Breakthrough Cases Research Articles

Two-decade battle with myasthenia gravis: A breakthrough case report on the long-term success with eculizumab and ravulizumab treatment.

This unique case of generalized myasthenia gravis shows sustained stability of a patient's condition for 3 years with eculizumab/ravulizumab treatment following 16 years of refractory disease. It highlights the long-term effectiveness of C5 inhibitors in a real-world setting, aiding physicians in their decision-making for refractory cases and treatment discontinuation scenarios.

Neutralizing Antibody-Mediated Protection from Prior Delta Variant Infection Against Omicron BA.5 Sub-Lineage Reinfection One Year Later: A Prospective Cohort Study

Background: Previous SARS-CoV-2 infection provides some level of protection against reinfection. However, few studies have evaluated the neutralizing antibody (NAb) response after Delta variant infection and its ability to prevent reinfection with Omicron BA.5 one year later. Methods: This prospective cohort study included 431 patients who recovered from Delta variant infection. We measured their serum NAb titers against both Delta and Omicron BA.5 using microneutralization tests. Results: Over a 17-month follow-up, 17.9% of the participants were reinfected with Omicron BA.5. Younger adults (18–65 years) and individuals who did not receive booster immunization had significantly higher reinfection rates than older adults (>65 years) and those who received boosters (p < 0.05). Notably, reinfection rates were higher in post-vaccination breakthrough cases than in individuals who were naturally infected. However, booster immunization reduced reinfection rates within the breakthrough group. We found no significant association between Delta NAb levels and protection against Omicron BA.5 reinfection (p > 0.05). Cross-neutralization assays showed a 7.1-fold reduction in NAb efficacy against Omicron BA.5. Conclusions: Delta-variant infection-induced NAbs did not strongly predict protection against Omicron BA.5 reinfection. However, booster immunization effectively reduced the reinfection rate approximately one year after the initial Delta infection.

A Global Network Analysis of COVID-19 Vaccine Distribution to Predict Breakthrough Cases among the Vaccinated Population

A Global Network Analysis of COVID-19 Vaccine Distribution to Predict Breakthrough Cases among the Vaccinated Population

Meningococcal Carriage in Children with Atypical Hemolytic Uremic Syndrome Receiving Eculizumab Therapy.

Eculizumab is a first-line treatment for atypical hemolytic uremic syndrome (aHUS), and patients undergoing eculizumab therapy may become more susceptible to infection caused by Neisseria meningitidis (Nm). While meningococcal vaccination is required for patients undergoing eculizumab therapy, there is limited knowledge about meningococcal carriage in children with aHUS. We aimed to evaluate (1) the prevalence of Nm carriage, (2) serogroup distribution, and (3) the immunization status of children undergoing eculizumab treatment for aHUS. The Meningo-aHUS study is a prospective, multi-center study evaluating meningococcal carriage in children and adolescents in Türkiye receiving eculizumab for aHUS. We noted the age, gender, daycare, school, or university attendance, passive smoking status, previous infection and antibiotic use, and previous immunization history, including meningococcal vaccines, from the medical records of those children with aHUS. We collected nasopharyngeal samples, tested them for Nm using real-time polymerase chain reaction, and performed a serogroup analysis on the positive samples. We collected nasopharyngeal samples from 62 children with aHUS. Out of 62 children, 61 (98.4%) had received at least one dose of the meningococcal vaccine. The median time since the last meningococcal vaccine dose was 15 months (1-59 months). We detected meningococcal carriage in three (4.8%, 95% CI 1.0-13.5) children, and all three strains were non-groupable (NG). No other serogroups were detected. Almost all the children received their risk-group meningococcal immunization, including booster doses. A 4.8% of children with aHUS carried NG meningococci and, no vaccine serogroups were detected. Patients treated with eculizumab remain profoundly susceptible to IMD due to these NG meningococcal strains. The occurrence of breakthrough cases and carriage of Nm, especially NG strains, highlights the significance of maintaining a state of constant alertness, promptly seeking medical attention, and swiftly treating any symptoms that align with IMD, regardless of their vaccination status or antibiotic prophylaxis.

SARS-CoV-2 Infection Risk Imposed by Fully-vaccinated Air Travelers Attending an Island-confined Quarantine System Enabling Tourism During the Pandemic: A Retrospective Cohort Study.

This study aimed to identify the incidence of SARS-CoV-2 infection among fully vaccinated air travelers participating in an island-confined quarantine system (Phuket Sandbox Program). It also compared the differential risk of SARS-CoV-2 infection across different COVID-19 vaccines and the difference in time-to-detection periods between asymptomatic and symptomatic cases. This retrospective cohort study determined the cumulative incidence of SARS-CoV-2 infection among 63,052 air travelers who participated in a quarantine program from July 1 to October 31, 2021. Using Poisson regression with robust standard errors, we estimated the relative risk of SARS-CoV-2 infection across different brands and types of COVID-19 vaccines, adjusting for relevant covariates. We visualized the time-to-detection periods for SARS-CoV-2 infection using Kaplan-Meier failure curves and compared these curves for asymptomatic and symptomatic travelers using the log-rank test. The overall incidence of SARS-CoV-2 infection was 0.3%. Individuals vaccinated with Ad26.COV2.S, Gam-COVID-Vac, CoronaVac, and replicating viral vector vaccines faced a significantly higher risk of infection than those who received the BNT162b2 and mRNA vaccines. The time-to-detection periods for asymptomatic and symptomatic cases did not differ significantly. Despite the relatively low risk of SARS-CoV-2 infection, a risk of breakthrough cases remained with certain vaccines. Given the high proportion of asymptomatic cases, quarantine and intermittent testing should be implemented. The mandatory quarantine system proved effective in managing positive cases without necessitating a complete shutdown of travel. Implementing an island quarantine could be a viable strategy for reintroducing travel and tourism during a future COVID-19 outbreak or a new pandemic.

COVID-19 breakthrough infections in vaccinated individuals at BPKIHS, Nepal

BackgroundAlthough there have been reports of COVID-19 breakthrough infections in vaccinated individuals, the vaccines have demonstrated a high efficacy in preventing severe illness and death. Nepal has reported fewer studies of COVID-19 breakthrough infections. Hence, this study has objective to assess the prevalence, and to describe clinical characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) breakthrough infection.MethodsThis descriptive study was conducted from January to December 2022. The study enrolled 200 individuals who had received the recommended doses of the COVID-19 vaccine and they were RT-PCR positive diagnosed with vaccine breakthrough infections after 14 days of completing the vaccination course. The patient’s demographic and clinical profiles, as well as their outcomes in terms of severity, length of hospital stay, and mortality were recorded.ResultsThe prevalence of SARS-CoV2 infection was 6.3% (547/8682). Among fully vaccinated personnel, the prevalence of breakthrough infections was 6.2% (200/3175). This study found the Omicron variants in respondents. The mean age of the patients was 38.28 years, and 41.5% (83/200) of the breakthrough cases were healthcare workers. The mean time gap between the second dose of vaccination and a positive RT-PCR test was 354.68 days. Of the 200 breakthrough cases, 89% (178) had mild symptoms, 9% (17) had moderate symptoms requiring hospitalization, and 2% (4) were severe cases that required intensive care facility. Among the severe cases, 3 out 4 were above 60 years old. Furthermore, the patients greater than 60 years had longer hospital stays (p < 0.0001) however no deaths were recorded.ConclusionFully vaccinated individuals can experience COVID-19 breakthrough infections and the majority of cases present with mild symptoms. Elderly patients have a higher likelihood of severe disease and longer hospital stay compared to younger patients. The results of this study emphasize the importance of vaccination in mitigating the severity of the disease.

The Effects of Vaccination Status and Age on Clinical Characteristics and Severity of Measles Cases in the United States in the Post-Elimination Era, 2001-2022.

Despite high vaccine-effectiveness, wild-type measles can occur in previously vaccinated persons. We compared the clinical presentation and disease severity of measles by vaccination status and age in the post-elimination era in the United States. We included U.S. measles cases reported from 2001-2022. Breakthrough measles was defined as cases with ≥1 documented dose of measles-containing vaccine, classic measles as the presence of rash, fever, and ≥1 symptoms (cough, coryza, or conjunctivitis), and severe disease as the presence of pneumonia, encephalitis, hospitalization, or death. Vaccinated cases with low and high avidity IgG were classified as primary (PVF) and secondary (SVF) vaccine failures, respectively. Among 4,056 confirmed measles cases, 2,799 (69%) were unvaccinated, 475 (12%) were breakthrough infections, and 782 (19%) had unknown vaccination; 1,526 (38%), 1,174 (29%), and 1,355 (33%) were aged <5, 5-19, and ≥20 years, respectively. We observed a general decline in classic presentation and severe disease with an increase in the number of doses, and less complications among children aged 5-19 years compared to other age-groups. Among 93 breakthrough cases with avidity results, 11 (12%) and 76 (82%) were classified as PVF and SVF, respectively, with a higher proportion of PVFs having a classic measles presentation and severe disease than SVFs. Breakthrough measles cases tended to have milder disease with less complications. A small proportion of breakthrough infections were due to PVF than SVF. It is critical to maintain high MMR vaccination coverage in the United States to prevent serious measles illnesses.

Understanding Mumps Dynamics: Epidemiological Traits and Breakthrough Infections in the Population under 15 Years of Age in Jiangsu Province, China, 2023.

Despite coverage of two doses of mumps-containing vaccines, mumps epidemics persist among children and young adults in China. This study aimed to analyze the epidemiological characteristics of mumps in Jiangsu Province, with a particular focus on breakthrough cases among high-incidence groups. Mumps cases reported in 2023 were systematically collected from the Infectious Disease Surveillance and Reporting System. A comprehensive descriptive epidemiological analysis was performed to elucidate the characteristics of the reported cases. A joinpoint regression (JPR) model was utilized to identify the temporal trends across various periods. Subsequently, immunization information for cases under 15 years of age was obtained through the Jiangsu Province Vaccination Integrated Service Management Information System to identify breakthrough cases and conduct exploratory analyses. A total of 4142 mumps cases were reported in Jiangsu Province in 2023, yielding an annual incidence rate of 4.86/100,000. A total of 81.75% of the cases were students and childcare children, and the gender ratio was 1.5:1 (male/female). The JPR model analysis of weekly reported cases identified five distinct trend segments (1st: 1-8, weekly percent change (WPC) = 26.67 *; 2nd: 9-28, WPC = 3.11 *; 3rd: 29-34, WPC = -5.31; 4th: 35-37, WPC = 15.48; 5th: 38-52, WPC = -4.06 *), and the gender subgroups demonstrated similar trends to the overall pattern. Notably, 89.14% (3692/4142) of the total cases were among individuals under 15 years, with 96.02% (3545/3692) having been vaccinated against mumps. The number of single-dose breakthrough cases (SdBCs) was approximately fourfold (2847/698) that of two-dose breakthrough cases (TdBCs). The main population composition of TdBCs was children aged 0-5 years old, and the classification was dominated by childcare children and scattered children. The median time interval between initial immunization and onset were shorter in TdBCs than in the SdBCs group, and the median time interval between the last immunization and onset was interestingly similarly shorter. However, these situations were interestingly reversed in 105 laboratory-confirmed breakthrough cases. Therefore, the current vaccination strategies have demonstrated tangible effectiveness in preventing and controlling mumps. However, the high incidence of breakthrough cases among high-risk pediatric populations indicates that mumps immunization strategies still deserve more attention and research for better herd protection.

Assessing the Impact of Pneumococcal Conjugate Vaccine Immunization Schedule Change From 3+0 to 2+1 in Australian Children: A Retrospective Observational Study.

In mid-2018, the Australian childhood 13-valent pneumococcal conjugate vaccine schedule changed from 3+0 to 2+1, moving the third dose to 12 months of age, to address increasing breakthrough cases of invasive pneumococcal disease (IPD), predominantly in children aged >12 months. This study assessed the impact of this change using national IPD surveillance data. Pre- and postschedule change 3-dose 13-valent pneumococcal conjugate vaccine breakthrough cases were compared by age group, serotype, and clinical syndrome. Annual rates of breakthrough cases were calculated (per 100 000) using respective birth cohort sizes and 3-dose vaccine coverage. Using time-series modelling, observed IPD rates in children aged <12 years were compared to that expected if the 3+0 schedule were continued. Over 2012-2022, rate of 3-dose breakthrough cases in children aged >12 months was 2.8 per 100 000 (n = 557; 11 birth cohorts). Serotype 3 replaced 19A as predominant breakthrough serotype (respectively, 24% and 65% in 2013 to 60% and 20% in 2022) followed by 19F. In breakthrough cases, the most frequent clinical phenotype was bacteremic pneumonia (69%), with meningitis accounting for 3%-4%. In cohorts eligible for 2+1 versus 3+0 schedules, rate of breakthrough cases was lower for all vaccine serotypes, except type 3 (incidence rate ratio, 0.50 [95% confidence interval, .28-.84] and 1.12 [0.71-1.76], respectively). Observed compared to expected IPD was 51.7% lower (95% confidence interval, -60.9 to -40.7%) for vaccine serotypes, but the change for nonvaccine types was not significant 12% (-9.6 to 39.7). The 2+1 schedule is likely superior to 3+0 for overall IPD control, a finding that may be worth consideration for other countries considering or using 3+0 PCV schedules.

Highly Effective Combined Antifungal Therapy with Liposomal Amphotericin B and Isavuconazole in a Severe Case of Breakthrough Disseminated Fusariosis in Acute Lymphoblastic Leukemia

Breakthrough Fusarium infection during antifungal prophylaxis is an emerging problem and a life threatening condition especially in immunocompromised hematological patients thus early identification of infection and appropriate and aggressive antifungal therapy are required

Adolescents With Breakthrough COVID-19 Infections Requiring Hospitalization: A Multicenter Retrospective Study.

Background Vaccines have the most important role in the battle against the COVID-19 pandemic. With the widespread use of vaccines, COVID-19 has remarkably declined. Adolescents were vaccinated after approvals for this age group, which was later than adults, and a nationwide vaccination program was implemented in August 2021 in Turkey for adolescents ≥12 years of age. Therefore, we aimed to determine the effects of the COVID-19 nationwide adolescent vaccination program on adolescent hospitalizations due to COVID-19 and multisystem inflammatory syndrome in children (MIS-C) by comparing two periods, including the vaccination period (VP) and the pre-VP (PVP). The second aim of this study is to compare the clinical features and disease severity of vaccine-breakthrough COVID-19 hospitalizations with unvaccinated individuals in the VP. Methods A retrospective multicenter study was conducted to determine and compare the number of hospitalizations due to COVID-19 and MIS-C between the VP (September 1, 2021, to August 31, 2022) and PVP (September 1, 2020, to August 31, 2021). We also compared the characteristics, risk factors, and outcomes of breakthrough infections of adolescents aged 12-18, which required hospitalization with the same age group of unvaccinated hospitalized individuals during the VP. Results During the study period, 3967 children (0-18 years) were hospitalized in the PVP and 5143 (0-18 years) in the VP. Of them, 35.4% were adolescents (12-18 years) in the PVP, and this rate was 18.6% in the VP; relative risk was 0.6467 (95% confidence interval [CI]: 0.6058-0.6904; p < 0.001). Patients with breakthrough COVID-19 were older (201 vs. 175 months, p < 0.001) and less commonly hospitalized for COVID-19 (81.5% vs. 60.4%, p < 0.001, odds ratio [OR]: 0.347 [95% CI: 0.184-0.654]). The majority of these infections were asymptomatic and mild (32% vs.72.9%: p < 0.001, OR: 5.718 [95% CI: 2.920-11.200]), and PICU admission was less frequently required (p = 0.011, OR: 0.188 [95% CI: 0.045-0.793]). Most breakthrough COVID-19 infections occurred within three months after the last vaccine dose (54.2%). Conclusions This study demonstrated a significant decrease in adolescent hospitalizations due to COVID-19 and MIS-C after implementing COVID-19 vaccines in Turkey. Breakthrough cases were less severe and mostly occurred three months after the last dose. This study emphasizes the importance of COVID-19 vaccines and that parents' decisions may be changed, particularly those who hesitate to or refuse vaccination.

Clinical and humoral response after SARS-CoV-2 breakthrough infection in patients receiving immunosuppressant therapy

BackgroundDespite impaired humoral responses in patients treated with immunosuppressants (ISPs), recent studies found similar severity of SARS-CoV-2 breakthrough infections compared to controls. One potential explanation is the rapid generation humoral responses upon infection, but evidence is lacking. ObjectivesTo investigate longitudinal dynamics of the SARS-CoV-2 antibody repertoire after SARS-CoV-2 delta and omicron breakthrough infections in patients with immune-mediated inflammatory diseases (IMID) on ISPs and controls. MethodsAs prospective sub-study of the national Target-to-B! (T2B!) consortium, we included IMID patients on ISPs and controls who reported SARS-CoV-2 breakthrough infections between July 1, 2021, and April 1, 2022. To get an impression of the dynamics of the antibody repertoire, three antibody titers of wild-type RBD, wild-type S, and omicron RBD were measured at four time points after SARS-CoV-2 breakthrough infections. ResultsWe included 302 IMID patients on ISPs and 178 controls. Antibody titers increased up to 28 days after breakthrough infections in both groups. However, in IMID patients on anti-CD20 therapy and sphingosine-1 phosphate receptor (S1P) modulators, antibody titers were considerably lower compared to controls. In the anti-TNF group, we observed slightly lower antibody titers in the early stages and a faster decline of antibodies after infection compared to controls. Breakthrough infections were mostly mild and hospitalization was required in less than 1% of the cases. ConclusionsMost ISPs do not influence the dynamics of the SARS-CoV-2 antibody repertoire and exhibit a rapid recall response with cross-reactive antibody clones towards new viral variants. However, in patients treated with anti-CD20 therapy or S1P modulators, the dynamics were greatly impaired, and to a lesser extent in those anti-TNF. Nevertheless, only a few severe breakthrough cases were reported.

Immune responses during COVID-19 breakthrough cases in vaccinated children and adolescents.

Vaccine effectiveness against SARS-CoV-2 infection has been somewhat limited due to the widespread dissemination of the Omicron variant, its subvariants, and the immune response dynamics of the naturally infected with the virus. Twelve subjects between 3-17 years old (yo), vaccinated with two doses of CoronaVac®, were followed and diagnosed as breakthrough cases starting 14 days after receiving the second dose. Total IgGs against different SARS-CoV-2 proteins and the neutralizing capacity of these antibodies after infection were measured in plasma. The activation of CD4+ and CD8+ T cells was evaluated in peripheral blood mononuclear cells stimulated with peptides derived from the proteins from the wild-type (WT) virus and Omicron subvariants by flow cytometry, as well as different cytokines secretion by a Multiplex assay. 2 to 8 weeks post-infection, compared to 4 weeks after 2nd dose of vaccine, there was a 146.5-fold increase in neutralizing antibody titers against Omicron and a 38.7-fold increase against WT SARS-CoV-2. Subjects showed an increase in total IgG levels against the S1, N, M, and NSP8 proteins of the WT virus. Activated CD4+ T cells showed a significant increase in response to the BA.2 subvariant (p<0.001). Finally, the secretion of IL-2 and IFN-γ cytokines showed a discreet decrease trend after infection in some subjects. SARS-CoV-2 infection in the pediatric population vaccinated with an inactivated SARS-CoV-2 vaccine produced an increase in neutralizing antibodies against Omicron and increased specific IgG antibodies for different SARS-CoV-2 proteins. CD4+ T cell activation was also increased, suggesting a conserved cellular response against the Omicron subvariants, whereas Th1-type cytokine secretion tended to decrease. clinicaltrials.gov #NCT04992260.

Survey of hepatitis B virus infection status after 35 years of universal vaccination implementation in Taiwan.

Hepatitis B virus (HBV) vaccination programs in Taiwan are one of the earliest programs in the world and have largely reduced the prevalence of HBV infection. We aimed to demonstrate the vaccination efficacy after 35 years and identify gaps toward HBV elimination. A total of 4717 individuals aged 1-60 years were recruited from four administrative regions based on the proportion of population distribution. Serum levels of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) levels were assessed. HBV viral load, genotypes and HBsAg 'ɑ' determinant variants were evaluated if indicated. After 35 years of vaccination, the overall seropositivity rates for HBsAg and anti-HBc in Taiwan were 4.05% and 21.3%, respectively. The vaccinated birth cohorts exhibited significantly lower seropositivity rates for both markers compared to the unvaccinated birth cohorts (HBsAg: 0.64% vs. 9.78%; anti-HBc: 2.1% vs. 53.55%, respectively; p < 0.0001). Maternal transmission was identified as the main route of HBV infection in breakthrough cases. Additionally, increased prevalences of genotype C and HBsAg escape mutants were observed. The 35-year universal HBV vaccination program effectively reduced the burden of HBV infection, but complete eradication of HBV infection has not yet been achieved. In addition to immunization, comprehensive screening and antiviral therapy for infected individuals, especially for pregnant women, are crucial strategies to eliminate HBV.

Adapting response to a measles outbreak in a context of high vaccination and breakthrough cases: an example from Vaud, Switzerland, January to March 2024.

A measles outbreak with 51 cases occurred in the canton of Vaud, Switzerland, between January and March 2024. The outbreak was triggered by an imported case, and 37 (72.5%) subsequent cases were previously vaccinated individuals. Epidemiological investigations showed that vaccinated measles cases were symptomatic and infectious. In a highly vaccinated population, it is important to raise awareness among healthcare professionals to suspect and test for measles virus when an outbreak is declared, irrespective of the vaccination status of the patients.

Differential Utility Losses in Herpes Zoster Cases Between Vaccinated and Unvaccinated Subjects: A Meta-analysis of Three Clinical Trials.

Recombinant zoster vaccine (RZV) is approved in adults for the prevention of herpes zoster. The effect of RZV in moderating the severity of breakthrough cases of herpes zoster has been noted but not explicitly quantified before. In this study, a meta-analysis was undertaken to estimate differential utility losses between unvaccinated (Placebo) and vaccinated (RZV) subjects in breakthrough cases of herpes zoster from three RZV clinical trials. Differential utility losses between the two groups were estimated in units of quality-adjusted life-years (QALYs), leveraging aggregate patient data from the ZOE-50 (NCT01165177), ZOE-70 (NCT01165229), and ZOE-HSCT (NCT01610414) clinical trials. Differential utility losses and the ratio of mean utility losses were analyzed using random-effects and fixed-effects meta-regression models. The mean QALY loss differences between the unvaccinated (Placebo) and vaccinated (RZV) groups were 0.008, 0.004, and 0.011 in the ZOE-50, ZOE-70, and ZOE-HSCT studies, respectively, yielding an overall estimated difference of 0.007 (95% confidence interval 0.002-0.012) QALYs. Quality-adjusted life-year loss in the vaccinated group was estimated to be 35.5% of the value in the placebo group. A sensitivity analysis estimated an overall difference of 0.005 (95% confidence interval 0.001-0.009) QALYs, corresponding to 48.6% of the QALY loss value in the placebo group. Recombinant zoster vaccine is effective in alleviating disease severity in breakthrough cases of herpes zoster. The results may be useful in distinguishing QALY losses between vaccinated and unvaccinated cohorts in health economics studies, particularly cost-effectiveness analyses.

Validation and Suitability Assessment of Multiplex Mesoscale Discovery Immunogenicity Assay for Establishing Serological Signatures Using Vaccinated, Non-Vaccinated and Breakthrough SARS-CoV-2 Infected Cases.

Antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are multi-targeted and variable over time. Multiplex quantitative serological assays are needed to provide accurate and robust seropositivity data for the establishment of serological signatures during vaccination and or infection. We describe here the validation and evaluation of an electro-chemiluminescence (ECL)-based Mesoscale Discovery assay (MSD) for estimation of total and functional IgG relative to SARS-CoV-2 spike, nucleocapsid and receptor binding (RBD) proteins in human serum samples to establish serological signatures of SARS-CoV-2 natural infection and breakthrough cases. The 9-PLEX assay was validated as per ICH, EMA, and US FDA guidelines using a panel of sera samples, including the NIBSC/WHO reference panel (20/268). The assay demonstrated high specificity and selectivity in inhibition assays, wherein the homologous inhibition was more than 85% and heterologous inhibition was below 10%. The assay also met predetermined acceptance criteria for precision (CV < 20%), accuracy (70-130%) and dilutional linearity. The method's applicability to serological signatures was demonstrated using sera samples (n = 45) representing vaccinated, infected and breakthrough cases. The method was able to establish distinct serological signatures and thus provide a potential tool for seroprevalence of SARS-CoV-2 during vaccination or infection.

Study anti-viral drugs for their efficiency against multiple SARS CoV-2 drug targets within molecular docking, molecular quantum similarity, and chemical reactivity indices frameworks

The study focused on drug discovery for COVID-19, emphasizing the challenges posed by the pandemic and the importance of understanding the virus’s biology. The research utilized molecular docking and quantum similarity analyses to explore potential ligands for SARS-CoV-2 RNA-dependent RNA polymerase. Docking Results Docking outcomes for various ligands, including Oseltamivir, Prochloraz, Valacyclovir, Baricitinib, Molnupiravir, Penciclovir, Famciclovir, Lamivudine, and Nitazoxanide, were presented. Interactions between ligands and specific residues in the RNA-dependent RNA polymerase were analyzed. Reactivity Descriptors Global parameters, such as electronic chemical potential, chemical hardness, global softness, and global electrophilicity, were computed for the ligands. For the local reactivity descriptors, the Fukui Functions were used. Fukui functions, representing electrophilic and nucleophilic sites, were calculated for selected ligands (Valacyclovir and Penciclovir). Nucleophilic character assignments for specific molecular regions were discussed, providing insights into potential charge-donating interactions. Results and Discussion Challenges in COVID-19 drug discovery, such as virus mutability, rapid evolution, and resource limitations, were summarized. Progress in vaccine development and the need for ongoing research to address variants and breakthrough cases were emphasized. Overlap Operator Analysis Higher MQSM between Lamivudine and Molnupiravir (0.5742) indicates structural and electronic similarity. Lowest MQSM between Oseltamivir and Prochloraz (0.2233) implies structural dissimilarity. Coulomb Operator Analysis Higher MQSM between Lamivudine and Molnupiravir (0.9178) suggests both structural and electronic similarity. Lowest MQSM between Baricitinib and Famciclovir (0.6001) indicates greater structural diversity. Measurements above 0.5 in Table 3 suggest electronic similarity, emphasizing the electronic aspects in molecular analysis. In this sense, it study employed a multi-faceted approach combining molecular docking, quantum similarity analyses, and chemical reactivity assessments to explore potential drug candidates for COVID-19. The findings provide valuable insights into ligand interactions, reactivity patterns, and the challenges associated with drug discovery in the context of the global pandemic.

Clinical outcomes and risk factors for SARS-CoV-2 breakthrough cases following vaccination with BNT162b2, CoronaVac, or ChAdOx1-S: A retrospective cohort study in Malaysia

BackgroundThe SARS-CoV-2 pandemic drove global vaccination. However, breakthrough infections raised concerns about vaccine performance, leading the World Health Organization (WHO) to recommend investigations thereof. This study aimed to evaluate the clinical outcomes (time to breakthrough infection, intensive care unit [ICU] admission, and in-hospital mortality) of hospitalised patients with SARS-CoV-2 breakthrough infection. This was the primary outcome and the risk factors associated with its severity were the secondary outcomes. MethodsThis retrospective cohort study at a multispecialty tertiary hospital in Selangor, Malaysia included 200 fully adult vaccinated patients, with confirmed SARS-CoV-2 infection, admitted from September 2021 to February 2022. Participants were selected by simple random sampling. Infection severity was categorised as CAT 2–3 (mild–moderate) and 4–5 (severe–critical). ResultsThe time to breakthrough infection was significantly longer for BNT162B2 recipients (128.47 ± 46.21 days) compared to CoronaVac (94.09 ± 48.71 days; P = 0.001) and ChAdOx1-S recipients (90.80 ± 37.59 days; P = 0.019). No significant associations were found between SARS-CoV-2-related ICU admission, mortality, and the vaccines. Multivariable analysis identified vaccine type, variant of concern, ethnicity, and hypertension as significant predictors of severity. BNT162b2 and ChAdOx1-S recipients had significantly (81 % and 74 %, respectively) lower odds of CAT 4–5 infection compared to CoronaVac recipients. Indian patients had a significantly (83 %) lower chance of CAT 4–5 infection compared to Malay patients. Patients with breakthrough infections during the Omicron period had a significantly (58 %) lower risk of CAT 4–5 compared to those in the Delta period. The CAT 4–5 risk was significantly (nearly threefold) higher in hypertensive patients. ConclusionThe results support the Malaysian Ministry of Health's recommended booster three months after primary vaccination and the WHO's recommended heterologous booster following CoronaVac. Certain ethnic groups, hypertensive patients, and viral variants may require attention in future pandemics.

Effectiveness of vaccination, travel load, and facemask use control strategies for controlling COVID Delta variant: the case of Sydney Metropolitan Area

AbstractThe Delta variant of SARS-CoV-2, specifically identified as B.1.617.2, is responsible for the severe outbreaks witnessed globally, including in various countries and cities, with Sydney Greater Metropolitan Area (Sydney GMA) being no exception. According to scientific studies, the Delta strain exhibits increased contagion and leads to a higher incidence of vaccine breakthrough cases, posing significant challenges to pandemic control efforts. In this study, we explore the efficacy of three fundamental control strategies—namely, vaccination rates, adherence to facemask usage, and the management of travel loads—in mitigating the spread of the disease and, consequently, eliminating the Delta variant pandemic in Sydney GMA. We employ an agent-based disease spread model to thoroughly investigate these strategies. Moreover, factorial MANOVA is utilised to assess the significance of variations in the impact of diverse compliance levels with the aforementioned control strategies on various attributes of the pandemic. As complete lockdowns and stringent travel regulations have the potential to induce physical and mental distress in individuals and economic crises for countries, our study examines the interactive effects of implementing control strategies to mitigate the necessity for a full lockdown. The simulation results suggest that suppressing a pandemic with similar characteristics to Delta variant of COVID is feasible with a vaccination rate of 80% or higher, as long as travel load and activity participation are maintained at pre-COVID levels. Alternatively, a more realistic and attainable combination of control measures—a vaccination rate of 60%, a facemask usage level of 60%, and a 50% compliance level for social distancing—demonstrates comparable efficacy, leading to effective pandemic control. Notably, the vaccination rate emerges as a more potent control strategy compared to others in the elimination of the disease within society.