A Robust Optimization Problem for Drone-based Equitable Pandemic Vaccine Distribution with Uncertain Supply☆

Widespread vaccination is the only way to overcome the COVID-19 global crisis. However, given the vaccine scarcity during the early outbreak of the pandemic, ensuring efficient and equitable distribution of vaccines, particularly in rural areas, has become a significant challenge. To this end, this study develops a two-stage robust vaccine distribution model that addresses the supply uncertainty incurred by vaccine shortages. The model aims to optimize the social and economic benefits by jointly deciding vaccination facility location, transportation capacity, and reservation plan in the first stage, and rescheduling vaccinations in the second stage after the confirmation of uncertainty. To hedge vaccine storage and transportation difficulties in remote areas, we consider using drones to deliver vaccines in appropriate and small quantities to vaccination points. Two tailored column-and-constraint generation algorithms are proposed to exactly solve the robust model, in which the subproblems are solved via the vertex traversal and the dual methods, respectively. The superiority of the dual method is further verified. Finally, we use real-world data to demonstrate the necessity to account for uncertain supply and equitable distribution, and analyze the impacts of several key parameters. Some managerial insights are also produced for decision-makers.

A robust optimization problem for drone-based equitable pandemic vaccine distribution with uncertain supply.

Widespread vaccination is the only way to overcome the COVID-19 global crisis. However, given the vaccine scarcity during the early outbreak of the pandemic, ensuring efficient and equitable distribution of vaccines, particularly in rural areas, has become a significant challenge. To this end, this study develops a two-stage robust vaccine distribution model that addresses the supply uncertainty incurred by vaccine shortages. The model aims to optimize the social and economic benefits by jointly deciding vaccination facility location, transportation capacity, and reservation plan in the first stage, and rescheduling vaccinations in the second stage after the confirmation of uncertainty. To hedge vaccine storage and transportation difficulties in remote areas, we consider using drones to deliver vaccines in appropriate and small quantities to vaccination points. Two tailored column-and-constraint generation algorithms are proposed to exactly solve the robust model, in which the subproblems are solved via the vertex traversal and the dual methods, respectively. The superiority of the dual method is further verified. Finally, we use real-world data to demonstrate the necessity to account for uncertain supply and equitable distribution, and analyze the impacts of several key parameters. Some managerial insights are also produced for decision-makers.

Protective antigenic epitopes revealed by immunosignatures after three doses of inactivated SARS-CoV-2 vaccine.

Background: SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has infected millions of people around the world. Vaccination is a pillar in the strategy to control transmission of the SARS-CoV-2 spread. Immune responses to vaccination require elucidation. Methods: The immune responses to vaccination with three doses of inactivated SARS-CoV-2 vaccine were followed in a cohort of 37 healthy adults (18-59 years old). Blood samples were collected at multiple time points and submitted to peptide array, machine learning modeling, and sequence alignment analyses, the results of which were used to generate vaccine-induced antibody-binding region (VIABR) immunosignatures (Registration number: ChiCTR2200058571). Results: Antibody spectrum signals showed vaccination stimulated antibody production. Sequence alignment analyses revealed that a third vaccine dose generated a new highly represented VIABR near the A570D mutation, and the whole process of inoculation enhanced the VIABR near the N501Y mutation. In addition, the antigen conformational epitopes varied between short- and long-term samples. The amino acids with the highest scores in the short-term samples were distributed primarily in the receptor binding domain (RBD) and N-terminal domain regions of spike (S) protein, while in the long-term samples (12 weeks after the 2nd dose), some new conformational epitopes (CEs) were localized to crevices within the head of the S protein trimer. Conclusion: Protective antigenic epitopes were revealed by immunosignatures after three doses of inactivated SARS-CoV-2 vaccine inoculation. A third dose results in a new top-10 VIABR near the A570D mutation site of S protein, and the whole process of inoculation enhanced the VIABR near the N501Y mutation, thus potentially providing protection from strains that have gained invasion and immune escape abilities through these mutation.

Performance comparison of two nucleic acid amplification systems for SARS-CoV-2 detection: A multi-center study.

BACKGROUND: Many rapid nucleic acid testing systems have emerged to halt the development and spread of COVID-19. However, so far relatively few studies have compared the diagnostic performance between these testing systems and conventional detection systems. Here, we performed a retrospective analysis to evaluate the clinical detection performance between SARS-CoV-2 rapid and conventional nucleic acid detection system. METHODS: Clinical detection results of 63,352 oropharyngeal swabs by both systems were finally enrolled in this analysis. Sensitivity (SE), specificity (SP), and positive and negative predictive value (PPV, NPV) of both systems were calculated to evaluate their diagnostic accuracy. Concordance between these two systems were assessed by overall, positive, negative percent agreement (OPA, PPA, NPA) and κ value. Sensitivity of SARS-CoV-2 rapid nucleic acid detection system (Daan Gene) was further analyzed with respect to the viral load of clinical specimens. RESULTS: Sensitivity of Daan Gene was slightly lower than that of conventional detection system (0.86 vs. 0.979), but their specificity was equivalent. Daan Gene had ≥98.0% PPV and NPV for SARS-CoV-2. Moreover, Daan Gene demonstrated an excellent test agreement with conventional detection system (κ = 0.893, p = 0.000). Daan Gene was 99.31% sensitivity for specimens with high viral load (Ct < 35) and 50% for low viral load (Ct ≥ 35). CONCLUSIONS: While showing an analytical sensitivity slightly below than that of conventional detection system, rapid nucleic acid detection system may be a diagnostic alternative to rapidly identify SARS-CoV-2-infected individuals with high viral loads and a powerful complement to current detection methods.

Protective antigenic epitopes revealed by immunosignatures after three doses of inactivated SARS-CoV-2 vaccine

Background SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has infected millions of people around the world. Vaccination is a pillar in the strategy to control transmission of the SARS-CoV-2 spread. Immune responses to vaccination require elucidation. Methods The immune responses to vaccination with three doses of inactivated SARS-CoV-2 vaccine were followed in a cohort of 37 healthy adults (18–59 years old). Blood samples were collected at multiple time points and submitted to peptide array, machine learning modeling, and sequence alignment analyses, the results of which were used to generate vaccine-induced antibody-binding region (VIABR) immunosignatures (Registration number: ChiCTR2200058571). Results Antibody spectrum signals showed vaccination stimulated antibody production. Sequence alignment analyses revealed that a third vaccine dose generated a new highly represented VIABR near the A570D mutation, and the whole process of inoculation enhanced the VIABR near the N501Y mutation. In addition, the antigen conformational epitopes varied between short- and long-term samples. The amino acids with the highest scores in the short-term samples were distributed primarily in the receptor binding domain (RBD) and N-terminal domain regions of spike (S) protein, while in the long-term samples (12 weeks after the 2nd dose), some new conformational epitopes (CEs) were localized to crevices within the head of the S protein trimer. Conclusion Protective antigenic epitopes were revealed by immunosignatures after three doses of inactivated SARS-CoV-2 vaccine inoculation. A third dose results in a new top-10 VIABR near the A570D mutation site of S protein, and the whole process of inoculation enhanced the VIABR near the N501Y mutation, thus potentially providing protection from strains that have gained invasion and immune escape abilities through these mutation.

Performance evaluation of an automatic chemiluminescence immune platform for SARS-CoV-2 neutralizing antibody after vaccination in real world.

OBJECTIVE: Reliable high-throughput serological assays for SARS-CoV-2 antibodies present an important role in the strength and duration of immunity after vaccination. The study investigated the analytical and clinical performances of neutralizing antibodies (NTAb) assay by chemiluminescent (CLIA), and SARS-CoV-2 neutralizing antibody after vaccination in real world. METHODS: The analytical performances of CLIA for SARS-CoV-2 NTAb were evaluated, followed by the sensitivity and specificity identified with a PRNT test from 50 volunteers. Then, a cohort of vaccine recipients (n = 37) were tracked with SARS-CoV-2 NTAb assay at prior to vaccination, one, three and six months post two doses. In real world, a total of 737 cases were recruited from physical examination center in Shenzhen Luohu People's Hospital (from Jun to August 2021) to analyze vaccination status. RESULTS: Serological assays on the CLIA were found with excellent characteristics including imprecision, repeatability and linearity. Besides, it was robust to icterus, lipemia and hemolysis. The good sensitivity and specificity were obtained at 98% and 100%, respectively. NTAb results showed a high correlation with PRNT50 titers (r 0.61). Until July 2021, the BBIBP-CorV (76.3%) and Sinovac CoronaVac (20.5%) were the predominant vaccines injection in Shenzhen, China. Adolescent less than 18 years was the main unvaccinated group (52.1%). The seropositive rate of inactive SRAR-CoV-2 vaccines exceeded 97% after inoculation. The NTAb generated by Sinovac CoronaVac with the schedule of 0-56 days was found significantly lower than that by BBIBP-CorV (P < 0.001). The follow-up of NTAb changes in a cohort and the dynamic variation of NTAb in real world disclosed steep downward by almost three times for NTAb level occurred at three months post twice vaccinations. The seropositive ratio was at least 50% over 6 months. CONCLUSIONS: SARS-CoV-2 neutralizing antibodies assay show excellent analytical and clinical performances, and a high correlation with neutralizing activity. Anti-epidemic measures and the urgent trial of SARS-CoV-2 vaccine was calling for adolescents.

Dynamic observation of SARS-CoV-2 IgM, IgG, and neutralizing antibodies in the development of population immunity through COVID-19 vaccination.

BACKGROUND: Currently, mass vaccine inoculation against coronavirus disease-2019 (COVID-19) has been being implemented globally. Rapid and the large-scale detection of serum neutralizing antibodies (NAbs) laid a foundation for assessing the immune response against SARS-CoV-2 infection and vaccine. Additional assessments include the duration of antibodies and the optimal time for a heightened immune response. METHODS: The performance of five surrogate NAbs-three chemiluminescent immunoassay (CLIA) and two enzyme-linked immunosorbent assays (ELISAs)-and specific IgM and IgG assays were compared using COVID-19-vaccinated serum (n = 164). Conventional virus neutralization test (cVNT) was used as a criterion and the diagnostic agreement and correlation of the five assays were evaluated. We studied the antibody responses after the two-dose vaccine in volunteers up to 6 months. RESULTS: The sensitivity and specificity of five surrogate NAb assays ranged from 84% to 100%. Our cVNT results indicated great consistency with the surrogate assays. At 28 days after primary vaccination, the seropositivities of the NAbs, IgG, and IgM were 6%, 4%, and 13%, respectively. After the booster dose, seropositivities reached 14%, 65%, and 97%, respectively. Six months after receipt of the second dose, the NAb positive rate was eventually maintained at 66%. In all COVID-19 convalescents, patients were detected with 100% NAb sat three months after discharge. CONCLUSION: COVID-19 vaccine induced a humoral immune response lasting at least six months. Rapid serological detection was used as a proxy for identifying changes in immunity levels and as a guide to whether an individual may require a booster vaccination.

Three cases of asymptomatic SARS-CoV-2 infections diagnosed by combination of nucleic acid and specific igm/IgG antibodies

Objective: Clinical value of SARS-CoV-2 nucleic acid detection combined with specific IgM/IgG in the diagnosis of three asymptomatic COVID-19 infections was investigated.

Evaluation of clinical application of three chemiluminescence detection kits for detection of novel coronavirus (SARS-CoV-2) antibody

Objective: To evaluate the performance of three kinds of chemiluminescence immunoassay (CLIA) kits for novel Coronavirus (SARS-COV-2) antibody, and study the clinical application of SARS-CoV-2 immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies detection.

Comparison of three automatic chemiluminescent immunoassays for monitoring dynamic profile of SARS-CoV-2 IgG and IgM.

BACKGROUND: Seldom performance evaluation and diagnosis comparison studies were reported for different chemiluminescent immunoassay (CLIA) kits approved under an emergency approval program for SARS-CoV-2 infection. METHODS: A total of 100 and 105 serum separately from non-infected populations and COVID-19 patients were detected with SARS-CoV-2 IgM and IgG kits. The characteristics including precision, functional sensitivity, linearity, and accuracy were evaluated for Axceed, iFlash, and Maglumi CLIA kits. RESULTS: Maglumi and iFlash had the best analytical sensitivity for IgM and IgG, respectively. Axceed kits had a linearity response in the detected concentration. The clinical sensitivity of Axceed, iFlash, and Maglumi was 68.0%, 64.9%, and 63.9% with a specificity of 99.0%, 96.0%, and 100% for IgM, 85.6%, 97.9%, and 94.8% with a specificity of 97.0% for IgG. ROC analysis indicated all kits had a diagnostic power greater than 0.9. Notably, either IgM or IgG kits obtained a poor agreement (Kappa value from 0.397 to 0.713) with others. Among 38 recovered patients, 94.7% had an effective immune response, and both seropositive IgM and IgG accounted for the biggest proportion (medium, 42 days onset), then followed by the single seropositive IgG (medium, 50 days onset) in Ab profile. CONCLUSION: The performance of CLIA kits satisfied the diagnosis of SARS-CoV-2 infection. Both positive of IgG and IgM contributes to improve the specificity, and a positive one will enhance the sensitivity.