Isolation of symptomatic infectious persons can reduce influenza transmission. However, virus shedding that occurs without symptoms will be unaffected by such measures. Identifying effective isolation strategies for influenza requires understanding the interplay between individual virus shedding and symptom presentation. From 2017 to 2020, we conducted a case-ascertained household transmission study using influenza real-time RT-qPCR testing of nasal swabs and daily symptom diary reporting for up to 7 days after enrolment (≤14 days after index onset). We assumed real-time RT-qPCR cycle threshold (Ct) values were indicators of quantitative virus shedding and used symptom diaries to create a score that tracked influenza-like illness (ILI) symptoms (fever, cough, or sore throat). We fit phenomenological nonlinear mixed-effects models stratified by age and vaccination status and estimated two quantities influencing isolation effectiveness: shedding before symptom onset and shedding that might occur once isolation ends. We considered different isolation end points (including 24 h after fever resolution or 5 days after symptom onset) and assumptions about the infectiousness of Ct shedding trajectories. Of the 116 household contacts with ≥2 positive tests for longitudinal analyses, 105 (91%) experienced ≥1 ILI symptom. On average, children <5 years experienced greater peak shedding, longer durations of shedding, and elevated ILI symptom scores compared with other age groups. Most individuals (63/105) shed <10% of their total shed virus before symptom onset, and shedding after isolation varied substantially across individuals, isolation end points, and infectiousness assumptions. Our results can inform strategies to reduce transmission from symptomatic individuals infected with influenza.

Lumpy skin disease (LSD) is one of the most economically significant viral diseases of cattle caused by the Lumpy Skin Disease Virus (LSDV), classified as a member of the genus Capripoxvirus and belongs to the family Poxviridae. Nodular skin samples were collected from clinically sick cattle in the districts of Amuru and Wara Jarso Ethiopia to isolate LSD virus. The virus was isolated using primary lamb testis and kidney cells. The isolated LSDV was infected into a healthy calf while maintaining the necessary biosecurity measures to generate skin lesions and to assess disease progression using postmortem examinations. On the fourth day after virus inoculation, the calf developed typical LSD skin nodules with increased rectal temperature, which lasted until the 12th day, when they began to decrease. Viral shedding was detected in nasal, oral, and conjunctival swabs from 6 to 14 days after infection using real-time PCR. Post-mortem tissue specimens tested positive for LSD virus using real-time PCR and virus isolation. This study showed that LSDV were responsible for the LSD outbreaks, and the appearance of typical skin nodules accompanied by fever (> 39.5 °C) defined the virus\'s virulent status. The experimental infection with the isolated infectious LSDV could serve as a platform for future vaccine evaluation study using an LSDV challenge model.

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.

UNASSIGNED: Fecal shedding of SARS-CoV-2 occurs during infection, particularly in pediatric populations. The gut microbiota are associated with resistance to enteric pathogens. COVID-19 is associated with alterations to the gut microbiome. We hypothesized that the gut microbiome of infants born to SARS-CoV-2+ mothers differs between infants with and without fecal shedding of the virus.
UNASSIGNED: We enrolled 10 infants born to SARS-CoV-2+ mothers. We used qPCR on fecal RNA to test for SARS-CoV-2 and 16S rRNA gene sequencing of the V4 region to assess the gut microbiome. Infant SARS-CoV-2 status from nasal swabs was abstracted from medical records.
UNASSIGNED: Of the 10 included infants, nine were tested for SARS-CoV-2 by nasal swab with 1 testing positive. Four infants, including the nasal swab positive infant, had at least one sample with detectable levels of SARS-CoV-2 fecal shedding. Detection of both SARS-CoV-2 genes in feces was associated with increased gut alpha diversity compared to no detection by a linear mixed effects model (p < 0.001). Detection of both SARS-CoV-2 genes was associated with increased levels Erysipelotrichaceae, Lactobacillaceae, and Ruminococceae by MaAsLin2.
UNASSIGNED: Fecal shedding of SARS-CoV-2 occurs in infants who test negative on nasal swabs and is associated with differences in the gut microbiome.

Patients on B cell immunosuppressive treatments have been shown to have persistent infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this report, a woman treated with ibrutinib for chronic lymphocytic leukemia experienced more than 40 days of coronavirus disease 2019 (COVID-19) infection. Unexpectedly, her peripheral blood experiments showed a normal SARS-CoV-2-specific antibody level and a relatively elevated percentage of CD19 + B cells, while an obvious decrease in the percentages of NK cells, CD4 + T cells and CD8 + T cells. Further SARS-CoV-2-specific T cell analysis in this patient indicated a significant decrease in the percentage of SARS-CoV-2-specific IFN-γ, TNF-α or IL-2 producing CD4 + T or CD8 + T cells. Most notably, ten days after the cease of ibrutinib, the PCR for SARS-CoV-2 turned negative and the reduced proportions of peripheral CD4 + T cells and CD8 + T cells recovered. Our research predicted that the depleted B-cell function therapies may play considerable role in the development of long COVID-19 and the abnormal T-cell subset distribution might be the underlying mechanism.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.

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.

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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.

The prevalence of avian influenza viruses is commonly found to increase dramatically as birds are transported from farms to live bird markets. Viral transmission dynamics along marketing chains are, however, poorly understood. To address this gap, we implemented a controlled field experiment altering chicken supply to a live bird market in Chattogram, Bangladesh. Broilers and backyard chickens traded along altered (intervention) and conventional (control) marketing chains were tested for avian influenza viruses at different time points. Upon arrival at the live bird market, the odds of detecting avian influenza viruses did not differ between control and intervention groups. However, 12 h later, intervention group odds were lower, particularly for broilers, indicating that viral shedding in live bird markets resulted partly from infections occurring during transport and trade. Curtailing avian influenza virus prevalence in live bird markets requires mitigating risk in marketing chain nodes preceding chickens\' delivery at live bird markets.