ObjectivesThe aim of this study was to conduct a rapid systematic review and meta-analysis of estimates of the incubation period of COVID-19.DesignRapid systematic review and meta-analysis of observational research.SettingInternational studies on incubation period of COVID-19.ParticipantsSearches were carried out in PubMed, Google Scholar, Embase, Cochrane Library as well as the preprint servers MedRxiv and BioRxiv. Studies were selected for meta-analysis if they reported either the parameters and CIs of the distributions fit to the data, or sufficient information to facilitate calculation of those values. After initial eligibility screening, 24 studies were selected for initial review, nine of these were shortlisted for meta-analysis. Final estimates are from meta-analysis of eight studies.Primary outcome measuresParameters of a lognormal distribution of incubation periods.ResultsThe incubation period distribution may be modelled with a lognormal distribution with pooled mu and sigma parameters (95% CIs) of 1.63 (95% CI 1.51 to 1.75) and 0.50 (95% CI 0.46 to 0.55), respectively. The corresponding mean (95% CIs) was 5.8 (95% CI 5.0 to 6.7) days. It should be noted that uncertainty increases towards the tail of the distribution: the pooled parameter estimates (95% CIs) resulted in a median incubation period of 5.1 (95% CI 4.5 to 5.8) days, whereas the 95th percentile was 11.7 (95% CI 9.7 to 14.2) days.ConclusionsThe choice of which parameter values are adopted will depend on how the information is used, the associated risks and the perceived consequences of decisions to be taken. These recommendations will need to be revisited once further relevant information becomes available. Accordingly, we present an R Shiny app that facilitates updating these estimates as new data become available.
ObjectivesOur objective was to review the literature on the inferred duration of the infectious period of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, and provide an overview of the variation depending on the methodological approach.DesignRapid scoping review. Literature review with fixed search terms, up to 1 April 2020. Central tendency and variation of the parameter estimates for infectious period in (A) asymptomatic and (B) symptomatic cases from (1) virological studies (repeated testing), (2) tracing studies and (3) modelling studies were gathered. Narrative review of viral dynamics.Information sourcesSearch strategies developed and the following searched: PubMed, Google Scholar, MedRxiv and BioRxiv. Additionally, the Health Information Quality Authority (Ireland) viral load synthesis was used, which screened literature from PubMed, Embase, ScienceDirect, NHS evidence, Cochrane, medRxiv and bioRxiv, and HRB open databases.ResultsThere was substantial variation in the estimates, and how infectious period was inferred. One study provided approximate median infectious period for asymptomatic cases of 6.5–9.5 days. Median presymptomatic infectious period across studies varied over <1–4 days. Estimated mean time from symptom onset to two negative RT-PCR tests was 13.4 days (95% CI 10.9 to 15.8) but was shorter when studies included children or less severe cases. Estimated mean duration from symptom onset to hospital discharge or death (potential maximal infectious period) was 18.1 days (95% CI 15.1 to 21.0); time to discharge was on average 4 days shorter than time to death. Viral dynamic data and model infectious parameters were often shorter than repeated diagnostic data.ConclusionsThere are limitations of inferring infectiousness from repeated diagnosis, viral loads and viral replication data alone and also potential patient recall bias relevant to estimating exposure and symptom onset times. Despite this, available data provide a preliminary evidence base to inform models of central tendency for key parameters and variation for exploring parameter space and sensitivity analysis.
The serial interval is the time between symptom onsets in an infector–infectee pair. The generation time, also known as the generation interval, is the time between infection events in an infector–infectee pair. The serial interval and the generation time are key parameters for assessing the dynamics of a disease. A number of scientific papers reported information pertaining to the serial interval and/or generation time for COVID-19. Objective Conduct a review of available evidence to advise on appropriate parameter values for serial interval and generation time in national COVID-19 transmission models for Ireland and on methodological issues relating to those parameters. Methods We conducted a rapid review of the literature covering the period 1 January 2020 and 21 August 2020, following predefined eligibility criteria. Forty scientific papers met our inclusion criteria and were included in the review. Results The mean of the serial interval ranged from 3.03 to 7.6 days, based on 38 estimates, and the median from 1.0 to 6.0 days (based on 15 estimates). Only three estimates were provided for the mean of the generation time. These ranged from 3.95 to 5.20 days. One estimate of 5.0 days was provided for the median of the generation time. Discussion Estimates of the serial interval and the generation time are very dependent on the specific factors that apply at the time that the data are collected, including the level of social contact. Consequently, the estimates may not be entirely relevant to other environments. Therefore, local estimates should be obtained as soon as possible. Careful consideration should be given to the methodology that is used. Real-time estimations of the serial interval/generation time, allowing for variations over time, may provide more accurate estimates of reproduction numbers than using conventionally fixed serial interval/generation time distributions.
Livestock production in Africa is key to national economies, food security and rural livelihoods, and > 85% of livestock keepers live in extreme poverty. With poverty elimination central to the Sustainable Development Goals, livestock keepers are therefore critically important. Foot-and-mouth disease is a highly contagious livestock disease widespread in Africa that contributes to this poverty. Despite its US$2.3 billion impact, control of the disease is not prioritized: standard vaccination regimens are too costly, its impact on the poorest is underestimated, and its epidemiology is too weakly understood. Our integrated analysis in Tanzania shows that the disease is of high concern, reduces household budgets for human health, and has major impacts on milk production and draft power for crop production. Critically, foot-and-mouth disease outbreaks in cattle are driven by livestock-related factors with a pattern of changing serotype dominance over time. Contrary to findings in southern Africa, we find no evidence of frequent infection from wildlife, with outbreaks in cattle sweeping slowly across the region through a sequence of dominant serotypes. This regularity suggests that timely identification of the epidemic serotype could allow proactive vaccination ahead of the wave of infection, mitigating impacts, and our preliminary matching work has identified potential vaccine candidates. This strategy is more realistic than wildlife-livestock separation or conventional foot-and-mouth disease vaccination approaches. Overall, we provide strong evidence for the feasibility of coordinated foot-and-mouth disease control as part of livestock development policies in eastern Africa, and our integrated socioeconomic, epidemiological, laboratory and modelling approach provides a framework for the study of other disease systems.
We examined the pathogens, morphologic patterns, and risk factors associated with bovine respiratory disease (BRD) in 136 recently weaned cattle ("weanlings"), 6-12 mo of age, that were submitted for postmortem examination to regional veterinary laboratories in Ireland. A standardized sampling protocol included routine microbiologic investigations as well as polymerase chain reaction and immunohistochemistry. Lungs with histologic lesions were categorized into 1 of 5 morphologic patterns of pneumonia. Fibrinosuppurative bronchopneumonia (49%) and interstitial pneumonia (48%) were the morphologic patterns recorded most frequently. The various morphologic patterns of pulmonary lesions suggest the involvement of variable combinations of initiating and compounding infectious agents that hindered any simple classification of the etiopathogenesis of the pneumonias. Dual infections were detected in 58% of lungs, with Mannheimia haemolytica and Histophilus somni most frequently recorded in concert. M. haemolytica (43%) was the most frequently detected respiratory pathogen; H. somni was also shown to be frequently implicated in pneumonia in this age group of cattle. Bovine parainfluenza virus 3 (BPIV-3) and Bovine respiratory syncytial virus (16% each) were the viral agents detected most frequently. Potential respiratory pathogens (particularly Pasteurella multocida, BPIV-3, and H. somni) were frequently detected (64%) in lungs that had neither gross nor histologic pulmonary lesions, raising questions regarding their role in the pathogenesis of BRD. The breadth of respiratory pathogens detected in bovine lungs by various detection methods highlights the diagnostic value of parallel analyses in respiratory disease postmortem investigation.
ObjectiveTo estimate the proportion of presymptomatic transmission of SARS-CoV-2 infection that can occur, and the timing of transmission relative to symptom onset.Setting/designSecondary analysis of international published data.Data sourcesMeta-analysis of COVID-19 incubation period and a rapid review of serial interval and generation time, which are published separately.ParticipantsData from China, the Islamic Republic of Iran, Italy, Republic of Korea, Singapore and Vietnam from December 2019 to May 2020.MethodsSimulations were generated of incubation period and of serial interval or generation time. From these, transmission times relative to symptom onset, and the proportion of presymptomatic transmission, were estimated.Outcome measuresTransmission time of SARS-CoV-2 relative to symptom onset and proportion of presymptomatic transmission.ResultsBased on 18 serial interval/generation time estimates from 15 papers, mean transmission time relative to symptom onset ranged from −2.6 (95% CI −3.0 to –2.1) days before infector symptom onset to 1.4 (95% CI 1.0 to 1.8) days after symptom onset. The proportion of presymptomatic transmission ranged from 45.9% (95% CI 42.9% to 49.0%) to 69.1% (95% CI 66.2% to 71.9%).ConclusionsThere is substantial potential for presymptomatic transmission of SARS-CoV-2 across a range of different contexts. This highlights the need for rapid case detection, contact tracing and quarantine. The transmission patterns that we report reflect the combination of biological infectiousness and transmission opportunities which vary according to context.
BackgroundIn Ireland bovine babesiosis is caused by the tick-borne blood parasite, Babesia divergens. A survey of veterinary practitioners and farmers in the 1980’s revealed an annual incidence of 1.7% associated with considerable economic losses. However, two subsequent surveys in the 1990’s indicated a decline in clinical babesiosis. Recent evidence from continental Europe suggests that, probably due to climate change, the distribution of the tick vector of B. divergens, Ixodes ricinus is extending to more northerly regions and higher altitudes. In addition, milder winters are thought to widen the window of tick activity.In order to determine whether any such changes have affected the incidence of bovine babesiosis in Ireland, a questionnaire survey of farmers and veterinarians was carried out and compared with data from previous surveys.ResultsOur survey indicates that while the incidence of clinical disease has continued to decline, cases can occur at any time of year. In contrast to previous surveys, affected farms were the same size as unaffected ones. There was no correlation between disease risk and the presence of deer on the land. Disease severity and mortality rates were increased because many infections were advanced by the time they were detected and treated.ConclusionWhile the precise reasons for the decline in the incidence of redwater are unknown, changes in agricultural practice are likely to be of importance. A reversal of the trend could be devastating, as vigilance among farmers and veterinarians is flagging and the national herd is losing its protective immunity to disease.
ObjectivesThe aim of this study was to determine the relative infectiousness of asymptomatic SARS-CoV-2 infected persons compared with symptomatic individuals based on a scoping review of available literature.DesignRapid scoping review of peer-reviewed literature from 1 January to 5 December 2020 using the LitCovid database and the Cochrane library.SettingInternational studies on the infectiousness of individuals infected with SARS-CoV-2.ParticipantsStudies were selected for inclusion if they defined asymptomatics as a separate cohort distinct from presymptomatics and if they provided a quantitative measure of the infectiousness of asymptomatics relative to symptomatics.Primary outcome measuresPCR result (PCR studies), the rate of infection (mathematical modelling studies) and secondary attack rate (contact tracing studies) - in each case from asymptomatic in comparison with symptomatic individuals.ResultsThere are only a limited number of published studies that report estimates of relative infectiousness of asymptomatic compared with symptomatic individuals. 12 studies were included after the screening process. Significant differences exist in the definition of infectiousness. PCR studies in general show no difference in shedding levels between symptomatic and asymptomatic individuals; however, the number of study subjects is generally limited. Two modelling studies estimate relative infectiousness to be 0.43 and 0.57, but both of these were more reflective of the infectiousness of undocumented rather than asymptomatic cases. The results from contact tracing studies include estimates of relative infectiousness of 0, but with insufficient evidence to conclude that it is significantly different from 1.ConclusionsThere is considerable heterogeneity in estimates of relative infectiousness highlighting the need for further investigation of this important parameter. It is not possible to provide any conclusive estimate of relative infectiousness, as the estimates from the reviewed studies varied between 0 and 1.
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