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1.
Viruses ; 13(11)2021 11 16.
Article in English | MEDLINE | ID: covidwho-1524173

ABSTRACT

With the exception of inactivated vaccines, all SARS-CoV-2 vaccines currently used for clinical application focus on the spike envelope glycoprotein as a virus-specific antigen. Compared to other SARS-CoV-2 genes, mutations in the spike protein gene are more rapidly selected and spread within the population, which carries the risk of impairing the efficacy of spike-based vaccines. It is unclear to what extent the loss of neutralizing antibody epitopes can be compensated by cellular immune responses, and whether the use of other SARS-CoV-2 antigens might cause a more diverse immune response and better long-term protection, particularly in light of the continued evolution towards new SARS-CoV-2 variants. To address this question, we explored immunogenicity and protective effects of adenoviral vectors encoding either the full-length spike protein (S), the nucleocapsid protein (N), the receptor binding domain (RBD) or a hybrid construct of RBD and the membrane protein (M) in a highly susceptible COVID-19 hamster model. All adenoviral vaccines provided life-saving protection against SARS-CoV-2-infection. The most efficient protection was achieved after exposure to full-length spike. However, the nucleocapsid protein, which triggered a robust T-cell response but did not facilitate the formation of neutralizing antibodies, controlled early virus replication efficiently and prevented severe pneumonia. Although the full-length spike protein is an excellent target for vaccines, it does not appear to be the only option for future vaccine design.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , Immunity, Cellular , Immunity, Humoral , Immunogenicity, Vaccine , SARS-CoV-2/immunology , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Antigens, Viral/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/pathology , COVID-19/prevention & control , COVID-19/virology , Coronavirus Nucleocapsid Proteins/genetics , Coronavirus Nucleocapsid Proteins/immunology , Cricetinae , Female , Inflammation , Lung/pathology , Lung/virology , Male , Mice, Inbred C57BL , Phosphoproteins/genetics , Phosphoproteins/immunology , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Viral Matrix Proteins/genetics , Viral Matrix Proteins/immunology
2.
Respiration ; 100(7): 594-599, 2021.
Article in English | MEDLINE | ID: covidwho-1194385

ABSTRACT

BACKGROUND AND OBJECTIVES: The 6-minute walk test (6MWT), as a clinical assessment tool for functional exercise capacity, is an integral component of lung allocation scores (LASs). In times of the coronavirus disease (COVID-19) pandemic, patients underwent 6MWTs wearing a surgical mask in ambulatory care. We investigated the impact of wearing a mask on 6-minute walk distances (6MWDs). METHOD: 6MWDs of 64 patients with end-stage lung diseases wearing an oronasal surgical mask were retrospectively compared to previously investigated 6MWDs of the same cohort, in a pre-COVID-19 pandemic era, without wearing a mask. Four patients were excluded due to a primary vascular disease, 29 patients due to clinically unstable pulmonary functions, and 1 patient due to a psychiatric disorder. RESULTS: The median age of the patients included was 55 (46-58) years; 15 (48%) were male. Ten (32.2%) were on the Eurotransplant lung transplant waiting list with a median LAS of 34.3 (31.9-36.2). Twenty (64.5%) patients had chronic obstructive pulmonary diseases, 7 (22.6%) had interstitial lung diseases, and 4 (12.9%) had other end-stage lung diseases. The mean 6MWD without versus with wearing a mask was 306.9 (101.9) versus 305.7 (103.8) m, with a mean difference of -1.19 m (95% confidence interval -13.4 to 11.03). The observed difference is statistically equivalent to zero (p < 0.001). No significant differences in 6MWDs were observed between the clinical groups. CONCLUSION: Wearing an oronasal surgical mask did not affect the 6MWDs of patients with advanced lung diseases. Therefore, a masked 6MWT appears to provide a reliable examination of functional exercise capacity in this cohort.


Subject(s)
COVID-19/prevention & control , Lung Diseases, Interstitial/physiopathology , Masks , Pulmonary Disease, Chronic Obstructive/physiopathology , Respiratory Insufficiency/physiopathology , Walk Test/methods , Blood Gas Analysis , Chronic Disease , Exercise Tolerance , Female , Forced Expiratory Volume , Humans , Lung Diseases/physiopathology , Lung Diseases/surgery , Lung Diseases, Interstitial/surgery , Lung Transplantation , Male , Middle Aged , Minimal Clinically Important Difference , Plethysmography, Whole Body , Pulmonary Disease, Chronic Obstructive/surgery , Reproducibility of Results , Respiratory Insufficiency/surgery , Retrospective Studies , SARS-CoV-2 , Vital Capacity
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