ABSTRACT
Little information is available for antibody levels against SARS-CoV-2 variants of concern induced by Omicron breakthrough infection and a third booster with an inactivated vaccine (InV) or Ad5-nCoV in people with completion of two InV doses. Plasma was collected from InV pre-vaccinated Omicron-infected patients (OIPs), unvaccinated OIPs between 0 and 22 days, and healthy donors (HDs) 14 days or 6 months after the second doses of an InV and 14 days after a homogenous booster or heterologous booster of Ad5-nCoV. Anti-Wuhan-, Anti-Delta-, and Anti-Omicron-receptor binding domain (RBD)-IgG titers were detected using enzyme-linked immunosorbent assay. InV pre-vaccinated OIPs had higher anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers compared to unvaccinated OIPs. Anti-Wuhan-RBD-IgG titers sharply increased in InV pre-vaccinated OIPs 0-5 days postinfection (DPI), while the geometric mean titers (GMTs) of anti-Delta- and anti-Omicron-RBD-IgG were 3.3-fold and 12.0-fold lower. Then, the GMT of anti-Delta- and anti-Omicron-RBD-IgG increased to 35 112 and 28 186 during 11-22 DPI, about 2.6-fold and 3.2-fold lower, respectively, than the anti-Wuhan-RBD-IgG titer. The anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers declined over time in HDs after two doses of an InV, with 25.2-fold, 5.6-fold, and 4.5-fold declination, respectively, at 6 months relative to the titers at 14 days after the second vaccination. Anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers elicited by a heterologous Ad5-nCoV booster were significantly higher than those elicited by an InV booster, comparable to those in InV pre-vaccinated OIPs. InV and Ad5-nCoV boosters could improve humoral immunity against Omicron variants. Of these, the Ad5-nCoV booster is a better alternative.
ABSTRACT
Homologous booster, heterologous booster, and Omicron variants breakthrough infection (OBI) could improve the humoral immunity against Omicron variants. Questions concerning about memory B cells (MBCs) and T cells immunity against Omicron variants, features of long-term immunity, after booster and OBI, needs to be explored. Here, comparative analysis demonstrate antibody and T cell immunity against ancestral strain, Delta and Omicron variants in Omicron breakthrough infected patients (OBIPs) are comparable to that in Ad5-nCoV boosted healthy volunteers (HVs), higher than that in inactivated vaccine (InV) boosted HVs. However, memory B cells (MBCs) immunity against Omicron variants was highest in OBIPs, followed by Ad5-nCoV boosted and InV boosted HVs. OBIPs and Ad5-nCoV boosted HVs have higher classical MBCs and activated MBCs, and lower naïve MBCs and atypical MBCs relative to both vaccine boosted HVs. Collectively, these data indicate Omicron breakthrough infection elicit higher MBCs and T cells against SARS-CoV-2 especially Omicron variants relative to homologous InV booster and heterologous Ad5-nCoV booster.
Subject(s)
Breakthrough Infections , COVID-19 , Humans , SARS-CoV-2 , Antibodies , Antibodies, Viral , Antibodies, NeutralizingABSTRACT
Condition:
CoVID-19Intervention:
Experimental group:Basic treatment + kolimycin;Control group:Basic treatment;Primary outcome:
Virus negative time;Medication 3, 5, 7, 9, 11, 13, 15 days mouthwash (pharyngeal swab) 2019-nCOVRNA negative rate (%);Criteria:
Inclusion criteria: 1. The subject or legal agent has signed the informed consent form; agreed to not participate in other clinical researchers within 30 days from the first administration of the study drug to the last administration.2. Aged 18 to 75 years old;
3. Meet the diagnostic criteria for pneumonia caused by new coronavirus (2019-nCoV) (seventh edition)
4. Treated patients or relapsed patients meet any of the following:
(1) Fever again, or the clinical symptoms worsened;
(2) The throat swab 2019nCOVRNA was positive;
(3) No clinical symptoms improved or 2019nCOVRNA continued positive;
(4) Chest CT showed lung inflammation or fibrosis progress.
Exclusion criteria: 1. Other viral pneumonia;
2. Patients who received tumor immunotherapy (such as PD-1 / L1, CTLA4, etc.) and inflammatory factor regulators such as ulinastatin in the past 1 month;
3. Patients who have used macrolides and other antibacterial drugs in the past week;
4. Patients who have undergone organ transplantation or surgery planning within the past 6 months;
5. Patients with coma and intestinal obstruction cannot eat or take medicine;
6. Serious basic diseases that affect survival, including: uncontrolled malignant tumors that have been metastasized and unresectable, blood diseases, cachexia, active bleeding, severe malnutrition, HIV, etc.
7. Pregnant women and lactating women, subjects (including male subjects) have pregnancy plans (including sperm donation and egg donation plans) or are unable to take effective contraceptive measures within the next 6 months;
8. Patients with allergies or allergies to macrolide drugs and lopinavir / ritonavir tablets;
9. Patients who have contraindications to the use of lopinavir / ritonavir tablets, plan or are using drugs that interact with the drug (including: highly dependent on CYP3A clearance and elevated plasma concentrations will be accompanied by serious and / or endangered Life events [narrow therapeutic index] drugs, CYP3A inducers [see instructions for details], and cannot be stopped or replaced with other drugs;
10. Alanine aminotransferase (ALT) / alanine aminotransferase (AST) rises more than 5 times the upper limit of normal, total bilirubin exceeds 3 times the upper limit of normal, or patients with child-Pugh C liver cirrhosis;
11. In vitro life support (ECMO, ECCO2R, RRT);
12. critically ill patients with an estimated survival time of less than 48 hours;
13. Those who participated in other clinical research within the past month;
14. According to the judgment of the investigator, it is considered unsuitable for the selected patients.