Infectivity of Severe Acute Respiratory Syndrome during Its Incubation Period

Objective To evaluate the infectivity of severe acute respiratory syndrome （SARS） during its incubation period by investigating chains of transmission and individuals isolated for medical observation with a view to providing scientific evidence for updating protocols of medical isolation. Methods Individuals related with the two SARS chains of transmission in Beijing in 2003 and a group of individuals isolated for medical observation in Haidian district of Beijing during the SARS outbreak were selected as subjects of study. Contactors with SARS patients and those with symptom development following the contacts were investigated via questionnaire. Serum samples were collected from super transmitters and tested for SARS-CoV antibody by neutralization test and enzyme linked immunosorbent assay （ELISA）. Results A total of 1 112 contactors were investigated in three surveys. Of them, 669 had a history of close contact with symptomatic SARS patients, 101 developed symptoms with a rate of 15.1%, 363 had a history of close contact with patients in their incubation period, none of whom developed symptoms （0%）. Serum samples were collected fi＇om 32 highly-exposed individuals, of whom 13 developing SARS symptoms atter contact had serum samples positive for SARS-CoV antibody. Samples collected from the asymptomatic contactors were all negative for SARS-CoV antibody. Conclusion SARS cases are infectious only during their symptomatic period and are non-infectious during the incubation period. Isolation for medical observation should be placed for individuals who are in close contact with symptomatic SARS patients. The results of our study are of decisive significance for the Ministry of Health to the definition of SARS close contactor.

Effect of incubation period on epidemic spreading in complex networks

We study the effect of incubation period on epidemic spreading in the Barabasi-Albert scale-free network and the Watts-Strogatz small world network by using a Suspectable-Incubated-Infected-Suspectable model. Our analytical investigations show that the epidemic threshold is independent of incubation period in both networks, which is verified by our large-scale simulation results. We also investigate the effect of incubation period on the epidemic dynamics in a supercritical regime. It is found that with the increase of incubation period Ω, a damped oscillation evolution of ρT （the ratio of persons in incubated state） appears and the time needed to reach a saturation value increases. Moreover, the steady value of ρT increases and approaches to an asymptotic constant with the value of Ω increasing. As a result, the infected ratio ρI decreases with the increase of Ω according to a power law.

COVID-19 patient with an incubation period of 27 d:A case report

BACKGROUND As a highly contagious disease,coronavirus disease 2019(COVID-19)is wreaking havoc around the world due to continuous spread among close contacts mainly via droplets,aerosols,contaminated hands or surfaces.Therefore,centralized isolation of close contacts and suspected patients is an important measure to prevent the transmission of COVID-19.At present,the quarantine duration in most countries is 14 d due to the fact that the incubation period of severe acute respiratory syndrome coronavirus type 2(SARS-CoV-2)is usually identified as 1-14 d with median estimate of 4-7.5 d.Since COVID-19 patients in the incubation period are also contagious,cases with an incubation period of more than 14 d need to be evaluated.CASE SUMMARY A 70-year-old male patient was admitted to the Department of Respiratory Medicine of The First Affiliated Hospital of Harbin Medical University on April 5 due to a cough with sputum and shortness of breath.On April 10,the patient was transferred to the Fever Clinic for further treatment due to close contact to one confirmed COVID-19 patient in the same room.During the period from April 10 to May 6,nucleic acid and antibodies to SARS-CoV-2 were tested 7 and 4 times,respectively,all of which were negative.On May 7,the patient developed fever with a maximum temperature of 39℃,and his respiratory difficulties had deteriorated.The results of nucleic acid and antibody detection of SARS-CoV-2 were positive.On May 8,the nucleic acid and antibody detection of SARS-CoV-2 by Heilongjiang Provincial Center for Disease Control were also positive,and the patient was diagnosed with COVID-19 and reported to the Chinese Center for Disease Control and Prevention.CONCLUSION This case highlights the importance of the SARS-CoV-2 incubation period.Further epidemiological investigations and clinical observations are urgently needed to identify the optimal incubation period of SARS-CoV-2 and formulate rational and evidence-based quarantine policies for COVID-19 accordingly.

Estimating Incubation Period and Predicting Risk of Developing Hepatocellular Carcinoma in Patients with HCV Infection from the Clinic of a County-Level City in China

Background: To estimate incubation period in patients infected with hepatitis C virus (HCV) and to predict patients’ risk of developing hepatocellular carcinoma (HCC) for indicating health policymaking. Methods: An outbreak of HCV infection from a clinic was occurred due to the injection treatment of varicose veins called minimally invasive thrombolysis and meridian activating therapy (MITMT) in a county-level city of China. Conventional method and bootstrapping approach were used to estimate HCV incubation period. Risk assessment model generated from the previous study was applied to predict the risk of developing HCC in the coming 5-, 10-, and 15-year for HCV infected patients from the above outbreak. Results: A total of 120 subjects were underwent MITMT between October 22, 2012 and January 28, 2013;of those, 99 subjects were diagnosed with HCV infection. Mean age of the subjects was 54.42 years old, and females were accounted for 51.5% in contracted subjects. Mean incubation period of hepatitis C (HC) was 45.76 days using first MITMT as infected date and 30.68 days using bootstrapping approach, their standard deviations were 23.01 and 15.05 days, respectively. A total of 1.3, 4.7, and 10.6 persons will be developed into HCC in the coming 5, 10, and 15 years in infected subjects based on a risk prediction model. Conclusion: Some patients with HCV infection from a nosocomial clinic in a county-level city will be suffered from more severe HCC in the coming decade;effective measures and controls were urgently needed to manage these patients with high risk of developing into end-stage liver disease.

The incubation period of COVID-19: a global meta-analysis of 53 studies and a Chinese observation study of 11 545 patients

Background:The incubation period is a crucial index of epidemiology in understanding the spread of the emerging Coronavirus disease 2019(COVID-19).In this study,we aimed to describe the incubation period of COVID-19 globally and in the mainland of China.Methods:The searched studies were published from December 1,2019 to May 26,2021 in CNKI,Wanfang,PubMed,and Embase databases.A random-efect model was used to pool the mean incubation period.Meta-regression was used to explore the sources of heterogeneity.Meanwhile,we collected 11545 patients in the mainland of China outside Hubei from January 19,2020 to September 21,2020.The incubation period ftted with the Log-normal model by the coarseDataTools package.Results:A total of 3235 articles were searched,53 of which were included in the meta-analysis.The pooled mean incubation period of COVID-19 was 6.0 days(95%confdence interval[CI]5.6–6.5)globally,6.5 days(95%CI 6.1–6.9)in the mainland of China,and 4.6 days(95%CI 4.1–5.1)outside the mainland of China(P=0.006).The incubation period varied with age(P=0.005).Meanwhile,in 11545 patients,the mean incubation period was 7.1 days(95%CI 7.0–7.2),which was similar to the fnding in our meta-analysis.Conclusions:For COVID-19,the mean incubation period was 6.0 days globally but near 7.0 days in the mainland of China,which will help identify the time of infection and make disease control decisions.Furthermore,attention should also be paid to the region-or age-specifc incubation period.

Calculation on the Incubation Period of Proeutectoid Ferrite Transformation for Si-Mn TRIP Steel

The incubation period of proeutectoid ferrite transformation for Si-Mn transformation induced plasticity (TRIP) steel has been calculated by the Aaronson's incubation period model for transformation.The influences of chemical compositions and hot deformation of austenite on the incubation period have been taken into consideration in the calculation,and some parameters have been proposed and validated with the measured time temperature transformation (TTT) curves from dilation tests.The calculation results show that it is essential to take into account of the effect of solute atoms on the interfacial energy in the austenite grain boundaries.For hypoeutectoid steel,the incubation period of ferrite transformation increases with the increase of C and Mn contents,and C has a greater impact than that of Mn,while the incubation period of ferrite transformation decreases with the increase of Si content.Hot deformation shortens the incubation time and promotes austenite to ferrite transformation.

Effects of alloying elements Mn,Mo,Ti,Si,P and C on the incubation period of void swelling in austenitic stainless steels

Void swelling,which induces the degradation of the original properties of nuclear materials under high-energy particleirradiation,is an important problem.The incubation period,a transient stage before the steady void growth,determines the duration of service of nuclear materials.Several experimental studies have been performed on void observations by transmission electron microscopy(TEM),which,however,has a resolution limit for the size of defect clusters.Positron annihilation lifetime spectroscopy(PALS)enables the detection of small vacancy clusters,single vacancies,dislocations and precipitates.The use of these two methods provides complementary information toward detecting defect information in the incubation period.Here,defect structures during the incubation period in austenitic stainless steels,by means of PALS and TEM are reviewed.The role of alloying elements into determining the period is explained.Furthermore,the existing problems and research directions in this field are presented.

More than a simple egg:Underlying mechanisms of cold tolerance in avian embryos

Avian embryos,which develop within eggs,exhibit remarkable tolerance to extremely low temperatures.Despite being a common trait among all birds,the mechanisms underlying this cold tolerance in avian embryos remain largely unknown.To gain a better understanding of this phenomenon and the coping mechanisms involved,we reviewed the literature on severe cold tolerance in embryos of both wild and domestic birds.We found that embryos of different bird orders exhibit tolerance to severe cold during their development.In response to cold stress,embryos slow down their heartbeat rates and metabolism.In severe cold temperatures,embryos can suspend these processes,entering a torpid-like state of cardiac arrest.To compensate for these developmental delays,embryos extend their regular incubation periods.Depending on their embryonic age,embryos of all bird species can tolerate acute severe cold regimes;only a few tolerate chronic severe cold regimes.We also discussed various extrinsic and intrinsic factors that affect the tolerance of bird embryos to low temperatures before and after incubation.Cold tolerance appears to be a heritable trait shared by wild and domestic embryos of all bird classes,regardless of egg size or development(altricial/precocial).Driven by environmental variability,cold tolerance in avian embryos is an optimal physiological and ecological strategy to mitigate the adverse effects of cold conditions on their development in response to fluctuating environmental temperatures.

The relationship between controllability, optimal testing resource allocation, and incubation-latent period mismatch as revealed by COVID-19

The severe shortfall in testing supplies during the initial COVID-19 outbreak and ensuing struggle to manage the pandemic have affirmed the critical importance of optimal supplyconstrained resource allocation strategies for controlling novel disease epidemics.To address the challenge of constrained resource optimization for managing diseases with complications like pre-and asymptomatic transmission,we develop an integro partial differential equation compartmental disease model which incorporates realistic latent,incubation,and infectious period distributions along with limited testing supplies for identifying and quarantining infected individuals.Our model overcomes the limitations of typical ordinary differential equation compartmental models by decoupling symptom status from model compartments to allow a more realistic representation of symptom onset and presymptomatic transmission.To analyze the influence of these realistic features on disease controllability,we find optimal strategies for reducing total infection sizes that allocate limited testing resources between‘clinical’testing,which targets symptomatic individuals,and‘non-clinical’testing,which targets non-symptomatic individuals.We apply our model not only to the original,delta,and omicron COVID-19 variants,but also to generically parameterized disease systems with varying mismatches between latent and incubation period distributions,which permit varying degrees of presymptomatic transmission or symptom onset before infectiousness.We find that factors that decrease controllability generally call for reduced levels of non-clinical testing in optimal strategies,while the relationship between incubation-latent mismatch,controllability,and optimal strategies is complicated.In particular,though greater degrees of presymptomatic transmission reduce disease controllability,they may increase or decrease the role of nonclinical testing in optimal strategies depending on other disease factors like transmissibility and latent period length.Importantly,our model allows a spectrum of diseases to be compared within a consistent framework such that lessons learned from COVID-19 can be transferred to resource constrained scenarios in future emerging epidemics and analyzed for optimality.

Clinical characteristics of perineal endometriosis:A case series

BACKGROUND The prevalence of perineal endometriosis(PEM)is low among women with endometriosis(EM)treated by surgery.It manifests as hard or cystic nodules with pain in the perineal wounds and surrounding areas.Implantation theory is regarded as the main pathogenesis of PEM.There are few clinical studies on the incidence and clinical characteristics of PEM.This study aims to summarize the clinical data of 14 PEM cases and analyze the factors that may be related to the incubation period and pain.AIM To analyze the medical history,clinical manifestations,diagnosis,treatment and treatment effect of PEM.METHODS The present study is a case series.We collected the clinical data and follow-up data of 14 patients with PEM who visited The International Peace Maternal and Child Health Hospital Affiliated to Shanghai Jiaotong University from January 2009 to December 2019.Paired t test and Pearson correlation analysis were used for statistical analysis.P<0.05 was considered statistically significant.RESULTS The 14 patients included had a history of vaginal delivery.All patients underwent PEM lesion resection.Three patients were treated by levator ani muscle repair at the same time and 1 patient underwent extensive PEM lesion resection and anal sphincter repair.Body mass index(BMI)at delivery and BMI within 1 mo after delivery were negatively correlated with the latent period,respectively(R2=0.53/0.86,P<0.05).The average visual analog scale score in lesions at the third month after surgery was 0.57±1.28 for all patients,which was significantly lower than that prior to surgery(P<0.05).One patient relapsed during the sixth month after surgery,and to date,no recurrence occurred after the second surgery.CONCLUSION The higher the BMI during delivery and within 1 mo after delivery,the shorter the incubation period of PEM.It is very important to evaluate the location of lesions before surgery.Surgical resection of the lesion is the best treatment for PEM and results in significant alleviation of symptoms.Therefore,following the diagnosis of PEM,immediate surgery is recommended.

An experimental approach for measuring carbon dioxide diffusion coefficient in water and oil under supercritical conditions

Several direct or indirect approaches have been proposed to measure diffusion coefficient of gases into liquids.The main complexity of indirect techniques such as pressure decay method is interpreting early pressure-time data which strongly affected by incubation period effect or convective instability.In the current approach,accurate apparatus and precise experimental setup including a high pressure and temperature PVT cell,a high precision Sanchez pump,heating and recording sub-system are implemented and a novel data analysis procedure is applied to modify pressure decay method.The effect of incubation period is reduced remarkably and diffusion coefficient of carbon dioxide in water in wide range of pressures and temperatures is determined and the effects of temperature,pressure and carbon dioxide phase alteration from gas to supercritical are investigated and the value of uncertainty is estimated.Furthermore,diffusion coefficient of CO_(2) and methane in an oil sample from one of the Iranian southwest oil formations is determined precisely using the experimental approach while no incubation period is detected.The results showed that incubation period duration decreases with increasing diffusion coefficient.Additionally,when CO_(2) state is gas,rate of increasing diffusion coefficient with pressure is decreased with temperature and when CO_(2) state is supercritical,the rate of increasing diffusion coefficient with pressure is decreased significantly.

Optimization of Growth Conditions to Identify the Superior Bacillus Strain Which Produce High Yield of Thermostable Alpha Amylase

Thermostable α-amylases hold a very important place in commercial industrial applications in Sri Lanka. Therefore, the main aim of this study was to identify superior Bacillus strain and optimize growth conditions that could yield high α-amylase production. Three Bacillus strains, B. amyloliquefaciens ATCC 23350, B. licheniformis ATCC 14580 and B. megaterium ATCC 14581 were used for the study. Shake flask culture experiments were conducted to identify the effect of various fermentation conditions such as growth temperature, incubation period, carbon source, nitrogen source, initial pH and carbon concentration on extracellular α-amylase production. DNSA assay was carried out to determine the enzyme activity. The highest temperature for enzyme activity was reported by B. licheniformis at 85°C, followed by B. amyloliquefaciens at 75°C and B. megaterium at 45°C. Both B. amyloliquefaciens and B. licheniformis were able to give their optimum enzyme production at 37°C, while B. megaterium at 30°C in 150 rpm with initial pH of 7. B. licheniformis and B. amyloliquefaciens gave their optimum yield of the enzyme after 48 h of incubation while B. megaterium gave after 24 h of incubation. Among the carbon sources tested cassava starch was able to give the highest enzyme production. For B. amyloliquefaciens, the highest yield of the enzyme was obtained with 2% of starch, tryptone as a nitrogen source and initial pH of 7. Maximum enzyme production for B. licheniformis was obtained with 1.5% of starch, KNO3 as a nitrogen source and initial pH of 6. For B. megaterium 1% of starch, tryptone and pH 7.5 induced the optimum α-amylase production. According to the results obtained, B. amyloliquefaciens is the highest thermostable alpha amylase producer. However, according to the industrial requirement, B. licheniformis can also be used as an enzyme producer due to its stability in higher temperatures.

Extreme Values Approach in Food Risk Modeling

In this paper we estimate the incubation period of a possible pathology following exposure to dioxins during a poor diet. The tools developed for this purpose include the probabilistic extremal model and the stochastic behavior of the distribution tails of the contamination. We propose a cumulative distribution function for a random variable that follows both a Gaussian distribution and a GPD. A global optimization method is also explored for the efficient estimation of parameters of GPD.

Demand for longer quarantine period among common and uncommon COVID-19 infections: a scoping review

Background:As one of the non-pharmacological interventions to control the transmission of COVID-19,determining the quarantine duration is mainly based on the accurate estimates of the incubation period.However,patients with coarse information of the exposure date,as well as infections other than the symptomatic,were not taken into account in previously published studies.Thus,by using the statistical method dealing with the interval-censored data,we assessed the quarantine duration for both common and uncommon infections.The latter type includes the presymptomatic,the asymptomatic and the recurrent test positive patients.Methods:As of 10 December 2020,information on cases have been collected from the English and Chinese databases,including Pubmed,Google scholar,CNKI(China National Knowledge Infrastructure)and Wanfang.Official websites and medias were also searched as data sources.All data were transformed into doubly interval-censored and the accelerated failure time model was applied.By estimating the incubation period and the time-to-event distribution of worldwide COVID-19 patients,we obtain the large percentiles for determining and suggesting the quarantine policies.For symptomatic and presymptomatic COVID-19 patients,the incubation time is the duration from exposure to symptom onset.For the asymptomatic,we substitute the date of first positive result of nucleic acid testing for that of symptom onset.Furthermore,the time from hospital discharge or getting negative test result to the positive recurrence has been calculated for recurrent positive patients.Results:A total of 1920 laboratory confirmed COVID-19 cases were included.Among all uncommon infections,34.1%(n=55)of them developed symptoms or were identified beyond fourteen days.Based on all collected cases,the 95th and 99th percentiles were estimated to be 16.2 days(95%Cl 15.5-17.0)and 22.9 days(21.7-24.3)respectively.Besides,we got similar estimates based on merely symptomatic and presymptomatic infections as 15.1 days(14.4-15.7)and 21.1 days(20.0-22.2).Conclusions:There are a certain number of infected people who require longer quarantine duration.Our findings well support the current practice of the extended active monitoring.To further prevent possible transmissions induced and facilitated by such infectious outliers after the 14-days quarantine,properly prolonging the quarantine duration could be prudent for high-risk scenarios and in regions with insufficient test resources.

Estimating effective reproduction number using generation time versus serial interval,with application to COVID-19 in the Greater Toronto Area,Canada

BACKGROUND.The effective reproduction number Re(t)is a critical measure of epidemic potential.Re(t)can be calculated in near real time using an incidence time series and the generation time distribution:the time between infection events in an infector-infectee pair.In calculating Re(t),the generation time distribution is often approximated by the serial interval distribution:the time between symptom onset in an infector-infectee pair.However,while generation time must be positive by definition,serial interval can be negative if transmission can occur before symptoms,such as in COVID-19,rendering such an approximation improper in some contexts.METHODS.We developed a method to infer the generation time distribution from parametric definitions of the serial interval and incubation period distributions.We then compared estimates of Re(t)for COVID-19 in the Greater Toronto Area of Canada using:negative-permitting versus non-negative serial interval distributions,versus the inferred generation time distribution.RESULTS.We estimated the generation time of COVID-19 to be Gamma-distributed with mean 3.99 and standard deviation 2.96 days.Relative to the generation time distribution,non-negative serial interval distribution caused overestimation of Re(t)due to larger mean,while negative-permitting serial interval distribution caused underestimation of Re(t)due to larger variance.IMPLICATIONS.Approximation of the generation time distribution of COVID-19 with non-negative or negative-permitting serial interval distributions when calculating Re(t)may result in over or underestimation of transmission potential,respectively.

A comparative analysis of epidemiological characteristics of MERS-CoV and SARS-CoV-2 in Saudi Arabia

In this study,we determine and compare the incubation duration,serial interval,pre-symptomatic transmission,and case fatality rate of MERS-CoV and COVID-19 in Saudi Arabia based on contact tracing data we acquired in Saudi Arabia.The date of infection and infector-infectee pairings are deduced from travel history to Saudi Arabia or exposure to confirmed cases.The incubation times and serial intervals are estimated using parametric models accounting for exposure interval censoring.Our estimations show that MERS-CoV has a mean incubation time of 7.21(95%CI:6.59–7.85)days,whereas COVID-19(for the circulating strain in the study period)has a mean incubation period of 5.43(95%CI:4.81–6.11)days.MERS-CoV has an estimated serial interval of 14.13(95%CI:13.9–14.7)days,while COVID-19 has an estimated serial interval of 5.1(95%CI:5.0–5.5)days.The COVID-19 serial interval is found to be shorter than the incubation time,indicating that pre-symptomatic transmission may occur in a significant fraction of transmission events.We conclude that during the COVID-19 wave studied,at least 75%of transmission happened prior to the onset of symptoms.The CFR for MERS-CoV is estimated to be 38.1%(95%CI:36.8–39.5),while the CFR for COVID-191.67%(95%CI:1.63–1.71).This work is expected to help design future surveillance and intervention program targeted at specific respiratory virus outbreaks,and have implications for contingency planning for future coronavirus outbreaks.

Heterogeneous epidemic modelling within an enclosed space and corresponding Bayesian estimation

Since March 11th,2020,COVID-19 has been a global pandemic for more than one years due to a long and infectious incubation period.This paper establishes a heterogeneous epidemic model that divides the incubation period into infectious and non-infectious and employs the Bayesian framework to model the‘Diamond Princess’enclosed space incident.The heterogeneity includes two different identities,two transmission methods,two different-size rooms,and six transmission stages.This model is also applicable to similar mixed structures,including closed schools,hospitals,and communities.As the COVID-19 pandemic continues,our mathematical modeling can provide management insights to the governments and policymakers on how the COVID-19 disease has spread and what prevention strategies still need to be taken.

Estimating the quarantine failure rate for COVID-19

Quarantine is a crucial control measure in reducing imported COVID-19 cases and community transmissions.However,some quarantined COVID-19 patients may show symptoms after finishing quarantine due to a long median incubation period,potentially causing community transmissions.To assess the recommended 14-day quarantine policy,we develop a formula to estimate the quarantine failure rate from the incubation period distribution and the epidemic curve.We found that the quarantine failure rate increases with the exponential growth rate of the epidemic curve.We apply our formula to United States,Canada,and Hubei Province,China.Before the lockdown of Wuhan City,the quarantine failure rate in Hubei Province is about 4.1%.If the epidemic curve flattens or slowly decreases,the failure rate is less than 2.8%.The failure rate in US may be as high as 8.3%-11.5%due to a shorter 10-day quarantine period,while the failure rate in Canada may be between 2.5%and 3.9%.A 21-day quarantine period may reduce the failure rate to 0.3%-0.5%.