CI, 83-100%), 75% (95%CI, 60-90%) and 100%. Quantitative titers were in line with qualitative ones. Predictors of negative serology were older age, diabetes, cancer history, lower lymphocyte count and lower vitamin D. Peritoneal dialysis predicted higher titers compared to hemodialysis. In TX, hypertension and higher levels of immnosupression predicated lower titers. Vaccination was associated with fewer subsequent COVID-19 infections (HR=0.23, 95% CI 0.05-0.99, p<0.05). Higher antibody titers associated with fewer events, HR 0.41/unit increase in log10 titer (p<0.05). Conclusions: Patients with ESRD, particularly TX, mounted delayed and diminished antibody response to vaccination, and lesser response was associated with more infections. Thus, measures to protect non-responsive patients are urgently required.

4.
ESMO Open ; 6(6): 100283, 2021 12.
Article in English | MEDLINE | ID: covidwho-1461066

ABSTRACT

BACKGROUND: It was shown that immunocompromised patients have significantly reduced immunologic responses to COVID-19 vaccines. The immunogenicity of COVID-19 vaccine/infection in patients with solid tumors is reduced. We evaluated the immunologic response to COVID-19 and/or the BNT162b2 mRNA COVID-19 vaccine among cancer patients on active treatments and reviewed previous literature to identify subgroups that may require third vaccination. PATIENTS AND METHODS: Anti-SARS-CoV-2 S1/S2 antibodies were measured in a cohort of 202 cancer patients on active treatment with chemotherapy (96), immunologic (52), biologic (46), and hormonal (12) treatments for early (n = 66, 32.7%) or metastatic disease (n = 136, 67.3%). Of those, 172 had received two vaccine doses, and 30 had COVID-19 infection (20/30 also received one dose of vaccine). Specific anti-S receptor-binding domain antibodies were further measured in patients with equivocal anti-S1/S2 results. RESULTS: Among cancer patients, the SARS-CoV-2 antibody response rate was 89.1% (180/202) after COVID-19 vaccination or infection and 87.2% (150/172) in patients after vaccination without a history of COVID-19, compared with 100% positive serologic tests in a control group of 30 health care workers (P < 0.001). Chemotherapy treatment was independently associated with significantly reduced humoral response to infection or vaccination, with an 81.3% response rate, compared with 96.2% in patients on other treatments (P = 0.001). In vaccinated patients on chemotherapy, the positive response rate was 77.5%. In a multiple regression model, a neutralizing antibody titer (>60 AU/ml) was more likely with immunotherapy (odds ratio 2.44) and less likely with chemotherapy (odds ratio 0.39). CONCLUSIONS: Overall, both COVID-19 vaccine and natural infection are highly immunogenic among cancer patients. Our study, however, identifies those under chemotherapy as significantly less responsive, and with lower antibody levels. These findings justify close virological and serological surveillance along with consideration of these patients for booster (third dose) vaccine prioritization, as new highly spreading SARS-CoV-2 variants emerge.


Subject(s)
COVID-19 , Neoplasms , Vaccines , COVID-19 Vaccines , Humans , Neoplasms/drug therapy , Prospective Studies , SARS-CoV-2
6.
Clin Microbiol Infect ; 26(9): 1248-1253, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-612024

ABSTRACT

INTRODUCTION: Testing for active SARS-CoV-2 infection is a fundamental tool in the public health measures taken to control the COVID-19 pandemic. Because of the overwhelming use of SARS-CoV-2 reverse transcription (RT)-PCR tests worldwide, the availability of test kits has become a major bottleneck and the need to increase testing throughput is rising. We aim to overcome these challenges by pooling samples together, and performing RNA extraction and RT-PCR in pools. METHODS: We tested the efficiency and sensitivity of pooling strategies for RNA extraction and RT-PCR detection of SARS-CoV-2. We tested 184 samples both individually and in pools to estimate the effects of pooling. We further implemented Dorfman pooling with a pool size of eight samples in large-scale clinical tests. RESULTS: We demonstrated pooling strategies that increase testing throughput while maintaining high sensitivity. A comparison of 184 samples tested individually and in pools of eight samples showed that test results were not significantly affected. Implementing the eight-sample Dorfman pooling to test 26 576 samples from asymptomatic individuals, we identified 31 (0.12%) SARS-CoV-2 positive samples, achieving a 7.3-fold increase in throughput. DISCUSSION: Pooling approaches for SARS-CoV-2 testing allow a drastic increase in throughput while maintaining clinical sensitivity. We report the successful large-scale pooled screening of asymptomatic populations.


Subject(s)
Betacoronavirus/isolation & purification , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Betacoronavirus/genetics , COVID-19 , COVID-19 Testing , Coronavirus Infections/epidemiology , Diagnostic Tests, Routine , Humans , Pandemics , Pneumonia, Viral/epidemiology , RNA, Viral/genetics , Reproducibility of Results , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2 , Sensitivity and Specificity , Specimen Handling
SELECTION OF CITATIONS
SEARCH DETAIL