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1.
Clinical Immunology ; Conference: 2023 Clinical Immunology Society Annual Meeting: Immune Deficiency and Dysregulation North American Conference. St. Louis United States. 250(Supplement) (no pagination), 2023.
Article in English | EMBASE | ID: covidwho-20244368

ABSTRACT

Bivalent COVID-19 vaccines that contain two mRNAs encoding Wuhan-1 and Omicron BA.4/5 spike proteins are successful in preventing infection from the original strain and Omicron variants, but the quality of adaptive immune responses is still not well documented. This study aims at characterizing adaptive immune responses to the bivalent booster vaccination in 46 healthy participants. Plasma and PBMC were collected prior and three weeks after bivalent booster. We measured anti-N, anti-S, and RBD IgM, IgA, IgG plasma titers against original, Omicron BA.1, and BA.5 variants (pending) as well as total anti-S IgG titers and surrogate Virus Neutralization capacity against the Alpha, Delta, and BA.1 variant. With spectral flow-cytometry we identified peripheral blood B-cells specific for the RBD of the S-protein of the original and BA.1 variants. T-cell-specific responses were assessed by cytokine release assay after stimulation with SARS-CoV-2 peptides from the original, BA.1, BA.4, and BA.5 variants (pending). Finally, we performed TRB and IGH repertoire studies on sorted CD4+, CD8+, CD19+ lymphocytes, to study breadth of SARS-CoV-2 specific clonotypes (pending). 27/46 participants were analyzed;9 had SARS-CoV-2 infection (COVID+), while 18 are infection naive (COVID-). In both groups, median time since last dose of SARS-CoV-2 vaccine (3rd or 4th) was 11 months. All subjects were positive for anti-S IgG prior to bivalent booster. The COVID + group displayed anti-S IgG pre-booster levels and neutralization against BA.1 higher than the COVID- group. Significant increase post-boost of total anti-S IgG and BA.1 neutralizing activity was detected in the COVID- but not in the COVID+ group;however, no difference in neutralization activity post-boost was detected between the two groups. Furthermore, the COVIDgroup showed significant increase in the frequency of CD19+ and CD27+ switched memory B-cells specific for BA.1 RBD in post-boost compared to pre-boost samples. However, post-boost frequencies of the same B-cells were higher in the COVID+ compared to the COVID- group. These preliminary findings confirm that among individual immunized with the original COVID-19 mRNAvaccine, prior COVID infection provides increased protection against SARS-CoV-2 variants. They also demonstrate that booster immunization with the bivalent vaccine induces robust adaptive immune responses against Omicron variant.[Formula presented][Formula presented]Copyright © 2023 Elsevier Inc.

2.
Topics in Antiviral Medicine ; 31(2):114, 2023.
Article in English | EMBASE | ID: covidwho-2315751

ABSTRACT

Background: Reliable biomarkers of COVID-19 severity and outcomes are critically needed for clinical and research applications. We evaluated associations between anti-Spike IgG and SARS-COV-2 nucleocapsid antigen (N Ag) in plasma with clinical outcomes in outpatients with COVID-19. Method(s): We used data from 229 non-hospitalized, US-based adults with COVID-19 who enrolled between January and July 2021 into the placebo arm of the ACTIV-2/A5401 platform trial within 10 days of symptom onset. Pretreatment (day 0) plasma was analyzed by the quantitative Simoa SARS-CoV-2 IgG antibody (anti-Spike) assay (lower limit of quantification [LLoQ] 0.77ug/ mL), and the quantitative Simoa SARS-CoV-2 N Protein Advantage (Quanterix) measuring N Ag (LLoQ 3pg/mL). In addition to analyses for < LLoQ vs >=LLoQ anti-Spike and N Ag, we categorized participants into five N Ag groups (< 3 pg/ml;3-< 100 pg/ml;100-< 1,000 pg/ml;1,000-< 2,500 pg/ml;>=2,500 pg/ ml). Associations between SARS-CoV-2 anti-Spike and N Ag levels and clinical outcomes (all-cause hospitalization/death through day 28 and time to symptom improvement or resolution for two consecutive days from day 0 status) were estimated using log-binomial and Cox regression models, respectively. Result(s): At day 0, 40% had anti-Spike levels >=LLoQ and 64% of participants had plasma N Ag levels >=LLoQ. Participants with anti-Spike levels < LLoQ compared to those who had quantifiable anti-Spike at day 0, had an increased risk of hospitalization/death (16% vs 2%, RR [95% confidence interval (CI)]: 7.3 [1.8, 30.1]), and a significantly longer time to symptom improvement (median [Q1, Q3] 14 days [8, >27] vs 9 days [4, 16], hazard ratio [HR]: 0.6 [95%: CI: 0.4, 0.8], p< 0.001). Participants with higher N Ag levels at day 0 had an increased risk of hospitalization or death, ranging from 1% for < 3 pg/ml to 70% for >=2500 pg/ml (Figure). Compared to individuals who had N Ag levels < LLoQ at day 0, those in the highest category of N Ag levels (>=2500 pg/mL) experienced a significantly longer time to symptom improvement (median [Q1, Q3]: 25 days [13, >27] vs 10 days [5, 20];HR: 0.4 [95% CI: 0.2, 0.7];p=0.04). Conclusion(s): At study entry, the absence of Spike antibodies and higher levels of plasma SARS-CoV-2 N Ag predicted hospitalizations and death in untreated outpatients with COVID-19. These parameters may serve as informative biomarkers for risk stratification in the evaluation of outpatients with COVID-19. (Figure Presented).

3.
J Hosp Infect ; 135: 28-36, 2023 May.
Article in English | MEDLINE | ID: covidwho-2255719

ABSTRACT

BACKGROUND: The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. AIM: To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. METHODS: A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. FINDINGS: In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. CONCLUSION: The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/epidemiology , Patient Discharge , Hospitalization , Hospitals
4.
The Journal of hospital infection ; 2023.
Article in English | EuropePMC | ID: covidwho-2255718

ABSTRACT

Background The first epidemic wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over a third of care homes reported an outbreak while there was limited testing of hospital patients discharged to care homes. Aim Investigate hospital discharges as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all discharges from hospitals to care homes starting 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease (COVID-19) test history, clinical assessment at discharge, whole genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis by cluster investigation and virus epidemiological tool (CIVET). Patient timelines were obtained using electronic hospital records. Findings In total 787 hospital discharges to care homes were identified. Out of these 776 (99%) were ruled out for hospital discharge introduction. However, for 10 episodes the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission leading to 10 further positive cases in the care home. Conclusion Majority of hospital discharges were ruled out for introduction into Lothian care homes highlighting the importance of screening all new admissions when faced with a novel emerging virus and no vaccine available.

5.
Open Forum Infectious Diseases ; 9(Supplement 2):S33-S34, 2022.
Article in English | EMBASE | ID: covidwho-2189510

ABSTRACT

Background. ACTT-1 demonstrated clinical efficacy of remdesivir (RDV) in hospitalized patients with COVID-19;subgroup analyses suggested those most likely to benefit presented with milder clinical illness. To further clarify what subsets of hospitalized patients might benefit from RDV, we analyzed virological and immunological biomarkers in this previously reported cohort. Methods. Serum and upper respiratory tract (URT) swabs were collected on Day 1, 3, 5, 8, and 11 while hospitalized;Day 15 and 29 as able were collected and tested for quantitative RNA (URT and plasma), serum nucleoprotein (NPR), IL-6, CRP through Day 6, and serostatus (baseline only). Participants with a baseline and at least one subsequent sample were used in this analysis. Associations of all these biomarkers with clinical outcomes (mortality, recovery) and response to therapy were assessed. Of the 1062 participants in ACTT-1, 642 had baseline and at least one subsequent sample within 6 days of randomization (Fig 1, Table 1). Results. RDV-treated patients with moderate/severe disease who had elevated baseline NPR levels recovered faster (RRR 1.95 vs 1.04, p = 0.01);similar trends were noted for plasma and URT RNA levels (Fig 2A);mortality treatment effects by viral load subgroups (high or low) were not seen (Fig 2B). In patients with less severe illness, RDV treatment was associated with an accelerated decline in NPR (difference -0.062 log10 pg/ml per day, p = 0.003) and plasma RNA levels (difference -0.040 log10 pg/ml per day, p = 0.004. Fig 3A), and a decrease in the proportion of patients with increasing and/or persistent viral loads (Fig 3B). Patients with increasing/persistent viral loads also took longer to recover than those with decreasing viral loads, irrespective of disease severity: RRR for plasma RNA 0.45, 95% CI 0.28-0.73, RRR for NPR 0.44, 95% CI 0.22-0.88 for moderate/severe disease;RRR for plasma RNA 0.26, 95% CI 0.10 - 0.70 , RRR for NPR n.e. (no recoveries) for critical disease (Fig 4). Conclusion. Our study demonstrates a systemic antiviral effect of remdesivir, shows the prognostic value of viral and immunologic biomarkers for mortality and failure to recover, and identifies a group of hospitalized patients with COVID-19 most likely to benefit from remdesivir treatment. (Figure Presented).

6.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927874

ABSTRACT

RATIONALE: Some biomarkers of host response to viral infection are associated with COVID-19 outcomes, but these biomarkers do not directly measure viral burden. The association between plasma viral antigen levels and clinical outcomes has not been previously studied. Our aim was to investigate the relationship between plasma SARS-CoV-2 viral antigen concentration and proximal clinical deterioration in hospitalized patients. METHODS: SARS-CoV-2 nucleocapsid antigen concentrations were measured using a validated microbead immunoassay (Quanterix, NIH/NIAID laboratory) in plasma collected at enrollment from 256 subjects in a prospective observational cohort of hospitalized patients with COVID-19 from 3 hospitals, admitted between March 2020 and August 2021. Relationships between viral antigen concentration and clinical status at 1 week as measured by the World Health Organization (WHO) ordinal scale as well as ICU admission were assessed. Models were adjusted for age and sex, baseline comorbidities including immunosuppression, endogenous neutralizing antibodies, baseline COVID-19 severity, smoking status, remdesivir therapy, steroid therapy, and vaccine status. Missing covariate data were imputed using multiple imputation by chained equations. RESULTS: The median viral antigen concentration for the 35 subjects who deteriorated by 1 week was 4507 (IQR 1225-9665) pg/mL compared to 494 (IQR 18-3882) pg/mL in the 212 subjects who did not (p = 0.0004 Figure a). Using ordinal regression, each doubling in viral antigen concentration was significantly associated with a worse WHO ordinal scale at 1 week (unadjusted OR 1.07, 95% CI 1.02-1.13;adjusted OR 1.10, 95% CI 1.02-1.18). Among 168 patients not in the ICU at baseline, the median viral antigen concentration for the 40 patients who progressed to the ICU was 4697 (IQR 482- 10410) pg/mL vs. 459 (IQR 15-3062) pg/mL in the 128 patients who did not progress to require ICU care (p = 0.0001 Figure b). Using logistic regression, each doubling in viral antigen concentration was significantly associated with ICU admission (unadjusted OR 1.18, 95% CI 1.06-1.32, adjusted OR 1.40, 95% CI 1.11-1.76). CONCLUSIONS: Higher plasma viral antigen concentration at hospital admission is independently associated with a significantly worse clinical status at 1 week and a higher odds of ICU admission among hospitalized patients with COVID-19. This novel finding indicates that plasma viral antigen concentration may identify hospitalized COVID-19 patients at highest risk of short-term clinical deterioration in both clinical practice and research. Results of plasma antigen tests are available within 2-3 hours and could be integrated for identifying hospitalized COVID-19 patients who might benefit from early intervention.

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