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The characterization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral kinetics in hospitalized patients and its association with mortality is unknown. We analyzed death and nasopharyngeal viral kinetics in 655 hospitalized patients from the prospective French COVID cohort. The model predicted a median peak viral load that coincided with symptom onset. Patients with age ≥65 y had a smaller loss rate of infected cells, leading to a delayed median time to viral clearance occurring 16 d after symptom onset as compared to 13 d in younger patients (P < 10−4). In multivariate analysis, the risk factors associated with mortality were age ≥65 y, male gender, and presence of chronic pulmonary disease (hazard ratio [HR] > 2.0). Using a joint model, viral dynamics after hospital admission was an independent predictor of mortality (HR = 1.31, P < 10−3). Finally, we used our model to simulate the effects of effective pharmacological interventions on time to viral clearance and mortality. A treatment able to reduce viral production by 90% upon hospital admission would shorten the time to viral clearance by 2.0 and 2.9 d in patients of age <65 y and ≥65 y, respectively. Assuming that the association between viral dynamics and mortality would remain similar to that observed in our population, this could translate into a reduction of mortality from 19 to 14% in patients of age ≥65 y with risk factors. Our results show that viral dynamics is associated with mortality in hospitalized patients. Strategies aiming to reduce viral load could have an effect on mortality rate in this population.

Virus spread at the single-cell level is largely uncharacterized. We have designed and constructed a microfluidic device in which each nanowell contains a single, infected cell (donor) and a single, uninfected cell (recipient). Using a GFP-expressing poliovirus as our model, we observed both lytic and non-lytic spread. Donor cells supporting lytic spread established infection earlier than those supporting non-lytic spread. However, non-lytic spread established infections in recipient cells substantially faster than lytic spread and yielded higher rates of genome replication. While lytic spread was sensitive to the presence of capsid entry/uncoating inhibitors, non-lytic spread was not. Consistent with emerging models for non-lytic spread of enteroviruses using autophagy, reduction in LC3 levels in cells impaired non-lytic spread and elevated the fraction of virus in donor cells spreading lytically. The ability to distinguish lytic and non-lytic spread unambiguously will enable discovery of viral and host factors and host pathways used for non-lytic spread of enteroviruses and other viruses as well.

SARS-CoV-2 is difficult to contain because many transmissions occur during pre-symptomatic infection. Unlike influenza, most SARS-CoV-2-infected people do not transmit while a small percentage infect large numbers of people. We designed mathematical models which link observed viral loads with epidemiologic features of each virus, including distribution of transmissions attributed to each infected person and duration between symptom onset in the transmitter and secondarily infected person. We identify that people infected with SARS-CoV-2 or influenza can be highly contagious for less than 1 day, congruent with peak viral load. SARS-CoV-2 super-spreader events occur when an infected person is shedding at a very high viral load and has a high number of exposed contacts. The higher predisposition of SARS-CoV-2 toward super-spreading events cannot be attributed to additional weeks of shedding relative to influenza. Rather, a person infected with SARS-CoV-2 exposes more people within equivalent physical contact networks, likely due to aerosolization.

In persons living with HIV-1 (PLWH) who start antiretroviral therapy (ART), plasma virus decays in a biphasic fashion to below the detection limit. The first phase reflects the short half-life (<1 d) of cells that produce most of the plasma virus. The second phase represents the slower turnover (t 1/2 = 14 d) of another infected cell population, whose identity is unclear. Using the intact proviral DNA assay (IPDA) to distinguish intact and defective proviruses, we analyzed viral decay in 17 PLWH initiating ART. Circulating CD4⁺ T cells with intact proviruses include few of the rapidly decaying first-phase cells. Instead, this population initially decays more slowly (t 1/2 = 12.9 d) in a process that largely represents death or exit from the circulation rather than transition to latency. This more protracted decay potentially allows for immune selection. After ∼3 mo, the decay slope changes, and CD4⁺ T cells with intact proviruses decay with a half-life of 19 mo, which is still shorter than that of the latently infected cells that persist on long-term ART. Two-long-terminal repeat (2LTR) circles decay with fast and slow phases paralleling intact proviruses, a finding that precludes their use as a simple marker of ongoing viral replication. Proviruses with defects at the 5′ or 3′ end of the genome show equivalent monophasic decay at rates that vary among individuals. Understanding these complex early decay processes is important for correct use of reservoir assays and may provide insights into properties of surviving cells that can constitute the stable latent reservoir.

The nonstructural 5A (NS5A) protein is a target for drug development against hepatitis C virus (HCV). Interestingly, the NS5A inhibitor daclatasvir (BMS-790052) caused a decrease in serum HCV RNA levels by about two orders of magnitude within 6 h of administration. However, NS5A has no known enzymatic functions, making it difficult to understand daclatasvir’s mode of action (MOA) and to estimate its antiviral effectiveness. Modeling viral kinetics during therapy has provided important insights into the MOA and effectiveness of a variety of anti-HCV agents. Here, we show that understanding the effects of daclatasvir in vivo requires a multiscale model that incorporates drug effects on the HCV intracellular lifecycle, and we validated this approach with in vitro HCV infection experiments. The model predicts that daclatasvir efficiently blocks two distinct stages of the viral lifecycle, namely viral RNA synthesis and virion assembly/secretion with mean effectiveness of 99% and 99.8%, respectively, and yields a more precise estimate of the serum HCV half-life, 45 min, i.e., around four times shorter than previous estimates. Intracellular HCV RNA in HCV-infected cells treated with daclatasvir and the HCV polymerase inhibitor NM107 showed a similar pattern of decline. However, daclatasvir treatment led to an immediate and rapid decline of extracellular HCV titers compared to a delayed (6–9 h) and slower decline with NM107, confirming an effect of daclatasvir on both viral replication and assembly/secretion. The multiscale modeling approach, validated with in vitro kinetic experiments, brings a unique conceptual framework for understanding the mechanism of action of a variety of agents in development for the treatment of HCV.

We modeled the viral dynamics of 13 untreated patients infected with severe acute respiratory syndrome‐coronavirus 2 to infer viral growth parameters and predict the effects of antiviral treatments. In order to reduce peak viral load by more than two logs, drug efficacy needs to be > 90% if treatment is administered after symptom onset; an efficacy of 60% could be sufficient if treatment is initiated before symptom onset. Given their pharmacokinetic/pharmacodynamic properties, current investigated drugs may be in a range of 6–87% efficacy. They may help control virus if administered very early, but may not have a major effect in severely ill patients.

Living with COVID-19 requires continued vigilance against the spread and emergence of variants of concern (VOCs). Rapid and accurate saliva diagnostic testing, alongside basic public health responses, is a viable option contributing to effective transmission control. Nevertheless, our knowledge regarding the dynamics of SARS-CoV-2 infection in saliva is not as advanced as our understanding of the respiratory tract. Here, we analyzed longitudinal viral load data of SARS-CoV-2 in saliva samples from 144 patients with mild COVID-19 (a combination of our collected data and published data). Using a mathematical model, we quantified individual-level viral dynamics and stratified them into three groups using a clustering approach. Notably, the three groups exhibited distinct differences in viral RNA detection durations: 11.5 days (95% CI: 10.6–12.4), 17.4 days (16.6–18.2), and 30.0 days (28.1–31.8), respectively. Surprisingly, this stratified grouping remained unexplained despite our analysis of 47 types of clinical data, including basic demographic information, clinical symptoms, results of blood tests, and vital signs. Additionally, we quantified the expression levels of 92 micro-RNAs in a subset of saliva samples, but these also failed to explain the observed stratification, although the mir-1846 level may have been weakly correlated with peak viral load. Our study provides insights into SARS-CoV-2 infection dynamics in saliva, highlighting the challenges in predicting the duration of viral RNA detection without indicators that directly reflect an individual’s immune response, such as antibody induction. Given the significant individual heterogeneity in the kinetics of saliva viral shedding, identifying biomarker(s) for viral shedding patterns will be crucial for improving public health interventions in the era of living with COVID-19.

Abstract Background The association between respiratory syncytial virus (RSV) loads and clinical outcomes in children remains to be defined. In most studies, viral loads (VL) were evaluated in hospitalized children and at a single time-point. We investigated the relationship between VLs and disease severity in both outpatients and inpatients with RSV infection. Methods We enrolled previously healthy children with RSV infection. Disease severity was defined by level of care (outpatients vs ward vs pediatric intensive care unit [PICU]), and a clinical disease severity score (CDSS). Nasopharyngeal VLs by polymerase chain reaction and CDSS were measured at enrollment and daily in inpatients. VL decay according to disease severity was analyzed using linear mixed modeling. Results From February 2015 to March 2017, we enrolled 150 infants: 39 outpatients and 111 inpatients. VLs were higher in outpatients than in age-matched inpatients. Among inpatients, initial VLs were comparable in ward and PICU patients, and preceded the peak CDSS. However, after excluding infants treated with steroids, those hospitalized in the ward had higher VLs than infants requiring PICU care (P < .001). Dynamic analyses showed that VL decay was delayed in PICU patients, especially in those treated with steroids. Conclusions Higher VLs at presentation and a faster and consistent VL decline were both associated with less severe RSV disease in children. Summary Infants with less severe respiratory syncytial virus (RSV) disease had higher viral loads (VL) at presentation, and faster and consistent VL decline. Conversely, VL decay and overall viral exposure were prolonged and higher in infants severe RSV disease receiving steroids.

Living with COVID-19 requires continued vigilance against the spread and emergence of variants of concern (VOCs). Rapid and accurate saliva diagnostic testing, alongside basic public health responses, is a viable option contributing to effective transmission control. Nevertheless, our knowledge regarding the dynamics of SARS-CoV-2 infection in saliva is not as advanced as our understanding of the respiratory tract. Here, we analyzed longitudinal viral load data of SARS-CoV-2 in saliva samples from 144 patients with mild COVID-19 (a combination of our collected data and published data). Using a mathematical model, we quantified individual-level viral dynamics and stratified them into three groups using a clustering approach. Notably, the three groups exhibited distinct differences in viral RNA detection durations: 11.5 days (95% CI: 10.6-12.4), 17.4 days (16.6-18.2), and 30.0 days (28.1-31.8), respectively. Surprisingly, this stratified grouping remained unexplained despite our analysis of 47 types of clinical data, including basic demographic information, clinical symptoms, results of blood tests, and vital signs. Additionally, we quantified the expression levels of 92 micro-RNAs in a subset of saliva samples, but these also failed to explain the observed stratification, although the mir-1846 level may have been weakly correlated with peak viral load. Our study provides insights into SARS-CoV-2 infection dynamics in saliva, highlighting the challenges in predicting the duration of viral RNA detection without indicators that directly reflect an individual's immune response, such as antibody induction. Given the significant individual heterogeneity in the kinetics of saliva viral shedding, identifying biomarker(s) for viral shedding patterns will be crucial for improving public health interventions in the era of living with COVID-19.

Abstract Background Viral load dynamics and shedding kinetics are critical factors for studying infectious diseases. However, evidence on the viral dynamics of mpox remains limited and inconclusive. Thus, we aimed to provide a comprehensive understanding of the viral load and viability of the re-emerged mpox virus since 2022. Methods For this systematic review and meta-analysis, we searched PubMed/MEDLINE, Embase and Google Scholar for published articles that are related to mpox viral dynamics up to April 2023. Results From 19 studies, 880 samples and 1477 specimens were collected. The pooled median Ct values appeared in the following order: skin lesion [Ct value 21.7 (IQR 17.8–25.5)], anorectal [22.3 (16.9–27.6)], saliva [25.9 (22.5–31.1)], oral [29.0 (24.5–32.8)], semen [29.6 (25.9–33.4)], urine [30.5 (24.6–36.4)], pharyngeal [31.9 (26.5–37.3)], urethra [33.0 (28.0–35.0)] and blood [33.2 (30.4–36.1)]. People living with human immunodeficiency virus (HIV) have a lower Ct value in the skin [skin HIV+, 19.2 (18.3–20.0) vs skin HIV−, 25.4 (21.2–29.0)]. From the Ct values and test day since symptom onset, we identified temporal trends of viral load for each specimen type. Changes in the trend were observed at 4 days in saliva, 5 days in blood, 6 days in skin, 7 days in anorectal, urine, semen and pharyngeal and 8 days in the urethra. We determined optimal Ct cutoff values for anorectal (34.0), saliva (27.7) and urethra (33.0) specimens, where a Ct value above each cutoff suggests minimal viral viability. Using these cutoff values, we derived the duration of viable viral isolation in each specific specimen type (anorectal 19 days, saliva 14 days and urethra 14 days). Conclusion Skin lesion, anorectal and saliva samples contained the highest viral load. The peak viral load manifests within 4–8 days after symptom onset, and viable virus detection was presumed to cease within 14–19 days from symptom onset in anorectal, saliva and urethral samples.