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Current poultry vaccines against influenza A viruses target the globular head region of the hemagglutinin (HA1), providing limited protection against antigenically divergent strains. Experimental subunit vaccines based on the conserved ectodomain of the matrix protein 2 (M2e) induce cross-reactive antibody responses, but fail to fully prevent virus shedding after low pathogenic avian influenza (LPAI) virus challenge, and are ineffective against highly pathogenic avian influenza (HPAI) viruses. This study assessed the benefits of combining nanoparticles bearing three tandem M2e repeats (NR-3M2e nanorings or NF-3M2e nanofilaments) with an HA1 subunit vaccine in protecting chickens against a heterologous HPAI H5N1 virus challenge. Chickens vaccinated with the combined formulations developed M2e and HA1-specific antibodies, were fully protected from clinical disease and mortality, and showed no histopathological lesions or virus shedding, unlike those given only HA1, NR-3M2e, or NF-3M2e. Thus, the combined vaccine formulations provided complete cross-protection against HPAI H5N1 virus, and prevented environmental virus shedding, crucial for controlling avian influenza outbreaks. [ABSTRACT FROM AUTHOR]

The most commonly used animal models for evaluating the efficacy of HSV-2 candidate vaccines are mice and guinea pigs. While numerous HSV-2 vaccine candidates have been tested in these animals and were effective in reducing disease and mortality, these results did not predict the effectiveness of the vaccines in human trials. Infection of rhesus macaques rarely results in lesions or HSV-2 specific antibody responses. In seeking an animal model that better recapitulates human disease and that might be more predictive of the efficacy of prophylactic vaccines than mice and guinea pigs, we evaluated Cebus apella (C. apella), a New World primate, in an HSV-2 genital infection model. Infectious HSV-2 was cultured from vaginal swabs from all 4 animals for 9–14 days after intravaginal inoculation of HSV-2 seronegative monkeys. Two of 4 monkeys had vesicular lesions in the vagina or vulva. No neurological symptoms were noted. Recurrent lesions and HSV-2 DNA shedding after acute disease resolved was infrequent. UV irradiation of the genital area did not induce recurrent genital lesions or virus shedding. All 4 monkeys developed HSV-2 neutralizing antibodies as well as virus-specific CD4 and CD8 T cell responses. Reinfection of animals 15 to 19 months after primary infection did not result in lesions; animals had reduced virus shedding and a shorter duration of shedding compared with that during primary infection, suggesting that primary infection induced protective immunity. Primary fibroblasts from C. apella monkeys supported the growth of HSV-2 in vitro; in contrast, HSV-2 did not replicate above the titer of the input inoculum in fibroblasts from rhesus macaques. These observations suggest that the C. apella monkey has potential to serve as a model for evaluating the efficacy of prophylactic vaccines, antivirals, or monoclonal antibodies to HSV-2. Author summary: Herpes simplex virus 2 (HSV-2) is a cause of genital herpes, neonatal herpes, and herpes encephalitis. The virus persists in the nervous system for life and periodically reactivates resulting in recurrent genital lesions and can be transmitted to susceptible individuals. Currently there is no cure for the disease and no licensed vaccine to prevent infection. Numerous HSV-2 vaccine candidates have been tested in animal models, mostly in mice and guinea pigs, and vaccine efficacy observed in these animals has been poorly predictive for effectiveness of HSV-2 vaccines in humans. Thus, there is a need for an animal model that better recapitulates human disease and is more predictive for the efficacy of prophylactic vaccines. We evaluated an HSV-2 genital infection model using Cebus apella, a New World primate. Infectious HSV-2 was cultured from vaginal swabs from all 4 animals for 9–14 days after intravaginal inoculation. The animals developed symptoms similar to most humans with genital vesicular lesions and no neurological signs. They also developed antibody and T cell responses to HSV-2. Prior infection generally reduced reinfection. These observations suggest that Cebus apella monkeys have the potential to serve as a good model for evaluating the efficacy of prophylactic HSV-2 vaccines. [ABSTRACT FROM AUTHOR]

Objectives To describe the management of haematological patients experiencing prolonged SARS-CoV-2 viral shedding, as the optimal management strategy for this condition remains undetermined. Methods We conducted a retrospective evaluation of our prospectively followed cohort of haematological patients treated with remdesivir for more than 10 days. Starting January 2023, upon COVID-19 diagnosis, the treatment strategy was based on symptoms and PCR cycle threshold (Ct) as follows: (i) when Ct was 25 or less or if the patient had symptoms, a course of remdesivir for at least 10 days, nirmatrelvir/ritonavir for 5 days (whenever possible) and convalescent plasma was administered; and (ii) when the patient was asymptomatic and had a PCR Ct of more than 25, when possible, a course of 5 days of nirmatrelvir/ritonavir was administered. The patient was considered to have achieved viral clearance and, thus, remdesivir was stopped, in either of these cases: (i) PCR negativity, or (ii) subgenomic RNA negativity. Results From January to November 2023, 18 patients benefited from a safe extended remdesivir administration, resulting in detection of SARS-CoV-2 viral clearance in a median time of 3.5 weeks (IQR 2.6–3.9) (min–max 1.6–8.0). No clinical or biological side effects were detected. No patient died or needed further treatment for their COVID-19 episode. Conclusions The extended course of remdesivir, combined with other active therapies for COVID-19 infection, was well tolerated. Cure and virus negativity were obtained in all these high-risk patients. [ABSTRACT FROM AUTHOR]

Introduction: This study sought to evaluate the cost-effectiveness of baloxavir marboxil compared with oseltamivir or no antiviral treatment from a US payer perspective using data from a real-world US administrative claims study. Given baloxavir's ability to rapidly stop viral shedding, the potential health economic implications of a baloxavir-induced population-level reduction in viral transmission was also explored. Methods: A decision tree cost-effectiveness model was developed for seasonal influenza (2018–2020) using a lifetime time horizon with 3.0% discounting for costs and quality-adjusted life-years (QALYs). Patients aged ≥ 12 years could receive baloxavir, oseltamivir or no antiviral treatment. Patient characteristics, complications, and costs were derived from the Merative™ MarketScan® Research Databases including US commercial claims and Medicare and Medicaid Supplemental databases. A scenario analysis explored the impact of reduced viral transmission with baloxavir. Results: In the base case analysis, baloxavir was cost-effective within a willingness-to-pay threshold of US$100,000/QALY compared with oseltamivir [incremental cost-effectiveness ratio (ICER), $6813/QALY gained] or no antiviral treatment (ICER, $669/QALY gained). The net monetary benefit (NMB) of baloxavir was $1180 and $6208 compared with oseltamivir and no treatment, respectively. The NMB of baloxavir increased linearly with reductions in viral transmission, where a 5% transmission reduction yielded an NMB of $2592 versus oseltamivir and $7621 versus no treatment. Baloxavir became dominant (more effective and less costly, with ICERs < 0) starting with a 12.0% reduction in viral transmission versus oseltamivir and 6.0% versus no antiviral treatment. Conclusion: Baloxavir was cost-effective compared with oseltamivir or no antiviral treatment. The potential of baloxavir to reduce viral transmission offers a substantial economic benefit from a US payer perspective. Plain Language Summary: Baloxavir is a prescription medicine that reduces the duration of flu symptoms and reduces the likelihood of complications from the flu, including serious complications that may require hospitalization. Baloxavir may reduce the spread of the flu to healthy people by reducing the amount and duration of virus shedding from infected people. We designed a model to estimate the cost benefits of using baloxavir versus another flu treatment, known as oseltamivir, or no flu treatment at all. Using baloxavir led to more cost savings than oseltamivir or no treatment for people in the US who have commercial health insurance. Baloxavir was even more cost-effective in the scenario where it reduced the number of flu cases (transmission benefit). This could ultimately have a meaningful benefit across a large health insurance population. [ABSTRACT FROM AUTHOR]

Objective: This retrospective cohort study aimed to assess the clinical features, treatment outcomes, and short-term prognosis in kidney transplant recipients (KTRs) with concurrent coronavirus disease 2019 (COVID-19) pneumonia. Methods: KTRs with COVID-19 pneumonia who were admitted to our hospital from December 28, 2022, to March 28, 2023 were included in the study. Their clinical symptoms, responses to antiviral medications, and short-term prognosis were analyzed. Results: A total of 64 KTRs with initial diagnosis of COVID-19 pneumonia were included in this study. The primary symptoms were fever, cough, and myalgia, with an incidence of 79.7%, 89.1%, and 46.9%, respectively. The administration of antiviral drugs (paxlovid or molnupiravir) within 1-5 days and for over 5 days demonstrated a statistically significant reduction in viral shedding time compared to the group without antiviral medication (P=0.002). Both the paxlovid and molnupiravir treatment groups exhibited a significantly shorter duration of viral shedding time in comparison to the group without antiviral drugs (P=0.002). After 6 months of recovery, there was no significantly negative impact on transplant kidney function (P=0.294). Conclusion: Fever, cough, and myalgia remain common initial symptoms of concurrent COVID-19 pneumonia in KTRs. Early use of antiviral drugs (paxlovid or molnupiravir) is associated with better therapeutic outcomes. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had a limited impact on the short-term renal function of the KTRs with concurrent moderate or severe COVID-19 pneumonia. [ABSTRACT FROM AUTHOR]

The global outbreak of mpox in 2022 and subsequent sporadic outbreaks in 2023 highlighted the importance of nonpharmaceutical interventions such as case isolation. Individual variations in viral shedding dynamics may lead to either premature ending of isolation for infectious individuals, or unnecessarily prolonged isolation for those who are no longer infectious. Here, we developed a modeling framework to characterize heterogeneous mpox infectiousness profiles – specifically, when infected individuals cease to be infectious – based on viral load data. We examined the potential effectiveness of three different isolation rules: a symptom-based rule (the current guideline in many countries) and rules permitting individuals to stop isolating after either a fixed duration or following tests that indicate that they are no longer likely to be infectious. Our analysis suggests that the duration of viral shedding ranges from 23 to 50 days between individuals. The risk of infected individuals ending isolation too early was estimated to be 8.8% (95% CI: 6.7–10.5) after symptom clearance and 5.4% (95% CI: 4.1–6.7) after 3 weeks of isolation. While these results suggest that the current standard practice for ending isolation is effective, we found that unnecessary isolation following the infectious period could be reduced by adopting a testing-based rule. Current guidelines recommend that individuals exposed to mpox should isolate for three weeks, based on the average estimated incubation period. Here, the authors use a quantitative model to characterise mpox infectiousness profiles and quantify the impacts of different isolation rules. [ABSTRACT FROM AUTHOR]

Despite the high prevalence of BK polyomavirus (BKPyV) and the associated risk for BKPyV-associated nephropathy (BKPyVAN) in kidney transplant (KTX) recipients, many details on viral processes such as replication, maturation, assembly and virion release from host cells have not been fully elucidated. VP1 is a polyomavirus-specific protein that is expressed in the late phase of its replicative cycle with important functions in virion assembly and infectious particle release. This study investigated the localization and time-dependent changes in the distribution of VP1-positive viral particles and their association within the spectrum of differing cell morphologies that are observed in the urine of KTX patients upon active BKPyV infection. We found highly differing recognition patterns of two anti-VP1 antibodies with respect to intracellular and extracellular VP1 localization, pointing towards independent binding sites that were seemingly associated with differing stages of virion maturation. Cells originating from single clones were stably cultured out of the urine sediment of KTX recipients with suspected BKPyVAN. The cell morphology, polyploidy, virus replication and protein production were investigated by confocal microscopy using both a monoclonal (mAb 4942) and a polyclonal rabbit anti-VP1-specific antibody (RantiVP1 Ab). Immunoblotting was performed to investigate changes in the VP1 protein. Both antibodies visualized VP1 and the mAb 4942 recognized VP1 in cytoplasmic vesicles exhibiting idiomorphic sizes when released from the cells. In contrast, the polyclonal antibody detected VP1 within the nucleus and in cytoplasm in colocalization with the endoplasmic reticulum marker CNX. At the nuclear rim, VP1 was recognized by both antibodies. Immunoblotting revealed two smaller versions of VP1 in urinary decoy cell extracts, potentially from different translation start sites as evaluated by in silico analysis. Oxford Nanopore sequencing showed integration of BKPyV DNA in chromosomes 3, 4 and 7 in one of the five tested primary cell lines which produced high viral copies throughout four passages before transcending into senescence. The different staining with two VP1-specific antibodies emphasizes the modification of VP1 during the process of virus maturation and cellular exit. The integration of BKPyV into the human genome leads to high virus production; however, this alone does not transform the cell line into a permanently cycling and indefinitely replicating one. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells play a critical role in virus control. However, it has remained largely unclear whether NK cell mobilization in SARS-CoV-2 infections is beneficial or pathologic. To address this deficit, we employed a validated experimental NK cell depletion non-human primate (NHP) model with SARS-CoV-2 Delta variant B.1.617.2 challenge. Viral loads (VL), NK cell numbers, activation, proliferation, and functional measures were evaluated in blood and tissues. In non-depleted (control) animals, infection rapidly induced NK cell expansion, activation, and increased tissue trafficking associated with VL. Strikingly, we report that experimental NK cell depletion leads to higher VL, longer duration of viral shedding, significantly increased levels of pro-inflammatory cytokines in the lungs, and overt lung damage. Overall, we find the first significant and conclusive evidence for NK cell-mediated control of SARS-CoV-2 virus replication and disease pathology. These data indicate that adjunct therapies for infection could largely benefit from NK cell-targeted approaches. Author summary: Natural killer (NK) cells play a critically understudied role in controlling SARS-CoV-2 viral replication, clearance, and disease sequelae. In this manuscript, we investigated the protective role of NK cells in acute infection using a well-established NK cell depletion strategy in cynomolgus macaques (CM) and a SARS-CoV-2 delta variant infection model. Circulating NK cells exhibited an increased proliferative and activated phenotype following infection, concomitant with peak NK cell expansion at 10 days post-infection (DPI). Importantly, following experimental NK cell depletion, CM exhibited increased viral shedding and delayed viral clearance compared to controls. NK cell-depleted animals also exhibited significantly increased lung pathology and Luminex cytokine analyses of broncho-alveolar lavage (BAL) fluid showed a 5-fold increase in interferon-alpha (IFNα) compared to controls during peak infection. Collectively, our findings suggest that NK cells play a crucial role in controlling SARS-CoV-2 replication and reducing lung damage. These results underscore the potential of NK cell-based vaccines and therapies for COVID-19 and other infectious diseases, warranting further investigation in this area. [ABSTRACT FROM AUTHOR]

High pathogenicity avian influenza viruses (HPAIVs) have caused major epizootics in recent years, with devastating consequences for poultry and wildlife worldwide. Domestic and wild ducks can be highly susceptible to HPAIVs, and infection leads to efficient viral replication and massive shedding (i.e., high titres for an extended time), contributing to widespread viral dissemination. Importantly, ducks are known to shed high amounts of virus in the earliest phase of infection, but the dynamics and impact of environmental contamination on the epidemiology of HPAIV outbreaks are poorly understood. In this study, we monitored mule ducks experimentally infected with two H5N8 clade 2.3.4.4b goose/Guangdong HPAIVs sampled in France in 2016–2017 and 2020–2021 epizootics. We investigated viral shedding dynamics in the oropharynx, cloaca, conjunctiva, and feathers; bird-to-bird viral transmission; and the role of the environment in viral spread and as a source of samples for early detection and surveillance. Our findings showed that viral shedding started before the onset of clinical signs, i.e., as early as 1 day post-inoculation (dpi) or post-contact exposure, peaked at 4 dpi, and lasted for up to 14 dpi. The detection of viral RNA in aerosols, dust, and water samples mirrored viral shedding dynamics, and viral isolation from these environmental samples was successful throughout the experiment. Our results confirm that mule ducks can shed high HPAIV titres through the four excretion routes tested (oropharyngeal, cloacal, conjunctival, and feather) while being asymptomatic and that environmental sampling could be a non-invasive tool for early viral RNA detection in HPAIV-infected farms. [ABSTRACT FROM AUTHOR]

Background: Reticuloendotheliosis virus (REV), a member of the family Retroviridae, is a hot area of research, and a previous study showed that exosomes purified from REV-positive semen were not blocked by REV-specific neutralizing antibodies and established productive infections. Methods: To further verify the infectivity of exosomes from REV-infected cells, we isolated and purified exosomes from REV-infected DF-1 cells and identified them using Western blot and a transmission electron microscope. We then inoculated 7-day-old embryonated eggs, 1-day-old chicks and 23-week-old hens with and without antibody treatment. REV was administered simultaneously as a control. Results: In the absence of antibodies, the results indicated that REV-exosomes and REV could infect chicks, resulting in viremia and viral shedding, compared with the infection caused by REV, REV-exosomes reduced the hatching rate and increased mortality after hatching, causing severe growth inhibition and immune organ damage in 1-day-old chicks; both REV and REV-exosomes also could infect hens, however, lead to transient infection. In the presence of antibodies, REV-exosomes were not blocked by REV-specific neutralizing antibodies and infected 7-day-old embryonated eggs. However, REV could not infect 1-day-old chicks and 23-week-old hens. Conclusion: In this study, we compared the infectious ability of REV-exosomes and REV, REV-exosomes could escape from REV-specific neutralizing antibodies in embryonated eggs, providing new insights into the immune escape mechanism of REV. [ABSTRACT FROM AUTHOR]

Introduction: SARS-CoV-2 infection is hypothesized to be more severe in immunocompromised patients; however, clinical outcomes in children with inborn errors of immunity (IEI) during the Omicron pandemic in China have not been reported. Methods: This cohort study retrospectively reviewed 71 SARS-CoV-2-infected children with IEI using nationwide data from the National Center for Children's Health of China. COVID-19 was diagnosed by a positive rapid antigen or nucleic acid test result. Results: Among 71 SARS-CoV-2-infected children with IEI, male preponderance (male: female ratio of ~1.8:1), a median age of 8 years (IQR 3-11), and a predominance of antibody deficiency (19/71, 26.8%) were detected. Most of the patients got infected through household transmission, while a small proportion of them did so during hospital visits. The mean time periods were 3.3 days (n=44) for incubation, 8.4 days for symptoms (n=69), and 8.8 days for viral shedding (n=37). The time to viral shedding was proportional to the symptomatic period (R² = 0.1243, p=0.0323) and prolonged in children with X-linked agammaglobulinemia. The most common symptoms of COVID-19 were fever, and some children showed only aggravation of the underlying disease. 15% of IEI children progress to pneumonia, 85% require medication, 17% are admitted to hospital, and 4.1% are classified as critical. Previously application of anti-infective medications was associated with an increased risk of hospitalization after COVID-19 infection. Of the 71 children with IEI, all recovered from COVID-19. Conclusion: Overall, Omicron variant did not cause significant life-threatening infections among children with IEI in China, and most of them had a good clinical outcome. Nevertheless, these children exhibit an increased vulnerability to higher hospitalization rates, pneumonia, and severe illness compared to the general pediatric population. [ABSTRACT FROM AUTHOR]

Introduction: Hereditary spastic paraparesis (HSP) is a group of central nervous system diseases primarily affecting the spinal upper motor neurons, with different inheritance patterns and phenotypes. SPG18 is a rare, early-onset, complicated HSP, first reported as linked to biallelic ERLIN2 mutations. Recent cases of late-onset, pure HSP with monoallelic ERLIN2 variants prompt inquiries into the zygosity of such genetic conditions. The observed relationship between phenotype and mode of inheritance suggests a potential dominant negative effect of mutated ERLIN2 protein, potentially resulting in a milder phenotype. This speculation suggests that a wider range of HSP genes could be linked to various inheritance patterns. Purpose and background: With documented cases of HSP loci exhibiting both dominant and recessive patterns, this study emphasizes that the concept of zygosity is no longer a limiting factor in the establishment of molecular diagnoses for HSP. Recent cases have demonstrated phenoconversion in SPG18, from HSP to an amyotrophic lateral sclerosis (ALS)-like syndrome. Methods and results: This report highlights two cases out of five exhibiting HSP-ALS phenoconversion, discussing an observed prevalence in autosomal dominant SPG18. Additionally, the study emphasizes the relatively high incidence of the c.502G>A variant in monoallelic SPG18 cases. This mutation appears to be particularly common in cases of HSPALS phenoconversion, indicating its potential role as a hotspot for a distinctive SPG18 phenotype with an ALS-like syndrome. Conclusions: Clinicians need to be aware that patients with HSP may show ALS signs and symptoms. On the other hand, HSP panels must be included in genetic testing methods for instances of familial ALS. [ABSTRACT FROM AUTHOR]

Among immunocompromised hosts, leukemia patients, and hematopoietic cell transplant recipients are particularly vulnerable, facing challenges in balancing coronavirus disease 2019 (COVID‐19) management with their underlying conditions. In this How I Treat article, we discuss how we approach severe acute respiratory syndrome coronavirus 2 infections in daily clinical practice, considering the existing body of literature and for topics where the available data are not sufficient to provide adequate guidance, we provide our opinion based on our clinical expertise and experience. Diagnostic approaches include nasopharyngeal swabs for polymerase chain reaction testing and chest computed tomography scans for symptomatic patients at risk of disease progression. Preventive measures involve strict infection control protocols and prioritizing vaccination for both patients and their families. Decisions regarding chemotherapy or hematopoietic cell transplantation in leukemia patients with COVID‐19 require careful consideration of factors such as COVID‐19 severity and treatment urgency. Treatment protocols include early initiation of antiviral therapy, with nirmatrelvir/ritonavir or remdesivir. For cases of prolonged viral shedding, distinguishing between viable and non‐viable viruses remains challenging but is crucial for determining contagiousness and guiding management decisions. Overall, individualized approaches considering immune status, clinical presentation, and viral kinetics are essential for effectively managing COVID‐19 in leukemia patients. [ABSTRACT FROM AUTHOR]

Background: Herpes simplex viruses (HSVs) frequently reactivate during immunosuppression and may be a risk factor for adverse outcomes after solid organ transplant (SOT). While suppressive antiviral therapy reduces the risk of symptomatic HSV reactivation, the kinetics of asymptomatic viral shedding with chronic immunosuppression after transplant are not well understood. We report the characteristics of oral HSV shedding among 15 HSV‐1 seropositive SOT recipients (n = 8 liver, n = 7 kidney, median age 58.5 years, median 20 months post‐transplant) who were not taking daily antiviral suppressive therapy. Methods: Participants self‐collected oral swabs three times daily for 6 weeks for HSV quantification and recorded the presence of oral symptoms or lesions in a diary. Results: Sample collection adherence was high (median 122 swabs/person, range: 85.7%–101.6% of expected swabs). Most participants (n = 12, 80%) experienced at least one shedding episode, with a median shedding rate of 8.9% (range: 0%–33.6%). There were 32 total shedding episodes, 24 (75%) of which occurred without symptoms or lesions. For episodes of known duration, the median length was 21.8 hrs (interquartile range: 10.8–46.1 hrs). Conclusion: Most shedding episodes (78.1%) lasted >12 hrs, suggesting that twice‐daily sampling may be sufficient to detect most episodes. These data show that self‐collection of oral swabs is feasible for patients who have undergone SOTs and can provide insight into the frequency of oral HSV reactivation, which can be used to design future studies in this population. [ABSTRACT FROM AUTHOR]

Oxygen as a key element has a high impact on cellular processes. Infection with a pathogen such as SARS-CoV-2 and after inflammation may lead to hypoxic conditions in tissue that impact cellular responses. To develop optimized translational in vitro models for a better understanding of physiologic and pathophysiologic oxygen conditions, it is a prerequisite to determine oxygen concentrations generated in vivo. Our study objective was the establishment of an invasive method for oxygen measurements using a luminescence-based microsensor to determine the dissolved oxygen in the lung tissue of ferrets as animal models for SARS-CoV-2 research. By way of analogy to humans, aged ferrets are more likely to show clinical signs after SARS-CoV-2 infection than are young animals. To investigate oxygen concentrations during a respiratory viral infection, we intratracheally infected nine aged (3-yr-old) ferrets with SARS-CoV-2. The aged SARS-CoV-2–infected ferrets showed mild to moderate clinical signs associated with prolonged viral RNA shedding until 14 days postinfection. SARS-CoV-2–infected ferrets showed histopathologic lung lesion scores that significantly negatively correlated with oxygen concentrations in lung tissue. At 4 days postinfection, oxygen concentrations in lung tissue were significantly lower (mean percentage O2, 3.89 ≙ ≈ 27.78 mm Hg) than in the negative control group (mean percentage O2, 8.65 ≙ ≈ 61.4 mm Hg). In summary, we succeeded in determining the pathophysiologic oxygen conditions in the lung tissue of aged SARS-CoV-2–infected ferrets. [ABSTRACT FROM AUTHOR]

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Introduction: The enteric microbiome and its possible modulation to improve feed conversion or vaccine efficacy is gaining more attention in pigs. Weaning pigs from their dam, along with many routine procedures, is stressful. A better understanding of the impact of this process on the microbiome may be important for improving pig production. The objective of this study was to develop a weaner pig cannulationmodel, thus allowing ileumcontent collection from the same pig over time for 16S rRNA sequencing under different porcine reproductive and respiratory syndrome virus (PRRSV) infection statuses. Methods: A total of 15 3-week-old pigs underwent abdominal surgery and were fitted with an ileum cannula, with ileum contents collected over time. In this pilot study, treatment groups included a NEG-CONTROL group (no vaccination, no PRRSV challenge), a POS-CONTROL group (no vaccination, challenged with PRRSV), a VAC-PRRSV group (vaccinated, challenged with PRRSV), a VAC-PRO-PRRSV group (vaccinated, supplemented with a probiotic, challenged with PRRSV), and a VAC-ANTI-PRRSV group (vaccinated, administered an antibiotic, challenged with PRRSV). We assessed the microbiome over time and measured anti-PRRSV serum antibodies, PRRSV load in serum and nasal samples, and the severity of lung lesions. Results: Vaccination was protective against PRRSV challenge, irrespective of other treatments. All vaccinated pigs mounted an immune response to PRRSV within 1 week after vaccination. A discernible impact of treatment on the diversity, structure, and taxonomic abundance of the entericmicrobiome among the groups was not observed. Instead, significant influences on the ileum microbiome were observed in relation to time and treatment. Discussion: The cannulationmodel described in this pilot study has the potential to be useful in studying the impact of weaning, vaccination, disease challenge, and antimicrobial administration on the enteric microbiome and its impact on pig health and production. Remarkably, despite the cannulation procedures, all vaccinated pigs exhibited robust immune responses and remained protected against PRRSV challenge, as evidenced by the development of anti-PRRSV serum antibodies and viral shedding data. [ABSTRACT FROM AUTHOR]

Swine influenza A virus (IAV-S) is a highly prevalent and transmissible pathogen infecting worldwide swine populations. Our previous work has shown that the computationally derived vaccine platform, Epigraph, can induce broadly cross-reactive and durable immunity against H3 IAV-S in mice and swine. Therefore, in this study, we assess the immunogenicity and protective efficacy of the Epigraph vaccine at increasingly lower doses to determine the minimum dose required to maintain protective immunity against three genetically divergent H3 IAV-S. We assessed both antibody and T cell responses and then challenged with three H3N2 IAV-S derived from either Cluster IV(A), Cluster I, or the 2010.1 "human-like" cluster and assessed protection through reduced pathology, reduced viral load in the lungs, and reduced viral shedding from nasal swabs. Overall, we observed a dose-dependent effect where the highest dose of Epigraph protected against all three challenges, the middle dose of Epigraph protected against more genetically similar IAV-S, and the lowest dose of Epigraph only protected against genetically similar IAV-S. The results of these studies can be used to continue developing a broadly protective and low-dose vaccine against H3 IAV-S. [ABSTRACT FROM AUTHOR]

The enormous effects of avian influenza on poultry production and the possible health risks to humans have drawn much attention to this disease. The H9N2 subtype of avian influenza virus is widely prevalent among poultry, posing a direct threat to humans through infection or by contributing internal genes to various zoonotic strains of avian influenza. Despite the widespread use of H9N2 subtype vaccines, outbreaks of the virus persist due to the rapid antigenic drift and shifts in the influenza virus. As a result, it is critical to develop a broader spectrum of H9N2 subtype avian influenza vaccines and evaluate their effectiveness. In this study, a recombinant baculovirus expressing the broad-spectrum HA protein was obtained via bioinformatics analysis and a baculovirus expression system (BES). This recombinant hemagglutinin (HA) protein displayed cross-reactivity to positive sera against several subbranch H9 subtype AIVs. An adjuvant and purified HA protein were then used to create an rHA vaccine candidate. Evaluation of the vaccine demonstrated that subcutaneous immunization of the neck with the rHA vaccine candidate stimulated a robust immune response, providing complete clinical protection against various H9N2 virus challenges. Additionally, virus shedding was more effectively inhibited by rHA than by the commercial vaccine. Thus, our findings illustrate the efficacy of the rHA vaccine candidate in shielding chickens against the H9N2 virus challenge, underscoring its potential as an alternative to conventional vaccines. [ABSTRACT FROM AUTHOR]

The spread of COVID-19 has significantly increased research on antiviral drugs and measures such as case isolation and contact tracing. This study compared the effects of lopinavir/ritonavir and remdesivir on COVID-19 patients with a control group receiving no antiviral drugs. Patients confirmed to have a SARS-CoV-2 infection via real-time RT-PCR were divided into three groups: lopinavir/ritonavir, remdesivir, and control. We assessed the efficacy of these drugs in reducing viral load and viral shedding duration using real-time RT-PCR and Vero E6 cell cultures. Lopinavir/ritonavir led to no detectable infectious SARS-CoV-2, with a median viral clearance time of one day, whereas one remdesivir-treated case remained culture-positive until day 12. Lopinavir/ritonavir significantly reduced viral load compared to remdesivir and control groups (p = 0.0117 and p = 0.0478). No infectious virus was detected in the lopinavir/ritonavir group, and the non-infectious SARS-CoV-2 proportion remained constant at 90%, higher than in the remdesivir and control groups (p = 0.0097). There was a significant difference in culture positivity among the groups (p = 0.0234), particularly between the lopinavir/ritonavir and remdesivir groups (p = 0.0267). These findings suggest that lopinavir/ritonavir reduces viral load and shortens the viral shedding duration compared to remdesivir, despite not being an effective treatment option. [ABSTRACT FROM AUTHOR]

The treatment of polycystic ovary syndrome (PCOS) faces challenges as all known treatments are merely symptomatic. The US Food and Drug Administration has not approved any drug specifically for treating PCOS. As the significance of genetics and epigenetics rises in drug development, their pivotal insights have greatly enhanced the efficacy and success of drug target discovery and validation, offering promise for guiding the advancement of PCOS treatments. In this context, we outline the genetic and epigenetic advancement in PCOS, which provide novel insights into the pathogenesis of this complex disease. We also delve into the prospective method for harnessing genetic and epigenetic strategies to identify potential drug targets and ensure target safety. Additionally, we shed light on the preliminary evidence and distinctive challenges associated with gene and epigenetic therapies in the context of PCOS. [ABSTRACT FROM AUTHOR]

Hand, foot, and mouth disease (HFMD) is widely spread in China Mainland, seriously threatening the health of infants and young children. We develop a meta‐population model that includes both local and ecdemic populations to study the impacts of fomites and immigration on the transmission of HFMD in Shanghai. The model includes both direct transmission between susceptible and infected individuals (asymptomatic or symptomatic) and indirect transmission via fomites. The forward bifurcation shows that if the basic reproduction number is less than unity, the epidemic will die out; otherwise, the epidemic will spread. The fitting results show that the basic reproduction numbers of the local population and the ecdemic population are 1.4696 and 1.7288, respectively. Sensitivity analysis of the basic reproduction number showed that there was a high correlation between the basic reproduction number and the transmission rate of asymptomatic infected individuals, as well as the parameters related to the fomites (such as indirect transmission rate and virus shedding rate). Hence, asymptomatic infected individuals and fomites have a significant impact on the new HFMD infection. The numerical simulations on the prevention and control strategy show that reducing the transmission rate between susceptible and asymptomatic infected individuals or reducing the fomites can delay the outbreak of the epidemic and weaken the severity of HFMD. Our findings can provide guidance for the eradication of HFMD epidemic in the presence of indirect transmission and other factors. [ABSTRACT FROM AUTHOR]

Background: The global impact of the coronavirus disease 2019 (COVID-19) pandemic has resulted in significant morbidity and mortality. Immunocompromised patients, particularly those treated for B-cell lymphoma, have shown an increased risk of persistent infection with SARS-CoV-2 and severe outcomes and mortality. Multi-mutational SARS-CoV-2 variants can arise during the course of such persistent cases of COVID-19. No optimal, decisive strategy is currently available for patients with persistent infection that allows clinicians to sustain viral clearance, determine optimal timing to stop treatment, and prevent virus reactivation. We introduced a novel treatment combining antivirals, neutralizing antibodies, and genomic analysis with frequent monitoring of spike-specific antibody and viral load for immunocompromised patients with persistent COVID-19 infection. The aim of this retrospective study was to report and evaluate the efficacy of our novel treatment for immunocompromised B-cell lymphoma patients with persistent COVID-19 infection. Methods: This retrospective descriptive analysis had no controls. Patients with B-cell lymphoma previously receiving immunotherapy including anti-CD20 antibodies, diagnosed as having COVID-19 infection, and treated in our hospital after January 2022 were included. We selected anti-SARS-CoV-2 monoclonal antibodies according to subvariants. Every 5 days, viral load was tested by RT-PCR, with antivirals continued until viral shedding was confirmed. Primary outcome was virus elimination. Independent predictors of prolonged viral shedding time were determined by multivariate Cox regression. Results: Forty-four patients were included in this study. Thirty-five patients received rituximab, 19 obinutuzumab, and 26 bendamustine. Median treatment duration was 10 (IQR, 10–20) days; 22 patients received combination antiviral therapy. COVID-19 was severe in 16 patients, and critical in 2. All patients survived, with viral shedding confirmed at median 28 (IQR, 19–38) days. Bendamustine use or within 1 year of last treatment for B-cell lymphoma, and multiple treatment lines for B-cell lymphoma significantly prolonged time to viral shedding. Conclusions: Among 44 consecutive patients treated, anti-SARS-CoV-2 monoclonal antibodies and long-term administration of antiviral drugs, switching, and combination therapy resulted in virus elimination and 100% survival. Bendamustine use, within 1 year of last treatment for B-cell lymphoma, and multiple treatment lines for B-cell lymphoma were the significant independent predictors of prolonged viral shedding time. [ABSTRACT FROM AUTHOR]

To protect against the constant threat of inhaled pathogens, the lung is equipped with cellular defenders. In coordination with resident and recruited immune cells, this defence is initiated by the airway and alveolar epithelium following their infection with respiratory viruses. Further support for viral clearance and infection resolution is provided by adjacent endothelial and stromal cells. However, even with these defence mechanisms, respiratory viral infections are a significant global health concern, causing substantial morbidity, socioeconomic losses, and mortality, underlining the need to develop effective vaccines and antiviral medications. In turn, the identification of new treatment options for respiratory infections is critically dependent on the availability of tractable in vitro experimental models that faithfully recapitulate key aspects of lung physiology. For such models to be informative, it is important these models incorporate human-derived, physiologically relevant versions of all cell types that normally form part of the lungs anti-viral response. This review proposes a guideline using human induced pluripotent stem cells (iPSCs) to create all the disease-relevant cell types. iPSCs can be differentiated into lung epithelium, innate immune cells, endothelial cells, and fibroblasts at a large scale, recapitulating in vivo functions and providing genetic tractability. We advocate for building comprehensive iPSC-derived in vitro models of both proximal and distal lung regions to better understand and model respiratory infections, including interactions with chronic lung diseases. [ABSTRACT FROM AUTHOR]

To evaluate how breakthrough rotavirus disease contributes to transmission, we examined the impact of rotavirus vaccination on fecal shedding and duration of illness. We used multivariable linear regression to analyze rotavirus quantity by RT-qPCR and duration among 184 episodes of rotavirus diarrhea positive by ELISA in the PROVIDE study. Vaccinated children had less fecal viral shedding compared to unvaccinated children (mean difference = −0.59 log copies per gram of stool; 95% confidence interval [CI], −.99 to −.19). Duration of illness was on average 0.47 days (95% CI, −.23 to 1.17 days) shorter among vaccinated children. Rotarix vaccination reduces shedding burden among breakthrough cases of rotavirus gastroenteritis. Clinical Trials Registration. NCT01375647. [ABSTRACT FROM AUTHOR]

Since the reintroduction of African swine fever virus (ASFV) in Europe in 2007 and its subsequent spread to Asia, wild boar has played a crucial role in maintaining and disseminating the virus. There are significant gaps in the knowledge regarding infection dynamics and disease pathogenesis in domestic pigs and wild boar, particularly at the early infection stage. We aimed to compare domestic pigs and wild boar infected intranasally to mimic natural infection with one of the original highly virulent genotype II ASFV isolates (Armenia 2007). The study involved euthanising three domestic pigs and three wild boar on days 1, 2, 3, and 5 post-infection, while four domestic pigs and four wild boar were monitored until they reached a humane endpoint. The parameters assessed included clinical signs, macroscopic lesions, viremia levels, tissue viral load, and virus shedding in nasal and rectal swabs from day 1 post-infection. Compared with domestic pigs, wild boar were more susceptible to ASFV, with a shorter incubation period and earlier onset of clinical signs. While wild boar reached a humane endpoint earlier than domestic pigs did, the macroscopic lesions were comparatively less severe. In addition, wild boar had earlier viremia, and the virus was also detected earlier in tissues. The medial retropharyngeal lymph nodes were identified as key portals for ASFV infection in both subspecies. No viral genome was detected in nasal or rectal swabs until shortly before reaching the humane endpoint in both domestic pigs and wild boar, suggesting limited virus shedding in acute infections. [ABSTRACT FROM AUTHOR]

A Newcastle disease virus (NDV)-vectored vaccine expressing clade 2.3.4.4b H5 Hemagglutinin was developed and assessed for efficacy against H5N1 highly pathogenic avian influenza (HPAI) in specific pathogen-free (SPF) chickens, broilers, and domestic ducks. In SPF chickens, the live recombinant NDV-vectored vaccine, rK148/22-H5, achieved complete survival against HPAI and NDV challenges and significantly reduced viral shedding. Notably, the live rK148/22-H5 vaccine conferred good clinical protection in broilers despite the presence of maternally derived antibodies. Good clinical protection was observed in domestic ducks, with decreased viral shedding. It demonstrated complete survival and reduced cloacal viral shedding when used as an inactivated vaccine from SPF chickens. The rK148/22-H5 vaccine is potentially a viable and supportive option for biosecurity measure, effectively protecting in chickens against the deadly clade 2.3.4.4b H5 HPAI and NDV infections. Furthermore, it aligns with the strategy of Differentiating Infected from Vaccinated Animals (DIVA). [ABSTRACT FROM AUTHOR]

The leading cause of gastroenteritis in children under the age of five is rotavirus infection, accounting for 37% of diarrhoeal deaths in infants and young children globally. Oral rotavirus vaccines have been widely incorporated into national immunisation programs, but whilst these vaccines have excellent efficacy in high-income countries, they protect less than 50% of vaccinated individuals in low- and middle-income countries. In order to facilitate the development of improved vaccine strategies, a greater understanding of the immune response to existing vaccines is urgently needed. However, the use of mouse models to study immune responses to human rotavirus strains is currently limited as rotaviruses are highly species-specific and replication of human rotaviruses is minimal in mice. To enable characterisation of immune responses to human rotavirus in mice, we have generated chimeric viruses that combat the issue of rotavirus host range restriction. Using reverse genetics, the rotavirus outer capsid proteins (VP4 and VP7) from either human or murine rotavirus strains were encoded in a murine rotavirus backbone. Neonatal mice were infected with chimeric viruses and monitored daily for development of diarrhoea. Stool samples were collected to quantify viral shedding, and antibody responses were comprehensively evaluated. We demonstrated that chimeric rotaviruses were able to efficiently replicate in mice. Moreover, the chimeric rotavirus containing human rotavirus outer capsid proteins elicited a robust antibody response to human rotavirus antigens, whilst the control chimeric murine rotavirus did not. This chimeric human rotavirus therefore provides a new strategy for studying human-rotavirus-specific immunity to the outer capsid, and could be used to investigate factors causing variability in rotavirus vaccine efficacy. This small animal platform therefore has the potential to test the efficacy of new vaccines and antibody-based therapeutics. [ABSTRACT FROM AUTHOR]

Dengue neurological disease is an uncommon yet severe complication of dengue infection. It can manifest as encephalitis, encephalopathy, neuro-ophthalmic complications, or neuromuscular disorders. Severe infection can result in viral shedding across multiple body sites. We describe a case of severe neuro-ophthalmic dengue infection in an otherwise healthy returned traveller, presenting with prolonged multiple-body-site viral detections by PCR. The dengue virus (DENV) dynamics and serological response support a direct DENV neuropathogenicity. A retrospective review of the laboratory data at the Victorian Infectious Diseases Reference Laboratory (VIDRL) suggests that blood is the most frequent sample type with DENV detection (92% of all DENV-positive samples). Genotype variation is seen across different sample types. The similarity of CSF and nasopharyngeal DENV subtypes (genotype 1 and 3) suggests a possible correlation between nasopharyngeal replication and neurological complications. The case presented highlights the direct neuropathogenicity of DENV early in the course of infection, and a potential correlation between nasopharyngeal replication and neurological disease. [ABSTRACT FROM AUTHOR]

Andes virus (ANDV) is a zoonotic Orthohantavirus leading to hantavirus cardiopulmonary syndrome. Although most transmissions occur through environmental exposure to rodent faeces and urine, rare person-to-person transmission has been documented, mainly for close contacts. This study investigates the presence and infectivity of ANDV in body fluids from confirmed cases and the duration of viraemia. In this prospective study, 131 participants with confirmed ANDV infection were enrolled in Chile in a prospective study between 2008 and 2022. Clinical samples (buffy coat, plasma, gingival crevicular fluid [GCF], saliva, nasopharyngeal swabs [NPS], and urine) were collected weekly for 3 weeks together with clinical and epidemiological data. Samples were categorised as acute or convalescent (up to and after 16 days following onset of symptoms). Infectivity of positive fluids was assessed after the culture of samples on Vero E6 cells and use of flow cytometry assays to determine the production of ANDV nucleoprotein. ANDV RNA was detected in 100% of buffy coats during acute phase, declining to 95% by day 17, and to 93% between days 23–29. ANDV RNA in GCF and saliva decreased from 30% and 12%, respectively, during the acute phase, to 12% and 11% during the convalescent phase. Successful infectivity assays of RT-qPCR-positive fluids, including GCF, saliva, NPS, and urine, were observed in 18 (42%) of 43 samples obtained during the acute phase of infection. After re-culture, the capacity to infect Vero E6 cells was maintained in 16 (89%) of 18 samples. Severity was associated with the presence of ANDV RNA in one or more fluids besides blood (odds ratio 2·58 [95% CI 1·42–5·18]). ANDV infection is a systemic and viraemic infection, that affects various organs. The presence of infectious particles in body fluids contributes to our understanding of potential mechanisms for person-to-person transmission, supporting the development of preventive strategies. Detection of ANDV RNA in additional fluids at hospital admission is a predictor of disease severity. National Institutes of Health and Agencia de Investigación y Desarrollo. For the Spanish translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

Background: Equine herpesvirus 4 (EHV-4) causes respiratory disease in horses, and the virus is considered endemic in the global equine population. However, outbreaks can occur when several horses are gathered in relation to shows, competitions, breeding units and at hospitals. In the spring year 2022, an EHV-4 outbreak occurred at the Large Animal Teaching Hospital, University of Copenhagen, Denmark. Nine horses were tested EHV-4 positive during the outbreak, which lasted approx. seven weeks. In addition, a tenth horse "Eq10" tested EHV-4 positive almost three weeks after the last of the outbreak horses tested positive. Detailed clinical registrations were obtained from all ten horses as well as their location and movement during hospitalization. Nasal swabs were obtained throughout the outbreak and tested by qPCR for EHV-4. Additionally, pre- and post-infection sera were tested for the presence of EHV-4 antibodies. Selected samples were characterized by partial and full genome sequencing. Results: The most common clinical signs of the EHV-4 infected horses during this outbreak were pyrexia, nasal discharge, mandibular lymphadenopathy and increased lung sounds upon auscultation. Based on the locations of the horses, EHV-4 detection and antibody responses the most likely "patient zero" was identified as being "Eq1". Partial genome sequencing revealed that Eq10 was infected by another wild type EHV-4 strain, suggesting that the hospital was able to eliminate the outbreak by testing and reinforcing biosecurity measures. The complete genome sequence of the outbreak strain was obtained and revealed a closer relation to Australian and Japanese EHV-4 strains rather than to other European EHV-4 strains, however, very limited sequence data are available from Europe. Conclusion: The study illustrated the transmission of EHV-4 within an equine facility/hospital and provided new insights into the viral shedding, antibody responses and clinical signs related to EHV-4 infections. Finally, sequencing proved a useful tool in understanding the transmission within the hospital, and in characterizing of the outbreak strain. [ABSTRACT FROM AUTHOR]

Vaccination is a feasible approach for controlling foot-and-mouth disease (FMD). In FMD-free countries, vaccines are stored as a precautionary measure to control potential outbreaks. However, the challenge lies in pre-stocking optimal vaccines against the newly emerging strains. This study examined the potency of pre-stocked vaccines administered at elevated doses during emergencies. We vaccinated the cows with either a single or double trivalent vaccine dose containing two serotype O and one serotype A strains. Subsequently, vaccinated and unvaccinated cows were exposed to virulent strains of serotype O (O/JPN/2010; topotype Southeast Asia/Mya-98 lineage) or A (A/IRN/2016; topotype ASIA/G-VII lineage), which were genetically and antigenically distinct from the vaccine strains. Following challenge infections, all cows that received a single dose vaccination exhibited vesicular lesions with excreted viruses in the oral and nasal discharges. However, a substantial reduction was observed in the total clinical scores and virus titers in the sera and nasal discharges compared to those in the unvaccinated group. Cows receiving a doubled dose vaccination were completely protected from infection with O/JPN/2010 or demonstrated a significant decrease in viral shedding and clinical scores against A/IRN/2016. To note, vesicular lesions harbor significant amounts of viruses; thus, by mitigating their formation, viral transmission can be impeded, thereby slowing viral spread in the field. Furthermore, increasing the vaccine dose induced higher neutralizing antibody titers against heterologous strains. These findings suggest an alternative strategy for the effective management of future epidemics using pre-stocked vaccines. [ABSTRACT FROM AUTHOR]

The systematic review and meta-analysis were conducted to determine the estimates of the prevalence and infection rates of natural and experimental infections of amphistome species in intermediate host snails (IHs) across different continents. A search of peer-reviewed literature on natural and experimental infections of freshwater snails with amphistome species was conducted from four electronic databases from 1984 to 2023. The estimates of the prevalence and/or infection rates were based on 36 eligible peer-reviewed articles, which met the inclusion criteria and reported on natural and experimental infections of amphistome species in freshwater snails. The results showed that a total of 1,67,081 snail species from the peer-reviewed articles were examined for natural infections and 7,659 snail species for experimental infections. The overall pooled prevalence of amphistome infections from naturally infected snails was 2% (95% CI: 0–4), while the overall pooled prevalence of amphistome infections from infections was 40% (95% CI: 18–64). The highest pooled prevalence of natural infection was 3%, which was recorded in Europe (95% CI: 1–7%). The highest overall prevalence of naturally infected amphistome was 6% (95% CI: 0–20%) for Paramphistomum epiclitum. The Americas had the highest pooled prevalence of experimental amphistome infection among freshwater snails (66%; 95% CI: 26–96%). The highest pooled infection rate of 65% (95% CI: 12–100%) was recorded for Paramphistomum cervi in experimental infections. Galba truncatula was the only snail that qualified for meta-analysis for natural infection with Calicophoron daubneyi, with a pooled prevalence of 3% (95% CI: 1–8%). Galba truncatula infected with C. daubneyi and P. cervi, and Bulinus tropicus infected with Calicophoron microbothrium in the experimental infection qualified for the meta-analysis, with an overall infection rate of 66% (95% CI: 34–92%) and 30% (95% CI: 0–74%), respectively. The pooled prevalence of amphistome species infection in the intermediate host (IH) snails based on detection techniques was higher with PCR compared to the dissection and shedding of cercariae. The results from the quality effects model revealed a high heterogeneity and publication bias between studies. This meta-analysis provided valuable insights into the prevalence and infection rates of amphistome species in snail IHs across different geographical regions. [ABSTRACT FROM AUTHOR]

Capripoxviruses are the causative agents of sheeppox, goatpox, and lumpy skin disease (LSD) in cattle, which cause economic losses to the livestock industry in Africa and Asia. Capripoxviruses are currently controlled using several live attenuated vaccines. It was previously demonstrated that a lumpy skin disease virus (LSDV) field isolate from Warmbaths (WB) South Africa, ORF 005 (IL-10) gene-deleted virus (LSDV WB005KO), was able to protect sheep and goats against sheeppox and goatpox. Subsequently, genes encoding the protective antigens for peste des petits ruminants (PPR) and Rift Valley fever (RVF) viruses have been inserted in the LSDV WB005KO construct in three different antigen forms (native, secreted, and fusion). These three multivalent vaccine candidates were evaluated for protection against PPR using a single immunization of 104 TCID50 in sheep. The vaccine candidates with the native and secreted antigens protected sheep against PPR clinical disease and decreased viral shedding, as detected using real-time RT-PCR in oral and nasal swabs. An anamnestic antibody response, measured using PPR virus-neutralizing antibody response production, was observed in sheep following infection. The vaccine candidates with the antigens expressed in their native form were evaluated for protection against RVF using a single immunization with doses of 104 or 105 TCID50 in sheep and goats. Following RVF virus infection, sheep and goats were protected against clinical disease and no viremia was detected in serum compared to control animals, where viremia was detected one day following infection. Sheep and goats developed RVFV-neutralizing antibodies prior to infection, and the antibody responses increased following infection. These results demonstrate that an LSD virus-vectored vaccine candidate can be used in sheep and goats to protect against multiple viral infections. [ABSTRACT FROM AUTHOR]

Simple Summary: Feline herpesvirus (FHV-1) is a common virus in cats that causes respiratory and ocular diseases. This research aimed to study FHV-1 by isolating it from nasal and ocular samples collected from symptomatic cats and evaluating its characteristics and virulence. We collected 35 samples from symptomatic cats with respiratory infections where FHV-1 was detected by polymerase chain reaction (PCR). The virus was isolated using feline kidney (F81) cell lines, identified using standard laboratory techniques, and analyzed for genetic characteristics. We found three different strains of FHV-1 that shared high homology among themselves and with domestic isolates and FHV-1 viruses isolated worldwide. However, these strains caused varying disease severities in their host. One strain (FHV-A1) was highly virulent, resulting in high morbidity and mortality. Our work enhances our understanding of the genetic diversity and pathogenesis of Chinese FHV-1 strains and also underscored FHV-A1 isolate as a potentially ideal candidate for establishing a challenge model and as a potential vaccine strain, which lays the groundwork for vaccine development. (1) Background: Feline herpesvirus (FHV-1) is a significant pathogen in cats, causing respiratory and ocular diseases with consequential economic and welfare implications. (2) Methods: This study aimed to isolate and characterize FHV-1 from clinical samples and assess its pathogenicity. We collected 35 nasal and ocular swabs from cats showing symptoms of upper respiratory tract infection and FHV positivity detected by polymerase chain reaction (PCR). Viral isolation was carried out using feline kidney (F81) cell lines. Confirmation of FHV-1 presence was achieved through PCR detection, sequencing, electron microscopy, and indirect immunofluorescence assay. The isolated strains were further characterized by evaluating their titers, growth kinetics, and genetic characteristics. Additionally, we assessed the pathogenicity of the isolated strains in a feline model, monitoring clinical signs, viral shedding, and histopathological changes. (3) Results: Three strains of FHV-1 were isolated, purified, and identified. The isolated FHV-1 strains exhibited high homology among themselves and with domestic isolates and FHV-1 viruses from around the world. However, they showed varying degrees of virulence, with one strain (FHV-A1) causing severe clinical signs and histopathological lesions. (4) Conclusion: This study advances our understanding of the genetic and pathogenic characteristics of FHV-1 in China. These findings underscore FHV-A1 isolate as a potentially ideal candidate for establishing a challenge model and as a potential vaccine strain for vaccine development. [ABSTRACT FROM AUTHOR]

Abstract High pathogenicity avian influenza viruses (HPAIVs) have caused major epizootics in recent years, with devastating consequences for poultry and wildlife worldwide. Domestic and wild ducks can be highly susceptible to HPAIVs, and infection leads to efficient viral replication and massive shedding (i.e., high titres for an extended time), contributing to widespread viral dissemination. Importantly, ducks are known to shed high amounts of virus in the earliest phase of infection, but the dynamics and impact of environmental contamination on the epidemiology of HPAIV outbreaks are poorly understood. In this study, we monitored mule ducks experimentally infected with two H5N8 clade 2.3.4.4b goose/Guangdong HPAIVs sampled in France in 2016–2017 and 2020–2021 epizootics. We investigated viral shedding dynamics in the oropharynx, cloaca, conjunctiva, and feathers; bird-to-bird viral transmission; and the role of the environment in viral spread and as a source of samples for early detection and surveillance. Our findings showed that viral shedding started before the onset of clinical signs, i.e., as early as 1 day post-inoculation (dpi) or post-contact exposure, peaked at 4 dpi, and lasted for up to 14 dpi. The detection of viral RNA in aerosols, dust, and water samples mirrored viral shedding dynamics, and viral isolation from these environmental samples was successful throughout the experiment. Our results confirm that mule ducks can shed high HPAIV titres through the four excretion routes tested (oropharyngeal, cloacal, conjunctival, and feather) while being asymptomatic and that environmental sampling could be a non-invasive tool for early viral RNA detection in HPAIV-infected farms.

Background: Despite the widespread administration of coronavirus disease 2019 (COVID-19) vaccines, the impact on patients with asymptomatic to mild illness remains unclear. Here, we aimed to assess the efficacy of various vaccine doses and types on the duration of isolation duration and discharge rates, the viral shedding duration, and negative rates in asymptomatic to mild COVID-19 patients. Methods: We included adult patients at the Fangcang isolation centres in Pazhou or Yongning between November and December 2022. We analysed data on basic demographics, admission details, laboratory indicators and vaccination information. Results: A total of 6560 infected patients were included (3584 from Pazhou and 2976 from Yongning). Of these, 90.6% received inactivated vaccines, 3.66% received recombinant SARS-CoV-2 spike protein subunit vaccines and 0.91% received adenovirus vaccines. Among the 6173 vaccinated individuals, 71.9% received a booster dose. By day 9, the isolation rate reached 50% among vaccinated patients. On day 7.5, the positive rate among vaccinated individuals reached 50%. Conclusions: Full vaccination was effective, with heterologous vaccines showing greater efficacy than inactivated vaccines alone. However, there was no significant difference in the vaccine protective effect 12 months after vaccination. [ABSTRACT FROM AUTHOR]

Background: The RECOVERY trial demonstrated that the use of dexamethasone is associated with a 36% lower 28-day mortality in hospitalized patients with COVID-19 on invasive mechanical ventilation. Nevertheless, the optimal timing to start dexamethasone remains uncertain. Methods: We conducted a quasi-experimental study at National Taiwan University Hospital (Taipei, Taiwan) using propensity score matching to simulate a randomized controlled trial to receive or not to receive early dexamethasone (6 mg/day) during the first 7 days following the onset of symptoms. Treatment was standard protocol-based, except for the timing to start dexamethasone, which was left to physicians’ decision. The primary outcome is 28-day mortality. Secondary outcomes include secondary infection within 60 days and fulfilling the criteria of de-isolation within 20 days. Results: A total of 377 patients with COVID-19 were enrolled. Early dexamethasone did not decrease 28-day mortality in all patients (adjusted odds ratio [aOR], 1.03; 95% confidence interval [CI], 0.97–1.10) or in patients who required O2 for severe/critical disease at admission (aOR, 1.05; 95%CI, 0.94–1.18); but is associated with a 24% increase in superinfection in all patients (aOR, 1.24; 95% CI, 1.12–1.37) and a 23% increase in superinfection in patients of O2 for several/critical disease at admission (aOR, 1.23; 95% CI, 1.02–1.47). Moreover, early dexamethasone is associated with a 42% increase in likelihood of delayed clearance of SARS-CoV-2 virus (adjusted hazard ratio, 1.42; 95% CI, 1.01–1.98). Conclusion: An early start of dexamethasone (within 7 days after the onset of symptoms) could be harmful to hospitalized patients with COVID-19.

Respiratory diseases constitute a major health problem for ruminants, resulting in considerable economic losses throughout the world. Parainfluenza type 3 virus (PIV3) is one of the most important respiratory pathogens of ruminants. The pathogenicity and phylogenetic analyses of PIV3 virus have been reported in sheep and goats. However, there are no recent studies of the vaccination of sheep or goats against PIV3. Here, we developed a purified inactivated ovine parainfluenza virus type 3 (OPIV3) vaccine candidate. In addition, we immunized sheep with the inactivated OPIV3 vaccine and evaluated the immune response and pathological outcomes associated with OPIV3 TX01 infection. The vaccinated sheep demonstrated no obvious symptoms of respiratory tract infection, and there were no gross lesions or pathological changes in the lungs. The average body weight gain significantly differed between the vaccinated group and the control group (P < 0.01). The serum neutralization antibody levels rapidly increased in sheep post-vaccination and post-challenge with OPIV3. Furthermore, viral shedding in nasal swabs and viral loads in the lungs were reduced. The results of this study suggest that vaccination with this candidate vaccine induces the production of neutralizing antibodies and provides significant protection against OPIV3 infection. These results may be helpful for further studies on prevention and control strategies for OPIV3 infections. [ABSTRACT FROM AUTHOR]

Background: Virome studies on birds, including chickens are relatively scarce, particularly from the African continent. Despite the continuous evolution of RNA viruses and severe losses recorded in poultry from seasonal viral outbreaks, the information on RNA virome composition is even scantier as a result of their highly unstable nature, genetic diversity, and difficulties associated with characterization. Also, information on factors that may modulate the occurrence of some viruses in birds is limited, particularly for domesticated birds. Viral metagenomics through advancements in sequencing technologies, has enabled the characterization of the entire virome of diverse host species using various samples. Methods: The complex RNA viral constituents present in 27 faecal samples of asymptomatic chickens from a South African farm collected at 3-time points from two independent seasons were determined, and the impact of the chicken's age and collection season on viral abundance and diversity was further investigated. The study utilized the non-invasive faecal sampling method, mRNA viral targeted enrichment steps, a whole transcriptome amplification strategy, Illumina sequencing, and bioinformatics tools. Results: The results obtained revealed a total of 48 viral species spanning across 11 orders, 15 families and 21 genera. Viral RNA families such as Coronaviridae, Picornaviridae, Reoviridae, Astroviridae, Caliciviridae, Picorbirnaviridae and Retroviridae were abundant, among which picornaviruses, demonstrated a 100% prevalence across the three age groups (2, 4 and 7 weeks) and two seasons (summer and winter) of the 27 faecal samples investigated. A further probe into the extent of variation between the different chicken groups investigated indicated that viral diversity and abundance were significantly influenced by age (P = 0.01099) and season (P = 0.00099) between chicken groups, while there was no effect on viral shedding within samples in a group (alpha diversity) for age (P = 0.146) and season (P = 0.242). Conclusion: The presence of an exceedingly varied chicken RNA virome, encompassing avian, mammalian, fungal, and dietary-associated viruses, underscores the complexities inherent in comprehending the causation, dynamics, and interspecies transmission of RNA viruses within the investigated chicken population. Hence, chickens, even in the absence of discernible symptoms, can harbour viruses that may exhibit opportunistic, commensal, or pathogenic characteristics. [ABSTRACT FROM AUTHOR]

Since SARS-CoV-2 emerged in late 2019, it spread from China to the rest of the world. An initial concern was the potential for vaccine- or antibody-dependent enhancement (ADE) of disease as had been reported with other coronaviruses. To evaluate this, we first developed a ferret model by exposing ferrets to SARS-CoV-2 by either mucosal inoculation (intranasal/oral/ocular) or inhalation using a small particle aerosol. Mucosal inoculation caused a mild fever and weight loss that resolved quickly; inoculation via either route resulted in virus shedding detected in the nares, throat, and rectum for 7–10 days post-infection. To evaluate the potential for ADE, we then inoculated groups of ferrets intravenously with 0.1, 0.5, or 1 mg/kg doses of a human polyclonal anti-SARS-CoV-2 IgG from hyper-immunized transchromosomic bovines (SAB-185). Twelve hours later, ferrets were challenged by mucosal inoculation with SARS-CoV-2. We found no significant differences in fever, weight loss, or viral shedding after infection between the three antibody groups or the controls. Signs of pathology in the lungs were noted in infected ferrets but no differences were found between control and antibody groups. The results of this study indicate that healthy, young adult ferrets of both sexes are a suitable model of mild COVID-19 and that low doses of specific IgG in SAB-185 are unlikely to enhance the disease caused by SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Background: Predictors of the outcome of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection remain to be fully determined. We evaluated selected viral characteristics and immunological responses that might predict and/or correlate to the clinical outcome of COVID-19. Methods: For individuals developing divergent clinical outcomes, the magnitude and breadth of T cell-mediated responses were measured within 36 h of symptom onset. Peripheral Blood Mononuclear Cells (PBMCs) were subjected to in vitro stimulation with SARS-CoV-2-based peptides. In addition, SARS-CoV-2 sequences were generated by metagenome, and HLA typing was performed using Luminex technology. Findings: CD4+ T cell activation was negatively correlated with SARS-CoV-2 basal viral load in patients with severe COVID-19 (p = 0·043). The overall cellular immune response, as inferred by the IFN-γ signal, was higher at baseline for patients who progressed to mild disease compared to patients who progressed to severe disease (p = 0·0044). Subjects with milder disease developed higher T cell responses for MHC class I and II-restricted peptides (p = 0·033). Interpretation: Mounting specific cellular immune responses in the first days after symptom onset, as inferred by IFN-γ magnitude in the ELISPOT assay, may efficiently favor a positive outcome. In contrast, progression to severe COVID-19 was accompanied by stronger cellular immune responses, higher CD4 + T cell activation, and a higher number of in silico predicted high-affinity class I HLA alleles. [ABSTRACT FROM AUTHOR]

Background: The innate immunity acts during the early phases of infection and its failure in response to a multilayer network of co-infections is cause of immune system dysregulation. Epidemiological SARS-CoV-2 infections data, show that Influenza Virus (FLU-A-B-C) and Respiratory Syncytial Virus (RSV) are co-habiting those respiratory traits. These viruses, especially in children (mostly affected by 'multi-system inflammatory syndrome in children' [MIS-C] and the winter pandemic FLU), in the aged population, and in 'fragile' patients are causing alteration in immune response. Then, bacterial and fungal pathogens are also co-habiting the upper respiratory traits (e.g., Staphylococcus aureus and Candida albicans), thus contributing to morbidity in those COVID-19 affected patients. Methods: Liquid chromatography coupled with high-resolution mass spectrometry using the quadrupole orbital ion trap analyser (i.e., UHPLC-Q-Orbitrap HRMS) was adopted to measure the polyphenols content of a new nutraceutical formula (Solution-3). Viral infections with SARS-CoV-2 (EG.5), FLU-A and RSV-A viruses (as performed in BLS3 authorised laboratory) and real time RT-PCR (qPCR) assay were used to test the antiviral action of the nutraceutical formula. Dilution susceptibility tests have been used to estimate the minimum inhibitory and bactericidal concentration (MIC and MBC, respectively) of Solution-3 on a variety of microorganisms belonging to Gram positive/ negative bacteria and fungi. Transcriptomic data analyses and functional genomics (i.e., RNAseq and data mining), coupled to qPCR and ELISA assays have been used to investigate the mechanisms of action of the nutraceutical formula on those processes involved in innate immune response. Results: Here, we have tested the combination of natural products containing higher amounts of polyphenols (i.e., propolis, Verbascum thapsus L., and Thymus vulgaris L.), together with the inorganic long chain polyphosphates 'polyPs' with antiviral, antibacterial, and antifungal behaviours, against SARS-CoV-2, FLU-A, RSV-A, Gram positive/ negative bacteria and fungi (i.e., Candida albicans). These components synergistically exert an immunomodulatory action by enhancing those processes involved in innate immune response (e.g., cytokines: IFNγ, TNFα, IL-10, IL-6/12; chemokines: CXCL1; antimicrobial peptides: HBD-2, LL-37; complement system: C3). Conclusion: The prophylactic antimicrobial success of this nutraceutical formula against SARS-CoV-2, FLU-A and RSV-A viruses, together with the common bacteria and fungi co-infections as present in human oral cavity, is expected to be valuable. [ABSTRACT FROM AUTHOR]

This study was aimed to investigate the frequency of PiCV recombination, the kinetics of PiCV viremia and shedding and the correlation between viral replication and host immune response in young pigeons subclinically infected with various PiCV variants and kept under conditions mimicking the OLR system. Fifteen racing pigeons originating from five breeding facilities were housed together for six weeks. Blood and cloacal swab samples were collected from birds every seven days to recover complete PiCV genomes and determine PiCV genetic diversity and recombination dynamics, as well as to assess virus shedding rate, level of viremia, expression of selected genes and level of anti-PiCV antibodies. Three hundred and eighty-eight complete PiCV genomes were obtained and thirteen genotypes were distinguished. Twenty-five recombination events were detected. Recombinants emerged during the first three weeks of the experiment which was consistent with the peak level of viremia and viral shedding. A further decrease in viremia and shedding partially corresponded with IFN-γ and MX1 gene expression and antibody dynamics. Considering the role of OLR pigeon rearing system in spreading infectious agents and allowing their recombination, it would be reasonable to reflect on the relevance of pigeon racing from both an animal welfare and epidemiological perspective. [ABSTRACT FROM AUTHOR]

Bovine coronavirus (BCoV) is a pneumoenteric virus that can infect the digestive and respiratory tracts of cattle, resulting in economic losses. Despite its significance, information regarding BCoV pathogenesis is limited. Hence, we investigated clinical signs, patterns of viral shedding, changes in antibody abundance, and cytokine/chemokine production in calves inoculated with BCoV via intranasal and oral. Six clinically healthy Korean native calves (< 30 days old), initially negative for BCoV, were divided into intranasal and oral groups and monitored for 15 days post-infection (dpi). BCoV-infected calves exhibited clinical signs such as nasal discharge and diarrhea, starting at 3 dpi and recovering by 12 dpi, with nasal discharge being the most common symptoms. Viral RNA was detected in nasal and fecal samples from all infected calves. Nasal shedding occurred before fecal shedding regardless of the inoculation route; however, fecal shedding persisted longer. Although the number of partitions was very few, viral RNA was identified in the blood of two calves in the oral group at 7 dpi and 9 dpi using digital RT-PCR analysis. The effectiveness of maternal antibodies in preventing viral replication and shedding appeared limited. Our results showed interleukin (IL)-8 as the most common and highly induced chemokine. During BCoV infection, the levels of IL-8, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1β were significantly affected, suggesting that these emerge as potential and reliable biomarkers for predicting BCoV infection. This study underscores the importance of BCoV as a major pathogen causing diarrhea and respiratory disease. [ABSTRACT FROM AUTHOR]

This single-centre retrospective cohort study reports on the results of a descriptive (non-comparative) retrospective cohort study of early initiation of antivirals and combined monoclonal antibody therapy (mAbs) in 48 severely immunocompromised patients with COVID-19. The study assessed the outcomes and the duration of viral shedding. The patients started early combined therapy (ECT) a median of 2 days (interquartile range [IQR]: 1–3 days) after the diagnosis of SARS-CoV-2 infection. Except for 1 patient who died due COVID-19-related respiratory failure, patients had their first negative nasopharyngeal swab result after a median of 11 days (IQR: 6–17 days) after starting combined therapy. There were no reports of severe side effects. During a follow-up period of 512 days (interquartile range [IQR]: 413–575 days), 6 patients (12.5%) died and 16 (33.3%) were admitted to hospital. Moreover, 12 patients (25%) were diagnosed with SARS-CoV-2 reinfection a median of 245 days (IQR: 138–401 days) after starting combined treatment. No relapses were reported. Although there was no comparison group, these results compare favourably with the outcomes of severely immunocompromised patients with COVID-19 reported in the literature. [ABSTRACT FROM AUTHOR]

Tecovirimat's application in treating mpox remains under-researched, leaving gaps in clinical and virological understanding. The Tecopox study in Japan evaluated the efficacy and safety of tecovirimat in patients with smallpox or mpox, who were divided into oral tecovirimat and control groups. Patients with mpox enrolled between June 28, 2022, and April 30, 2023, were included. Demographic and clinical details along with blood, urine, pharyngeal swab, and skin lesion samples were gathered for viral analysis. A multivariable Tobit regression model was employed to identify factors influencing prolonged viral detection. Nineteen patients were allocated to the tecovirimat group, and no patients were allocated to the control group. The median age was 38.5 years, and all patients were males. Ten patients (52.6%) were infected with human immunodeficiency virus (HIV). Sixteen patients (84.2%) had severe disease. Nine of the 15 patients (60.0%) (four patients withdrew before day 14) had negative PCR results for skin lesion specimens 14 days after inclusion. The mortality rates were 0% on days 14 and 30. No severe adverse events were reported. HIV status and the number of days from symptom onset to tecovirimat administration were associated with lower Ct values (p = 0.027 and p < 0.001, respectively). The median number of days when PCR testing did not detect the mpox virus in each patient was 19.5 days. Early tecovirimat administration might reduce viral shedding duration, thereby mitigating infection spread. Moreover, patients infected with HIV showed prolonged viral shedding, increasing the transmission risk compared to those without HIV. [ABSTRACT FROM AUTHOR]

Recently, hepatitis E virus (HEV, Paslahepevirus balayani) particles were detected for the first time in the ejaculate of two chronically infected patients. Since then, we have been able to detect HEV in ejaculate in five further patients, and thus in a total of seven out of nine (78%) chronically infected men (age 36–67 years, median 56 years). In five patients, the HEV RNA concentration was more than 100‐fold higher compared to the serum, while in two patients, the viral load was more than 10‐fold lower. However, it has remained unclear whether viral particles shed in the ejaculate were infectious, as a previous cell culture model had failed to demonstrate the infectivity. In the current study, we employed an optimized HEV cell culture system based on overconfluent PLC/PRF/5 cells to investigate the infectivity of HEV particles from ejaculate and other body fluids. With this approach, we were able to show for the first time that HEV particles in the ejaculate from several patients were infectious. HEV replicated to high viral loads of 1e9 HEV RNA copies per ml. This indicates that HEV‐positive ejaculate could bear a risk of infection for sexual partners. [ABSTRACT FROM AUTHOR]

HIV drug resistance mutations (HIVDRMs) are important determinants of therapeutic effects and outcomes even in end‐stage kidney failure (ESKF) people living with HIV (PLWHIV). This study evaluated the prevalence of HIVDRMs and their effect on the shedding of HIV‐1 into peritoneal dialysis (PD) effluents. This cross‐sectional study of PLWHIV and having ESKF and managed with antiretroviral therapy (ART) and PD, collected enrolled patients' demographic information, clinical and laboratory data, and sequenced HIV‐1 RNA in unsuppressed plasma and PD effluent samples. HIV viral load and HIVDRMs were determined using qualitative polymerase chain reaction (qPCR) and Stanford University HIVDRM Database, respectively. There were 60 participants recruited with a median age of 43.0 (interquartile range [IQR], 38.0–47) years and were predominantly on abacavir (88.3%), lamivudine (98.3%), and efavirenz (70%) for a median duration of 8 (IQR, 5–11) years. Among participants with detectable HIV‐1 in PD effluents, the prevalence of HIVDRMs was 62.5% (5/8) compared to 7.7% (4/52) among those with undetectable HIV‐1 (p = 0.001) with non‐nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations predominating. On Spearman's correlation analysis, high plasma HIV levels (ρ = 0.649, p < 0.001), T‐cell CD4 count (ρ = −0370, p < 0.004), serum creatinine (ρ = −0.396, p < 0.002), and white blood cell count (ρ = −0.294, p < 0.023) levels were significant factors correlated with the detection of HIV‐1 in PD effluents. Moreover, HIVDRMs presence (ρ = 0.504, p < 0.001) particularly NNRTI resistance (ρ = 0.504, p < 0.001) were also significantly correlated with detection of HIV‐1 in PD effluents. The presence of HIVDRMs, high plasma HIV viral load, and T‐cell CD4 count were correlated with HIV‐1 shedding into PD effluents. [ABSTRACT FROM AUTHOR]

Background: Liver transplant (LT) recipients are classified as a high-risk group and should receive regular surveillance for COVID-19 and are expected to have higher viral load and prolonged viral shedding. Virus-specific neutralizing antibodies (NAb), induced by infection, can prevent viral infection by deactivating viral access to host receptors. Aim: To estimate the incidence of SARS-CoV-2 infections and ascertain the levels of NAb among LT recipients. Method: This cross-sectional study included LT recipients. The survey included 14 parameters about demography, date since operation, and immunosuppressant medications and 11 parameters about COVID-19 infection. NAb was done by electrochemiluminescence immunoassay. Results: Only 39 LT recipients responded to this survey. Their median age was 57, and 74.4% of them were men. Comorbidities were present in 64% of cases, and DM was the most common comorbidity. Immunosuppressants used were Tacrolimus in 56.4% and Tacrolimus with mycophenolate mofetil in 15.4%. Fifteen cases (38.5%) had suspected infection, and 2 (5.1%) had confirmed infection. Three patients (17.6%) were hospitalized with no mortality. NAb was done in 34 cases, and it was positive in 5 cases (14.7%) with a median level (range) of 0.075 (0.04–27). Three out of 5 cases with a positive NAb test did not give a history of either suspected or confirmed COVID-19 infection. Conclusion: COVID-19 surveillance in LT recipients is important and suggests a relatively favorable clinical course despite the presumed challenges of immunosuppression. COVID-19 was associated with low hospitalization in LT recipients. NAb indicates a potential immune response even in asymptomatic LT recipients. Trial registration: Clinical Trial.gov NCT04565782. September 15 2022. [ABSTRACT FROM AUTHOR]