Duration Of Shedding Research Articles

P-2012. Predicting Persistent SARS-CoV-2 Shedding in Immunocompromised Patients: A Probability-Based Approach

Abstract Background Prolonged SARS-CoV-2 shedding frequently occurs in immunocompromised patients, making the determination of their isolation periods challenging. This study aims to estimate the probability of viral clearance in immunocompromised patients, stratified by elapsed days and other relevant variables. Figure 1 The estimated probability of viral clearance along days, stratified by SARS-CoV-2 PCR Ct value and immunocompromised conditions Methods This prospective study was conducted at Asan Medical Center, a 2,732-bed tertiary teaching hospital in the Republic of Korea, from January 2022 to May 2023 during the prevalence of the Omicron variant. We enrolled immunocompromised patients, defined as 'moderately or severely immunocompromised' according to CDC guidelines. All participants, diagnosed with COVID-19 via nasopharyngeal swab PCR, provided weekly respiratory specimens for viral load measurement using real-time RT-PCR. Positive samples underwent viral culture. The Cox time-varying proportional hazard model was applied to identify significant predictors of viral culture negative conversion, employing backward elimination for model refinement. Analyses were conducted using R software, version 4.3.2, and included the assessment of viral copy number dynamics and treatment effects on viral shedding probabilities. Baseline characteristics of the immunocompromised patients Results In a cohort of 70 immunocompromised patients, 48 (68.6%) had hematologic malignancies and 22 (31.4%) underwent solid organ transplants. Univariate and multivariate analyses revealed that the use of B-cell depleting agents, CAR T-cell therapy, and viral copy number significantly influenced viral culture negative conversion. These findings were incorporated into a refined model to predict viral shedding probabilities. Patients with a history of both B-cell depleting agents and CAR T-cell therapy exhibited the lowest negative conversion rates, with median durations of viral shedding from 76 days to undeterminable depending on SARS-CoV-2 Ct values. In contrast, patients receiving neither treatment showed markedly faster viral clearance, typically within one to two months after COVID-19 diagnosis, regardless of Ct values. Predictive factors for viral culture negative conversion in the immunocompromised patients Conclusion Ending the isolation of immunocompromised patients with COVID-19 should be determined individually, based on the viral copy number at specific time points and treatment conditions. Table 3 Probability of culture-negative conversion among immunocompromised patients based on treatments received, days elapsed after diagnosis, and SARS-CoV-2 PCR results Disclosures All Authors: No reported disclosures

516. Cytomegalovirus (CMV) Saliva Shedding Kinetics in Children with Congenital Cytomegalovirus Infection (cCMV)

Abstract Background CMV is the most common cause of congenital viral infection worldwide and the leading cause of non-genetic sensorineural hearing loss (SNHL). Children with congenital CMV infection (cCMV) shed the virus in urine and saliva for prolonged but variable durations. However, data on CMV saliva shedding kinetics in cCMV is limited because of the lack of longitudinal virological follow-up. The objective of this study is to describe CMV shedding kinetics in saliva during early childhood in a cohort of children with cCMV identified through universal newborn screening. Methods As part of the CMV and Hearing Multicenter Screening study (CHIMES), >100,000 newborns were screened for cCMV. Data from 211 children with ≥ 5 visits each with audiological follow-up and serial saliva samples collected every six months through four years of life was analyzed. Saliva CMV shedding duration and intermittent shedding according to presence of newborn symptoms, hearing status and antiviral treatment are described. Results Of the 211 children with cCMV, 14 received anti-viral treatment in early infancy. Most children shed CMV in saliva during infancy with a gradual decrease in frequency on follow-up (Figure 1). The median duration of shedding did not differ between children with asymptomatic and symptomatic cCMV (25 vs 26 months respectively; p = 0.61); children with SNHL and normal hearing (22 vs 26 months respectively; p = 0.26); and between those treated with antiviral agents and untreated children (23 vs 25 months; p = 0.9). Salivary CMV shedding was intermittent in about a third of the cohort (71/197 - 36%), mostly (91.5%) in those with asymptomatic cCMV. CMV shedding duration was significantly longer in children with intermittent shedding compared to those who did not (34 vs 17 months; p < 0.0001). Conclusion In this large cohort of children with cCMV identified through newborn screening, children shed CMV DNA in saliva for a median of two years, irrespective of newborn symptoms, hearing status, and receipt of anti-viral therapy. A third of the cohort shed CMV intermittently. Based on these observations, we conclude that a negative saliva CMV PCR result during infancy in newborns with findings consistent with cCMV but not tested in the newborn period likely excludes a diagnosis of cCMV. Disclosures Swetha Pinninti, MD, Moderna: Grant/Research Support|Pfizer: Grant/Research Support Karen Fowler, DrPH, Moderna: Advisor/Consultant Suresh Boppana, MD, GSK: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Grant/Research Support

The immune landscape and viral shedding of Omicron SARS-CoV-2 variants implicate immune escape

BackgroundThree years into the SARS-CoV-2 pandemic, the virus continues to mutate despite widespread vaccination, posing ongoing challenges for epidemic prevention and control. The relationship between viral shedding and immune escape remains under investigation. This study aims to examine the association between viral shedding and immune escape in the BA.4/5 and BF.7 variants.MethodWe included 542 patients infected with the Omicron variant from Beijing Xiaotangshan shelter hospital. Based on the viral strain, patients were divided into BA.4/5 group and BF.7 group. Additionally, we categorized patients into rapid viral shedding and slow viral shedding groups according to their viral shedding rates. We explored the relationship between viral shedding and immune-related clinical indicators during this period.ResultOf the 542 patients, 118 were infected with BA.4/5 variant, and 424 were infected with BF.7 variant. The viral shedding duration differed significantly between BA.4/5 and BF.7 groups (p < 0.0001). However, there was no statistically significant correlation between viral shedding duration and immune-related indicators, such as WBC, Hb, PLT, Neu, Lym, CRP, allergy, fever, and vaccination status (p > 0.05). Furthermore, viral shedding duration was not associated with vaccination status, intervals between vaccinations, or vaccine types (p > 0.05).ConclusionThe duration of viral shedding in patients infected with Omicron variants BA.4/5 and BF.7 is not associated with WBC, Hb, Lym, CRP, fever, allergy, or vaccine-related indicators. This lack of association may be attributed to immune escape mechanisms.

Duration of infectious virus shedding of SARS-CoV-2 Omicron variant among immunocompromised patients.

The duration of viral shedding and criteria for de-isolation in the hospital among immunocompromised patients with coronavirus disease 2019 (COVID-19) remain unclear. This study aimed to evaluate viral shedding duration in immunocompromised patients infected with the Omicron variant of severe acute respiratory syndrome coronavirus 2. A prospective cohort study was performed at 2 tertiary medical centers in Japan during the Omicron epidemic waves from July 2022 to January 2023. Nasopharyngeal swabs were serially collected from immunocompromised patients with COVID-19, including those with hematological malignancies, solid tumors, autoimmune diseases, and human immunodeficiency virus infection. Patients were classified as severely or moderately immunocompromised according to the Japanese national guidelines for tixagevimab-cilgavimab. The relationship between patient characteristics, immune status, duration of viral RNA presence, and infectious virus shedding were assessed using Mann-Whitney U and Fisher's exact tests. Among 41 patients (163 samples), 9 (47 samples) were severely and 32 (116 samples) were moderately immunocompromised. In the severely and moderately immunocompromised groups, 87.2% and 75.0% of the samples were viral RNA-positive, while 36.2% and 35.3% were culture-positive, respectively. Five culture-positive samples after day 20 were from 2 severely immunocompromised patients on B cell depletion therapy. No culture-positive samples were found for the moderately immunocompromised patients after day 10. Long-term viral shedding should be closely monitored in severely immunocompromised patients with COVID-19.

Shortened SARS-CoV-2 viral RNA shedding in saliva during early Omicron compared to wild-type pandemic phase.

This study compared the dynamics of SARS-CoV-2 viral shedding in saliva between wild-type virus-infected and Omicron-infected household cohorts. Pre-existing immunity in participants likely shortens the viral RNA shedding duration and lowers viral load peaks. Frequent saliva sampling can be a convenient tool to study viral load dynamics.

Duration and clinical relevance of viral shedding of HEV by the stool: results from an observational prospective study

Duration and clinical relevance of viral shedding of HEV by the stool: results from an observational prospective study

Defining the Critical Requisites for Accurate Simulation of SARS-CoV-2 Viral Dynamics: Patient Characteristics and Data Collection Protocol.

Mathematical models of viral dynamics are crucial in understanding infection trajectories. However, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load data often includes limited sparse observations with significant heterogeneity. This study aims to: (1) understand the impact of patient characteristics in shaping the temporal viral load trajectory and (2) establish a data collection protocol (DCP) to reliably reconstruct individual viral load trajectories. We collected longitudinal viral load data for SARS-CoV-2 Delta and Omicron variants from 243 patients in Singapore (2021-2022). A viral dynamics model was calibrated using patients' age, symptom presence, and vaccination status. We accessed associations between these patient characteristics and aspects of viral dynamics using linear regression models. We evaluated the accuracy of viral load trajectory estimation under different simulated DCPs by varying patient numbers, test frequencies, and test intervals. Older unvaccinated individuals had a longer viral shedding duration due to lower infection and cell death rates. Higher peak viral loads were found in older, symptomatic, and vaccinated individuals, with earlier peaks in younger vaccinated individuals. Symptom presence and vaccination resulted in a shorter time from infection to diagnosis. To accurately estimate viral dynamics, more frequent tests, longer test intervals, and larger patient samples are required. For 500 patients, a 21-day follow-up with measurements every 3 days and an 8-day follow-up with daily measurements was optimal for the Delta and Omicron variants, respectively. Patient characteristics significantly impacted viral dynamics. Our analytic approach and recommended DCPs can enhance preparedness and response to emerging pathogens beyond SARS-CoV-2.

Virological Aspects of COVID-19 in Patients with Hematological Malignancies: Duration of Viral Shedding and Genetic Analysis.

Coronavirus disease 2019 (COVID-19) has been associated with a significant fatality rate and persistent evolution in immunocompromised patients. In this prospective study, we aimed to determine the duration of excretion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 37 Tunisian patients with hematological malignancies (40.5% with lymphoma and 37.8% with leukemia). In order to investigate the accumulation of viral mutations, we carried out genetic investigation on longitudinal nasopharyngeal samples using RT-PCR and whole-genome sequencing. Patients' samples were collected until the RT-PCR results became negative. SARS-CoV-2 infection was symptomatic in 48.6% of cases with fever, and cough was symptomatic in 61% of cases; the mortality rate was estimated to be 13.5%. The duration of viral RNA shedding ranged from 7 to 92 days after onset; it exceeded 18 days in 79.4% of cases. An intermittent PCR positivity was observed in two symptomatic patients. Persistent PCR positivity, defined as the presence of viral RNA for more than 30 days, was found in 51.4% of cases. No significant differences were observed for age, sex, type of hematological malignancy, or COVID-19 evolution between this group and a second one characterized by non-persistent PCR positivity. Lymphopenia was an independent predictor of prolonged SARS-CoV-2 RNA detection (p = 0.04). Three types of variants were detected; the most frequent was the Omicron. Globally, the mean intra-host variability in the SARS-CoV-2 genome was 1.31 × 10-3 mutations per site per year; it was 1.44 × 10-3 in the persistent group and 1.3 × 10-3 in the non-persistent group. Three types of mutations were detected; the most frequent were nucleotide substitutions in the spike (S) gene. No statistically significant difference was observed between the two groups as to the type and mean number of observed mutations in the whole genome and the S region (p = 0.650). Sequence analysis revealed the inclusion of one to eight amino acid-changing events in seventeen cases; it was characterized by genetic stability from the third to the twentieth day of evolution in six cases. For the two patients with intermittent PCR positivity, sequences obtained from samples before and after negative PCR were identical in the whole genome, confirming an intra-host evolution of the same viral strain. This study confirms the risk of persistent viral shedding in patients with hematological malignancies. However, persistence of PCR positivity seems to be correlated only with a continuous elimination of viral RNA debris. Additional studies based on cell culture analysis are needed to confirm these findings.

Defining within-host SARS-CoV-2 RNA viral load kinetics during acute COVID-19 infection within different respiratory compartments and their respective associations with host infectiousness: a protocol for a systematic review and meta-analysis

IntroductionUnderstanding how RNA viral load changes (viral load kinetics) during acute infection in SARS-CoV-2 can help to identify when and which patients are most infectious. We seek to summarise existing...

Risk of canine distemper virus vaccination of domestic dogs in giant panda habitat to giant pandas

The giant panda (Ailuropioda melanoleuca), a unique relic species in China and a global biodiversity conservation symbol, faces the threat of canine distemper virus (CDV). Vaccinating domestic dogs in panda habitats against CDV is crucial, yet the associated risks remain understudied. We investigated the safety of CDV vaccination in 69 domestic dogs within panda habitats, employing enzyme-linked immunosorbent assay for CDV antibodies and quantitative reverse transcription polymerase chain reaction for viral RNA, a marker of viral shedding. Results revealed that vaccinated dogs posed a risk through viral shedding, mainly starting from the ninth day post-vaccination. Unvaccinated dogs exhibited increased CDV antibodies and subsequent shedding, with phylogenetic analysis confirming infection from vaccinated dogs in shared kennels. Dogs with higher initial antibodies displayed reduced shedding and a markedly abbreviated shedding duration (6.7 days) than those with lower initial antibodies (9.8 days). Habitat area analysis revealed substantial overlaps between domestic dogs and wild giant pandas in two nature reserves in China. To safeguard wildlife, particularly giant pandas, we recommend restricting vaccinated dogs’ activity for at least three weeks post-vaccination, complementing existing management practices. We advocate collaborative efforts among local authorities, reserve management and villagers for effective vaccination and post-vaccination management of domestic dogs.

Similar Kinetics of Pulmonary SARS-CoV-2 Load in Intensive Care Unit Patients with COVID-19 Pneumonia with or Without Autoantibodies Neutralizing Type I Interferons.

The pathogenesis of life-threatening coronavirus disease 2019 (COVID-19) pneumonia in ICU patients can involve pre-existing auto-antibodies (auto-Abs) neutralizing type I interferons (IFNs). The impact of these auto-Abs on SARS-CoV-2 clearance in the lower respiratory tract (LRT) is unclear. We performed a retrospective study in 99 ICU patients with COVID-19 pneumonia between March and May 2020. LRT SARS-CoV-2 load (intensity and duration) was analyzed according to the presence or not of circulating auto-Abs neutralizing type I IFNs. Among the 99 included patients, 38 (38%) were positive for auto-Abs neutralizing type I IFNs, with 5 (5%) harboring auto-Abs neutralizing IFN-α2 at any concentration, while 33 (33%) had auto-Abs neutralizing only IFN-ω at the lower concentration. SARS-CoV-2 load in the LRT and duration of viral shedding, were similar in patients with or without auto-Abs neutralizing type I IFNs. Patients with auto-Abs had the same mortality than those without auto-Abs, despite greater occurrence of renal failure and ECMO support, and longer duration of mechanical ventilation and ICU stay. In summary, 5% of patients with critical COVID-19 pneumonia carried auto-Abs neutralizing IFN-α2, while about 1/3 harbored auto-Abs neutralizing low concentrations of IFN-ω. The detection of either type of auto-Abs did not impact LRT viral clearance and mortality, although it was associated with greater morbidity and a longer hospitalization. These findings suggest that similar albeit hitherto unknown mechanisms of disease drive critical COVID-19 pneumonia in patients without auto-Abs against type I IFNs.

Influenza A virus shedding and reinfection during the post-weaning period in swine: longitudinal study of two nurseries.

Influenza A virus in swine (IAV-S) is common in the United States commercial swine population and has the potential for zoonotic transmission. To elucidate influenza shedding the domestic pig population, we evaluated two commercial swine farms in Illinois, United States, for 7 weeks. Farm 1 had a recent IAV-S outbreak. Farm 2 has had IAV-S circulating for several years. Forty post-weaning pigs on Farm 1 and 51 pigs from Farm 2 were individually monitored and sampled by nasal swabs for 7 weeks. RT-PCR results over time showed most piglets shed in the first 2 weeks post weaning, with 91.2% shedding in week one, and 36.3% in week two. No difference in the number of pigs shedding was found between the two nurseries. Reinfection events did differ between the farms, with 30% of piglets on Farm 1 becoming reinfected, compared to 7.8% on Farm 2. In addition, whole genome sequencing of nasal swab samples from each farm showed identical viruses circulating between the initial infection and the reinfection periods. Sequencing also allowed for nucleic and amino acid mutation analysis in the circulating viruses, as well the identification of a potential reverse zoonosis event. We saw antigenic site mutations arising in some pigs and MxA resistance genes in almost all samples. This study provided information on IAV-S circulation in nurseries to aid producers and veterinarians to screen appropriately for IAV-S, determine the duration of IAV-S shedding, and predict the occurrence of reinfection in the nursery period.

Efficacy of an Inactivated Whole-Virus A/Victoria/361/2011 (IVR-165) (H3N2) Influenza Vaccine in Ferrets.

It has been reported that the high-growth reassortant (HGR) A(H3N2) influenza viruses used for split influenza vaccine (SV) production have some amino acid substitutions in hemagglutinin due to egg adaptation during virus propagation, causing antigenic differences between HGR and epidemic viruses. To clarify whether inactivated whole-virus vaccine (WV) derived from the A(H3N2) HGR virus possessing egg adaptation could induce cross-protective immune responses against epidemic A(H3N2) viruses, the efficacy of WV was compared with that of SV in a ferret model. When the ferrets immunized with WV or SV derived from HGR A/Victoria/361/2011 (IVR-165) virus were challenged with the homologous virus A/Victoria/361/2011 (IVR-165) or its original cell-propagated A/Victoria/361/2011 virus, respectively, WV successfully shortened the duration of virus shedding of both challenge viruses, whereas SV shortened only that of the homologous virus, A/Victoria/361/2011 (IVR-165). When WV-immunized ferrets were challenged with A/Fukushima/69/2015 virus, which is an epidemic virus antigenically different from the A/Victoria/361/2011 virus, WV could shorten the duration of shedding of this virus. In addition, we found that early induction of nasal IgG and IgA antibodies by vaccines helped shorten the virus-shedding period, although this was dependent on the degree of difference in antigenicity of the challenge virus. These results indicate that vaccination with WV, not with SV, would be a solution to avoid decreased vaccine effectiveness due to the antigenic change of HGR virus by egg adaptation during virus propagation.

The Clinical Characteristics and Virus Shedding of Omicron Patients in a Shanghai Mobile Cabin Hospital

Background Information about characteristics of Omicron-infected patients and estimation of risk factors for the duration of viral shedding were unclear. Methods This retrospective study included asymptomatic patients and patients with mild symptoms, who were infected with Omicron and hospitalized in a Shanghai mobile cabin hospital. The clinical characteristics of those patients were summarized, and the influencing factors of severe acute respiratory syndrome coronavirus 2 virus shedding were explored. Results Multivariate logistic regression analysis indicated that comorbidities (odds ratio [OR], 1.991; 95% confidence interval [CI], 1.365–2.904; P = 0.000), 2 doses of vaccines (OR, 2.421; 95% CI, 1.636–3.584; P = 0.000), 3 doses of vaccine/booster shots (OR, 3.797; 95% CI, 2.607–5.529; P = 0.000), and virus shedding time (OR, 1.078; 95% CI, 1.053–1.103; P = 0.000) were associated with increased odds of mild symptoms in Omicron patients, whereas age (OR, 0.951; 95% CI, 0.940–0.963; P = 0.000) was associated with a reduced risk of mild symptoms. The median length of virus ribonucleic acid shedding time was 10 days. Being male (OR, 1.868; 95% CI, 1.488–2.345; P < 0.001), age (OR, 1.018; 95% CI, 1.008–1.028; P < 0.001), and a diagnosis of mild symptoms (OR, 1.508; 95% CI, 1.244–1.895; P < 0.001) were risk factors of prolonged shedding time in multivariate regression analysis. The cycle threshold values of nucleocapsid protein and open reading frame 1ab genes in Omicron patients with virus shedding time ≤10 days are significantly different from that in patients with virus shedding time >20 days (P < 0.001). Conclusions Being male, being older, and having a mild case were all risk factors for prolonged virus shedding time, and patients with high viral load may have long virus shedding time. Patients who are young, have complications, and have been vaccinated with 2 or 3 doses/enhanced vaccines with long virus shedding time increased the risk of clinical symptoms.

Impact of early antiviral therapy on SARS-CoV-2 clearance time in high-risk COVID-19 subjects: A propensity score matching study

BackgroundEffective treatments for COVID-19 are needed to mitigate disease progression and reduce the burden on healthcare systems. This study investigates the impact of early treatments on SARS-CoV-2 viral shedding duration among high-risk individuals with mild symptoms. MethodsA single-center, retrospective observational study was conducted at Luigi Sacco Hospital in Milan from December 2021 to March 2023. Hospitalized and nonhospitalized adults with a confirmed SARS-CoV-2 infection and at high-risk of disease progression were enrolled. Unadjusted and adjusted negative binomial regression models and a Random Forest regression model were performed before and after matching subjects based on their propensity of being treated or not. ResultsResults from 518 subjects (428 treated and 90 untreated) revealed a significant reduction in SARS-CoV-2 viral shedding duration among those who received early treatment compared to untreated individuals. Propensity score matching and multivariable regression analyses confirmed this finding. Early treatment significantly reduced the risk of COVID-19-related hospitalization and pneumonia development. Subgroup analysis identified COPD as a potential factor influencing effectiveness of early treatments. ConclusionsEarly treatments play a crucial role in reducing SARS-CoV-2 viral shedding and preventing disease progression among high-risk individuals. Shorter viral shedding duration also contributes to improved healthcare resource utilization and infection control measures.

Effects of vaccination on antibody level and duration of viral shedding in Omicron patients.

We compared the clinical characteristics of vaccinated and non-vaccinated Omicron patients in order to provide a reference for the clinical diagnosis and treatment of coronavirus disease 2019 (COVID-19). This study included 360 patients diagnosed with COVID-19. The serum immunoglobulin G (IgG) and serum immunoglobulin M (IgM) antibody levels of the patients and the duration of virus shedding were analyzed according to age, gender, vaccine dose, and the time from the most recent vaccination to the onset of Omicron infection. Age (OR = 0.974), days from last vaccination to onset ≤ 180 days (OR = 4.409), and booster dose of the vaccine (OR = 4.999) were protective factors associated with patients who were IgG antibody positive. The duration of virus shedding in IgG -antibody-positive patients was 9 (8-11) days; and this was significantly lower than that in IgG-antibody-negative patients, who had virus shedding duration of 10 (8-12) days (p < 0.05). Booster immunizations could increase IgG-antibody in patients who have already been infected with the Omicron variant and enhance immune protection. In addition, COVID-19 vaccination may shorten the duration of virus shedding.

Comparison of viraemia and nasal shedding after PRRSV-1 challenge following vaccination with three commercially available PRRS modified live virus vaccines

The effectiveness of three Porcine Reproductive and Respiratory Syndrome (PRRS) Modified Live Virus (MLV) vaccines against PRRSV viraemia and nasal shedding following experimental challenge was compared. The study comprised a negative control (T01), and three treatment groups (T02, T03 and T04) each vaccinated with a single dose of a commercial PRRS MLV vaccine, given in accordance with the vaccine's Summary of Product Characteristics (SPC). Pigs aged 21 days were vaccinated (day 0), challenged intranasally (day 28) with heterologous PRRSV-1-1 strain Olot/91, then monitored for PRRSV viraemia and nasal shedding for 12 days. After challenge, pigs were viraemic on fewer days in group T04 (0.67) than groups T01 (0.91), T02 (0.81) and T03 (0.97) (P < 0.0296). From day 34, inclusive, serum PRRSV titres were lower in group T04 than negative controls (P ≤ 0.0001) and groups T02 and T03 (P ≤ 0.0047); serum PRRSV titre Area Under the Curve (AUC) for group T04 (42.34) was lower than in T01 (65.49), T02 (60.67) and T03 (67.38) (P < 0.0100); pigs exhibited nasal shedding on fewer days in group T04 (0.40) than T01 (0.78), T02 (0.64) and T03 (0.56) (P < 0.0101); and nasal shedding AUC for group T04 (8.52) was lower than in groups T01 (23.59, P < 0.0001) and T02 (19.37, P = 0.0001). The ability of PRRS MLV vaccines to reduce the duration of viraemia and nasal shedding after intranasal challenge with a heterologous PRRSV-1-1 strain differ significantly.

A nonhuman primate model for genital herpes simplex virus 2 infection that results in vaginal vesicular lesions, virus shedding, and seroconversion.

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.

Modelling the effectiveness of an isolation strategy for managing mpox outbreaks with variable infectiousness profiles

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.

Effect of SARS-CoV-2 shedding rate distribution of individuals during their disease days on the estimation of the number of infected people. Application of wastewater-based epidemiology to the city of Thessaloniki, Greece

During the COVID-19 pandemic, wastewater-based epidemiology has proved to be an important tool for monitoring the spread of a disease in a population. Indeed, wastewater surveillance was successfully used as a complementary approach to support public health monitoring schemes and decision-making policies. An essential feature for the estimation of a disease transmission using wastewater data is the distribution of viral shedding rate of individuals in their personal human wastes as a function of the days of their infection. Several candidate shapes for this function have been proposed in literature for SARS-CoV-2. The purpose of the present work is to explore the proposed function shapes and examine their significance on analyzing wastewater SARS-CoV-2 shedding rate data. For this purpose, a simple model is employed applying to medical surveillance and wastewater data of the city of Thessaloniki during a period of Omicron variant domination in 2022. The distribution shapes are normalized with respect to the total virus shedding and then their basic features are investigated. Detailed analysis reveals that the main parameter determining the results of the model is the difference between the day of maximum shedding rate and the day of infection reporting. Since the latter is not part of the distribution shape, the major feature of the distribution affecting the estimation of the number of infected people is the day of maximum shedding rate with respect to the initial infection day. On the contrary, the duration of shedding (total number of disease days) as well as the exact shape of the distribution are by far less important. The incorporation of such wastewater surveillance models in conventional epidemiological models - based on recorded disease transmission data- may improve predictions for disease spread during outbreaks.