Quantifying the relationship between SARS-CoV-2 viral load and infectiousness.
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ABSTRACT:
SUBMITTER: Marc A
PROVIDER: S-EPMC8476126 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundViral load kinetics and duration of viral shedding are important determinants for disease transmission. We aimed to characterise viral load dynamics, duration of viral RNA shedding, and viable virus shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in various body fluids, and to compare SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) viral dynamics.MethodsIn this systematic review and meta-analysis, we searched databases, including MEDLINE, Embase, Europe PubMed Central, medRxiv, and bioRxiv, and the grey literature, for research articles published between Jan 1, 2003, and June 6, 2020. We included case series (with five or more participants), cohort studies, and randomised controlled trials that reported SARS-CoV-2, SARS-CoV, or MERS-CoV infection, and reported viral load kinetics, duration of viral shedding, or viable virus. Two authors independently extracted data from published studies, or contacted authors to request data, and assessed study quality and risk of bias using the Joanna Briggs Institute Critical Appraisal Checklist tools. We calculated the mean duration of viral shedding and 95% CIs for every study included and applied the random-effects model to estimate a pooled effect size. We used a weighted meta-regression with an unrestricted maximum likelihood model to assess the effect of potential moderators on the pooled effect size. This study is registered with PROSPERO, CRD42020181914.Findings79 studies (5340 individuals) on SARS-CoV-2, eight studies (1858 individuals) on SARS-CoV, and 11 studies (799 individuals) on MERS-CoV were included. Mean duration of SARS-CoV-2 RNA shedding was 17·0 days (95% CI 15·5-18·6; 43 studies, 3229 individuals) in upper respiratory tract, 14·6 days (9·3-20·0; seven studies, 260 individuals) in lower respiratory tract, 17·2 days (14·4-20·1; 13 studies, 586 individuals) in stool, and 16·6 days (3·6-29·7; two studies, 108 individuals) in serum samples. Maximum shedding duration was 83 days in the upper respiratory tract, 59 days in the lower respiratory tract, 126 days in stools, and 60 days in serum. Pooled mean SARS-CoV-2 shedding duration was positively associated with age (slope 0·304 [95% CI 0·115-0·493]; p=0·0016). No study detected live virus beyond day 9 of illness, despite persistently high viral loads, which were inferred from cycle threshold values. SARS-CoV-2 viral load in the upper respiratory tract appeared to peak in the first week of illness, whereas that of SARS-CoV peaked at days 10-14 and that of MERS-CoV peaked at days 7-10.InterpretationAlthough SARS-CoV-2 RNA shedding in respiratory and stool samples can be prolonged, duration of viable virus is relatively short-lived. SARS-CoV-2 titres in the upper respiratory tract peak in the first week of illness. Early case finding and isolation, and public education on the spectrum of illness and period of infectiousness are key to the effective containment of SARS-CoV-2.FundingNone.
| S-EPMC7837230 | biostudies-literature
Project description:ObjectiveTo investigate the association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and infection-to-delivery interval with maternal and cord serum concentrations of anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies and transplacental transfer ratio in pregnant women with active or recovered SARS-CoV-2 infection.MethodsThis was a prospective case series of consecutive pregnant women with laboratory-confirmed SARS-CoV-2 infection between 27 March 2020 and 24 January 2021. We collected information regarding deep throat saliva or nasopharyngeal swab (NPS) reverse transcription polymerase chain reaction (RT-PCR) test results, serial cycle threshold (Ct) values at and after diagnosis, demographic, clinical and outcome data, and neonatal NPS RT-PCR results. Qualitative and quantitative analysis of IgG and immunoglobulin M (IgM) antibodies against SARS-CoV-2 was performed in maternal and cord blood serum samples obtained at delivery. Correlation of maternal Ct values, infection-to-delivery interval, infection duration and viral load area under the curve (AUC) with gestational age (GA) at diagnosis, maternal and cord serum IgG concentrations and transplacental transfer ratio of IgG were evaluated using Pearson's correlation.ResultsTwenty pregnant women who consented to participate and who had delivered their babies by 31 January 2021 were included in the study, comprising 14 who had recovered from coronavirus disease 2019 (COVID-19) and six with active infection at delivery. The median GA at clinical manifestation was 32.7 (range, 11.9-39.4) weeks. The median infection-to-delivery interval and infection duration were 41.5 (range, 2-187) days and 10.0 (range, 1-48) days, respectively. The median GA at delivery was 39.1 (range, 32.4-40.7) weeks and the median seroconversion interval was 14 (range, 1-19) days. Of 13 neonates born to seropositive mothers with recovered infection at delivery, 12 tested positive for anti-SARS-CoV-2 IgG. All neonatal NPS samples were negative for SARS-CoV-2 and all cord sera tested negative for IgM. The median transplacental transfer ratio of IgG was 1.3 (interquartile range, 0.9-1.6). There was a negative correlation between infection-to-delivery interval and anti-SARS-CoV-2 IgG concentrations in maternal (r = -0.6693, P = 0.0087) and cord (r = -0.6554, P = 0.0068) serum and a positive correlation between IgG concentration in maternal serum and viral load AUC (r = 0.5109, P = 0.0310). A negative correlation was observed between transfer ratio and viral load AUC (r = -0.4757, P = 0.0409).ConclusionsIn pregnant women who have recovered from COVID-19, anti-SARS-CoV-2 IgG concentrations at delivery increased with increasing viral load during infection and decreased with increasing infection-to-delivery interval. The median transplacental transfer ratio of IgG was 1.3 and it decreased with increasing viral load during infection. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
| S-EPMC8250926 | biostudies-literature
Project description:OBJECTIVES:To summarise the evidence on the detection pattern and viral load of SARS-CoV-2 over the course of an infection (including any asymptomatic or pre-symptomatic phase), and the duration of infectivity. METHODS:A systematic literature search was undertaken in PubMed, Europe PubMed Central and EMBASE from 30 December 2019 to 12 May 2020. RESULTS:We identified 113 studies conducted in 17 countries. The evidence from upper respiratory tract samples suggests that the viral load of SARS-CoV-2 peaks around symptom onset or a few days thereafter, and becomes undetectable about two weeks after symptom onset; however, viral loads from sputum samples may be higher, peak later and persist for longer. There is evidence of prolonged virus detection in stool samples, with unclear clinical significance. No study was found that definitively measured the duration of infectivity; however, patients may not be infectious for the entire duration of virus detection, as the presence of viral ribonucleic acid may not represent transmissible live virus. CONCLUSION:There is a relatively consistent trajectory of SARS-CoV-2 viral load over the course of COVID-19 from respiratory tract samples, however the duration of infectivity remains uncertain.
| S-EPMC7323671 | biostudies-literature
Project description: Not available
| S-EPMC7836878 | biostudies-literature
Project description:The within-host viral kinetics of SARS-CoV-2 infection and how they relate to a person's infectiousness are not well understood. This limits our ability to quantify the impact of interventions on viral transmission. Here, we develop viral dynamic models of SARS-CoV-2 infection and fit them to data to estimate key within-host parameters such as the infected cell half-life and the within-host reproductive number. We then develop a model linking viral load (VL) to infectiousness and show a person's infectiousness increases sublinearly with VL and that the logarithm of the VL in the upper respiratory tract is a better surrogate of infectiousness than the VL itself. Using data on VL and the predicted infectiousness, we further incorporated data on antigen and RT-PCR tests and compared their usefulness in detecting infection and preventing transmission. We found that RT-PCR tests perform better than antigen tests assuming equal testing frequency; however, more frequent antigen testing may perform equally well with RT-PCR tests at a lower cost but with many more false-negative tests. Overall, our models provide a quantitative framework for inferring the impact of therapeutics and vaccines that lower VL on the infectiousness of individuals and for evaluating rapid testing strategies.
| S-EPMC8670484 | biostudies-literature
Project description:The within-host viral kinetics of SARS-CoV-2 infection and how they relate to a person's infectiousness are not well understood. This limits our ability to quantify the impact of interventions on viral transmission. Here, we develop data-driven viral dynamic models of SARS-CoV-2 infection and estimate key within-host parameters such as the infected cell half-life and the within-host reproductive number. We then develop a model linking VL to infectiousness, showing that a person's infectiousness increases sub-linearly with VL. We show that the logarithm of the VL in the upper respiratory tract (URT) is a better surrogate of infectiousness than the VL itself. Using data on VL and the predicted infectiousness, we further incorporated data on antigen and reverse transcription polymerase chain reaction (RT-PCR) tests and compared their usefulness in detecting infection and preventing transmission. We found that RT-PCR tests perform better than antigen tests assuming equal testing frequency; however, more frequent antigen testing may perform equally well with RT-PCR tests at a lower cost, but with many more false-negative tests. Overall, our models provide a quantitative framework for inferring the impact of therapeutics and vaccines that lower VL on the infectiousness of individuals and for evaluating rapid testing strategies. Quantifying the kinetics of SARS-CoV-2 infection and individual infectiousness is key to quantitatively understanding SARS-CoV-2 transmission and evaluating intervention strategies. Here we developed data-driven within-host models of SARS-CoV-2 infection and by fitting them to clinical data we estimated key within-host viral dynamic parameters. We also developed a mechanistic model for viral transmission and show that the logarithm of the viral load in the upper respiratory tract serves an appropriate surrogate for a person's infectiousness. Using data on how viral load changes during infection, we further evaluated the effectiveness of PCR and antigen-based testing strategies for averting transmission and identifying infected individuals.
| S-EPMC8259912 | biostudies-literature
Project description:Relationships between viral load, severity of illness, and transmissibility of virus are fundamental to understanding pathogenesis and devising better therapeutic and prevention strategies for COVID-19. Here we present within-host modelling of viral load dynamics observed in the upper respiratory tract (URT), drawing upon 2172 serial measurements from 605 subjects, collected from 17 different studies. We developed a mechanistic model to describe viral load dynamics and host response and contrast this with simpler mixed-effects regression analysis of peak viral load and its subsequent decline. We observed wide variation in URT viral load between individuals, over 5 orders of magnitude, at any given point in time since symptom onset. This variation was not explained by age, sex, or severity of illness, and these variables were not associated with the modelled early or late phases of immune-mediated control of viral load. We explored the application of the mechanistic model to identify measured immune responses associated with the control of the viral load. Neutralising antibodies correlated strongly with modelled immune-mediated control of viral load amongst subjects who produced neutralising antibodies. Our models can be used to identify host and viral factors which control URT viral load dynamics, informing future treatment and transmission blocking interventions.
| S-EPMC8755404 | biostudies-literature
Project description:A majority of SARS-CoV-2 infections are transmitted from a minority of infected subjects, some of which may be symptomatic or pre-symptomatic. We aimed to quantify potential infectiousness among asymptomatic healthcare workers (HCWs) in relation to prior or later symptomatic disease. We previously (at the onset of the SARS-CoV-2 epidemic) performed a cohort study of SARS-CoV-2 infections among 27,000 healthcare workers (HCWs) at work in the capital region of Sweden. We performed both SARS-CoV-2 RT-PCR and serology. Furthermore, the cohort was comprehensively followed for sick leave, both before and after sampling. In the present report, we used the cohort database to quantify potential infectiousness among HCWs at work. Those who had sick leave either before or after sampling were classified as post-symptomatic or pre-symptomatic, whereas the virus-positive subjects with no sick leave were considered asymptomatic. About 0.2% (19/9449) of HCW at work were potentially infectious and pre-symptomatic (later had disease) and 0.17% (16/9449) were potentially infectious and asymptomatic (never had sick leave either before nor after sampling). Thus, 33% and 28% of all the 57 potentially infectious subjects were pre-symptomatic or asymptomatic, respectively. When a questionnaire was administered to HCWs with past infection, only 10,5% of HCWs had had no indication at all of having had SARS-CoV-2 infection ("truly asymptomatic"). Our findings provide a unique quantification of the different groups of asymptomatic, potentially infectious HCWs.
| S-EPMC8682911 | biostudies-literature
Project description:ObjectivesThe aim was to understand persistence of the virus in body fluids the and immune response of an infected host to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), an agent of coronavirus disease 2019 (COVID-19).MethodsWe determined the kinetics of viral load in several body fluids through real time reverse transcription polymerase chain reaction, serum antibodies of IgA, IgG and IgM by enzyme-linked immunosorbent assay and neutralizing antibodies by microneutralization assay in 35 COVID-19 cases from two hospitals in Guangdong, China.ResultsWe found higher viral loads and prolonged shedding of virus RNA in severe cases of COVID-19 in nasopharyngeal (1.3 × 106 vs 6.4 × 104, p < 0.05; 7∼8 weeks) and throat (6.9 × 106 vs 2.9 × 105, p < 0.05; 4∼5 weeks), but similar in sputum samples (5.5 × 106 vs 0.9 × 106, p < 0.05; 4∼5 weeks). Viraemia was rarely detected (2.8%, n = 1/35). We detected early seroconversion of IgA and IgG at the first week after illness onset (day 5, 5.7%, n = 2/35). Neutralizing antibodies were produced in the second week, and observed in all 35 included cases after the third week illness onset. The levels of neutralizing antibodies correlated with IgG (rs = 0.85, p < 0.05; kappa = 0.85) and IgA (rs = 0.64, p < 0.05; kappa = 0.61) in severe, but not mild cases (IgG, rs = 0.42, kappa = 0.33; IgA, rs = 0.32, kappa = 0.22). No correlation with IgM in either severe (rs = 0.17, kappa = 0.06) or mild cases (rs = 0.27, kappa = 0.15) was found.DiscussionWe revealed a prolonged shedding of virus RNA in the upper respiratory tract, and evaluated the consistency of production of IgG, IgA, IgM and neutralizing antibodies in COVID-19 cases.
| S-EPMC7474805 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-07-21 | GSE154770 | GEO