Erratum: Enhanced cross-recognition of SARS-CoV-2 Omicron variant by peptide vaccine-induced antibodies.

[This corrects the article DOI: 10.3389/fimmu.2022.1044025.].

Enhanced cross-recognition of SARS-CoV-2 Omicron variant by peptide vaccine-induced antibodies.

Current vaccines against SARS-CoV-2, based on the original Wuhan sequence, induce antibodies with different degrees of cross-recognition of new viral variants of concern. Despite potent responses generated in vaccinated and infected individuals, the Omicron (B.1.1.529) variant causes breakthrough infections, facilitating viral transmission. We previously reported a vaccine based on a cyclic peptide containing the 446-488 S1 sequence (446-488cc) of the SARS-CoV-2 spike (S) protein from Wuhan isolate. To provide the best immunity against Omicron, here we compared Omicron-specific immunity induced by a Wuhan-based 446-488cc peptide, by a Wuhan-based recombinant receptor-binding domain (RBD) vaccine and by a new 446-488cc peptide vaccine based on the Omicron sequence. Antibodies induced by Wuhan peptide 446-488cc in three murine strains not only recognized the Wuhan and Omicron 446-488 peptides similarly, but also Wuhan and Omicron RBD protein variants. By contrast, antibodies induced by the Wuhan recombinant RBD vaccine showed a much poorer cross-reactivity for the Omicron RBD despite similar recognition of Wuhan and Omicron peptide variants. Finally, although the Omicron-based 446-488cc peptide vaccine was poorly immunogenic in mice due to the loss of T cell epitopes, co-immunization with Omicron peptide 446-488cc and exogenous T cell epitopes induced strong cross-reactive antibodies that neutralized Omicron SARS-CoV-2 virus. Since mutations occurring within this sequence do not alter T cell epitopes in humans, these results indicate the robust immunogenicity of 446-488cc-based peptide vaccines that induce antibodies with a high cross-recognition capacity against Omicron, and suggest that this sequence could be included in future vaccines targeting the Omicron variant.

Acute infectious supraglottitis in adult population: epidemiology, management, outcomes and predictors of airway intervention.

PURPOSE: The purpose is to analyze the incidence of acute infectious supraglottitis in our center between 2010 and 2020, define the characteristics and trends of those patients and identify factors associated with the need of airway intervention. METHODS: A retrospective single-center observational study of a cohort of patients diagnosed with acute infectious supraglottitis between January 2010 and December 2020. Patients were stratified according to airway management. RESULTS: Eighty eight patients were included: 59 men (67%) and 29 women (33%). A significant upward trend of 9% in the annual incidence rate of supraglottitis was seen during 2010-2020, with an important increase in cases during 2019. Muffled voice (41%) and respiratory distress (38%) were the most common presenting symptoms; and the median duration of symptoms before hospital admission was 2 days [IQR 1; 3]. Airway intervention was performed in fifteen patients (17%). Nine patients (10%) were intubated and six required tracheotomy (7%). Comparing the patients who required airway intervention with those who received a conservative treatment, younger patients (p < 0.01) were more likely to need airway intervention. In logistic regression analysis, we found that epiglottic abscess (p = 0.015), hypersalivation (p = 0.027) and smoking (p = 0.036) were independent factors with a significant association with airway intervention. CONCLUSION: There was an important increase in cases and its severity in 2019, but due to COVID-19 pandemic, it was not possible to define if it was an isolate event or an upward trend. Epiglottic abscess, hypersalivation and smoking could be possible risk factors for airway intervention.

Outcomes and survival of tracheostomised patients during the COVID-19 pandemic in a third level hospital.

PURPOSE: Analyse the evolution and outcomes of COVID-19 tracheostomised patients. Clarify if this cohort presents an increased risk of haemorrhagic complications and verify the correlation between some risk factors with increased mortality. METHODS: A retrospective single-centre observational study of a prospective cohort of all COVID-19 patients admitted to our centre between March and April 2020. A control group was obtained from a historical cohort of patients who required tracheostomy due to prolonged invasive mechanical ventilation (IMV) before 2020. RESULTS: A total of 1768 patients were included: 67 tracheostomised non-COVID-19 patients (historic cohort), 1371 COVID-19 patients that did not require ICU admission, 266 non-tracheostomised COVID-19 patients and 64 tracheostomised COVID-19 patients. Comparing the obesity prevalence, 54.69% of the tracheostomised COVID-19 patients were obese and 10.53% of the non-tracheostomised COVID-19 patients (p < 0.001). The median of ICU admission days was lower (p < 0.001) in the non-tracheostomised cohort (12.5 days) compared with the COVID-19 tracheostomised cohort (34 days). The incidence of haemorrhagic complications was significantly higher in tracheostomised COVID-19 patients (20.31%) compared with tracheostomised non-COVID-19 patients (5.97%) and presented a higher percentage of obesity, hypertension, diabetes and smoking, significantly different from the historic cohort (p < 0.001). A Cox model showed that tracheostomy had no statistically significant effect on mortality in COVID-19 patients. CONCLUSION: Obesity and smoking may be risk factors for tracheostomy in COVID-19 patients, tracheostomised COVID-19 patients present a higher risk of bleeding complications than those admitted for other reasons and an elevated LDH and INR on ICU admission may be associated with increased mortality.

Preclinical evaluation of a synthetic peptide vaccine against SARS-CoV-2 inducing multiepitopic and cross-reactive humoral neutralizing and cellular CD4 and CD8 responses.

Identification of relevant epitopes is crucial for the development of subunit peptide vaccines inducing neutralizing and cellular immunity against SARS-CoV-2. Our aim was the characterization of epitopes in the receptor-binding domain (RBD) of SARS-CoV-2 spike (S) protein to generate a peptide vaccine. Epitope mapping using a panel of 10 amino acid overlapped 15-mer peptides covering region 401-515 from RBD did not identify linear epitopes when tested with sera from infected individuals or from RBD-immunized mice. However, immunization of mice with these 15-mer peptides identified four peptides located at region 446-480 that induced antibodies recognizing the peptides and RBD/S1 proteins. Immunization with peptide 446-480 from S protein formulated with Freund's adjuvant or with CpG oligodeoxinucleotide/Alum induced polyepitopic antibody responses in BALB/c and C56BL/6J mice, recognizing RBD (titres of 3 × 104-3 × 105, depending on the adjuvant) and displaying neutralizing capacity (80-95% inhibition capacity; p < 0.05) against SARS-CoV-2. Murine CD4 and CD8T-cell epitopes were identified in region 446-480 and vaccination experiments using HLA transgenic mice suggested the presence of multiple human T-cell epitopes. Antibodies induced by peptide 446-480 showed broad recognition of S proteins and S-derived peptides belonging to SARS-CoV-2 variants of concern. Importantly, vaccination with peptide 446-480 or with a cyclic version of peptide 446-488 containing a disulphide bridge between cysteines 480 and 488, protected humanized K18-hACE2 mice from a lethal dose of SARS-CoV-2 (62.5 and 75% of protection; p < 0.01 and p < 0.001, respectively). This region could be the basis for a peptide vaccine or other vaccine platforms against Covid-19.

Frequency and phenotype of headache in covid-19: a study of 2194 patients.

To estimate the frequency of headache in patients with confirmed COVID-19 and characterize the phenotype of headache attributed to COVID-19, comparing patients depending on the need of hospitalization and sex, an observational study was done. We systematically screened all eligible patients from a reference population of 261,431 between March 8 (first case) and April 11, 2020. A physician administered a survey assessing demographic and clinical data and the phenotype of the headache. During the study period, 2194 patients out of the population at risk were diagnosed with COVID-19. Headache was described by 514/2194 patients (23.4%, 95% CI 21.7-25.3%), including 383/1614 (23.7%) outpatients and 131/580 (22.6%) inpatients. The headache phenotype was studied in detail in 458 patients (mean age, 51 years; 72% female; prior history of headache, 49%). Headache was the most frequent first symptom of COVID-19. Median headache onset was within 24 h, median duration was 7 days and persisted after 1 month in 13% of patients. Pain was bilateral (80%), predominantly frontal (71%), with pressing quality (75%), of severe intensity. Systemic symptoms were present in 98% of patients. Headache frequency and phenotype was similar in patients with and without need for hospitalization and when comparing male and female patients, being more intense in females.Trial registration: This study was supported by the Institute of Health Carlos III (ISCIII), code 07.04.467804.74011 and Regional Health Administration, Gerencia Regional de Salud, Castilla y Leon (GRS: 2289/A/2020).

Association between red blood cell distribution width and mortality of COVID-19 patients.

PURPOSE: We have previously reported an association between high red blood cell distribution width (RDW) and mortality in septic and brain infarction patients. However, no association between RDW and mortality in coronavirus disease 2019 (COVID-19) patients has been reported so far; thus, the objective of this study was to determine if that association exists. METHODS: Prospective and observational study carried out in 8 Intensive Care Units from 6 hospitals of Canary Islands (Spain) including COVID-19 patients. We recorded RDW at ICU admission and 30-day survival. RESULTS: We found that patients who did not survive (n=25) compared to surviving patients (n=118) were older (p=0.004), showed higher RDW (p=0.001), urea (p<0.001), APACHE-II (p<0.001) and SOFA (p<0.001), and lower platelet count (p=0.007) and pH (p=0.008). Multiple binomial logistic regression analysis showed that RDW was associated with 30-day mortality after controlling for: SOFA and age (OR=1.659; 95% CI=1.130-2.434; p=0.01); APACHE-II and platelet count (OR=2.062; 95% CI=1.359-3.129; p=0.001); and pH and urea (OR=1.797; 95% CI=1.250-2.582; p=0.002). The area under the curve (AUC) of RDW for mortality prediction was of 71% (95% CI=63-78%; p<0.001). We did not find significant differences in the predictive capacity between RDW and SOFA (p=0.66) or between RDW and APACHE-II (p=0.12). CONCLUSIONS: Our study provides new information regarding the ability to predict mortality in patients with COVID-19. There is an association between high RDW and mortality. RDW has a good performance to predict 30-day mortality, similar to other severity scores (such as APACHE II and SOFA) but easier and faster to obtain.