A comprehensive analysis of the mutational landscape of the newly emerging Omicron (B.1.1.529) variant and comparison of mutations with VOCs and VOIs.

The Omicron variant is spreading rapidly throughout several countries. Thus, we comprehensively analyzed Omicron's mutational landscape and compared mutations with VOC/VOI. We analyzed SNVs throughout the genome, and AA variants (NSP and SP) in VOC/VOI, including Omicron. We generated heat maps to illustrate the AA variants with high mutation prevalence (> 75% frequency) of Omicron, which demonstrated eight mutations with > 90% prevalence in ORF1a and 29 mutations with > 75% prevalence in S-glycoprotein. A scatter plot for Omicron and VOC/VOI's cluster evaluation was computed. We performed a risk analysis of the antibody-binding risk among four mutations (L452, F490, P681, D614) and observed three mutations (L452R, F490S, D614G) destabilized antibody interactions. Our comparative study evaluated the properties of 28 emerging mutations of the S-glycoprotein of Omicron, and the ΔΔG values. Our results showed K417N with minimum and Q954H with maximum ΔΔG value. Furthermore, six important RBD mutations (G339D, S371L, N440K, G446S, T478K, Q498R) were chosen for comprehensive analysis for stabilizing/destabilizing properties and molecular flexibility. The G339D, S371L, N440K, and T478K were noted as stable mutations with 0.019 kcal/mol, 0.127 kcal/mol, 0.064 kcal/mol, and 1.009 kcal/mol. While, G446S and Q498R mutations showed destabilizing results. Simultaneously, among six RBD mutations, G339D, G446S, and Q498R mutations increased the molecular flexibility of S-glycoprotein. This study depicts the comparative mutational pattern of Omicron and other VOC/VOI, which will help researchers to design and deploy novel vaccines and therapeutic antibodies to fight against VOC/VOI, including Omicron.

A mathematical model of protein subunits COVID-19 vaccines.

We consider a general mathematical model for protein subunit vaccine with a focus on the MF59-adjuvanted spike glycoprotein-clamp vaccine for SARS-CoV-2, and use the model to study immunological outcomes in the humoral and cell-mediated arms of the immune response from vaccination. The mathematical model is fit to vaccine clinical trial data. We elucidate the role of Interferon-γ and Interleukin-4 in stimulating the immune response of the host. Model results, and results from a sensitivity analysis, show that a balance between the TH1 and TH2 arms of the immune response is struck, with the TH1 response being dominant. The model predicts that two-doses of the vaccine at 28 days apart will result in approximately 85% humoral immunity loss relative to peak immunity approximately 6 months post dose 1.

Milk of Cow and Goat, Immunized by Recombinant Protein Vaccine ZF-UZ-VAC2001(Zifivax), Contains Neutralizing Antibodies Against SARS-CoV-2 and Remains Active After Standard Milk Pasteurization.

Here, we present the first experimental validation of the possibility for obtaining immune milk with neutralizing antibodies against SARS-CoV-2 from vaccinated cows and goat using approved recombinant protein human coronavirus vaccine, ZF-UZ-VAC2001, in the Republic of Uzbekistan. In the period of 2 weeks after first vaccination, we detected the neutralizing antibodies against coronavirus in the blood serum of vaccinated animals. The neutralizing activity, in its peak on the 21st day after receiving the third dose (77th day from first dose), was effective in neutralization test using a live SARS-CoV-2 in Vero E6 cells, even after 120-fold serum titration. In cows receiving three dose of human vaccine, the MAGLUMI® SARS-CoV-2 neutralizing antibody competitive chemiluminescence immunoassay revealed that colostrum of the first day after calving had a greater activity to neutralize the SARS-CoV-2 compared to colostrum of subsequent three days (4.080 µg/ml vs 2.106, 1.960 and 1.126 µg/ml). In comparison, the neutralizing activity for goat and cow milk was 1.486 µg/ml and 0.222 µg/ml, respectively. We observed a positive correlation of receptor-binding domain (RBD)-specific IgG antibodies between the serum of actively immunized cow and milk-feeding calf during the entire course of vaccination (r = 0.95, p = 0.05). We showed an optimal regime for immune milk pasteurization at 62.5°C for 30 min, which retained specific neutralizing activity to SARS-CoV-2, potentially useful for passive immunization against coronavirus infection threats as an additive approach to the vaccination. This strategy, as a supportive approach to the vaccination, could also be applicable for directly reducing the effect of COVID-19 infection in gastrointestinal tract, supporting mucosal immunity.

A Modified Regimen of 21-day Nab-Paclitaxel Plus Gemcitabine in Locally Advanced or Metastatic Pancreatic Cancer: A Retrospective Real-World Study.

BACKGROUND: It is 1 of the standard treatment options for metastasis pancreatic cancer to receive nab-paclitaxel (125 mg/m2) plus gemcitabine (1000 mg/m2) on days 1, 8 and 15 every 28 days. Some patients showed intolerance and inconvenience to this therapeutic regimen. Thus, we conducted this retrospective real-world study to determine the efficacy and tolerability of a modified 21-day nab-paclitaxel plus gemcitabine (nab-P/Gem) regimen for the first-line treatment of locally advanced or metastatic pancreatic cancer. METHODS: Patients with locally advanced and metastatic pancreatic cancer treated with nab-paclitaxel (125 mg/m2) plus gemcitabine (1000 mg/m2) on days 1 and 8 every 21-day at West China Hospital and Shang Jin Hospital of Sichuan University from Mar 2018 to Dec 2021 were reviewed retrospectively. Clinical characteristics of patients were collected. The progression-free survival, overall survival, objective response rate, disease control rate, and toxicity were evaluated. RESULTS: A total of 113 patients who received the modified regimen of 21-day nab-P/Gem chemotherapy were included. The median overall survival was 9.3 months and the median progression-free survival was 4.4 months. The objective response rate and disease control rate were 18.6% and 56.7%, respectively. The median relative dose intensity for this modified regimen was 65%. The adverse events were mild to moderate, and the most common grade 3 or 4 treatment-related adverse events were neutropenia (21%) and leukopenia (16%). CONCLUSIONS: Our study showed that this modified regimen of 21-day nab-P/Gem for locally advanced and metastatic pancreatic cancer had comparable efficacy and tolerable toxicity. This treatment may provide a considerable option for pancreatic cancer patients who desire a modified schedule. The modified regimen of 21-day nab-P/Gem is also an option worth considering during the coronavirus disease 2019 pandemic for minimizing the number of visits and limiting the risk of exposure.

Transient expression of antinuclear RNP-A antibodies in patients with acute COVID-19 infection.

Introduction: Viral infections have been implicated in the initiation of the autoimmune diseases. Recent reports suggest that a proportion of patients with COVID-19 develop severe disease with multiple organ injuries. We evaluated the relationship between COVID-19 severity, prevalence and persistence of antinuclear and other systemic and organ specific autoantibodies as well as SARS-CoV-2 infection specific anti-nucleocapsid (N) IgG antibodies and protective neutralizing antibody (Nab) levels. Methods: Samples from 119 COVID-19 patients categorized based on their level of care and 284 healthy subjects were tested for the presence and persistence of antinuclear and other systemic and organ specific autoantibodies as well as SARS-CoV-2 and neutralizing antibody levels. Results: The data shows significantly increased levels of anti RNP-A, anti-nucleocapsid and neutralizing antibody among patients receiving ICU care compared to non-ICU care. Furthermore, subjects receiving ICU care demonstrated significantly higher nucleocapsid IgG levels among the RNP-A positive cohort compared to RNP-A negative cohort. Notably, the expression of anti RNP-A antibodies is transient that reverts to non-reactive status between 20 and 60 days post symptom onset. Conclusions: COVID-19 patients in ICU care exhibit significantly higher levels of transient RNP-A autoantibodies, anti-nucleocapsid, and SARS-CoV-2 neutralizing antibodies compared to patients in non-ICU care.

Comparison of the Safety and Immunogenicity of FAKHRAVAC and BBIBP-CorV Vaccines when Administrated as Booster Dose: A Parallel Two Arms, Randomized, Double Blind Clinical Trial.

Purpose: This study was completed to assess the immunogenicity and safety of the FAKHRAVAC and BBIBP-CorV vaccines as a booster dose in the population with a history of receiving two doses of BBIBP-CorV vaccine. Methods: In this double-blind, parallel clinical trial, we randomly assigned healthy adults with a history of receiving two doses of the BBIBP-CorV vaccine, who then received either the FAKHRAVAC or BBIBP-CorV vaccine as a booster dose. The trial is registered in the Iranian Registry of Clinical Trial document depository (Code: IRCT20210206050259N4). Results: The outcomes that were monitored in this study were serum neutralizing antibody (Nab) activity, immunoglobulin G (IgG) level, local and systemic adverse reactions, serious adverse events, suspected unexpected serious adverse reactions, and medically attended adverse events. After administering vaccines to 435 participants, the most frequent local and systemic adverse reactions were tenderness and nausea in 23.7% and 1.4% of cases, respectively. All adverse events were mild, occurred at a similar incidence in the two groups, and were resolved within a few days. Conclusions: On the 14th day after the booster dose injection, the seroconversion rate (i.e., four-fold increase) of Nabs for seronegative participants were 87% and 84.6% in the FAKHRAVAC® and BBIBP-CorV groups, respectively. This study shows that the FAKHRAVAC® vaccine, as a booster dose, has a similar function to the BBIBP-CorV vaccine in terms of increasing the titer of virus-neutralizing antibodies, the amount of specific antibodies, and safety.

A mathematical model of the within-host kinetics of SARS-CoV-2 neutralizing antibodies following COVID-19 vaccination.

Compelling evidence continues to build to support the idea that SARS-CoV-2 Neutralizing Antibody (NAb) levels in an individual can serve as an important indicator of the strength of protective immunity against infection. It is not well understood why NAb levels in some individuals remain high over time, while in others levels decline rapidly. In this work, we present a two-state mathematical model of within-host NAb dynamics in response to vaccination. By fitting only four host-specific parameters, the model is able to capture individual-specific NAb levels over time as measured by the AditxtScore™ for NAbs. The model can serve as a foundation for predicting NAb levels in the long-term, understanding connections between NAb levels, protective immunity, and breakthrough infections, and potentially guiding decisions about whether and when a booster vaccination may be warranted.

Technology-assisted adaptive recruitment strategy for a large nation-wide COVID-19 vaccine immunogenicity study in Brunei.

A national study was conducted in Brunei to assess and compare the immunogenicity of the various brands of COVID-19 vaccines administered to the population as part of the National COVID-19 Vaccination Programme. Most of the population have had received at least 2 doses of BBIBP-CorV, AZD1222 or MRNA-1273 vaccines. Neutralising antibodies against SARS-CoV-2 induced by these vaccines will be analysed to infer population-level immune protection against COVID-19. During the 5-week recruitment period, 24,260 eligible individuals were invited to the study via SMS, out of which 2,712 participants were enrolled into the study. This paper describes the novel adaptive strategy used to recruit the study participants. Digital technology was leveraged to perform targeted online recruitment to circumvent the limitations of traditional recruitment methods. Technology also enabled stratified random selection of these eligible individuals who were stratified based on age, gender and vaccine brand. Data was extracted from the electronic health records, the national mobile health application and a third-party survey platform and integrated into a dedicated research platform called EVYDResearch. The instant availability and access to up-to-date data on EVYDResearch enabled the study team to meet weekly and adopt an adaptive recruitment strategy informed by behavioural science, where interventions could be quickly implemented to improve response rates. Some examples of these include incorporating nudge messaging into SMS invitations, involving the Minister of Health to make press announcements on this study, media coverage, setting up an enquiries hotline and reaching out to foreign language speaking expatriates of a local multinational company to participate in this study. Data integration from various data sources, real time information sharing and a strong teamwork led to good outcomes adaptable to the progress of recruitment, compared to the more time-consuming and static traditional recruitment methods.

Omicron (B.1.1.529) - A new heavily mutated variant: Mapped location and probable properties of its mutations with an emphasis on S-glycoprotein.

Omicron, another SARS-CoV-2 variant, has been recorded and reported as a VoC. It has already spread across >30 countries and is a highly mutated variant. We tried to understand the role of mutations in the investigated variants by comparison with previous characterized VoC. We have mapped the mutations in Omicron S-glycoprotein's secondary and tertiary structure landscape using bioinformatics tools and statistical software and developed different models. In addition, we analyzed the effect of diverse mutations in antibody binding regions of the S-glycoprotein on the binding affinity of the investigated antibodies. This study has chosen eight significant mutations in Omicron (D614G, E484A, N501Y, Q493K, K417N, S477N, Y505H G496S), and seven of them are located in the RBD region. We also performed a comparative analysis of the ΔΔG score of these mutations to understand the stabilizing or destabilizing properties of the investigated mutations. The analysis outcome shows that D614G, Q493K, and S477N mutations are stable mutations with ΔΔG scores of 0.351 kcal/mol, 0.470 kcal/mol, and 0.628 kcal/mol, respectively, according to DynaMut estimations. While other mutations (E484A, N501Y, K417N, Y505H, G496S) showed destabilizing results. The D614G, E484A, N501Y, K417N, Y505H, and G496S mutations increased the molecular flexibility of S-glycoprotein to interact with the ACE2 receptor, increasing the variant's infectivity. Our study will contribute to research on the SARS-CoV-2 variant, Omicron, by providing information on the mutational pattern and exciting properties of these eight significant mutations, such as antibody escape and infectivity quotient (stabilizing or destabilizing; increased or decreased molecular flexibility of S-glycoprotein to interact with the human ACE2 receptor).

Nab-paclitaxel plus S-1 versus oxaliplatin plus S-1 as first-line treatment in advanced gastric cancer: results of a multicenter, randomized, phase III trial (GAPSO study).

Background: This study aimed to investigate the superiority of nab-paclitaxel plus S-1 (AS) over oxaliplatin plus S-1 (SOX) in patients with advanced gastric cancer (AGC). Methods: In this multicenter, randomized, phase III superiority trial, eligible patients with unresectable, locally advanced gastric adenocarcinoma were recruited and randomly assigned (1:1) to receive AS (nab-paclitaxel 260 mg/m2 on day 1 or 130 mg/m2 on days 1 and 8; oral S-1 40-60 mg twice daily for 14 days) or SOX (130 mg/m2 oxaliplatin on day 1; oral S-1 40-60 mg twice daily for 14 days) every 3 weeks for up to six cycles. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival, objective response rate, and safety. Results: Owing to slow enrolment, an unplanned interim analysis was performed, resulting in the early termination of the study on 31 December 2021 (data cutoff). Between March 2019 and March 2021, 97 patients (AS, n = 48; SOX, n = 49) were treated and evaluated for efficacy and safety of AS and SOX. As of the data cutoff, the median follow-up was 23.13 months [95% confidence interval (CI), 13.39-32.87]. The median PFS was 9.03 months (95% CI, 6.50-11.56) in the AS group and 5.07 months (95% CI, 4.33-5.81) in the SOX group, demonstrating a better PFS tendency following AS treatment than SOX treatment (hazard ratio = 0.59; 95% CI, 0.37-0.94; p = 0.03). The most common grade 3 or worse adverse events were anemia, neutropenia, and leukopenia in both groups, with a higher incidence of thrombocytopenia in the SOX group. Conclusion: Although this study was terminated early, the results demonstrated a better PFS tendency in patients with AGC who were treated with AS than in those treated with SOX, with controllable toxicities. Trial registration: Clinical Trials.gov identifiers: NCT03801668. Registered January 11, 2019.

Kinetics of anti-SARS-CoV-2 responses post complete vaccination with coronavac: A prospective study in 50 health workers.

Background: COVID-19 pandemic causes severe acute respiratory syndrome and requires rapid action. The development of effective safe vaccines become a global priority for achieving herd immunity. Vaccination is expected to form specific antibodies against the SARS-CoV-2 spike protein which can neutralize the virus, preventing the virus from binding with ACE 2 receptors. Objective: Evaluating and to know if there any differences of kinetics antibody levels from recipient's anti-IgG S-RBD and NAb with complete second dose CoronaVac Vaccine, to determine the antibody response in preventing SARS-CoV-2. Method: A prospective-cohort study using observational analytics was conducted from January-April 2021 at Dr. Soetomo Hospital, Surabaya. A total of 50 subjects are healthcare workers who received two doses of CoronaVac. The IgG S-RBD and NAb levels were measured on Maglumi 800 device (SNIBE, China). Differences in IgG S-RBD and NAb levels before vaccination and after second dose CoronaVac vaccination on 14th day, on 28th day, ware tested using Friedman and Wilcoxon tests. Result: Mean values of IgG S-RBD and NAb have fluctuated. There was a significant difference between IgG S-RBD and NAb levels on day-0 (0.090 vs 18.630; p < 0.001) and day-28 (141.266 vs 116.640; p = 0.037). The median value showed the IgG S-RBD level on day-28 was much better than NAb value (141,266 v 116,640). Conclusion: CoronaVac will form persistent antibodies. Despite antibody development, the acquired humoral immunity decreased at 28 days after full CoronaVac immunization. Kinetics of antibody NAb decreased more rapidly than IgG S-RBD.

Structural Study of SARS-CoV-2 Antibodies Identifies a Broad-Spectrum Antibody That Neutralizes the Omicron Variant by Disassembling the Spike Trimer.

The continuous emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses new challenges in the fight against the coronavirus disease 2019 (COVID-19) pandemic. The newly emerging Omicron strain caused serious immune escape and raised unprecedented concern all over the world. The development of an antibody targeting a conserved and universal epitope is urgently needed. A subset of neutralizing antibodies (NAbs) against COVID-19 from convalescent patients were isolated in our previous study. In this study, we investigated the accommodation of these NAbs to SARS-CoV-2 variants of concern (VOCs), revealing that IgG 553-49 neutralizes pseudovirus of the SARS-CoV-2 Omicron variant. In addition, we determined the cryo-electron microscopy (cryo-EM) structure of the SARS-CoV-2 spike (S) protein complexed with three monoclonal antibodies targeting different epitopes, including 553-49, 553-15, and 553-60. Notably, 553-49 targets a novel conserved epitope and neutralizes the virus by disassembling S trimers. IgG 553-15, an antibody that neutralizes all of the VOCs except Omicron, cross-links two S trimers to form a trimer dimer, demonstrating that 553-15 neutralizes the virus by steric hindrance and virion aggregation. These findings suggest the potential to develop 553-49 and other antibodies targeting this highly conserved epitope as promising therapeutic reagents for COVID-19. IMPORTANCE The emergence of the Omicron strain of SARS-CoV-2 caused higher immune escape, raising unprecedented concerns about the effectiveness of antibody therapies and vaccines. In this study, we identified a SARS-CoV-2 neutralizing antibody, 553-49, which neutralizes all variants by targeting a completely conserved novel epitope. In addition, we revealed that IgG 553-15 neutralizes SARS-CoV-2 by cross-linking virions and that 553-60 functions by blocking receptor binding. Comparison of different receptor binding domain (RBD) epitopes revealed that the 553-49 epitope is hidden in the S trimer and keeps a high degree of conservation during SARS-CoV-2 evolution, making 553-49 a promising therapeutic reagent against the emerging Omicron and future variants of SARS-CoV-2.

Nanoparticle Albumin-Bound-Paclitaxel Instead of Standard Paclitaxel in Adjuvant Chemotherapy Regimen for Breast Cancer Under COVID-19 Pandemic-A Single Center Feasibility Study in China

The management of breast cancer patients in the current COVID-19 outbreak is challenging. Myelosuppres-sion associated with cancer treatment may increase the risk of infection in both hospitals and at home. We implemented the following strategy to reduce myelosuppression of adjuvant chemotherapy during the COVID-19 pandemic: (1) changing the original regimen of AC x 4-* wT x 12 to wT x 12-* AC x 4. (2) substitution of standard paclitaxel with nanoparticle albumin-bound (nab)-paclitaxel (nab-paclitaxel). For 43 patients who com-IP: 14.98.160.66 On: Fri, 13 May 2022 09:27:55 pleted nab-paclitaxel treatment, the compliance rate was 100%, without interruption or delay of nab-paclitaxel Copyright: American Scientific Publishers Delivered by Ingenta treatment. Dose reduction was necessary in 2 patients (4.6%) due to peripheral neuropathy. Thus, 98.6% of the planned doses were administered. As expected, the adjusted adjuvant regimen was safe and well toler-ated. Therefore wT x 12-* AC x 4 treatment procedure may be considered for breast cancer patients during COVID-19 pandemic.

Decreased and Heterogeneous Neutralizing Antibody Responses Against RBD of SARS-CoV-2 Variants After mRNA Vaccination.

The rapid spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) emerging variants raises concerns about their capacity to evade immune protection provided by natural infection or vaccination. The receptor-binding domain (RBD) of the viral spike protein is the major target of neutralizing antibodies, and viral variants accumulate mutations in this region. In this study, we determined the antibody neutralization capacity against the RBD of SARS-CoV-2 variants Alpha (B.1.1.7), Gamma (P.1), Epsilon (B.1.427), Kappa (B.1.617.1), and Delta (B.1.617.2) in a cohort of healthcare workers naturally infected or receiving COVID-19 mRNA vaccines from Moderna or Pfizer-BioNTech. We show that the five RBD variants displayed an augmented binding to ACE2 compared to the original Wuhan strain. The most significant increase was observed in variants Epsilon and Delta, containing mutation L452R. Using a flow cytometry cell-based assay, we found that SARS-CoV-2-infected subjects presented low levels of RBD-specific neutralizing antibodies against all variants analyzed, except Alpha. However, the neutralizing activity incremented considerably after a subsequent mRNA-vaccine dose, to levels significantly higher than those in naïve individuals receiving two vaccine doses. Importantly, we observed partially impaired neutralizing responses against most variants in fully vaccinated individuals. Variants Gamma and Kappa encompassing RBD E484K/Q mutations presented the highest neutralizing resistance. Furthermore, a wide heterogeneity in the magnitude of RBD-specific neutralizing responses against all tested SARS-CoV-2 variants following both mRNA vaccines was detected. Altogether, our findings provide important knowledge regarding SARS-CoV-2 vaccine-induced immunity, and should be very useful to guide future vaccination regimens and personalized vaccine approaches.

Patient and Clinical Factors at Admission Affect the Levels of Neutralizing Antibodies Six Months after Recovering from COVID-19.

The rate of decline in the levels of neutralizing antibodies (NAbs) greatly varies among patients who recover from Coronavirus disease 2019 (COVID-19). However, little is known about factors associated with this phenomenon. The objective of this study is to investigate early factors at admission that can influence long-term NAb levels in patients who recovered from COVID-19. A total of 306 individuals who recovered from COVID-19 at the Tongji Hospital, Wuhan, China, were included in this study. The patients were classified into two groups with high (NAbhigh, n = 153) and low (NAblow, n = 153) levels of NAb, respectively based on the median NAb levels six months after discharge. The majority (300/306, 98.0%) of the COVID-19 convalescents had detected NAbs. The median NAb concentration was 63.1 (34.7, 108.9) AU/mL. Compared with the NAblow group, a larger proportion of the NAbhigh group received corticosteroids (38.8% vs. 22.4%, p = 0.002) and IVIG therapy (26.5% vs. 16.3%, p = 0.033), and presented with diabetes comorbidity (25.2% vs. 12.2%, p = 0.004); high blood urea (median (IQR): 4.8 (3.7, 6.1) vs. 3.9 (3.5, 5.4) mmol/L; p = 0.017); CRP (31.6 (4.0, 93.7) vs. 16.3 (2.7, 51.4) mg/L; p = 0.027); PCT (0.08 (0.05, 0.17) vs. 0.05 (0.03, 0.09) ng/mL; p = 0.001); SF (838.5 (378.2, 1533.4) vs. 478.5 (222.0, 1133.4) µg/L; p = 0.035); and fibrinogen (5.1 (3.8, 6.4) vs. 4.5 (3.5, 5.7) g/L; p = 0.014) levels, but low SpO2 levels (96.0 (92.0, 98.0) vs. 97.0 (94.0, 98.0)%; p = 0.009). The predictive model based on Gaussian mixture models, displayed an average accuracy of 0.7117 in one of the 8191 formulas, and ROC analysis showed an AUC value of 0.715 (0.657-0.772), and specificity and sensitivity were 72.5% and 67.3%, respectively. In conclusion, we found that several factors at admission can contribute to the high level of NAbs in patients after discharge, and constructed a predictive model for long-term NAb levels, which can provide guidance for clinical treatment and monitoring.

Analysis of Host Immunological Response of Adenovirus-Based COVID-19 Vaccines.

During the SARS-CoV-2 global pandemic, several vaccines, including mRNA and adenovirus vector approaches, have received emergency or full approval. However, supply chain logistics have hampered global vaccine delivery, which is impacting mass vaccination strategies. Recent studies have identified different strategies for vaccine dose administration so that supply constraints issues are diminished. These include increasing the time between consecutive doses in a two-dose vaccine regimen and reducing the dosage of the second dose. We consider both of these strategies in a mathematical modeling study of a non-replicating viral vector adenovirus vaccine in this work. We investigate the impact of different prime-boost strategies by quantifying their effects on immunological outcomes based on simple system of ordinary differential equations. The boost dose is administered either at a standard dose (SD) of 1000 or at a low dose (LD) of 500 or 250 vaccine particles. Results show dose-dependent immune response activity. Our model predictions show that by stretching the prime-boost interval to 18 or 20, in an SD/SD or SD/LD regimen, the minimum promoted antibody (Nab) response will be comparable with the neutralizing antibody level measured in COVID-19 recovered patients. Results also show that the minimum stimulated antibody in SD/SD regimen is identical with the high level observed in clinical trial data. We conclude that an SD/LD regimen may provide protective capacity, which will allow for conservation of vaccine doses.

Recovery scenario and immunity in COVID-19 disease: A new strategy to predict the potential of reinfection.

Background: The recent ongoing outbreak of coronavirus disease 2019 (COVID-19), still is an unsolved problem with a growing rate of infected cases and mortality worldwide. The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is targeting the angiotensin-converting enzyme 2 (ACE2) receptor and mostly causes a respiratory illness. Although acquired and resistance immunity is one of the most important aspects of alleviating the trend of the current pandemic; however, there is still a big gap of knowledge regarding the infection process, immunopathogenesis, recovery, and reinfection. Aim of Review: To answer the questions regarding "the potential and probability of reinfection in COVID-19 infected cases" or "the efficiency and duration of SARS-CoV-2 infection-induced immunity against reinfection" we critically evaluated the current reports on SARS-CoV-2 immunity and reinfection with special emphasis on comparative studies using animal models that generalize their finding about protection and reinfection. Also, the contribution of humoral immunity in the process of COVID-19 recovery and the role of ACE2 in virus infectivity and pathogenesis has been discussed. Furthermore, innate and cellular immunity and inflammatory responses in the disease and recovery conditions are reviewed and an overall outline of immunologic aspects of COVID-19 progression and recovery in three different stages are presented. Finally, we categorized the infected cases into four different groups based on the acquired immunity and the potential for reinfection. Key Scientific Concepts of Review: In this review paper, we proposed a new strategy to predict the potential of reinfection in each identified category. This classification may help to distribute resources more meticulously to determine: who needs to be serologically tested for SARS-CoV-2 neutralizing antibodies, what percentage of the population is immune to the virus, and who needs to be vaccinated.

An update on COVID-19 infection control measures, plasma-based therapeutics, corticosteroid pharmacotherapy and vaccine research.

This communication provides a compilation on aspects of COVID-19 infection control measures, describes the potential role of therapeutic plasma exchange to reduce fatality rates, addresses precautions concerning dexamethasone pharmacotherapy and updates the current status on the availability of vaccines. As part of passive immunotherapy, it focuses on various blood derivatives. These include coronavirus neutralising antibodies extracted from different sources to be administered as a pure hyper concentrate intramuscularly or for upgrading and standardising the specific potency of high affinity antibodies. These processes are intended to compose standardised pooled bioproducts of corona convalescent plasma/cryosupernatant that are pathogen inactivated for additional safety by well-established UV technologies. For the best practice of optimising plasma exchange, hyper concentrate NAb should be added to the cryosupernatant, which contains some of the active principles of corona convalescent plasma. The cryosupernatant apart from the high molecular weight viscous part of cold insoluble proteins that are removed, is equivalent to CCP, but makes it safer for general application. Such a bioproduct is often used routinely for substitution therapy of thrombotic thrombocytopaenic purpura. Alternative resources of large-scale specific coronavirus antibodies warrant further exploration such as cadaveric donations. The early uses of therapeutic plasma exchange and low molecular weight heparin, for any clinical trial in development is warranted, in order to interdict the intense inflammatory/kinin driven cascade. Because coronavirus positive patients are highly prone to thrombosis, thromboprophylaxis is necessary, even some time after recovery guided by the laboratory data.