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BACKGROUND: Despite immunization, patients on antineoplastic and immunomodulating agents have a heightened risk of COVID-19 infection. However, accurately attributing this risk to specific medications remains challenging. METHODS: An observational cohort study from December 11, 2020 to September 22, 2022, within a large healthcare system in San Diego, California, USA was designed to identify medications associated with greatest risk of postimmunization SARS-CoV-2 infection. Adults prescribed WHO Anatomical Therapeutic Chemical (ATC) classified antineoplastic and immunomodulating medications were matched (by age, sex, race, and number of immunizations) with control patients not prescribed these medications yielding a population of 26 724 patients for analysis. From this population, 218 blood samples were collected from an enrolled subset to assess serological response and cytokine profile in relation to immunization. RESULTS: Prescription of WHO ATC classified antineoplastic and immunomodulatory agents was associated with elevated postimmunization SARS-CoV-2 infection risk (HR 1.50, 95% CI 1.38 to 1.63). While multiple immunization doses demonstrated a decreased association with postimmunization SARS-CoV-2 infection risk, antineoplastic and immunomodulatory treated patients with four doses remained at heightened risk (HR 1.23, 95% CI 1.06 to 1.43). Risk variation was identified among medication subclasses, with PD-1/PD-L1 inhibiting monoclonal antibodies, calcineurin inhibitors, and CD20 monoclonal antibody inhibitors identified to associate with increased risk of postimmunization SARS-CoV-2 infection. Antineoplastic and immunomodulatory treated patients also displayed a reduced IgG antibody response to SARS-CoV-2 epitopes alongside a unique serum cytokine profile. CONCLUSIONS: Antineoplastic and immunomodulating medications associate with an elevated risk of postimmunization SARS-CoV-2 infection in a drug-specific manner. This comprehensive, unbiased analysis of all WHO ATC classified antineoplastic and immunomodulating medications identifies medications associated with greatest risk. These findings are crucial in guiding and refining vaccination strategies for patients prescribed these treatments, ensuring optimized protection for this susceptible population in future COVID-19 variant surges and potentially for other RNA immunization targets.

There is clearly a need for novel antifungal agents, not only concerning spectrum, but also oral bioavailability, tolerability, and drug-drug interactions. There is growing concern for antifungal resistance for current available antifungals, mainly driven by environmental fungicide use or long-term exposure to antifungals, in the setting of mould-active prophylaxis or for chronic antifungal infections, such as chronic pulmonary aspergillosis. Moreover, the incidence of breakthrough infections is increasing, because of the introduction of (mould-active) prophylaxis (1-4). There is emergence of difficult to treat invasive fungal infections, such as those caused by Lomentospora prolificans, cryptic species of Aspergillus, Scedosporium and Coccidioides. Olorofim (F901318) is the first-in class of the orotomides, a novel antifungal class targeting dihydroorotate dehydrogenase (DHODH), a key enzyme in the biosynthesis of pyrimidines. Olorofim shows good in vitro and in vivo activity against Aspergillus species, rare and difficult to treat moulds and endemic dimorphic fungi, including azole- and amphotericin-resistant isolates. It lacks activity against yeasts and the Mucorales species. It is only orally available and shows very promising results in ongoing clinical trials. In this review we will describe the mechanism of action of olorofim, the spectrum of activity in vitro and in vivo, pharmacokinetics, pharmacodynamics, drug-drug interactions, resistance, and clinical outcomes. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aim Methods Results Conclusions Variant‐adapted COVID‐19 vaccines are recommended for patients with inflammatory bowel disease (IBD). However, many patients rely on pre‐existing immunity by original vaccines or prior infections.To assess whether such immunity sufficiently combats the highly immune‐evasive SARS‐CoV‐2 JN.1 variant.Utilising two longitudinal cohorts, we evaluated immunity against JN.1 induced by original vaccines (IBD: n = 98; healthy: n = 48), omicron breakthrough infection (IBD: n = 55; healthy: n = 57) or XBB.1.5‐adapted vaccines (IBD: n = 18). Neutralisation and anti‐receptor‐binding domain (RBD) IgG levels against wild‐type SARS‐CoV‐2 and JN.1 were assessed using multiplex immunoassays. Study outcomes were wild‐type and JN.1 neutralisation following three doses of original mRNA vaccines, stratified by immunosuppressive therapy (primary outcome), and JN.1 neutralisation following third‐dose breakthrough infection or a fourth dose of XBB.1.5‐adapted mRNA vaccines (secondary outcomes).Following original vaccines, JN.1 neutralisation was lower than wild‐type neutralisation in all study groups (healthy, anti‐TNF and non‐anti‐TNF; each p < 0.001); most individuals lacked JN.1 neutralisation (healthy: 97.9%; anti‐TNF: 98.3% and non‐anti‐TNF: 92.3%). Confounder‐adjusted multivariable modelling strongly associated anti‐TNF therapy with low levels of anti‐JN.1‐RBD IgG (fold‐change 0.48 [95% CI 0.39–0.59]). JN.1 neutralisation was similar in patients with or without breakthrough infection (anti‐TNF, non‐anti‐TNF; each p > 0.05); neutralisation failure was 100% despite breakthrough infection. XBB.1.5‐adapted vaccines enhanced JN.1 neutralisation (p < 0.001) and reduced neutralisation failure rates in patients with IBD (94.4% pre‐vaccination vs. 44.4% post‐vaccination; p = 0.003).Only variant‐adapted vaccines protect against emerging SARS‐CoV‐2 variants. Patients with IBD and healthy individuals without recent vaccination may lack protection against the JN.1 subvariant KP.3 which causes current COVID‐19 surges. [ABSTRACT FROM AUTHOR]

The rapid development of vaccines to combat the spread of COVID-19, caused by the SARS-CoV-2 virus, is a great scientific achievement. Before the development of the COVID-19 vaccines, most studies capitalized on the available data that did not include pharmaceutical measures. Such studies focused on the impact of non-pharmaceutical measures such as social distancing, sanitation, use of face masks, and lockdowns to study the spread of COVID-19. In this study, we used the SIDARTHE-V model, an extension of the SIDARTHE model, which includes vaccination rollouts. We studied the impact of vaccination on the severity of the virus, specifically focusing on death rates, in African countries. The SIRDATHE-V model parameters were extracted by simultaneously fitting the COVID-19 cumulative data of deaths, recoveries, active cases, and full vaccinations reported by the governments of Ghana, Kenya, Mozambique, Nigeria, South Africa, Togo, and Zambia. Using South Africa as a case study, our analysis showed that the cumulative death rates declined drastically with the increased extent of vaccination drives. Whilst the infection rates sometimes increased with the arrival of new coronavirus variants, the death rates did not increase as they did before vaccination. Author summary: The onset of the COVID-19 pandemic prompted swift global responses. These included non-pharmaceutical control measures at the beginning of the pandemic such as social distancing, masks, and the later development of vaccines. In our first paper, we studied the evolution of the pandemic in the African continent by fitting the observed data with the SIRDATHE model in the first year (March 2020—March 2021) of the pandemic, before vaccination. We examined the impact of non-pharmaceutical control measures on COVID-19 transmission in the first year of the pandemic. As vaccination campaigns commenced, we extended our model to SIDARTHE-V model, which included the vaccination component. The SIRDATHE-V model assumes total immunity in the vaccinated population. However, our observations revealed breakthrough infections even amongst the vaccinated population. Therefore, in our application of the SIRDATHE-V model, we considered the fact that even the vaccinated could become infected. In this study, we investigated the impact of COVID-19 vaccination in Africa. We analysed COVID-19 data from seven African countries: Ghana, Kenya, Mozambique, Nigeria, South Africa, Togo, and Zambia over approximately two years, from March 2020 to March 2022. Considering variations in vaccination programs in each country, for example, the use of different vaccines and different starting dates, this study focused on the impact of vaccination on the death rates. Our findings showed a decline in cumulative death rates due to COVID-19 when vaccination drives were coupled with non-pharmaceutical control measures. We therefore conclude that in combating the spread of acute viral infections with dynamics similar to COVID-19, a comprehensive strategy involving both pharmaceutical (vaccination) and non-pharmaceutical (social measures) interventions is crucial. [ABSTRACT FROM AUTHOR]

BACKGROUND Kidney transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV is an emerging practice. It has been performed since 2016 under the U.S. congressional HIV Organ Policy Equity Act and is currently approved for research Only. The Department of Health and Human Services is considering expanding the procedure to clinical practice, but data are limited to small case series that did not include donors without HIV as controls. METHODS In an observational study conducted at 26 U.S. centers, we compared transplantation of kidneys from deceased donors with HIV and donors without HIV to recipients with HIV. The primary outcome was a safety event (a composite of death from any cause, graft loss, serious adverse event, HIV breakthrough infection, persistent failure of HIV treatment, or opportunistic infection), assessed for noninferiority (margin for the upper bound of the 95 % confidence interval, 3.00). Secondary outcomes included overall survival, survival without graft loss, rejection, infection, cancer, and HIV superinfection. RESULTS We enrolled 408 transplantation candidates, of whom 198 received a kidney from deceased donor; 99 received a kidney from a donor with HIV and 99 from a donor without HIV. The adjusted hazard ratio for the composite primary outcome was 1.00 (95% confidence interval ICI], 0.73 to 1.38), which showed noninferiority. The following secondary outcomes were similar whether the donor had HIV or not: overall survival at 1 year (94% vs. 9596) and 3 years (85% vs. 87%), survival without graft loss at 1 year (93% vs. 9096) and 3 years (84% vs. 81%), and rejection at 1 year (13% vs. 21°/0) and 3 years (21% vs. 2496). The incidence of serious adverse events, infections, surgical or vascular complications, and cancer was similar in the groups. The incidence of HIV breakthrough infection was higher among recipients of kidneys from donors with HIV (incidence rate ratio, 3.14; 95°/0, CI, 1.02 to 9.63), with one potential HIV superinfection among the 58 recipients in this group with sequence data and no persistent failures of HIV treatment. CONCLUSIONS In this observational study of kidney transplantation in persons with HIV, transplantation from donors with HIV appeared to be noninferior to that from donors without HIV. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT03500315.). [ABSTRACT FROM AUTHOR]

Liver-stage genetically attenuated malaria parasites (GAPs) are powerful immunogens that provide protection against sporozoite challenge. We previously generated two late liver-stage-arresting GAPs by deleting the stearoyl-CoA desaturase (Scd) or sporozoite conserved orthologous transcript 1 (Scot1) genes in Plasmodium berghei. Immunization with Scd or Scot1 GAP conferred complete protection against a sporozoite challenge. In a safety study, we observed rare breakthrough blood-stage infections in mice inoculated with high doses of sporozoites, indicating that both GAPs were incompletely attenuated. In this study, we generated a Scd/Scot1 GAP by dual gene deletion. This resulted in complete attenuation of the parasites in the liver and did not transition to blood-stage infection despite a high-dose sporozoite challenge. The Scd/Scot1 KO and WT GFP parasites were indistinguishable during blood, mosquito and early liver stage development. Moreover, Scd/Scot1 KO liver-stage schizonts exhibited an abnormal apicoplast biogenesis and nuclear division phenotype, failed to form hepatic merozoites, and exhibited late liver-stage arrest. Compared with early-arresting Speld KO immunization, late-stage liver-arresting Scd/Scot1 KO induces greater and broader CD8+ T-cell responses and elicits stage-transcending immunity that provides superior protection in C57BL/6 mice. These data prove that multiple gene deletions lead to complete attenuation of the parasite and support the development of late liver stage-arresting P. falciparum GAP. [ABSTRACT FROM AUTHOR]

Understanding the genetic basis of COVID-19 vaccine seroconversion is crucial to study the role of genetics on vaccine effectiveness. In our study, we used UK Biobank data to find the genetic determinants of COVID-19 vaccine-induced seropositivity and breakthrough infections. We conducted four genome-wide association studies among vaccinated participants for COVID-19 vaccine seroconversion and breakthrough susceptibility and severity. Our findings confirmed a link between the HLA region and seroconversion after the first and second doses. Additionally, we identified 10 genomic regions associated with breakthrough infection (SLC6A20, ST6GAL1, MUC16, FUT6, MXI1, MUC4, HMGN2P18-KRTCAP2, NFKBIZ and APOC1), and one with breakthrough severity (APOE). No significant evidence of genetic colocalisation was found between those traits. Our study highlights the roles of individual genetic make-up in the varied antibody responses to COVID-19 vaccines and provides insights into the potential mechanisms behind breakthrough infections occurred even after the vaccination. Here, the authors use a large cohort to corroborate a link between genetic variants in the HLA region and COVID−19 vaccine responses, and locate 10 independent genetic loci significantly associated with breakthrough infection phenotypes after the vaccination. These findings support the notion that genetics play important roles in COVID−19 response and effectiveness. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic posed a challenge for people living with HIV (PLWH), particularly immune non-responders (INR) with compromised CD4 T-cell reconstitution following antiretroviral therapy (CD4 count <350 cells per mm3). Their diminished vaccine responses raised concerns about their vulnerability to SARS-CoV-2 breakthrough infections (BTI). Our in-depth study here revealed chronic inflammation in PLWH and a limited anti-Spike IgG response after vaccination in INR. Nevertheless, the imprinting of Spike-specific B cells by vaccination significantly enhanced the humoral responses after BTI. Notably, the magnitude of cellular CD4 response in all PLWH was comparable to that in healthy donors (HD). However, the polyfunctionality and phenotype of Spike-specific CD8 T cells in INR differed from controls. The findings highlight the need for additional boosters with variant vaccines, and for monitoring ART adherence and the durability of both humoral and cellular anti-SARS-CoV-2 immunity in INR. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusion Vancomycin‐resistant Enterococci (VRE) infections cause significant morbidity and mortality in liver transplant (LT) recipients. Management is challenging, especially in the setting of daptomycin resistance (DR).Single‐center retrospective review of patients who underwent LT between January 1, 2020, and December 31, 2022, and developed VRE infections. Descriptive statistics were used and Kaplan‐Meier curves estimated freedom from treatment failure and survival.Forty‐two patients (median age 58; 64% female; 67% white) were included. Alcohol‐related cirrhosis (48%) and metabolic dysfunction‐associated steatohepatitis (31%) were the most common indications for LT, and most were from deceased donors (86%). VRE infection occurred at a median of 21 days after LT, and 16% had known prior VRE colonization. Common infection sites were blood (45%, n = 19), intraabdominal (36%, n = 15), and urine (36%, n = 15). Most were initially treated with daptomycin alone (64%) or in combination with other agents (21%); 7% received linezolid alone. Twelve (29%) developed breakthrough infections during treatment and 11 (26%) had recurrent infections after discontinuation of treatment. All‐cause mortality was 36% (n = 15) at a median of 90 days after VRE infection diagnosis and was nearly twice as high in patients with DR (63%).VRE infection in LT recipients relapsed or recurred in over 25%. Mortality was high, especially in cases with DR. More data is needed to establish an optimal treatment approach, particularly for relapse and DR. [ABSTRACT FROM AUTHOR]

Background: Omicron variants have rapidly diversified into sublineages with mutations that enhance immune evasion, posing challenges for vaccination and antibody responses. This study aimed to compare serum cross‐neutralizing antibody responses against various SARS‐CoV‐2 Omicron sublineages (BA.1, BA.5, XBB.1.17.1, FK.1.1, and JN.1) in recipients of monovalent COVID‐19 boosters, bivalent booster recipients, and individuals who had recovered from Omicron BA.5 infections. Methods: We conducted a micro‐neutralization assay on serum samples from monovalent BNT162b2 booster recipients (N = 54), bivalent BNT162b2 booster recipients (N = 24), and SARS‐CoV‐2 Omicron BA.5‐recovered individuals (N = 13). The history of SARS‐CoV‐2 Omicron infection was assessed using ELISA against the SARS‐CoV‐2 NP protein. Results: Bivalent booster recipients exhibited significantly enhanced neutralization efficacy against Omicron sublineages compared to those who had received monovalent booster vaccinations. Omicron BA.5‐recovered individuals displayed similar neutralizing antibodies (NAbs) to the bivalent booster recipients. Despite the improved neutralization in bivalent recipients and BA.5‐recovered individuals, there were limitations in neutralization against the recently emerged Omicron subvariants: XBB.1.17.1 FK.1.1, and JN.1. In both monovalent and bivalent booster recipients, a history of Omicron breakthrough infection was associated with relatively higher geometric mean titers of NAbs against Omicron BA.1, BA.5, and XBB.1.17.1 variants. Conclusion: This study underscores the intricate interplay between vaccination strategies, immune imprinting, and the dynamic landscape of SARS‐CoV‐2 variants. Although bivalent boosters enhance neutralization, addressing the challenge of emerging sublineages like XBB.1.17.1, FK.1.1, and JN.1 may necessitate the development of tailored vaccines, underscoring the need for ongoing adaptation to effectively combat this highly mutable virus. [ABSTRACT FROM AUTHOR]

Invasive pulmonary mucormycosis (IPM) is a deadly opportunistic mold infection in patients with hematological malignancies (HM). Radiologic imaging is essential for its timely diagnosis. Here, we compared IPM lesions visualized by chest computed tomography (CCT) and chest X-ray (CXR) and determined the prognostic significance of discordant imaging. Therefore, we reviewed 44 consecutive HM patients with probable/proven IPM at MD Anderson Cancer Center in 2000–2020 who had concurrent CCT and CXR studies performed. All 44 patients had abnormal CCTs and 39 (89%) had anormal CXR findings at IPM diagnosis. However, only 26 patients (59%) showed CCT-matching IPM-suspicious lesions on CXR. Acute Physiology and Chronic Health Evaluation II score > 18 at IPM diagnosis and breakthrough infection to Mucorales-active antifungals were the only independent risk factors for 42-day and/or 84-day mortality. Absence of neutropenia at IPM diagnosis, neutrophil recovery in neutropenic patients, and surgical revision of mucormycosis lesions were protective factors. Although not reaching significance on multivariable analysis, visualization of CCT-matching lesions on CXR was associated with significantly increased 84-day mortality (log-rank test, p = 0.033), possibly as a surrogate of extensive lesions and tissue necrosis. This observation supports the exploration of radiologic lesion kinetics as a prognostic staging tool in IPM patients. [ABSTRACT FROM AUTHOR]

This study analyzes immune responses to SARS-CoV-2 vaccination and infection, including asymptomatic cases, focusing on infection risks during the Omicron wave, particularly among high-risk healthcare workers. In the KoCo-Impf study, we monitored 6088 vaccinated participants in Munich aged 18 and above. From 13 May to 31 July 2022, 2351 participants were follow-uped. Logistic regression models evaluated primary, secondary, and breakthrough infections (BTIs). Roche Elecsys® Anti-SARS-CoV-2 assays detected prior infections (via anti-Nucleocapsid antibodies) and assessed vaccination/infection impact (via anti-Spike antibodies) using dried blood spots. Our findings revealed an anti-Nucleocapsid seroprevalence of 44.1%. BTIs occurred in 38.8% of participants, with reinfections in 48.0%. Follow-up participation was inversely associated with current smoking and non-vaccination, while significantly increasing with age and receipt of three vaccine doses. Larger household sizes and younger age increased infection risks, whereas multiple vaccinations and older age reduced them. Household size and specific institutional subgroups were risk factors for BTIs. The anti-Nucleocapsid value prior to the second infection was significantly associated with reinfection risk. Institutional subgroups influenced all models, underscoring the importance of tailored outbreak responses. The KoCo-Impf study underscores the importance of vaccination, demographic factors, and institutional settings in understanding SARS-CoV-2 infection risks during the Omicron wave. [ABSTRACT FROM AUTHOR]

The high transmissibility, rapid evolution, and immune escape of SARS-CoV-2 variants can influence the course of infection and, in turn, morbidity and mortality in COVID-19, posing a challenge in controlling transmission rates and contributing to the emergence and spread of new variants. Understanding the factors that shape viral genetic variation is essential for comprehending the evolution and transmission of SARS-CoV-2, especially in vaccinated individuals where immune response plays a role in the progression and spread of this disease. In this context, we evaluated the impact of immunity induced by the CoronaVac vaccine (Butantan/Sinovac) on intra-host genetic diversity, analyzing 118 whole-genome sequences of SARS-CoV-2 from unvaccinated and vaccinated patients infected with the Gamma variant. Vaccination with CoronaVac favors negative selection at the intra-host level in different genomic regions. It prevents greater genetic diversity of SARS-CoV-2, reinforcing the importance of vaccination in reducing the emergence of new mutations and virus transmission. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to identify COVID-19 breakthrough infections among people with HIV (PWH) across different phases of the pandemic and explore whether differential immune dysfunctions are associated with breakthrough infections. Design and methods: This retrospective population-based cohort study used data from an integrated electronic health record (EHR) database in South Carolina (SC). Breakthrough infection was defined as the first COVID-19 diagnosis documented in the state agency after the date an individual was fully vaccinated (ie, 2 doses of Pfizer/BNT162b2 or Moderna/mRNA-1273, or 1 dose of Janssen/Ad26.COV2.S) through June 14, 2022. We analyzed the risk and associated factors of the outcome using Cox proportional hazards models. Results: Among 7596 fully vaccinated PWH, the overall rate of breakthrough infections was 118.95 cases per 1000 person-years. When compared with the alpha-dominant period, the breakthrough infection rate was higher during both delta-dominant (HR: 1.50; 95% CI: 1.25 to 1.81) and omicron-dominant (HR: 2.86; 95% CI: 1.73 to 4.73) periods. Individuals who received a booster dose had a lower likelihood of breakthrough infections (HR: 0.19; 95% CI: 0.15 to 0.24). There was no association of breakthrough infections with degree of HIV viral suppression, but a higher CD4 count was significantly associated with fewer breakthroughs among PWH (.500 vs,200 cells/mm3: HR: 0.68; 95% CI: 0.49 to 0.94). Conclusions: In our PWH population, the incidence of breakthrough infections was high (during both delta-dominant and omicron-dominant periods) and mainly associated with the absence of a booster dose in patients older than 50 years, with comorbidities and low CD4 count. [ABSTRACT FROM AUTHOR]

Background: Cytomegalovirus (CMV) is a driver of negative outcomes after lung transplant (LTX) and primary prophylaxis (PPX) with valganciclovir (VGC) is standard‐of‐care. VGC is associated with myelosuppression, prompting interest in letermovir (LTV). Methods: Adults receiving LTX between April 1, 2015, and July 30, 2022, at our institution were evaluated. Patients were excluded if low CMV risk (D‐/R‐), survived <90 days post‐LTX, or transferred care before PPX withdrawal. Primary outcomes were leukopenia (white blood cell count [WBC] ≤ 3.0 × 109/L), severe leukopenia (WBC ≤ 2.0 × 109/L), and neutropenia (absolute neutrophil count ≤ 1500 cells/µL) requiring granulocyte‐colony stimulating factor (GCSF) on PPX. Secondary outcomes included breakthrough CMV infection and post‐PPX CMV infection. Results: 204 patients met inclusion criteria: 175 patients on VGC and 29 patients on LTV (after VGC conversion). Most patients received bilateral LTX (62.7%) with non‐lymphocyte‐depleting induction (96.6%) and moderate‐risk serostatus (D+/R+, 48.5%). Patients transitioned from VGC to LTV after a mean of 178 days (SD 80.8 days) post‐transplant. Patients on VGC experienced significantly more leukopenia (82.3% vs. 58.6%, p = 0.008), severe leukopenia (57.1% vs. 31.0%, p = 0.016), and neutropenia requiring GCSF (70.9% vs. 51.7%, p = 0.048). Breakthrough (5.7% vs. 3.4%, p = 0.955) and post‐PPX (24.6% vs. 37.9%, p = 0.199) infections were similar. A subgroup analysis of patients with high‐risk serostatus showed similar trends, though did not reach statistical significance. Conclusions: In this single‐center study, the incidence of leukopenia and neutropenia requiring GCSF were reduced with LTV compared to VGC. Breakthrough and post‐PPX infections were not significantly different. This evidence suggests that LTV has comparable efficacy with reduced myelosuppression compared to VGC in LTX recipients, and may be an appropriate alternative for PPX. [ABSTRACT FROM AUTHOR]

Objective: To determine the occurrence of breakthrough COVID-19 infections (BIs) in patients with systemic lupus erythematosus (SLE) compared with patients with other rheumatic autoimmune diseases (rAIDs), patients with non-rheumatic autoimmune diseases (nrAIDs), and healthy controls (HCs). Methods: The study was based on data from 7035 fully vaccinated respondents to the online COVAD questionnaire with SLE (N = 852), rAIDs (N = 3098), or nrAIDs (N = 414), and HCs (N = 2671). BI was defined as COVID-19 infection occurring in individuals vaccinated with ≥ 2 doses (or 1 dose of J&J) ≥ 14 days after vaccination and not after 6 months since the last vaccine dose. Data were analysed using linear and logistic regression models. Results: A total of 91/852 (10.7%) SLE patients reported at least one BI. The frequency of BIs in SLE patients was comparable to that among HCs (277/2671; p = 0.847) and patients with nrAID (39/414; p = 0.552) but higher than that among patients with other rAIDs (235/3098; p = 0.005). No demographic factors or treatments were associated with BIs in SLE patients (p ≥ 0.05 for all). Joint pain was more frequent in SLE patients than in HCs (odds ratio [OR]: 3.38; 95% confidence interval [CI]: 1.89–6.04; p < 0.001) or nrAID patients (OR: 2.44; 95% CI: 1.04–5.75; p = 0.041). Patient with SLE did not report a higher frequency of hospitalisation or need for advanced treatment for COVID-19 infection compared with disease controls and HCs, respectively. Conclusion: COVID-19 vaccination conferred similar protection against COVID-19 infection in terms of frequency and severity in patients with SLE to that reported by healthy individuals. [ABSTRACT FROM AUTHOR]

Background: Although vaccination is the most effective and specific approach for prevention of infectious diseases, but in a small percentage of vaccinated person's breakthrough infections can occur. This study aimed to determine the effectiveness of different common coronavirus vaccines in this area. Methods: 109 COVID-19 vaccinated patients were enrolled, with different types of vaccines (Sinopharm, AstraZeneca, Sputnic, Bharath, CovIran Barkat and Pasto-CoV) and time of administration in 2021 in Babol, Iran. Patients after 14 days of administration of the final dose of corona vaccines with positive COVID-19 RT-PCR test entered to study. Patients' data such as RT-PCR, type of vaccine, age, sex and outcome were collected using electronic medical records. Results: 47 patients were not fully vaccinated, 62 had two vaccine doses and 51 were fully vaccinated and considered to a breakthrough infection. Although, most of the patients with SARS-CoV-2 infection were either mild (n=18 [16.56%]), or moderate (n=86 [78.9%]), 5 (4.6%) patients had severe or critical illness, of whom 3 admitted in intensive care unit, 3 intubated, and 4 died. The average age of the participants with COVID-19 infections was 61.23 ± 19.91 years. Conclusion: Based on our results, the COVID-19 breakthrough occurring with two doses of current vaccines were mild and moderate. [ABSTRACT FROM AUTHOR]

(1) Background: After the COVID-19 pandemic, there is concern regarding the immunity of the population to SARS-CoV-2 variants, particularly the Omicron variant and its sub-lineages. (2) Methods: The study involved analyzing the immune response and symptomatology of 27 vaccinated individuals who were subsequently infected by Omicron sub-lineages. Blood samples were collected for serological analysis, including the detection of IgG antibodies reactive to the Nucleocapsid (N) and Spike (S) antigens of SARS-CoV-2. Additionally, participants were interviewed to assess the intensity of symptoms during the infection. (3) Results: Despite the high levels of anti-Spike IgG observed after vaccination, all participants were infected by Omicron sub-lineages. The most common symptoms reported by participants were fever or chills, sore throat, and cough. The levels of anti-Spike IgG found prior to infection did not correlate with symptom intensity post-infection. However, it was observed that high post-infection anti-Nucleocapsid IgG levels correlated with mild symptoms during the course of the disease, suggesting a potential role for anti-N antibodies in symptom intensity. (4) Conclusions: In line with previous studies, the high levels of IgG anti-Spike resulting from vaccination did not provide complete protection against infection by the Omicron variant. Additionally, our data suggest that anti-Nucleocapsid IgG titers are negatively correlated with the intensity of the symptoms during mild infections. [ABSTRACT FROM AUTHOR]

Background and aims: The transplacental vertical transfer of maternal antibodies was determined to be a crucial factor in conferring protective immunity to infants following delivery, and this study aimed to evaluate the protective effect of maternal preconception COVID-19 vaccination on infants. Methods: A prospective cohort study was conducted at the National Clinical Medical Research Center for Child Health and Diseases in Chongqing, China, spanning from July 2022 to April 2023. The study included infants from mothers with a preconception COVID-19 vaccination and (or) a SARS-CoV-2 infection during pregnancy. Titers of SARS-CoV-2 immunoglobulin G (IgG) and cross-neutralizing activity against SARS-CoV-2 variants were detected. Results: In this cohort study comprising 158 infants, it was observed that infants born to mothers who experienced a pregnancy-related breakthrough infection following a preconception vaccination had the highest titers of SARS-CoV-2 IgG and cross-neutralizing antibody activity against different variants compared to those with either of these factors alone. The transplacental vertical transmission of anti-SARS-CoV-2 antibodies decreased significantly with increasing age, from 3.16 ODs at birth to 2.29 ODs at two months, and persisted for approximately four months after birth. The predominant subclass of passively transmitted antibodies via the placenta was found to be IgG1, and a positive correlation was observed between the titers of SARS-CoV-2 IgG and IgG1 (R = 0.59, p < 0.001; Slope: 0.49 ± 0.070, p < 0.001). Conclusions: Maternal preconception COVID-19 vaccination represents a promising immunological strategy for conferring postnatal protection to infants, especially during the period of heightened risk of exposure to SARS-CoV-2 infection. It is imperative to underscore the significance of vaccination for women who are preparing to become pregnant or are pregnant, and concerted efforts must be made to promote vaccination among eligible women. [ABSTRACT FROM AUTHOR]

Background: Limited data are available describing the effects of SARS-CoV-2 breakthrough infections on the plasma proteome. Methods: PCR-positive SARS-CoV-2 patients, enrolled in a natural history study, underwent analysis of the plasma proteome. A prospective cohort of 66 unvaccinated and 24 vaccinated persons with different degrees of infection severity were evaluated acutely (within 40 days of symptom onset), and at three and ten months. Comparisons based on vaccination status alone and unsupervised hierarchical clustering were performed. A second cohort of vaccinated Omicron patients were evaluated acutely and at ten months. Results: Acutely, unvaccinated patients manifested overexpression of proteins involved in immune and inflammatory responses, while vaccinated patients exhibited adaptive immune responses without significant inflammation. At three and ten months, only unvaccinated patients had diminished but sustained inflammatory (C3b, CCL15, IL17RE) and immune responses (DEFA5, TREM1). Both groups had underexpression of pathways essential for cellular function, signaling, and angiogenesis (AKT1, MAPK14, HSPB1) across phases. Unsupervised clustering, based on protein expression, identified four groups of patients with variable vaccination rates demonstrating that additional clinical factors influence the plasma proteome. The proteome of vaccinated Omicron patients did not differ from vaccinated pre-Omicron patients. Conclusions: Vaccination attenuates the inflammatory response to SARS-CoV-2 infection across phases. However, at ten months after symptom onset, changes in the plasma proteome persist in both vaccinated and unvaccinated individuals, which may be relevant to post-acute sequelae of SARS-CoV-2 and other viral infections associated with post-acute infection syndromes. [ABSTRACT FROM AUTHOR]

Background: Although 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. Methods: This 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. Results: The 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. Conclusion: Fully 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. [ABSTRACT FROM AUTHOR]

Background: This study examines the humoral and cellular response in multiple sclerosis (MS) patients on anti-CD20 therapy before and after the 1st to 4th BNT162b2 mRNA SARS-CoV-2 vaccination and the relationship with breakthrough infection. Methods: Participants with McDonald 2017 MS that were treated with ocrelizumab were included. The study duration was throughout the COVID-19 pandemic until four months after fourth mRNA SARS-CoV-2 vaccination (BNT162b2). Longitudinal blood samples were analysed for: IgG antibodies of SARS-CoV-2 spike anti-receptor binding domain (anti-RBD), nucleocapsid IgG antibodies (anti-N) and activation induced marker expressing CD4+, CD8+ Tcells and concentration of ocrelizumab and anti-drug antibodies. Incidences of breakthrough infection were confirmed with SARS-CoV-2 PCR tests. Results: The rate of anti-RBD positive participants increased substantially between the third and fourth vaccination from 22.2% to 55.9% (median 54.7 BAU/mL; IQR: 14.5 - 221.2 BAU/mL and 607.7 BAU/mL; IQR: 29.4 - 784.6 BAU/mL, respectively). Within the same period 75% of participants experienced breakthrough infection. The fourth vaccination resulted in an additional increase in seropositive individuals (64.3%) (median 541.8 BAU/mL (IQR: 19.1-1007 BAU/mL). Breakthrough infection did not influence the cellular response without a significant change after the fourth vaccination. During the study period two participants had detectable anti-N, both after the fourth vaccination. No correlation was found between serum concentration of ocrelizumab and the humoral and cellular response. Discussion: Low levels or absence of specific anti-RBD following vaccination, with a significant increase after breakthrough infections and boosted by the fourth vaccination. T-cell reactivity remained sustained and unaffected by breakthrough infections. [ABSTRACT FROM AUTHOR]

In this study, we conducted a case-control investigation to assess the immunogenicity and effectiveness of primary and first booster homologous and heterologous COVID-19 vaccination regimens against infection and hospitalization, targeting variants circulating in Lebanon during 2021–2022. The study population comprised active Lebanese military personnel between February 2021 and September 2022. Vaccine effectiveness (VE) against laboratory-confirmed SARS-CoV-2 infection and associated hospitalization was retrospectively determined during different variant-predominant periods using a case-control study design. Vaccines developed by Sinopharm, Pfizer, and AstraZeneca as well as Sputnik V were analyzed. Prospective assessment of humoral immune response, which was measured based on the SARS-CoV-2 antispike receptor binding domain IgG titer, was performed post vaccination at various time points, focusing on Sinopharm and Pfizer vaccines. Statistical analyses were performed using IBM SPSS and GraphPad Prism. COVID-19 VE remained consistently high before the emergence of the Omicron variant, with lower estimates during the Delta wave than those during the Alpha wave for primary vaccination schemes. However, vaccines continued to offer significant protection against infection. VE estimates consistently decreased for the Omicron variant across post-vaccination timeframes and schemes. VE against hospitalization declined over time and was influenced by the variant. No breakthrough infections progressed to critical or fatal COVID-19. Immunogenicity analysis revealed that the homologous Pfizer regimen elicited a stronger humoral response than Sinopharm, while a heterologous Sinopharm/Pfizer regimen yielded comparable results to the Pfizer regimen. Over time, both Sinopharm's and Pfizer's primary vaccination schemes exhibited decreased humoral immunity titers, with Pfizer being a more effective booster than Sinopharm. This study, focusing on healthy young adults, provides insights into VE during different pandemic waves. Continuous research and monitoring are essential for understanding vaccine-mediated immune responses under evolving circumstances. [ABSTRACT FROM AUTHOR]

Background: Hybrid immunity provides better protection against COVID-19 than vaccination or prior natural infection alone. It induces high magnitude and broadly cross-reactive neutralising anti-Spike IgG antibodies. However, it is not clear how long these potent antibodies last, especially in the context of adenovirus-based COVID-19 vaccines. Methods: We conducted a longitudinal cohort study and enrolled 20 adults who had received an adenovirus-based COVID-19 vaccine before a laboratory-confirmed SARS-CoV-2 infection. We followed up the study participants for 390 days post the initial breakthrough infection. We assessed the longevity and cross-reactive breadth of serum antibodies against SARS-CoV-2 variants of concern (VOCs), including Omicron. Results: The binding anti-Spike IgG antibodies remained within the reported putative levels for at least 360 days and were cross-neutralising against Beta, Gamma, Delta, and Omicron. During the follow up period, a median of one SARS-CoV-2 re-infection event was observed across the cohort, but none resulted in severe COVID-19. Moreover, the re-exposure events were associated with augmented anti-Spike and anti-RBD IgG antibody titres. Conclusions: This study confirms that hybrid immunity provides durable broadly cross-reactive antibody immunity against SARS-CoV-2 variants of concern for at least a year (360 days), and that it is further augment by SARS-CoV-2 re-exposure. [ABSTRACT FROM AUTHOR]

Background: Natural infection or vaccination have provided robust immune defense against SARS-CoV-2 invasion, nevertheless, Omicron variants still successfully cause breakthrough infection, and the underlying mechanisms are poorly understood. Methods: Sequential blood samples were continuously collected at different time points from 252 volunteers who were received the CanSino Ad5-nCoV (n = 183) vaccine or the Sinovac CoronaVac inactivated vaccine (n= 69). The anti- SARS-CoV-2 prototype and Omicron BA.5.2 as well as XBB.1.16 variant neutralizing antibodies (Nab) in sera were detected by ELISA. Sera were also used to measure pseudo and live virus neutralization assay. The associations between the anti-prototype Nab levels and different HLA-ABC alleles were analyzed using artificial intelligence (AI)-deep learning techniques. The frequency of B cells in PBMCs was investigated by flow cytometry assay (FACs). Results: Individuals carrying the HLA-B*15 allele manifested the highest concentrations of anti-SARS-CoV-2 prototype Nab after vax administration. Unfortunately, these volunteers are more susceptible to Omicron BA.5.2 breakthrough infection due to their sera have poorer anti-BA.5.2 Nab and lower levels of viral neutralization efficacy. FACs confirmed that a significant decrease in CD19+CD27+RBD+ memory B cells in these HLA-B*15 population compared to other cohorts. Importantly, generating lower concentrations of cross-reactive anti-XBB.1.16 Nab post-BA.5.2 infection caused HLA-B*15 individuals to be further infected by XBB.1.16 variant. Conclusions: Individuals carrying the HLA-B*15 allele respond better to COVID-19 vax including the CanSino Ad5-nCoV and the Sinovac CoronaVac inactivated vaccines, but are more susceptible to Omicron variant infection, thus, a novel vaccine against this population is necessary for COVID-19 pandemic control in the future. [ABSTRACT FROM AUTHOR]

Breakthrough infection of rabies is rarely reported. And it is difficult to make a definite diagnosis of rabies for patients with atypical clinical manifestations. Here we report a rabies breakthrough infection who presented atypical clinical manifestations. The diagnosis of rabies was confirmed by the detection of rabies virus in cerebrospinal fluid by metagenomics next-generation sequencing (mNGS). [ABSTRACT FROM AUTHOR]

Background Uncertainty exists regarding the effectiveness of COVID-19 vaccine to prevent postacute sequelae of COVID-19 (PASC) following a breakthrough infection. While most studies based on symptom surveys found an association between preinfection vaccination status and PASC symptoms, studies of medically attended PASC are less common and have reported conflicting findings. Methods In this retrospective cohort of patients with an initial SARS-CoV-2 infection who were continually empaneled for primary care in a large US health system, the electronic health record was queried for preinfection vaccination status, demographics, comorbidity index, and diagnosed conditions. Multivariable logistic regression was used to model the outcome of a medically attended PASC diagnosis within 6 months of SARS-CoV-2 infection. Likelihood ratio tests were used to assess the interaction between vaccination status and prevalent variant at the time of infection and between vaccination status and hospitalization for SARS-CoV-2 infection. Results During the observation period, 6.9% of patients experienced medically attended and diagnosed PASC. A diagnosis of PASC was associated with older age, female sex, hospitalization for the initial infection, and an increased severity-weighted comorbidity index and was inversely associated with infection during the Omicron period. No difference in the development of diagnosed PASC was observed between unvaccinated patients and those vaccinated with either 2 doses of an mRNA vaccine or >2 doses. Conclusions We found no association between vaccination status at the time of infection and development of medically diagnosed PASC. Vaccine remains an important measure to prevent SARS-CoV-2 infection and severity. Further research is needed to identify effective measures to prevent and treat PASC. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the clinical usefulness of VirClia IgM/IgG single-assay chemiluminescence tests for the diagnosis of tick-borne encephalitis (TBE) in an endemic part of Norway. Patients hospitalized at Vestfold or Telemark Hospitals with suspected infection in the central nervous system (CNS) in the period between May 2021 and December 2023 were included, with 85 TBE cases identified. The VirClia IgM assay was positive in the initial serum sample in 75/85 cases, giving a sensitivity of 88.2% (95% CI, 79.4–94.2). The ReaScan TBE IgM rapid test was positive in 80/85 cases, with an estimated sensitivity of 94.1% (95% CI, 86.8–98.1). Vaccine breakthrough infections were the predominant cause of non-reactive IgM cases. The calculated specificity for the VirClia IgM was 95.8% (95% CI, 92.5–98.0). In conclusion, the sensitivity of the VirClia IgM was non-inferior to the ReaScan TBE IgM rapid test. However, isolated IgM reactive results must be interpreted with caution, since false-reactive results occur. [ABSTRACT FROM AUTHOR]

Mucorales infections continue to cause significant morbidity and mortality in immunocompromised hosts despite the advent of new approaches for diagnosis and treatment of fungal infections. We aimed to evaluate risk factors and outcomes of Mucorales infection in solid organ transplant, hematopoietic cell transplant, and chimeric antigen receptor T-cell therapy recipients. This single-center retrospective study included solid organ transplant, hematopoietic cell transplant, and chimeric antigen receptor T-cell patients with cultures positive for Mucorales. Forty-three patients were included for analysis; 34 solid organ transplant (79%) and 9 hematopoietic stem cell transplant or chimeric antigen receptor T-cell (21%). Infection with Mucorales occurred a median of 184 days after transplant. At the time of diagnosis, 36 patients were on antifungal prophylaxis with the majority receiving posaconazole (53%). Thirty-three had clinically significant disease; 30 received definitive anti-Mucorales therapy and 3 empiric antifungal therapy. Isavuconazole was the most common azole used for treatment in monotherapy recipients. All-cause mortality was 64% and, of these deaths, 18 (75%) were directly related to Mucormycosis. The highest mortality was seen in disseminated and intra-abdominal disease (100%), followed by pulmonary disease (50%). There was no significant association with mortality and transplant type or number of immunosuppressive agents. Mucormycosis is an important cause of morbidity and mortality in immunocompromised patients. Breakthrough infection was not uncommon in this study. Data regarding the incidence of infection at approximately 6 months after transplantation can inform prophylaxis and treatment regimens. The spectrum of antifungal regimens used reflects the lack of consensus on ideal regimens for these organisms and a need for more studies. [ABSTRACT FROM AUTHOR]

SpikoGen® vaccine is a subunit COVID-19 vaccine composed of an insect cell expressed recombinant spike protein extracellular domain formulated with Advax-CpG55.2™ adjuvant. A randomized double-blind, placebo-controlled Phase II clinical trial was conducted in 400 adult subjects who were randomized 3:1 to receive two intramuscular doses three weeks apart of either SpikoGen® vaccine 25 μg or saline placebo, as previously reported. This study reports a post hoc analysis of the trial data to explore potential immune correlates of SpikoGen® vaccine protection. A range of humoral markers collected pre- and post-vaccination, including spike- and RBD-binding IgG and IgA, surrogate (sVNT), and conventional (cVNT) virus neutralization tests were compared between participants who remained infection-free or got infected over three months of follow-up. From 2 weeks after the second vaccine dose, 21 participants were diagnosed with SARS-CoV-2 infection, 13 (4.2%) in the SpikoGen® group and 8 (9%) in the placebo group. Those in the vaccinated group who experienced breakthrough infections had significantly lower sVNT titers (GMT 5.75 μg/mL, 95% CI; 3.72–8.91) two weeks after the second dose (day 35) than those who did not get infected (GMT 21.06 μg/mL, 95% CI; 16.57–26.76). Conversely, those who did not develop SARS-CoV-2 infection during follow-up had significantly higher baseline sVNT, cVNT, spike-binding IgG and IgA, and RBD-binding IgG, consistent with a past SARS-CoV-2 infection. SpikoGen® further reduced the risk of re-infection (OR 0.29) in baseline seropositive (previously infected) as well as baseline seronegative participants. This indicates that while SpikoGen vaccine is protective in seronegative individuals, those with hybrid immunity have the most robust protection. [ABSTRACT FROM AUTHOR]

Objective: Given the limited studies on types of vaccination and infection rates among health care workers (HCWs) in Türkiye, we analyzed the demographic, clinical, and vaccination characteristics as well as the attitudes of HCWs who have been infected with COVID-19. Methods: We retrospectively analyzed demographic and clinical data on breakthrough COVID-19 infections in HCWs from hospital surveillance data collected between April 5, 2020, and November 1, 2022. The comparison was based on four subgroups that consisted of unvaccinated, one-shot-vaccinated, homologous vaccinated, and heterologous vaccinated individuals. Participants who received various combinations of Sinovac/CoronaVac and/or BioNTech/Pfizer vaccines were compared for detection of COVID-19. Results: During a 33-month period of 744 HCWs who contracted COVID-19, women (65.3%) and nurses (28.9%) were the most affected, followed by doctors (25.8%). Of the infected HCWs, only 1.3% required hospitalization, 0.3% required ICU support, and 98.4% were outpatients. By vaccination status, 143 of the HCWs (19.2%) were unvaccinated, 292 (39.2%) were homologously vaccinated, 294 (39.5%) were heterologously vaccinated, 15 (2%) received a single shot, 206 (27.7%) received two shots, and 165 (22.2%) received three shots. All HCWs contracted COVID-19 at a mean of 134- days (range:1-539) after vaccination. While the proportions of homologously and heterologously vaccinated HCWs were similar, the time elapsed from vaccination to contracting COVID-19 varied (mean 143.4±106.7 vs.126.4±82.43 days). Conclusions: Among both outpatients and inpatients with COVID-19, women HCWs outnumbered men HCWs. HCWs who received homologous vaccination contracted COVID-19 later than those who received heterologous vaccination. [ABSTRACT FROM AUTHOR]

Notwithstanding the wealth of literature on COVID-19, studies focusing on young adults with autoimmune diseases (AD) are lacking. To determine early (within 7 days) and late (after 7 days) anti-SARS-CoV-2 vaccine-related adverse events (AEs), post-vaccine disease flares, COVID-19 severity and breakthrough infections (B-INFs) in young people with rheumatic diseases (RMDs) and non-rheumatic autoimmune diseases (nr-ADs) compared to healthy controls (HC). Data were captured through the international COVID-19 vaccination in autoimmune diseases (COVAD) 1 and 2 questionnaires. Of 20,685 complete responses, we identified 6010 from patients aged 18–35 years (1692 RMD, 400 nrADs, 3918 HC) who received up to 4 vaccine doses. BNT162b2 was the most frequently administered vaccine and prior to vaccination, 7% of people with nrAD were taking immunosuppressants (IS) versus 80% in RMDs. Early mild AEs were more frequent in RMDs (93%) and nr-ADs (92%) compared to HC (85%). The frequency of late mild AEs was < 20% in all groups. Severe AEs were rare. SARS-CoV-2 infection rates were similar across all groups, however, RMD patients reported a single episode of infection more frequently than nrADs and HC, while nrADs reported multiple infections more frequently than RMD. Self-reported disease flares were reported by 10% or RMD and 7% of nrAD patients. Our study reinforces the safety of anti-SARS-CoV-2 vaccine also in young people with ADs, but it also highlights that among young individuals the number and clinical picture of SARS-CoV-2 infections is affected more by the type of AD rather than by coexisting IS therapy. [ABSTRACT FROM AUTHOR]

Background: Mpox infection is a zoonotic illness that resembles smallpox. Vaccination is widely regarded as a vital effective method of preventing mpox, however, there is lack of consensus of effectiveness of a single dose of mpox vaccine in the current 2022–2023 outbreak. We pooled data from real‐world studies to evaluate the efficacy of the JYNNEOS vaccination given as a single dosage. Method: We carried out a thorough literature search in PubMed, Web of Science, and Scopus up until August 2023. We estimated the pooled vaccine effectiveness (VE) for mpox using inverse variance method in a random‐effects meta‐analysis. We expressed the results as VE, 95% confidence interval (95% CI), and 95% prediction interval (95% PI) using R v4.3.0. We assessed influence, heterogeneity contribution, and influence of studies using several tests and conducted sensitivity analysis accordingly. We used Doi plot and Luis Furuya‐Kanamori (LFK) index to evaluate publication bias. Results: With a total sample size of 35,326 individuals, we involved 11 studies in the meta‐analysis. The VE of a single dose of JYNNEOS vaccine was 78.23% (95% CI: 62.79%–87.27%) by pooling data of 24,784 individuals over seven studies. The findings were heterogenous with a 95% PI of −32.14% to 96.41% depicting the expected range of VE in similar settings. Notably, VE increased to 83.02% (74.62%–88.64%) with a prediction interval of (44.67%–94.79) after sensitivity analysis by leaving out outliers. The results were robust in light of several sensitivity analyses. An asymmetric Doi plot with LFK index of −2.25 showed potential publication bias. Pooled prevalence of mpox infection among vaccinated individuals (breakthrough infection) in six studies was 2.19% (0.37%–5.32%). Conclusion: The present findings provide compelling evidence that a single dose of JUNNEOS vaccine can protect recipients from mpox infection. With a 78.23% estimated efficacy rate, the vaccine is thought to be a useful tool in preventing further spread of mpox. However, more research and ongoing surveillance are required to fully understand the reasons behind breakthrough infections and to improve immunization strategies for better protection against mpox. [ABSTRACT FROM AUTHOR]

Background: In this post hoc exploratory study of the APHP-COVIBOOST trial (NCT05124171), we used statistical modeling to describe the evolution of neutralizing antibody (nAb) titers over time, asses its impact on SARS-CoV-2 infection, and explore potential differences between three booster vaccine formulations (D614, B.1.351, and BNT162b2). Methods: Antibody titers were measured for 208 adult participants at day 28, 3 months, and 6 months using a microneutralization assay against different Omicron subvariants. We developed four specific Bayesian statistical models based on a core model, accounting for vaccine-specific antibody decline, boosting of nAb for breakthrough infection, and risk of infection according to nAb levels. The model findings were cross-verified using another validated microneutralization assay. Results: The decrease in nAb titers was significantly lower for the B.1.351 vaccine than for the other booster formulations. An inverse relationship was found between risk of infection upon exposure and nAb levels. With Omicron BA.1 data, these results translated into a positive relative vaccine efficacy against any infection over 6 months for the B.1.351 vaccine compared to the BNT162b2 (31%) and D614 (21%) vaccines. Conclusions: Risk of infection decreased with increasing nAb titers for all vaccines. Statistical models predicted significantly better antibody persistence for the B.1.351 booster formulation compared to the other evaluated vaccines. [ABSTRACT FROM AUTHOR]

Breakthrough COVID-19 (occurring in fully vaccinated people) has been described. Data on its characteristics among immune-mediated rheumatic disease (IMRD) patients are scarce. This study describes breakthrough COVID-19 occurring in IMRD patients participating in the SAFER-study, a Brazilian multicentric cohort evaluating the safety, effectiveness, and immunogenicity of SARS-CoV-2 vaccines in patients with autoimmune diseases. A descriptive analysis of the population and a binary logistic regression model were performed to evaluate the predictors of COVID-19-related hospitalization. A p-value < 0.05 was significant. The included 160 patients were predominantly females (83.1%), with a mean (SD) age of 40.23 (13.19) years. The patients received two (19%), three (70%), or four (11%) vaccine doses. The initial two-dose series was mainly with ChAdOx1 (Oxford/AstraZeneca) (58%) or BBIBP-CorV (Sinopharm-Beijing) (34%). The first booster (n = 150) was with BNT162b2 (BioNtech/Fosun Pharma/Pfizer) (63%) or ChAdOx1 (29%). The second booster (n = 112) was with BNT162b2 (40%) or ChAdOx1 (26%). The COVID-19 hospitalization rate was 17.5%. IMRD moderate/high activity (OR: 5.84; CI: 1.9–18.5; p = 0.002) and treatment with corticosteroids (OR: 2.94; CI: 1.02–8.49; p = 0.0043) were associated with higher odds of hospitalization, while increasing the number of vaccine doses was protective (OR: 0.37; CI: 0.15–0.9; p = 0.032). These findings, along with previous reassuring results about the safety of the COVID-19 vaccines, argue in favor of booster vaccination in IMRD patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective. Incidence and manifestations of postacute sequelae of coronavirus disease 2019 (PASC) are poorly defined among immunosuppressed populations. We reported, phenotyped, and assessed risk factors for PASC in adults with systemic autoimmune diseases. Methods. Persons aged = 18 years with systemic autoimmune diseases were recruited into a national, prospective observational cohort of SARS-CoV-2 vaccination and infection between December 2020 and April 2021. Serial surveys assessed vaccination status, SARS-CoV-2 infection incidence, and disease flares. Participants reporting SARS-CoV-2 infection received a questionnaire assessing symptom duration, severity, and quality of life (QOL) effect; PASC was defined as = 1 symptom persisting for > 12 weeks. PASC syndromes were mapped by overlapping symptom domains. Characteristics were compared between participants who did vs did not report PASC. Results. Among 1615 participants, 590 (36.5%) reported SARS-CoV-2 infection and were sent PASC surveys, 299 (50.7%) of whom responded > 12 weeks following the reported infection. Respondents were 91.6% female, 91.2% White, median (IQR) age was 48 (40-60) years with median (IQR) 3 (2-3) vaccine doses at time of first infection. Common diagnoses included inflammatory arthritis (38.5%) and inflammatory bowel disease (14.4%). Eighty-nine of 299 (29.8%) reported PASC, with the most reported symptom domain being neurological/psychological (83.1%); 84% reported an effect on QOL. Participants with PASC reported lower number of preceding vaccines (median [IQR] 2 [2-3] vs 3 [2-3]; P < 0.001) and more reinfections (16.9% vs 5.7%; P = 0.004). Conclusion. In a large, real-world cohort, 29.8% of persons with systemic autoimmune disease reported PASC, often affecting QOL. Preceding vaccination may reduce PASC, whereas multiple infections may increase risk, supporting ongoing booster vaccine campaigns and efforts to limit breakthrough infections. [ABSTRACT FROM AUTHOR]

Abstract Breakthrough infection of rabies is rarely reported. And it is difficult to make a definite diagnosis of rabies for patients with atypical clinical manifestations. Here we report a rabies breakthrough infection who presented atypical clinical manifestations. The diagnosis of rabies was confirmed by the detection of rabies virus in cerebrospinal fluid by metagenomics next-generation sequencing (mNGS).

Prevention of COVID-19 with vaccine requires multiple doses and updated boosters to maintain protection; however currently there are no tests that can measure immunity and guide clinical decisions about timing of booster doses. This study examined the association between the risk of COVID-19 breakthrough infections and receptor binding domain (RBD) antibody levels and receipt of booster of COVID-19 vaccines. A community sample of Los Angeles County adults were surveyed between 2021 and 2022 to determine if they had a self-reported breakthrough infection. Predictors included RBD antibody levels, measured by binding antibody responses to the ancestral strain at baseline and self-reported booster shot during the study period. Of the 859 participants, 182 (21%) reported a breakthrough infection. Irrespective of the level of antibodies, the risk of breakthrough infection was similar, ranging from 19 to 23% (P = 0.78). The risk of breakthrough infections was lower among participants who had a booster shot (P = 0.004). The protective effect of a booster shot did not vary by antibody levels prior to receiving the booster. This study found no association between RBD antibody levels and risk of breakthrough infections, while the receipt of booster was associated with lower risk of breakthrough infections, which was independent of pre-booster antibody levels. Therefore, antibody levels might not be a useful guide for clinical decisions about timing of booster doses.

Tixagevimab and cilgavimab (T/C) are neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be used to prevent SARS-CoV-2 infection in solid organ transplant (SOT) recipients. However, their neutralizing activity against recent variants was reduced, raising concerns regarding the emergence of breakthrough coronavirus diseases 2019 (COVID-19). This study aimed to investigate the status of the COVID-19 breakthrough after T/C administration. We retrospectively investigated breakthrough COVID-19 in SOT recipients administered T/C at Kyoto University Hospital, Japan, from November 2022 to March 2023. Patients were monitored for 6 months after T/C administration. SARS-CoV-2 infection was diagnosed using polymerase chain reaction or antigen tests. The monthly incidence rates of SARS-CoV-2 infection were calculated using the person–time method. T/C were administered to 67 SOT recipients (liver, 16; lung, 36; and kidney, 15), of whom five were infected with SARS-CoV-2. All five cases were classified as mild, and none of these patients required admission to the intensive care unit (ICU) or died. All infected individuals tested positive for SARS-CoV-2 after March 2023, when T/C-resistant subvariant strains became predominant. The monthly incidence rate of SARS-CoV-2 infection, calculated using the person–time method, suggested an increasing trend. During the T/C-resistant variant epidemic, SARS-CoV-2 infections were identified even after T/C administration, suggesting that the prophylactic effects of T/C were invalid. Therefore, emerging variants must be carefully monitored and characterized to determine appropriate antiviral strategies, such as the use of suitable neutralizing antibodies. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) continues its significant health and economic impact globally. Despite the success of spike-protein vaccines in preventing severe disease, long-lasting protection against emerging variants and the prevention of breakthrough infections and transmission remain elusive. We generate an intranasal live-attenuated SARS-CoV-2 vaccine, CDO-7N-1, using codon deoptimization. CDO-7N-1 shows highly attenuated replication and minimal or no lung pathology in vivo over multiple passages. It induces robust mucosal and systemic neutralizing antibody and T-cell subset responses, in mice (female K18-hACE2 and male HFH4-hACE2 mice), hamsters, and macaques triggered by a single immunization. Mice and hamsters vaccinated with CDO-7N-1 are protected from challenge with wild-type (WT) SARS-CoV-2 and other variants of concern. Serum from vaccinated animals neutralizes WT SARS-CoV-2, variants of concern (beta and delta), variants of interest (omicron XBB.1.5) and SARS-CoV-1. Antibody responses are sustained and enhanced by repeated immunization or infection with WT SARS-CoV-2. Immunity against all SARS-CoV-2 proteins by CDO-7N-1 should improve efficacy against future SARS-CoV-2 variants. Current SARS-CoV-2 vaccines require several injections for optimal immune protection. Here, the authors report an intranasal live-attenuated vaccine that induces long-term immunity following a single dose and protects from SARS-CoV-2 wildtype and variants in non-human primate and small animal models. [ABSTRACT FROM AUTHOR]

Hybrid immunity against SARS-CoV-2 has not been well studied in pregnancy. We conducted a comprehensive analysis of neutralizing antibodies (nAb) and binding antibodies in pregnant individuals who received mRNA vaccination, natural infection, or both. A third vaccine dose augmented nAb levels compared to the two-dose regimen or natural infection alone; this effect was more pronounced in hybrid immunity. There was reduced anti-Omicron nAb, but the maternal-fetal transfer efficiency remained comparable to that of other variants. Vaccine-induced nAbs were transferred more efficiently than infection-induced nAbs. Anti-spike receptor binding domain (RBD) IgG was associated with nAb against wild-type (Wuhan-Hu-1) following breakthrough infection. Both vaccination and infection-induced anti-RBD IgA, which was more durable than anti-nucleocapsid IgA. IgA response was attenuated in pregnancy compared to non-pregnant controls. These data provide additional evidence of augmentation of humoral immune responses in hybrid immunity in pregnancy. [ABSTRACT FROM AUTHOR]

Background The emergence of rapidly evolving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, coupled with waning vaccine-induced immunity, has contributed to the rise of vaccine breakthrough infections. It is crucial to understand how vaccine-induced protection is mediated. Methods We examined 2 prospective cohorts of mRNA vaccinated and boosted individuals during the Omicron wave of infection in Singapore. Results We found that individuals who remain uninfected over the follow-up period had a higher variant-specific IgA, but not IgG, antibody response at 1 month after booster vaccination, compared with individuals who became infected. Conclusions We conclude that IgA may have a potential contributory role in protection against Omicron infection. Clinical Trials Registration. NCT05142319. [ABSTRACT FROM AUTHOR]

Invasive fungal disease (IFD) presents a life-threatening condition in immunocompromised patients, thus often prompting empirical administration of antifungal treatment, without adequate mycological evidence. Over the past years, wide use of antifungal prophylaxis resulted in decreased occurrence of IFD but has contributed to changes in the spectrum of fungal pathogens, revealing the occurrence of previously rare fungal genera causing breakthrough infections. The expanding spectrum of clinically relevant fungal pathogens required the implementation of screening approaches permitting broad rather than targeted fungus detection to support timely onset of pre-emptive antifungal treatment. To address this diagnostically important aspect in a prospective setting, we analyzed 935 serial peripheral blood (PB) samples from 195 pediatric and adult patients at high risk for IFD, involving individuals displaying febrile neutropenia during treatment of hematological malignancies or following allogeneic hematopoietic stem cell transplantation. Two different panfungal-PCR-screening methods combined with ensuing fungal genus identification by Sanger sequencing were employed. In the great majority of PB-specimens displaying fungal DNAemia, the findings were transient and revealed fungi commonly regarded as non-pathogenic or rarely pathogenic even in the highly immunocompromised patient setting. Hence, to adequately exploit the diagnostic potential of panfungal-PCR approaches for detecting IFD, particularly if caused by hitherto rarely observed fungal pathogens, it is necessary to confirm the findings by repeated testing and to identify the fungal genus present by ensuing analysis. If applied appropriately, panfungal-PCR-screening can help prevent unnecessary empirical therapy, and conversely, contribute to timely employment of effective pre-emptive antifungal treatment strategies. [ABSTRACT FROM AUTHOR]

Tick-borne encephalitis virus (TBEV) vaccine breakthrough (VBT) infections are not uncommon in endemic areas. The clinical and immunological outcomes have been poorly investigated. We assessed the magnitude and specificity of virus-specific antibody and T cell responses after TBE in previously vaccinated subjects and compared the results with those of unvaccinated TBE patients and study subjects that received vaccination without VBT infection. Symptomatic TBEV infection of unvaccinated study subjects induced virus-specific antibody responses to the E protein and non-structural protein 1 (NS1) as well as T cell responses to structural and other non-structural (NS) proteins. After VBT infections, significantly impaired NS1-specific antibody responses were observed, while the virus-specific T cell responses to the NS proteins were relatively strong. VBT infection caused predominantly moderate to severe disease during hospitalization. The level of TBEV EDIII- and NS1-specific antibodies in unvaccinated convalescent patients inversely correlated with TBE severity and neurological symptoms early after infection. [ABSTRACT FROM AUTHOR]

Background: SARS-CoV-2 vaccines are safe and effective against infection and severe COVID-19 disease worldwide. Certain co-morbid conditions cause immune dysfunction and may reduce immune response to vaccination. In contrast, those with co-morbidities may practice infection prevention strategies. Thus, the real-world clinical impact of co-morbidities on SARS-CoV-2 infection in the recent post-vaccination period is not well established. This study was performed to understand the epidemiology of Omicron breakthrough infection and evaluate associations with number of comorbidities in a vaccinated and boosted population. Methods and findings: A retrospective clinical cohort study was performed utilizing the Northwestern Medicine Enterprise Data Warehouse. Our study population was identified as fully vaccinated adults with at least one booster. The primary risk factor of interest was the number of co-morbidities. The primary outcome was the incidence and time to the first positive SARS-CoV-2 molecular test in the Omicron predominant era. Multivariable Cox modeling analyses to determine the hazard of SARS-CoV-2 infection were stratified by calendar time (Period 1: January 1 –June 30, 2022; Period 2: July 1 –December 31, 2022) due to violations in the proportional hazards assumption. In total, 133,191 patients were analyzed. During Period 1, having 3+ comorbidities was associated with increased hazard for breakthrough (HR = 1.16 CI 1.08–1.26). During Period 2 of the study, having 2 comorbidities (HR = 1.45 95% CI 1.26–1.67) and having 3+ comorbidities (HR 1.73, 95% CI 1.51–1.97) were associated with increased hazard for Omicron breakthrough. Older age was associated with decreased hazard in Period 1 of follow-up. Interaction terms for calendar time indicated significant changes in hazard for many factors between the first and second halves of the follow-up period. Conclusions: Omicron breakthrough is common with significantly higher risk for our most vulnerable patients with multiple co-morbidities. Age plays an important role in breakthrough infection with the highest incidence among young adults, which may be due to age-related behavioral factors. These findings reflect real-world differences in immunity and exposure risk behaviors for populations vulnerable to COVID-19. [ABSTRACT FROM AUTHOR]