Lack of SARS-CoV-2-specific cellular response in critically ill COVID-19 patients despite apparent effective vaccination.
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ABSTRACT:
SUBMITTER: Bidar F
PROVIDER: S-EPMC9176157 | biostudies-literature | 2022 Jun
REPOSITORIES: biostudies-literature
Publications
Lack of SARS-CoV-2-specific cellular response in critically ill COVID-19 patients despite apparent effective vaccination.
Bidar Frank F Monneret Guillaume G Berthier Franck F Lukaszewicz Anne-Claire AC Venet Fabienne F
Critical care (London, England) 20220608 1
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Project description:The SARS-CoV-2 Delta Variant of Concern is highly transmissible and contains mutations that confer partial immune escape. The emergence of Delta in North America caused the first surge in COVID-19 cases after SARS-CoV-2 vaccines became widely available. To determine whether individuals infected despite vaccination might be capable of transmitting SARS-CoV-2, we compared RT-PCR cycle threshold (Ct) data from 20,431 test-positive anterior nasal swab specimens from fully vaccinated (n = 9,347) or unvaccinated (n = 11,084) individuals tested at a single commercial laboratory during the interval 28 June- 1 December 2021 when Delta variants were predominant. We observed no significant effect of vaccine status alone on Ct value, nor when controlling for vaccine product or sex. Testing a subset of low-Ct (<25) samples, we detected infectious virus at similar rates, and at similar titers, in specimens from vaccinated and unvaccinated individuals. These data indicate that vaccinated individuals infected with Delta variants are capable of shedding infectious SARS-CoV-2 and could play a role in spreading COVID-19.
| S-EPMC9555632 | biostudies-literature
Project description:BackgroundSARS-CoV-2 is described to cause mild to moderate symptoms in children. To date, clinical data and symptoms of the Delta variant in pediatric patients are lacking.AimTo describe clinical characteristics and outcomes of infants admitted in the pediatric intensive care unit (PICU) during the period of Delta variant predominance.MethodsWe performed a retrospective study, between June 23, 2021 and August 16, 2021. We included children aged under 15 years, admitted to PICU with severe and critical form of SARS-CoV-2 infection as confirmed by RT-PCR. We reviewed medical records for all patients.ResultsDuring the study period, 20 infants were included. The median age was 47 days (IQR: 26.5-77). The sex ratio was 0.8 (9 males). No underlying medical conditions were noted. Parents were not vaccinated. Respiratory involvement was the main feature to be observed in our cohort. Eleven patients had pediatric acute respiratory distress (PARDS) with a median oxygen saturation index (OSI) of 9 (IQR: 7-11). PARDS was mild in 4 cases, moderate in 5 cases and severe in 2 cases. Hemodynamic instability was observed in 4 cases. The main radiological finding was ground glass opacities in 11 cases. Seventeen patients were mechanically ventilated and 3 of them were escalated to high-frequency oscillatory ventilation. The median duration of mechanical ventilation was 6 days (IQR 2.5-12.5). The remaining patients were managed with high flow nasal cannula. Four patients died.ConclusionWe report herein a case series of very young infants, with no comorbidities, and with a life-threatening illness due to SARS-CoV-2 Delta variant.
| S-EPMC9767656 | biostudies-literature
Project description:BackgroundThe current outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses an unprecedented health crisis. The most common chronic illness among patients infected with SARS-CoV-2 is hypertension. Immune dysregulation plays an important role in SARS-CoV-2 infection and in the development of hypertension; however, the dynamic immunological characteristics of COVID-19 patients with hypertension remain largely unclear.MethodsIn total, 258 hypertensive patients infected with SARS-CoV-2 were included in this study. CD38+HLA-DR+ and CD38+PD-1+ CD8+ T cells, IFNγ+CD4+ and IFNγ+CD8+ T cells, the titers of IgG, IgM, and IgA against SARS-CoV-2 spike protein, and SARS-CoV-2 throat viral loads were measured weekly over 4 weeks after the onset of symptoms. Clinical outcomes were also monitored.FindingsCD4+ T lymphopenia was observed in 100% of the severe and critical cases. Compared with the surviving patients, the patients with fatal outcomes exhibited high and prolonged expression of CD38+HLA-DR+ and CD38+PD-1+ on CD8+ T cells, low expression of SARS-CoV-2-specific IFNγ+CD4+ and IFNγ+CD8+ T cells, low titers of IgG, IgM, and IgA against SARS-CoV-2 spike protein, and high SARS-CoV-2 viral load during the illness. In the surviving patients, the viral load was significantly inversely correlated with SARS-CoV-2-specific IFNγ+CD8+and IFNγ+CD4+ T cells, IgG, IgM, and IgA.InterpretationT lymphopenia is common in critical or severe COVID-19 cases with hypertension. Prolonged activation and exhaustion of CD8+ T cells were associated with severe disease. The delayed SARS-CoV-2-specific antibody responses may be insufficient for overcoming severe SARS-CoV-2 infection in the absence of SARS-CoV-2-specific cellular responses.
| S-EPMC7758245 | biostudies-literature
Project description: Not available
| S-EPMC7258645 | biostudies-literature
Project description:Patients with severe cases of COVID-19 are at high nutritional risk during their ICU stay. Prolonged immobilization associated with an exacerbated systemic inflammatory response is a major provider of ICU-acquired muscle weakness. Early enteral nutrition is recommended to gradually reach the energy target of 25 kcal/kg/day and protein target of 1.3 g/kg/day around D4. The occurrence of a Refeeding syndrome should be closely monitored. In case of feeding intolerance refractory to a prokinetic treatment, complementary or total parenteral nutrition is advised, favouring new generation mixed lipid emulsions (containing fish oil) and regular monitoring of triglyceridemia. Nutrition care of critically ill patients should be carried out with limited procedures that may pose a risk of contamination for the healthcare staff.
| S-EPMC7351417 | biostudies-literature
Project description:Longitudinal Gene expression profiling of whole blood from critically ill influenza and bacterial pneumonia patients. In addition before vs 7 days post influenza vaccination volunteer samples are assayed. 3 groups of samples. First is bacterial pneumonia patients with 6 subjects sampled for up to 5 days. Second group is severe influenza infection with 4 subjects sampled for up to 5 days. Third group is influenza vaccination with 18 subjects sampled before and 7 days post vaccination.
2011-06-30 | E-GEOD-20346 | biostudies-arrayexpress
Project description:Longitudinal Gene expression profiling of whole blood from critically ill influenza and bacterial pneumonia patients. In addition before vs 7 days post influenza vaccination volunteer samples are assayed.
2011-06-30 | GSE20346 | GEO
Project description:BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA loads in patient specimens may act as a clinical outcome predictor in critically ill patients with coronavirus disease 2019 (COVID-19).MethodsWe evaluated the predictive value of viral RNA loads and courses in the blood compared with the upper and lower respiratory tract loads of critically ill COVID-19 patients. Daily specimen collection and viral RNA quantification by reverse transcription quantitative polymerase chain reaction were performed in all consecutive 170 COVID-19 patients between March 2020 and February 2021 during the entire intensive care unit (ICU) stay (4145 samples analyzed). Patients were grouped according to their 90-day outcome as survivors (n=100) or nonsurvivors (n=70).ResultsIn nonsurvivors, blood SARS-CoV-2 RNA loads were significantly higher at the time of admission to the ICU (P=.0009). Failure of blood RNA clearance was observed in 33/50 (66%) of the nonsurvivors compared with 12/64 (19%) survivors (P<.0001). As determined by multivariate analysis, taking sociodemographic and clinical parameters into account, blood SARS-CoV-2 RNA load represents a valid and independent predictor of outcome in critically ill COVID-19 patients (odds ratio [OR; log10], 0.23; 95% CI, 0.12-0.42; P<.0001), with a significantly higher effect for survival compared with respiratory tract SARS-CoV-2 RNA loads (OR [log10], 0.75; 95% CI, 0.66-0.85; P<.0001). Blood RNA loads exceeding 2.51×103 SARS-CoV-2 RNA copies/mL were found to indicate a 50% probability of death. Consistently, 29/33 (88%) nonsurvivors with failure of virus clearance exceeded this cutoff value constantly.ConclusionsBlood SARS-CoV-2 load is an important independent outcome predictor and should be further evaluated for treatment allocation and patient monitoring.
| S-EPMC8522363 | biostudies-literature
Project description:BackgroundData on cellular immune responses in persons with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection following vaccination are limited. The evaluation of these patients with SARS-CoV-2 breakthrough infections may provide insight into how vaccinations limit the escalation of deleterious host inflammatory responses.MethodsWe conducted a prospective study of peripheral blood cellular immune responses to SARS-CoV-2 infection in 21 vaccinated patients, all with mild disease, and 97 unvaccinated patients stratified based on disease severity.ResultsWe enrolled 118 persons (aged 50 years [SD 14.5 years], 52 women) with SARS-CoV-2 infection. Compared to unvaccinated patients, vaccinated patients with breakthrough infections had a higher percentage of antigen-presenting monocytes (HLA-DR+), mature monocytes (CD83+), functionally competent T cells (CD127+), and mature neutrophils (CD10+); and lower percentages of activated T cells (CD38+), activated neutrophils (CD64+), and immature B cells (CD127+CD19+). These differences widened with increased disease severity in unvaccinated patients. Longitudinal analysis showed that cellular activation decreased over time but persisted in unvaccinated patients with mild disease at 8-month follow-up.ConclusionsPatients with SARS-CoV-2 breakthrough infections exhibit cellular immune responses that limit the progression of inflammatory responses and suggest mechanisms by which vaccination limits disease severity. These data may have implications for developing more effective vaccines and therapies. Clinical Trials Registration. NCT04401449.
| S-EPMC10304754 | biostudies-literature
Project description:The pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has had a profound impact on the global health and economy. While mass vaccination for herd immunity is effective, emerging SARS-CoV-2 variants can evade spike protein-based COVID-19 vaccines. In this study, we develop a new immunization strategy by utilizing a nanocarrier, dendritic mesoporous silica nanoparticle (DMSN), to deliver the receptor-binding domain (RBD) and conserved T-cell epitope peptides (DMSN-P-R), aiming to activate both humoral and cellular immune responses in the host. The synthesized DMSN had good uniformity and dispersion and showed a strong ability to load the RBD and peptide antigens, enhancing their uptake by antigen-presenting cells (APCs) and promoting antigen delivery to lymph nodes. The DMSN-P-R vaccine elicited potent humoral immunity, characterized by highly specific RBD antibodies. Neutralization tests demonstrated significant antibody-mediated neutralizing activity against live SARS-CoV-2. Crucially, the DMSN-P-R vaccine also induced robust T-cell responses that were specifically stimulated by the RBD and conserved T-cell epitope peptides of SARS-CoV-2. The DMSN demonstrated excellent biocompatibility and biosafety in vitro and in vivo, along with degradability. Our study introduces a promising vaccine strategy that utilizes nanocarriers to deliver a range of antigens, effectively enhancing both humoral and cellular immune responses to prevent virus transmission.
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