| Objective: This study aims to analyze the transmission characteristics,transmission heterogeneity,super-spreading risk,and vaccine effectiveness of the Omicron BA.5variant,with the goal of providing deeper research experience and technical reserves for current or future studies on emerging infectious diseases.This endeavor seeks to advance our understanding of the transmission mechanisms and control strategies of emerging pathogens,thereby facilitating more effective prevention and response measures within the global public health system.Methods: 1)The first part of the study employed a retrospective cohort study design,focusing on 1,139 laboratory-confirmed COVID-19 cases reported in Urumqi City from August 7th to September 7th,2022,along with 51,786 close contacts.A detailed epidemiological investigation was conducted,capturing demographic characteristics of confirmed cases,time records from exposure to laboratory test results,contact tracing history,and types of contacts.Using the Markov Chain Monte Carlo(MCMC)method,four key epidemiological parameters of virus transmission were estimated for known cases,including the generation interval,infectious period until viral shedding,viral shedding period,and incubation period(only for symptomatic cases).Transmission risks were assessed across different control measures and types of contacts.2)The second part of the study describes the heterogeneity of contacts and transmission among different demographic strata,vaccination statuses,and contact settings,using detailed contact tracing information and exposure histories of case-contact pairs.The secondary attack ratio(SAR)among close contacts is described using a beta-binomial distribution.Simultaneously,this study models the transmission of COVID-19 as a process with negative binomial distribution,utilizing two parameters of the distribution,namely the effective reproduction number(R)and the dispersion parameter(k),to quantify the disease’s potential for super-spreading.3)The third part of this study employed a matched cohort study design,including all 37,628 adult close contacts who had contact with individuals infected with COVID-19 between August 1st and September 7th,2022.Based on gender,age,date of contact,and contact settings,a 1:5 ratio was employed to match close contacts who received only two doses of the vaccine with those who received a booster dose.A multivariable conditional Logistic regression model was utilized to estimate the marginal effectiveness of the booster in preventing Omicron BA.5 infection after adjusting for confounding variables.Kaplan-Meier curves were employed to visualize the follow-up process and test results of different subgroups within the matched cohorts.4)The fourth part of this study employed a prospective cohort study method to investigate pregnant women aged 18 and above who delivered at the Maternal and Child Health Hospital of Xinjiang Uygur Autonomous Region from February 1,2023,to May31,2023.Pregnant women who had been infected with the COVID-19 were grouped based on the number of vaccine doses received(0 doses,2 doses,and 3 doses),and the Bayesian approach of Logistic regression modeling were utilized to explore the relationship between vaccination status among pregnant women and the occurrence of adverse pregnancy outcomes.Results: Part One: 1)Among 1,139 COVID-19 cases,a total of 436 transmission pairs were identified,with 178 pairs having both infected and transmitting individuals simultaneously exposed.This study analyzed these 178 transmission chains,and after right-censoring correction,the estimated average generation interval was 4.3 days(95% Cr I: 2.6-6.9).The average generation interval estimate in non-household contacts was longer than in household settings(3.2 vs.2.3 days),and it was shorter after lockdown compared to before lockdown(1.8 vs.3.9 days).2)Out of 709 cases,individuals had both contact time and the time of the first positive detection.Based on these 709 data records,This study estimated the average time interval from infection to viral shedding to be 3.3 days(95% Cr I: 3.0-3.6).The average time from exposure to viral shedding was relatively longer for asymptomatic cases and cases in the age group 0-15.3)There were 770 cases where individuals simultaneously had first positive and first negative detections.The overall average duration of viral shedding was estimated to be 6.7days(95% Cr I: 6.4-7.1).4)The incubation period was estimated for 60 symptomatic cases,with an average of 5.7 days(95% Cr I: 4.8-6.6).5)The overall secondary attack ratio was0.9%(95% Cr I: 0.8-1.0),with relatively higher SAR observed among individuals aged0-15 years,those aged over 65 years,and household contacts,with SAR values of 2.5(95% Cr I: 1.9-3.1),2.2(95% Cr I: 1.5-3.0),and 14.7(95% Cr I: 13.0-16.5)respectively.Part Two: 1)After lockdown measures,the average size of case clusters decreased from2.0 before lockdown to 1.6,with a relative reduction in the proportion of contacts in workplaces and community settings compared to household contacts.2)This study estimated the overall R value to be 0.47(95% Cr I: 0.40-0.54),the k value was 0.27(95%Cr I: 0.21-0.34).And infer that about 14% of BA.5.2 infection cases resulted in 80% of local transmission.3)With the highest heterogeneity observed in transmission within community contacts,where 5% of cases led to 80% of transmission.4)In the household setting,the transmission risk is highest,with an estimated R value of 0.50(95% Cr I:0.42-0.60).Part Three: 1)Before matching,a total of 37,099 adult close contacts met the eligibility criteria for inclusion in the cohort.After matching,there were 3,317 and 16,051 contacts in the two-dose and three-dose groups,respectively.The proportions of Omicron infections in the two-dose and three-dose groups were 1.03% and 0.62%,respectively.2)This study estimate that the adjusted effectiveness of booster doses of inactivated vaccines against Omicron infection,compared to two doses,is 35.5%(95% Cr I: 2.0-57.5).3)Booster vaccines provide a higher level of protection,with effectiveness ranging at 60.2%(95% Cr I: 22.8-79.5)between 15 to 180 days post-vaccination,but after 180 days,this VE decreases to 35.0%(95% Cr I: 2.8-56.5).Part Four: 1)The rates of major adverse pregnancy outcomes in the unvaccinated group,two-dose vaccinated group,and three-dose vaccinated group were as follows: 13.92%(22/158),12.06%(24/199),and11.40%(79/693).2)Compared to the unvaccinated group,the relative risk of adverse pregnancy outcomes decreased by 15% in the two-dose vaccinated group(RR: 0.85,95%Cr I: 0.77-0.93)and by 20% in the three-dose vaccinated group(RR: 0.80,95% Cr I:0.69-0.92).3)Vaccination significantly reduces the risk of adverse pregnancy outcomes in older mothers(pregnant women aged >33 years),those with underlying comorbidities,and those with unhealthy lifestyle habits.4)This study further analyzed the impact of vaccine administration on various specific adverse pregnancy outcomes,revealing a significant advantage of vaccination in preventing pregnancy-induced hypertension and vaginal bleeding.Conclusion: 1)Compared to other strains,the BA.5.2 variant exhibits a shorter generation interval and time from exposure to viral shedding,indicating higher transmissibility.Furthermore,a shorter duration from exposure to viral shedding for the BA.5.2 variant.This implies that individuals infected with BA.5.2 begin shedding the virus earlier after becoming ill,thereby increasing the risk of infecting others.Additionally,study results indicate that the mean estimated incubation period for the BA.5.2 variant is longer than the average estimate from exposure to viral shedding,suggesting the presence of a certain proportion of pre-symptomatic transmission for this variant.2)In situations with intensive control measures,active case detection,and relatively high vaccine coverage but a lack of immunity in the population,this study results indicate a high degree of heterogeneity in the risk of contact and transmission of the Omicron BA.5 variant among different demographic strata,vaccine dosages,and contact settings.The transmission heterogeneity of the Omicron BA.5 variant underscores the need for personalized prevention and control measures targeting different populations and environments.3)This study confirms the ability of booster vaccines to reduce the risk of Omicron infection.Additionally,booster vaccines demonstrate significant effectiveness in preventing transmission,specifically in breaking the chain of virus transmission and interrupting community spread.This provides important scientific evidence for the strategy of booster vaccine administration in response to the COVID-19 pandemic.4)Receiving the COVID-19 inactivated vaccine can partially reduce the risk of adverse pregnancy outcomes among pregnant women infected with COVID-19,providing preliminary validation of the indirect effectiveness of COVID-19 inactivated vaccine administration for the pregnant population. |
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