Risks and Hazards of Post-Vaccine SARS-CoV-2 Infection in Antibody Naive Populations during the Mass Vaccination Campaign Against COVID-19 in Mongolia

Risks and Hazards of Post-Vaccine SARS-CoV-2 Infection in Antibody Naive Populations during the Mass Vaccination Campaign Against COVID-19 in Mongolia | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Risks and Hazards of Post-Vaccine SARS-CoV-2 Infection in Antibody Naive Populations during the Mass Vaccination Campaign Against COVID-19 in Mongolia Dashpagam Otgonbayar, Burenjargal Batmunkh, Shatar Shaarii, Otgonjargal Byambaa, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6660450/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Introduction In this study, we aimed to compare the risks and hazards of new infection and hospitalization in seronegative before-vaccination population groups and its association with sociodemographic, initial, and booster vaccination patterns. Materials and Methods We enrolled a total of 1,709 vaccinees who tested negative for anti-SARS-CoV-2 receptor binding domain (RBD) specific antibodies before receiving two doses of one of four COVID-19 vaccines. Data on vaccinations, new infections, hospitalizations and fatal outcomes during the 80-weeks follow-up were obtained from national health registry operators using participants' national registration IDs. Results We observed a new infection rate of 49.1% among the antibody-naïve population over an 80-week follow-up period. We found frontline workers (FWs), especially those who worked in rural health facilities and those who worked in direct contact with infected patients (red-zone FWs) at increased risk and hazard for new infections and followed hospitalizations beginning with milestone of 24 weeks compared to rest population groups prioritized for mass immunization. Both the Pfizer BioNTech and Sputnik V vaccines demonstrated greater effectiveness in preventing new infections while the Sinopharm BBIBP vaccine showed lower preventive effects of hospitalization. We identified age cut points adjusted for sex, showing that COVID-19 significantly affected younger females. COVID-19 mass vaccination relative risk hazard function hazard ratio Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Mongolia reported 1,007,314 confirmed COVID-19 cases, accounting for 29.1% of the total population, and 2,179 COVID-related deaths, which is 0.06% of the total population (0.21% of infected cases) as of December 25, 2022. [1] The nationwide vaccination campaign in Mongolia began on February 23, 2021. It uses four types of vaccines that are listed on the World Health Organization's (WHO) Emergency Use List. These vaccines include: the non-replicating viral vector vaccine AstraZeneca (ChAdOx1-S), the mRNA-based vaccine Pfizer-BioNTech (BNT162b2), the inactivated virus vaccine Sinopharm BBIBP-CorV, and the non-replicating viral vector vaccine Sputnik V. The Government of Mongolia identified three priority groups for mass immunization based on a strategic approach: 1) Frontline employees, including healthcare workers and government personnel who are directly involved in managing pandemics; 2) Individuals at higher risk of developing severe disease; and 3) The general adult population aged 18 to 59 years who do not fall into the first two categories. Frontline workers were reported to have an increased risk of SARS-CoV-2 infection since the early periods of the pandemic, while vaccinated healthcare workers exhibited a reduced risk.[2-5] Elderly people and people with certain underlying medical conditions, especially patients treated with corticosteroids and other immunosuppressive medications demonstrated an increased risk of being hospitalized or having fatal outcomes.[6] As of 2024, Mongolia’s population is estimated at around 3.5 million people. The population density is very low, approximately 2.2 people per square kilometer. Mongolia’s vast and sparsely populated territory makes it difficult to establish healthcare infrastructure in remote regions. Many people, especially in rural areas, live far from medical facilities. This creates challenges in terms of access to healthcare professionals, medical supplies, and emergency services. Infectious diseases remain a concern, especially in rural areas where healthcare services are limited.[7, 8] Our earlier studies confirmed the successful completion of the first stage of the COVID-19 immunization campaign in Mongolia, showing a high rate of RBD-specific antibody response in the population at increased risk for severe disease.[9] In this study, we aimed to compare the risks and hazards of new infection and hospitalization in seronegative before-vaccination population groups and its association with sociodemographic and vaccination patterns. Materials and Methods Study population and eligibility We enrolled a total of 1,709 vaccinees who tested negative for anti-SARS-CoV-2 receptor binding domain (RBD) specific antibodies. These individuals had received two doses of one of four COVID-19 vaccines listed on the World Health Organization's Emergency Use List (EUL). From April to August 2021, we collected socio-demographic, biometric, and risk-related information of the vaccinees during the initial vaccination series.[10] We analyzed three population groups determined as a priority strategy for immunization by the Government of Mongolia (Table 1). The first group consisted of frontline employees with an increased risk of being infected, including healthcare and hospital workers, and government officials working in the frontline of deployed handling professional in pandemics. This group was further divided into subgroups by residence (urban and rural, and various rural sites) and occupational exposure risk type (worked with and without direct contact with infected patients). The second group, or the group of increased severity risk, included participants who may develop severe illness or fatal outcomes if infected. This group included immunocompromised patients who received immunosuppressive interventions within the last six months due to systemic/autoimmune diseases and cancer, people aged above 60, and pregnant women at 12 – 36 weeks of pregnancy. Initially, we were uncertain about including pregnant women into the increased severity group when designing the study in early April 2021, however, studies published later documented an increased risk of hospitalization and intensive care unit admission in pregnant women compared to non-pregnant individuals.[11] The third group or the general adult population was consisted of participants of 18 – 59 years. Table 1. The sociodemographic, vaccination, and epidemiological characteristics of study participants Characteristics Distribution Sex, count (%)† Male 619 (36.2) Female 1090 (63.8) Age (year) Mean (M ± SD) 41.2 ± 14.3 CI95 40.5 – 41.9 Median (IQR) 38.0 Age intervals, count (%)† < 20 26 (1.5) 20 – 29 368 (21.5) 30 – 39 511 (29.9) 40 – 49 350 (20.5) 50 – 59 251 (14.7) 60 – 69 128 (7.5) ≥ 70 75 (4.4) Population groups regarding the priority for immunization, count (%)† Frontline workers (FWs) 924 (54.1) Population with increased severity risk (IRP) 413 (24.2) General adult population aged 18 – 59 years (GAP) 372 (21.8) Subgroups, frontline employees, count (%)‡ Residence, count (%) Urban 250 (27.1) Rural 674 (72.9) Occupational risk, count (%) Direct contact with infected patients (red-zone) ¶ 554 (40.0) No direct contact with infected patients (yellow-zone) ⁋ 370 (60.0) Subgroups, individuals in increased risk for severe disease, count (%)‡ Immunocompromised, including patients passed radiation or chemotherapy due to: Systemic or autoimmune diseases Cancer 221 (53.5) 133 (32.2) 88 (21.3) Elderly & 111 (26.9) Pregnant ⁑ 81 (19.6) Vaccine types, initial two shots, count (%) # AstraZeneca (ChadOx1-S) 151 (8.8) Pfizer/BioNTech (BNT162b2) 333 (19.5) Sinopharm (BBIBP-CorV) 1158 (67.8) Sputnik V (Gam-COVID-Vac) 67 (3.9) Antibody response after two shot initial vaccination, count (%)^ Response 838 (80.3) No response 205 (19.7) Notes: †-percent calculated within total; ‡-percent calculated within population group; ¶ -included medical doctors, nurses, nurse assistants serving COVID-19 patients, radiologists, laboratory technicians collected samples, ambulance drivers and hospital porters, ward serving personnel, health officers from the emergency ward, and epidemiologists; ⁋ -included police and security officers, officers of emergency service, personnel of hospital kitchen, inspectors, and administrative and service workers; & -patients aged ≥ 60 years; ⁑ - 12 – 36 weeks of pregnancy at the time of initial vaccination; #- the distribution of vaccine types was based on the immunization priorities identified by the Government (for details, see Supplementary Table 1); ^-there were available data from 1103 vaccinees. Abbreviations: M, mean; SD, standard deviation; CI95, 95% confidence interval of variables The follow-up flow chart is shown in Figure 1 Data on infection, hospitalization, vaccination, and fatal outcomes Participants who had positive PCR tests for SARS-CoV-2 from the fourth week after the first dose of the initial vaccine series were considered infected. Reinfection was determined when a PCR-confirmed SARS-CoV-2 infection was diagnosed in participants who had recovered from their first infection and had passed at least 90 days (12 weeks).[12] Data on vaccinations, infections, hospitalizations, and fatal outcomes were obtained from national health registry operators using participants' national registration IDs. We accessed individual data with the necessary permissions, including PCR-confirmed infections and reinfections from the Gerege digital database (Gerege MedTech LLC, https://gerege.mn/en/gerege-medtech), vaccination information from the General Health Insurance Authority of Mongolia (https://vis.health.gov.mn/), and hospital admission dates, diagnoses, and outcomes from the national health database of the Center for Health Development (https://hdc.gov.mn). Hospital services were provided following the "Interim Guidelines for the Diagnosis and Treatment of Coronavirus Infections (COVID-19)" issued by the Ministry of Health in Mongolia, which were developed based on WHO recommendations.[13, 14] This document states that medical care providers hospitalized patients with moderate or severe diseases, as well as those with known chronic comorbidities, regardless of the severity of their condition. We tracked the time in weeks for infection, hospitalization, and fatal outcomes starting from the day after the second dose of the vaccine was administered. Supplementary Table 1 shows the distribution of vaccine types administered for the initial series of vaccination among population groups prioritized by immunization strategy. Data analysis The distribution of nominal or ordinal variables among exposure groups was analyzed using Pearson’s chi-square (χ²) test. The infection hospitalization rate (IHR) was calculated as the percentage of hospitalization cases among new infection cases. The overall risk of being infected or hospitalized was assessed through logistic regression, employing Fisher’s exact test, odds ratio (OR), and relative risk (RR). The optimal cut-point (OCP) for age was determined using the Youden index (J), derived from the coordinates of the receiver operating characteristics (ROC) curve. To compare hazards across different study groups, we employed the Kaplan-Meier survival function using the Log Rank (LR) test expressed in chi-square (c 2 ) along with Cox regression to determine the exponentiation of the B coefficient (Exp(B)) expressed in hazard ratio (HR) for follow-up within 80 weeks after the initial vaccination. Results During the 80-week follow-up, we identified 839 new cases of infection, represented by 49.1% of all participants. We observed a significant increase in the cumulative rate of new infections between the 12-week and 48-week intervals (Figure 2A). However, the prevalence of new infections began to decline after reaching the 24-week milestone (Figure 2B). Risks and hazards of new infection The risk of new infections within 80 weeks of observation for populations prioritized for vaccination was comparable, with FWs experiencing an increased RR compared to other groups at all follow-up milestones (Supplementary Figure 1A). FWs in urban and rural health facilities, as well as those in occupational risk groups, showed no significant differences in new infection rates during all milestones of the observation period (p > 0.05). Similarly, the antibody response rate following the initial vaccination was not associated with risk to new infections. No significant risk of new infections was found during the follow-up period for participants who were at higher risk for severe COVID-19 due to factors such as immunocompromising conditions, aging, and pregnancy. However, an increased risk was observed in pregnant women who were between 12 and 36 weeks of pregnancy at the time of initial vaccination, during the first 12 weeks following their initial immunization (OR = 6.1; RR = 5.2; p < 0.001). Individuals who received the Pfizer BioNTech and Sputnik V vaccines showed a reduced risk of new infection since the observation milestone of a 24-week compared to those who received the AstraZeneca and Sinopharm CorV vaccines (Supplementary Figure 1B). The new infection rate in male and female participants and participants of various age strata was comparable since the observation milestone of a 24-week. Furthermore, we found the optimal cut-points (OCP) for age, adjusted for sex, using receiver operating characteristic (ROC) analysis at the 24-week and 80-week observation milestones (Supplementary Figure 2). We then compared the relative risk of new infections across sex-adjusted age groups. Our analysis revealed an increased risk of new infections among younger female participants, specifically those under 50 years of age at 24 weeks and under 57 years of age at 80 weeks (Supplementary Figures 1C). The mean infection-free time during the observation gradually decreased, reaching 52.1 ± 0.7 weeks at the 80-week milestone (Supplementary Figures 3A). The hazard function for infection varied significantly across the different population groups prioritized for immunization. This analysis identified FWs as the population group most susceptible to new infections. As expected, the increased hazard ratio (HR) for FWs compared to other population groups remained consistent at all observation milestones (Figure 3A). At any observation milestones, FWs' residence and occupational risk were not associated with the hazard function for new infections. During the 12-week observation period, pregnant women were the most susceptible to new infection among the IRP subgroup (c 2 = 22.9; HR = 5.5; p< 0.001). No significant hazard ratio for cumulative new infections was observed within 80 weeks when comparing different population groups based on the types of vaccine administered during the initial vaccination. However, recipients of the Pfizer BioNTech or Sputnik V vaccines showed a significantly shorter infection-free period and a lower hazard ratio of new infections than recipients of the AstraZeneca ChadOX1-S or Sinopharm vaccines since observation milestones of 24 weeks (Figure 3B). The seroconversion state after initial vaccination showed no significant hazard ratio at all follow-up milestones. The age of participants showed a significantly declined impact on the hazard function for new infections beginning with the 24-week observation milestone (Figure 3C) with especially increased HR in subjects aged 20 – 59 years (Figure 3D). Female participants, compared to males, showed an increased HR to new infections starting from the 24-week milestone (Figure 3E). Sex-adjusted age OCPs regarding the risk of new infection (Supplementary Figure 5) also demonstrated significantly increased differences for infection-free time and hazard ratio at observation milestones 24 (Supplementary Figure 4A) and 80 (Supplementary Figure 4B) weeks. Risks and hazards of hospitalization among various population groups The hospitalization rate during follow-up mirrored the new infection rate, except that the increase in cumulative hospitalization cases persisted until the 24-week milestone (Figures 2C and 2D), but not beyond that. Interestingly, the IHR remained unchanged throughout the entire follow-up period (Figure 2E). The hospitalization rate significantly varied among prioritized vaccination populations over a 24-week observation period, with FWs facing a higher risk of hospitalization than other groups (Supplementary Figure 5A). The residence of FWs also influenced hospitalization rates, showing an increased risk for hospitalization among FWs in rural areas compared to those in urban areas since the observation milestone of 24 weeks (Supplementary Figure 5B). In the observation milestones at 24, 48, and 80 weeks, frontline workers (FWs) who had direct contact with infected patients (red-zone FWs) showed a significantly higher risk of hospitalization compared to yellow-zone FWs (Supplementary Figure 5C). Pregnant women who were between 12 and 36 weeks of pregnancy at the time of their initial vaccination showed an increased risk of hospitalization during the first 12 weeks following the vaccination compared to other IRP (OR = 5.1; RR = 1.8; p < 0.01). The hospitalization rates varied significantly depending on the type of vaccine administered during the initial vaccination period. Notably, beginning the observation milestone of 24 weeks, participants who received the Sinopharm vaccine exhibited a higher risk of hospitalization compared to those who received other types of vaccines (Supplementary Figure 5D). The age of participants significantly influenced their hospitalization rates beginning with the 24-week observation period, with higher-than-mean rates in the age strata of 40 – 59 years (Supplementary Figures 5E). Male participants demonstrated reduced RR compared to females at all observation milestones (Supplementary Figures 5F). The mean-time for period from initial vaccination to hospitalization was 70.2 ± 0.5 weeks (Supplementary Figure 3B). A shorter time between the initial vaccine administration and hospitalization, along with a higher HR in FWs compared to other prioritized population groups, was observed starting at 24 weeks (Figure 4A). Subgroups of frontline workers, such as those in rural areas and those in red zones, exhibited a significantly increased hazard for hospitalization starting at 24 weeks compared to their counterparts (Figures 4B and 4C, respectively). Pregnant women were discovered to be more susceptible to hospitalization than immunocompromised and elderly individuals during the 12 weeks after the initial vaccine series (c 2 = 10.1; HR = 4.9; p< 0.005). Recipients of the Sinopharm BBIBP vaccine for the initial series of vaccination showed a significantly shorter time for hospitalization and increased HR compared to recipients of other types of vaccine beginning with the period of 24 weeks (Figure 4D). Female participants experienced shorter hospitalization times and higher HR than males throughout the observation periods (Figure 4E). The age of participants and seroconversion state after the initial vaccine series were not associated with the hospitalization. Fatal outcomes We observed two COVID-related deaths during the 80-week follow-up period. Both cases occurred in IRP. The first case involved a 67-year-old man, categorized as elderly, who passed away after 42 days of hospitalization. His death was caused by embolism and thrombosis of the arteries in the lower extremities, resulting from complications related to diabetes mellitus. The second case involved a 42-year-old man who had previously been treated with corticosteroids for tubulointerstitial nephritis. Patient died due to pneumonia caused by an unspecified agent. Discussion We observed a new infection rate of 49.1% among the antibody-naïve population over an 80-week follow-up period. In this study we were not able to provide unvaccinated population for the comparison. According to Chimeddorj B et al., in late 2021, the estimated new infection rate among the vaccinated population was 62.4% (95% CI: 60.2 – 64.5%).[17] In contrast, we calculated the new infection rate for the same period, which was approximately week 36 in our cohort, and identified 689 new infection cases, resulting in a rate of 40.4%. We found FWs at increased risk and hazard for new infections and followed hospitalizations beginning with milestone of 24 weeks compared to rest antibody naïve before vaccine population groups prioritized for mass immunization. Notably, the relative risk (RR) and hazard ratio (HR) for hospitalization were higher among FWs working in rural areas and those who had direct contact with infected patients. The susceptibility of healthcare workers (HCWs) to SARS-CoV-2 infection is documented, with special attention given to occupational risks such as HCW-to-HCW transmission, patient-to-HCW transmission, and community-to-HCW transmission.[18] A retrospective analysis of infection cases at Indraprastha Apollo Hospitals in New Delhi, India, found that SARS-CoV-2 infection occurred in 2.63% of vaccinated healthcare workers within three months of observation. [19] In our study, the infection rate among red-zone frontline workers over a 12-week period was 9.9%, which was higher than that of the Indian cohort. We noted an increased risk of infection and hospitalization in pregnant women who were between 12 and 36 weeks of pregnancy at the time of their initial vaccination, during the first 12 weeks following vaccination. Pregnant women face heightened risks during the pandemic due to cardiovascular, pulmonary, hormonal, and immunological changes. These factors increase susceptibility to infections and reduce tolerance to hypoxia and dyspnea. Consequently, infections with SARS-CoV-2 in pregnant women are associated with a severe disease.[20] We identified age cut points adjusted for sex, showing that COVID-19 significantly affected females who are under 56. A meta-analysis conducted by Pijls BG et al. (2021), which included 59 studies, found that males have a higher overall relative risk (RR) compared to females, with an RR of 1.18 (95% CI: 1.10 – 1.27). Specifically, out of the 35 studies examined, nine reported a higher risk in females (RR ranging from 0.74 to 0.99), while the remaining studies indicated an increased risk for males, with an RR ranging from 1.01 to 2.38.[21] A variation in sex steroid levels in men and women might, to some extent, explain the sex disparities in susceptibility to SARS-CoV-2, however, the underlying mechanisms are still open to speculation.[22] In this study, recipients of the Pfizer BioNTech or Sputnik V vaccines demonstrated a significantly lower RR and HR for new infections compared to those who received the AstraZeneca ChadOX1-S or Sinopharm vaccines after a 24-week observation period. Furthermore, individuals who received the Sinopharm vaccine showed a significantly increased risk and hazard for hospitalization. According to the Vaccine Updates document issued by the University of Melbourne in December 2022 [23], the Pfizer BioNTech vaccine demonstrated an effectiveness of 47% to 65% in preventing any new COVID-19 infections. It provided 87% to 92% effectiveness in preventing hospitalization or severe disease, and 92% effectiveness in preventing COVID-related deaths for 3 to 6 months following vaccination. However, the vaccine's effectiveness decreased after 6 months, showing only 0% to 64% prevention of new infections, 68% to 81% prevention of hospitalization or severe disease, and 70% to 84% prevention of COVID-related deaths. We did not observe any association between the seroconversion status after the initial vaccine series and the risk of new infection or hospitalization. The hospitalization rate within the first 12 weeks among seropositive individuals was lower than that of seronegative individuals; however, no significant difference was found. The interim guideline from the Ministry of Health [14]was issued on March 18, 2021, but it has not been consistently implemented. For example, among 150 hospitalized patients observed by Batmunkh et al. [10] from October 11, 2020, to June 30, 2021, 80 were diagnosed with mild to moderate COVID-19. The case-fatality rate (CFR) in our cohort (0.12) was found lower than the country’s CFR (0.21), however, it was close to the findings of Chimiddorj et al. (0.100).[6] Our findings indicate that healthcare professionals on the frontlines of pandemics face heightened risks and hazards, particularly in resource-limited rural areas. Both the Pfizer BioNTech and Sputnik V vaccines demonstrated greater effectiveness in preventing new infections and subsequent hospitalizations, while the Sinopharm BBIBP vaccine showed lower preventive effects of hospitalization. Study limitations In this study, we were unable to investigate the unvaccinated population; therefore, we did not establish the effectiveness of the initial vaccine series. The registration of hospitalizations in the country does not indicate the severity of cases, making it difficult to assess the severity of COVID-19 through hospitalization data, especially during the initial stages of the outbreak. Declarations Data availability statement The original contributions presented in the study are included in the Supplementary Material. Further inquiries can be directed to the corresponding author, or requested from the Division of Science and Technology, Mongolian National University of Medical Sciences via email ( [email protected] ), or via phone (+976-7775-7575 (1010)), for researchers who meet the criteria for access to confidential data. Ethics Statement This study was conducted in accordance with the principles of the Declaration of Helsinki. Ethical approval was obtained from the Ethical Review Committee of the Ministry of Health, Mongolia (resolutions 216, 217, and 219 dated April 6, 2021). All participants were informed about the purpose, procedures, potential risks, and benefits of the study. Written informed consent was obtained from all participants prior to data collection. Funding statement This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Acknowledgment We appreciate the Ministry of Health and the State Emergency Commission for their assistance in conducting the study. We also thank the Health Development Agency of Mongolia for providing the necessary data. 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Scientific Reports. 2022;12(1):20763. Rahman MO, Kamigaki T, Thandar MM, Haruyama R, Yan F, Shibamura-Fujiogi M, et al. Protection of the third-dose and fourth-dose mRNA vaccines against SARS-CoV-2 Omicron subvariant: a systematic review and meta-analysis. BMJ Open. 2023;13(12):e076892. Additional Declarations No competing interests reported. Supplementary Files SupplementaryTables.docx ConsentDeclaration.pdf Suplfigure1.Riskestimatesfornewinfectionsamongvariouspopulationgroupswithin80weeksfollowupafterinitialvaccination.tif Supplfigure2.ROCcurvesofsexadjustedageofparticipantsstratifiedbythenewinfectionstate.tif Supplfigure3.HazardfunctionsofCOVID19exposuresindifferentfollowupperiodsaftertheinitialvaccination.tif Supplfigure4.Hazardfunctionsofnewinfectionindifferentsexadjustedagegroups.tif Supplfigure5.Riskestimatesforhospitalizationamongvariouspopulationgroupswithin80weeksfollowupafterinitialvaccination.tif SupplementaryFigures.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers invited by journal 24 Jun, 2025 Editor assigned by journal 18 Jun, 2025 Editor invited by journal 30 May, 2025 Submission checks completed at journal 28 May, 2025 First submitted to journal 28 May, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6660450","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":475509233,"identity":"01554ff5-f261-4180-b4ce-515677efdac1","order_by":0,"name":"Dashpagam Otgonbayar","email":"","orcid":"","institution":"National Center for Communicable Diseases","correspondingAuthor":false,"prefix":"","firstName":"Dashpagam","middleName":"","lastName":"Otgonbayar","suffix":""},{"id":475509234,"identity":"55bb1a32-cd00-4969-968f-c6975e56327c","order_by":1,"name":"Burenjargal Batmunkh","email":"","orcid":"","institution":"Mongolian National University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Burenjargal","middleName":"","lastName":"Batmunkh","suffix":""},{"id":475509235,"identity":"9274d040-8b0b-4796-a3ba-93133d836cd0","order_by":2,"name":"Shatar Shaarii","email":"","orcid":"","institution":"Mongolian National University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Shatar","middleName":"","lastName":"Shaarii","suffix":""},{"id":475509236,"identity":"acb484fd-fefa-4a0f-b7db-95e38de8a8ee","order_by":3,"name":"Otgonjargal Byambaa","email":"","orcid":"","institution":"Mongolian National University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Otgonjargal","middleName":"","lastName":"Byambaa","suffix":""},{"id":475509237,"identity":"3cd51445-5319-4072-a40e-3d96258570ba","order_by":4,"name":"Khongorzul Togoo","email":"","orcid":"","institution":"Mongolian National University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Khongorzul","middleName":"","lastName":"Togoo","suffix":""},{"id":475509238,"identity":"55251982-f511-4ac8-8895-29a740648d8f","order_by":5,"name":"Azjargal Batjargal","email":"","orcid":"","institution":"National Center for Communicable Diseases","correspondingAuthor":false,"prefix":"","firstName":"Azjargal","middleName":"","lastName":"Batjargal","suffix":""},{"id":475509239,"identity":"45222747-730a-4fb5-93fd-41ac11c82ebb","order_by":6,"name":"Battogtokh Chimeddorj","email":"","orcid":"","institution":"Mongolian National University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Battogtokh","middleName":"","lastName":"Chimeddorj","suffix":""},{"id":475509240,"identity":"d0ecf121-0244-445d-9950-3a914c3e0726","order_by":7,"name":"Davaalkham Dambadarjaa","email":"","orcid":"","institution":"Mongolian National University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Davaalkham","middleName":"","lastName":"Dambadarjaa","suffix":""},{"id":475509241,"identity":"b3784787-723c-4395-97f3-70456ff91e63","order_by":8,"name":"Batbaatar Gunchin","email":"","orcid":"","institution":"Mongolian National University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Batbaatar","middleName":"","lastName":"Gunchin","suffix":""},{"id":475509242,"identity":"4b7f2b45-4053-4e72-af66-8096e3778b55","order_by":9,"name":"Tsogtsaikhan Sandag","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABEklEQVRIiWNgGAWjYBADHgkJMG0DE2DGrRREHEBoSSNeCwNUy2HCWuz5Dx9+/eGPnYzk7OZnDxj+nI82l8hO/sBQYZ3YIHb2AHY/pKVZHGxL5pGWOWZuwNh2O3fnjNxtEgxn0hMbpPMSsGvhMTM42MDMIyeRYCbB2HA7d8ON3G0MjG2HgVpyDLBq4T9jZnDgTz1QS/o3CYY/50BaNn9g/IdHC0OO8YMDbId5pCVyzCQY2A6AtGwAWodHy420NIazbcd5JGfklEkktiXnbjjzdptEwrF04zYcWtj7Dx/+UPGn2l7iRvo2CWDQ5W44DnTYhxpr2X4cWoCATQLOTEBmsOFQDwTMH3DLjYJRMApGwSgAAgBPJGHgFO7HaAAAAABJRU5ErkJggg==","orcid":"","institution":"Mongolian National University of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Tsogtsaikhan","middleName":"","lastName":"Sandag","suffix":""}],"badges":[],"createdAt":"2025-05-14 05:08:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6660450/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6660450/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":85617810,"identity":"59fa8b3a-bd54-406a-9dc5-207dc4937fc9","added_by":"auto","created_at":"2025-06-29 14:47:45","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":656197,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlow chart of the follow-up.\u003c/strong\u003e The Government of Mongolia has identified three priority population groups for mass immunization using a strategic approach. The first group consists of healthcare workers and government employees who are directly involved in managing pandemics (referred to as \"frontline workers, FWs\"). The second group includes individuals at higher risk of developing severe disease (referred to as \"with increased risk population, IRP”). The third group is the general adult population aged 18 to 59 years who do not belong to the first two categories (referred to as \"general adult population, GAP\"). *-There is no disclosed data on the infection and hospitalization rates of People Living with Human Immunodeficiency Virus (HIV) and acquired immunodeficiency syndrome (AIDS) as per the Law on HIV/AIDS in Mongolia\u003c/p\u003e","description":"","filename":"Figure1.Flowchartofthefollowup.png","url":"https://assets-eu.researchsquare.com/files/rs-6660450/v1/70a83392bad7c3f17bf5a4f8.png"},{"id":85617809,"identity":"799a3740-0aa5-4540-83d6-5d67ced386de","added_by":"auto","created_at":"2025-06-29 14:47:45","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":667217,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eNew infection and hospitalization in antibody naïve population during the 80 weeks after the initial vaccination.\u003c/strong\u003e \u0026nbsp;n, number of exposed cases; %, percent of exposed cases; OR, odds ratio; RR, relative risk; p, statistical significance level (Fisher’s exact test) when compared with the rate of previous period\u003c/p\u003e","description":"","filename":"Figure2.Newinfectionandhospitalizationinantibodynavepopulationduringthe80weeksaftertheinitialvaccination.png","url":"https://assets-eu.researchsquare.com/files/rs-6660450/v1/132414b284a24f8283f55df6.png"},{"id":85617813,"identity":"af52159a-3c01-47e2-b251-c581b5fe20a4","added_by":"auto","created_at":"2025-06-29 14:47:45","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1286595,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eHazard functions of new infection among different population groups during the 80 weeks after the initial vaccination.\u003c/strong\u003e A. Hazard function of FWs compared to other population groups prioritized by immunization strategy; B. Hazard function of new infection in recipients of different types of vaccine for the initial vaccination; C and D. Hazard function of new infection in different age groups; E. Hazard function of new infection in male and female participants. t, mean infection-free time, and its standard error; c\u003csup\u003e2\u003c/sup\u003e, chi square; HR, hazard ratio. Abbreviations: FWs, frontline workers; IRP, increased risk population; GAP, general adult population; AZ, AstraZeneca ChadOX1; Pf, Pfizer BioNTech; SP, Sinopharm BBIBP; SpV, Sputnik V\u003c/p\u003e","description":"","filename":"Figure3.Hazardfunctionsofnewinfectionamongdifferentpopulationgroupsduringthe80weeksaftertheinitialvaccination.png","url":"https://assets-eu.researchsquare.com/files/rs-6660450/v1/ae49c5a0b9d066e81099bb85.png"},{"id":85617815,"identity":"adc9b36b-d35d-415e-9e28-34d07a850cab","added_by":"auto","created_at":"2025-06-29 14:47:45","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1073801,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cbr\u003e\n\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHazard functions of hospitalization among different population groups during the 80 weeks after the initial vaccination.\u003c/strong\u003e A. Hazard function of hospitalization in FWs compared to other population groups prioritized by immunization strategy; B. Hazard function of hospitalization in FWs compared by the residence; C. Hazard function of hospitalization in FWs compared by occupational risk; D. Hazard function of hospitalization in recipients of different types of vaccine for the initial vaccination; E. Hazard function of hospitalization in male and female participants. t, mean hospitalization-free time, and its standard error; c\u003csup\u003e2\u003c/sup\u003e, chi square; HR, hazard ratio. Abbreviations: FWs, frontline workers; IRP, increased risk population; GAP, general adult population; AZ, AstraZeneca ChadOX1; Pf, Pfizer BioNTech; SP, Sinopharm BBIBP; SpV, Sputnik V\u003c/p\u003e","description":"","filename":"Figure4.Hazardfunctionsofhospitalizationamongdifferentpopulationgroupsduringthe80weeksaftertheinitialvaccination.png","url":"https://assets-eu.researchsquare.com/files/rs-6660450/v1/491b69d9593a624df3e0d84d.png"},{"id":85619940,"identity":"915bce79-e54a-4f56-902c-b4c4910bbfb3","added_by":"auto","created_at":"2025-06-29 15:03:47","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4260791,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6660450/v1/0d0b5dba-4be7-4ae2-84cf-b105644fe93f.pdf"},{"id":85617806,"identity":"0e185511-309b-49e1-86b4-1d5354167de2","added_by":"auto","created_at":"2025-06-29 14:47:45","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":14104,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTables.docx","url":"https://assets-eu.researchsquare.com/files/rs-6660450/v1/a693cc60cc5ab9b59e4b86d6.docx"},{"id":85617808,"identity":"8a4222fd-b9e5-44d8-bf1e-04cd9b4c9d94","added_by":"auto","created_at":"2025-06-29 14:47:45","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":89184,"visible":true,"origin":"","legend":"","description":"","filename":"ConsentDeclaration.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6660450/v1/eb4c593e3c9a1b35468c5414.pdf"},{"id":85617816,"identity":"d9490f2c-4ef1-4331-a54c-2147e38f1f87","added_by":"auto","created_at":"2025-06-29 14:47:45","extension":"tif","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":2470384,"visible":true,"origin":"","legend":"","description":"","filename":"Suplfigure1.Riskestimatesfornewinfectionsamongvariouspopulationgroupswithin80weeksfollowupafterinitialvaccination.tif","url":"https://assets-eu.researchsquare.com/files/rs-6660450/v1/16243aac9ac31013850ae128.tif"},{"id":85619259,"identity":"08983c34-bddb-456f-a73d-0501bc062f27","added_by":"auto","created_at":"2025-06-29 14:55:45","extension":"tif","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":422968,"visible":true,"origin":"","legend":"","description":"","filename":"Supplfigure2.ROCcurvesofsexadjustedageofparticipantsstratifiedbythenewinfectionstate.tif","url":"https://assets-eu.researchsquare.com/files/rs-6660450/v1/3b4843826ff559025ce53501.tif"},{"id":85617829,"identity":"4ebb4dac-20bd-42bf-bace-49f02e74b53d","added_by":"auto","created_at":"2025-06-29 14:47:46","extension":"tif","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":2569940,"visible":true,"origin":"","legend":"","description":"","filename":"Supplfigure3.HazardfunctionsofCOVID19exposuresindifferentfollowupperiodsaftertheinitialvaccination.tif","url":"https://assets-eu.researchsquare.com/files/rs-6660450/v1/8e6cf5b777ef2df9bf7e4a60.tif"},{"id":85617822,"identity":"d3384891-51bc-48d3-bf4e-66c9db4afa66","added_by":"auto","created_at":"2025-06-29 14:47:46","extension":"tif","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":1101248,"visible":true,"origin":"","legend":"","description":"","filename":"Supplfigure4.Hazardfunctionsofnewinfectionindifferentsexadjustedagegroups.tif","url":"https://assets-eu.researchsquare.com/files/rs-6660450/v1/fea9beb52c700d3e132fc56c.tif"},{"id":85617831,"identity":"097ab7ce-2314-4c8c-b135-eead94ad457b","added_by":"auto","created_at":"2025-06-29 14:47:46","extension":"tif","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":5563520,"visible":true,"origin":"","legend":"","description":"","filename":"Supplfigure5.Riskestimatesforhospitalizationamongvariouspopulationgroupswithin80weeksfollowupafterinitialvaccination.tif","url":"https://assets-eu.researchsquare.com/files/rs-6660450/v1/10768a82177d62619f3bae42.tif"},{"id":85617827,"identity":"f1990572-07e1-4b92-a9a3-0ef500619227","added_by":"auto","created_at":"2025-06-29 14:47:46","extension":"docx","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":12254131,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigures.docx","url":"https://assets-eu.researchsquare.com/files/rs-6660450/v1/5b67d9e20bfc646376ef752b.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Risks and Hazards of Post-Vaccine SARS-CoV-2 Infection in Antibody Naive Populations during the Mass Vaccination Campaign Against COVID-19 in Mongolia","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMongolia reported 1,007,314 confirmed COVID-19 cases, accounting for 29.1% of the total population, and 2,179 COVID-related deaths, which is 0.06% of the total population (0.21% of infected cases) as of December 25, 2022. [1] The nationwide vaccination campaign in Mongolia began on February 23, 2021. It uses four types of vaccines that are listed on the World Health Organization's (WHO) Emergency Use List. These vaccines include: the non-replicating viral vector vaccine AstraZeneca (ChAdOx1-S), the mRNA-based vaccine Pfizer-BioNTech (BNT162b2), the inactivated virus vaccine Sinopharm BBIBP-CorV, and the non-replicating viral vector vaccine Sputnik V. The Government of Mongolia identified three priority groups for mass immunization based on a strategic approach: 1) Frontline employees, including healthcare workers and government personnel who are directly involved in managing pandemics; 2) Individuals at higher risk of developing severe disease; and 3) The general adult population aged 18 to 59 years who do not fall into the first two categories.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFrontline workers were reported to have an increased risk of SARS-CoV-2 infection since the early periods of the pandemic, while vaccinated healthcare workers exhibited a reduced risk.[2-5]\u0026nbsp;Elderly people and people with certain underlying medical conditions, especially patients treated with corticosteroids and other immunosuppressive medications demonstrated an increased risk of being hospitalized or having fatal outcomes.[6]\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAs of 2024, Mongolia’s population is estimated at around 3.5 million people. The population density is very low, approximately 2.2 people per square kilometer. Mongolia’s vast and sparsely populated territory makes it difficult to establish healthcare infrastructure in remote regions. Many people, especially in rural areas, live far from medical facilities. This creates challenges in terms of access to healthcare professionals, medical supplies, and emergency services. Infectious diseases remain a concern, especially in rural areas where healthcare services are limited.[7, 8]\u003c/p\u003e\n\u003cp\u003eOur earlier studies confirmed the successful completion of the first stage of the COVID-19 immunization campaign in Mongolia, showing a high rate of RBD-specific antibody response in the population at increased risk for severe disease.[9]\u003c/p\u003e\n\u003cp\u003eIn this study, we aimed to compare the risks and hazards of new infection and hospitalization in seronegative before-vaccination population groups and its association with sociodemographic and vaccination patterns. \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStudy population and eligibility\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe enrolled a total of 1,709 vaccinees who tested negative for anti-SARS-CoV-2 receptor binding domain (RBD) specific antibodies. These individuals had received two doses of one of four COVID-19 vaccines listed on the World Health Organization\u0026apos;s Emergency Use List (EUL). From April to August 2021, we collected socio-demographic, biometric, and risk-related information of the vaccinees during the initial vaccination series.[10]\u003c/p\u003e\n\u003cp\u003eWe analyzed three population groups determined as a priority strategy for immunization by the Government of Mongolia (Table 1). The first group consisted of frontline employees with an increased risk of being infected, including healthcare and hospital workers, and government officials working in the frontline of deployed handling professional in pandemics. This group was further divided into subgroups by residence (urban and rural, and various rural sites) and occupational exposure risk type (worked with and without direct contact with infected patients). The second group, or the group of increased severity risk, included participants who may develop severe illness or fatal outcomes if infected. This group included immunocompromised patients who received immunosuppressive interventions within the last six months due to systemic/autoimmune diseases and cancer, people aged above 60, and pregnant women at 12 \u0026ndash; 36 weeks of pregnancy. Initially, we were uncertain about including pregnant women into the increased severity group when designing the study in early April 2021, however, studies published later documented an increased risk of hospitalization and intensive care unit admission in pregnant women compared to non-pregnant individuals.[11] The third group or the general adult population was consisted of participants of 18 \u0026ndash; 59 years.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e The sociodemographic, vaccination, and epidemiological characteristics of study participants\u003c/p\u003e\n\u003ctable width=\"623\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003eCharacteristics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eDistribution\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003eSex, count (%)\u0026dagger;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e619 (36.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e1090 (63.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003eAge (year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003eMean (M \u0026plusmn; SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e41.2 \u0026plusmn; 14.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003eCI95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e40.5 \u0026ndash; 41.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003eMedian (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e38.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003eAge intervals, count (%)\u0026dagger;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003e\u0026lt; 20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e26 (1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003e20 \u0026ndash; 29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e368 (21.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003e30 \u0026ndash; 39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e511 (29.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003e40 \u0026ndash; 49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e350 (20.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003e50 \u0026ndash; 59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e251 (14.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003e60 \u0026ndash; 69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e128 (7.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003e\u0026ge; 70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e75 (4.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003ePopulation groups regarding the priority for immunization, count (%)\u0026dagger;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003eFrontline workers (FWs)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e924 (54.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003ePopulation with increased severity risk (IRP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e413 (24.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003eGeneral adult population aged 18 \u0026ndash; 59 years (GAP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e372 (21.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003eSubgroups, frontline employees, count (%)\u0026Dagger;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003eResidence, count (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003eUrban\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e250 (27.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003eRural\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e674 (72.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003eOccupational risk, count (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003eDirect contact with infected patients (red-zone)\u003csup\u003e\u0026para;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e554 (40.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003eNo direct contact with infected patients (yellow-zone)\u003csup\u003e⁋\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e370 (60.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003eSubgroups, individuals in increased risk for severe disease, count (%)\u0026Dagger;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003eImmunocompromised, including patients passed radiation or chemotherapy due to:\u003c/p\u003e\n \u003cp\u003eSystemic or autoimmune diseases\u003c/p\u003e\n \u003cp\u003eCancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e221 (53.5)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e133 (32.2)\u003c/p\u003e\n \u003cp\u003e88 (21.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003eElderly\u003csup\u003e\u0026amp;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e111 (26.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003ePregnant\u003csup\u003e⁑\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e81 (19.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003eVaccine types, initial two shots, count (%)\u003cstrong\u003e\u003csup\u003e#\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003eAstraZeneca (ChadOx1-S)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e151 (8.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003ePfizer/BioNTech (BNT162b2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e333 (19.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003eSinopharm (BBIBP-CorV)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e1158 (67.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003eSputnik V (Gam-COVID-Vac)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e67 (3.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003eAntibody response after two shot initial vaccination, count (%)^\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003eResponse\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e838 (80.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 472px;\"\u003e\n \u003cp\u003eNo response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e205 (19.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNotes: \u0026dagger;-percent calculated within total; \u0026Dagger;-percent calculated within population group; \u003csup\u003e\u0026para;\u003c/sup\u003e-included medical doctors, nurses, nurse assistants serving COVID-19 patients, radiologists, laboratory technicians collected samples, ambulance drivers and hospital porters, ward serving personnel, health officers from the emergency ward, and epidemiologists; \u003csup\u003e⁋\u003c/sup\u003e-included police and security officers, officers of emergency service, personnel of hospital kitchen, inspectors, and administrative and service workers; \u003csup\u003e\u0026amp;\u003c/sup\u003e-patients aged \u0026ge; 60 years; \u003csup\u003e⁑\u003c/sup\u003e\u003cstrong\u003e-\u003c/strong\u003e12 \u0026ndash; 36 weeks of pregnancy at the time of initial vaccination; #- the distribution of vaccine types was based on the immunization priorities identified by the Government (for details, see Supplementary Table 1);\u0026nbsp; ^-there were available data from 1103 vaccinees. Abbreviations: M, mean; SD, standard deviation; CI95, 95% confidence interval of variables\u003c/p\u003e\n\u003cp\u003eThe follow-up flow chart is shown in Figure 1\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eData on infection, hospitalization, vaccination, and fatal outcomes\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants who had positive PCR tests for SARS-CoV-2 from the fourth week after the first dose of the initial vaccine series were considered infected. Reinfection was determined when a PCR-confirmed SARS-CoV-2 infection was diagnosed in participants who had recovered from their first infection and had passed at least 90 days (12 weeks).[12] Data on vaccinations, infections, hospitalizations, and fatal outcomes were obtained from national health registry operators using participants\u0026apos; national registration IDs. We accessed individual data with the necessary permissions, including PCR-confirmed infections and reinfections from the Gerege digital database (Gerege MedTech LLC, https://gerege.mn/en/gerege-medtech), vaccination information from the General Health Insurance Authority of Mongolia (https://vis.health.gov.mn/), and hospital admission dates, diagnoses, and outcomes from the national health database of the Center for Health Development (https://hdc.gov.mn). Hospital services were provided following the \u0026quot;Interim Guidelines for the Diagnosis and Treatment of Coronavirus Infections (COVID-19)\u0026quot; issued by the Ministry of Health in Mongolia, which were developed based on WHO recommendations.[13, 14] This document states that medical care providers hospitalized patients with moderate or severe diseases, as well as those with known chronic comorbidities, regardless of the severity of their condition.\u003c/p\u003e\n\u003cp\u003eWe tracked the time in weeks for infection, hospitalization, and fatal outcomes starting from the day after the second dose of the vaccine was administered. Supplementary Table 1 shows the distribution of vaccine types administered for the initial series of vaccination among population groups prioritized by immunization strategy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eData analysis\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe distribution of nominal or ordinal variables among exposure groups was analyzed using Pearson\u0026rsquo;s chi-square (\u0026chi;\u0026sup2;) test. The infection hospitalization rate (IHR) was calculated as the percentage of hospitalization cases among new infection cases. The overall risk of being infected or hospitalized was assessed through logistic regression, employing Fisher\u0026rsquo;s exact test, odds ratio (OR), and relative risk (RR). The optimal cut-point (OCP) for age was determined using the Youden index (J), derived from the coordinates of the receiver operating characteristics (ROC) curve. To compare hazards across different study groups, we employed the Kaplan-Meier survival function using the Log Rank (LR) test expressed in chi-square (c\u003csup\u003e2\u003c/sup\u003e) along with Cox regression to determine the exponentiation of the B coefficient (Exp(B)) expressed in hazard ratio (HR) for follow-up within 80 weeks after the initial vaccination.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eDuring the 80-week follow-up, we identified 839 new cases of infection, represented by 49.1% of all participants. We observed a significant increase in the cumulative rate of new infections between the 12-week and 48-week intervals (Figure 2A). However, the prevalence of new infections began to decline after reaching the 24-week milestone (Figure 2B).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eRisks and hazards of new infection \u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe risk of new infections within 80 weeks of observation for populations prioritized for vaccination was comparable, with FWs experiencing an increased RR compared to other groups at all follow-up milestones (Supplementary Figure 1A).\u003c/p\u003e\n\u003cp\u003eFWs in urban and rural health facilities, as well as those in occupational risk groups, showed no significant differences in new infection rates during all milestones of the observation period (p \u0026gt; 0.05). Similarly, the antibody response rate following the initial vaccination was not associated with risk to new infections.\u003c/p\u003e\n\u003cp\u003eNo significant risk of new infections was found during the follow-up period for participants who were at higher risk for severe COVID-19 due to factors such as immunocompromising conditions, aging, and pregnancy. However, an increased risk was observed in pregnant women who were between 12 and 36 weeks of pregnancy at the time of initial vaccination, during the first 12 weeks following their initial immunization (OR = 6.1; RR = 5.2; p \u0026lt; 0.001).\u003c/p\u003e\n\u003cp\u003eIndividuals who received the Pfizer BioNTech and Sputnik V vaccines showed a reduced risk of new infection since the observation milestone of a 24-week compared to those who received the AstraZeneca and Sinopharm CorV vaccines (Supplementary Figure 1B).\u003c/p\u003e\n\u003cp\u003eThe new infection rate in male and female participants and participants of various age strata was comparable since the observation milestone of a 24-week. Furthermore, we found the optimal cut-points (OCP) for age, adjusted for sex, using receiver operating characteristic (ROC) analysis at the 24-week and 80-week observation milestones (Supplementary Figure 2). We then compared the relative risk of new infections across sex-adjusted age groups. Our analysis revealed an increased risk of new infections among younger female participants, specifically those under 50 years of age at 24 weeks and under 57 years of age at 80 weeks (Supplementary Figures 1C).\u003c/p\u003e\n\u003cp\u003e\u003cbr /\u003e The mean infection-free time during the observation gradually decreased, reaching 52.1 \u0026plusmn; 0.7 weeks at the 80-week milestone (Supplementary Figures 3A). The hazard function for infection varied significantly across the different population groups prioritized for immunization. This analysis identified FWs as the population group most susceptible to new infections. As expected, the increased hazard ratio (HR) for FWs compared to other population groups remained consistent at all observation milestones (Figure 3A). At any observation milestones, FWs' residence and occupational risk were not associated with the hazard function for new infections.\u003c/p\u003e\n\u003cp\u003eDuring the 12-week observation period, pregnant women were the most susceptible to new infection among the IRP subgroup (c\u003csup\u003e2\u003c/sup\u003e = 22.9; HR = 5.5; p\u0026lt; 0.001).\u003c/p\u003e\n\u003cp\u003eNo significant hazard ratio for cumulative new infections was observed within 80 weeks when comparing different population groups based on the types of vaccine administered during the initial vaccination. However, recipients of the Pfizer BioNTech or Sputnik V vaccines showed a significantly shorter infection-free period and a lower hazard ratio of new infections than recipients of the AstraZeneca ChadOX1-S or Sinopharm vaccines since observation milestones of 24 weeks (Figure 3B). The seroconversion state after initial vaccination showed no significant hazard ratio at all follow-up milestones.\u003c/p\u003e\n\u003cp\u003eThe age of participants showed a significantly declined impact on the hazard function for new infections beginning with the 24-week observation milestone (Figure 3C) with especially increased HR in subjects aged 20 \u0026ndash; 59 years (Figure 3D). Female participants, compared to males, showed an increased HR to new infections starting from the 24-week milestone (Figure 3E).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSex-adjusted age OCPs regarding the risk of new infection (Supplementary Figure 5) also demonstrated significantly increased differences for infection-free time and hazard ratio at observation milestones 24 (Supplementary Figure 4A) and 80 (Supplementary Figure 4B) weeks.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eRisks and hazards of hospitalization among various population groups\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe hospitalization rate during follow-up mirrored the new infection rate, except that the increase in cumulative hospitalization cases persisted until the 24-week milestone (Figures 2C and 2D), but not beyond that. Interestingly, the IHR remained unchanged throughout the entire follow-up period (Figure 2E).\u003c/p\u003e\n\u003cp\u003eThe hospitalization rate significantly varied among prioritized vaccination populations over a 24-week observation period, with FWs facing a higher risk of hospitalization than other groups (Supplementary Figure 5A). The residence of FWs also influenced hospitalization rates, showing an increased risk for hospitalization among FWs in rural areas compared to those in urban areas since the observation milestone of 24 weeks (Supplementary Figure 5B).\u003c/p\u003e\n\u003cp\u003eIn the observation milestones at 24, 48, and 80 weeks, frontline workers (FWs) who had direct contact with infected patients (red-zone FWs) showed a significantly higher risk of hospitalization compared to yellow-zone FWs (Supplementary Figure 5C). Pregnant women who were between 12 and 36 weeks of pregnancy at the time of their initial vaccination showed an increased risk of hospitalization during the first 12 weeks following the vaccination compared to other IRP (OR = 5.1; RR = 1.8; p \u0026lt; 0.01).\u003c/p\u003e\n\u003cp\u003eThe hospitalization rates varied significantly depending on the type of vaccine administered during the initial vaccination period. Notably, beginning the observation milestone of 24 weeks, participants who received the Sinopharm vaccine exhibited a higher risk of hospitalization compared to those who received other types of vaccines (Supplementary Figure 5D).\u003c/p\u003e\n\u003cp\u003eThe age of participants significantly influenced their hospitalization rates beginning with the 24-week observation period, with higher-than-mean rates in the age strata of 40 \u0026ndash; 59 years (Supplementary Figures 5E). Male participants demonstrated reduced RR compared to females at all observation milestones (Supplementary Figures 5F).\u003c/p\u003e\n\u003cp\u003eThe mean-time for period from initial vaccination to hospitalization was 70.2 \u0026plusmn; 0.5 weeks (Supplementary Figure 3B). A shorter time between the initial vaccine administration and hospitalization, along with a higher HR in FWs compared to other prioritized population groups, was observed starting at 24 weeks (Figure 4A). Subgroups of frontline workers, such as those in rural areas and those in red zones, exhibited a significantly increased hazard for hospitalization starting at 24 weeks compared to their counterparts (Figures 4B and 4C, respectively).\u003c/p\u003e\n\u003cp\u003ePregnant women were discovered to be more susceptible to hospitalization than immunocompromised and elderly individuals during the 12 weeks after the initial vaccine series (c\u003csup\u003e2\u003c/sup\u003e = 10.1; HR = 4.9; p\u0026lt; 0.005).\u003c/p\u003e\n\u003cp\u003eRecipients of the Sinopharm BBIBP vaccine for the initial series of vaccination showed a significantly shorter time for hospitalization and increased HR compared to recipients of other types of vaccine beginning with the period of 24 weeks (Figure 4D).\u003c/p\u003e\n\u003cp\u003eFemale participants experienced shorter hospitalization times and higher HR than males throughout the observation periods (Figure 4E).\u003c/p\u003e\n\u003cp\u003eThe age of participants and seroconversion state after the initial vaccine series were not associated with the hospitalization.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFatal outcomes\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe observed two COVID-related deaths during the 80-week follow-up period. Both cases occurred in IRP. The first case involved a 67-year-old man, categorized as elderly, who passed away after 42 days of hospitalization. His death was caused by embolism and thrombosis of the arteries in the lower extremities, resulting from complications related to diabetes mellitus. The second case involved a 42-year-old man who had previously been treated with corticosteroids for tubulointerstitial nephritis. Patient died due to pneumonia caused by an unspecified agent.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe observed a new infection rate of 49.1% among the antibody-naïve population over an 80-week follow-up period. In this study we were not able to provide unvaccinated population for the comparison. According to Chimeddorj B et al., in late 2021, the estimated new infection rate among the vaccinated population was 62.4% (95% CI: 60.2 – 64.5%).[17] In contrast, we calculated the new infection rate for the same period, which was approximately week 36 in our cohort, and identified 689 new infection cases, resulting in a rate of 40.4%.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe found FWs at increased risk and hazard for new infections and followed hospitalizations beginning with milestone of 24 weeks compared to rest antibody naïve before vaccine population groups prioritized for mass immunization. Notably, the relative risk (RR) and hazard ratio (HR) for hospitalization were higher among FWs working in rural areas and those who had direct contact with infected patients. The susceptibility of healthcare workers (HCWs) to SARS-CoV-2 infection is documented, with special attention given to occupational risks such as HCW-to-HCW transmission, patient-to-HCW transmission, and community-to-HCW transmission.[18] A retrospective analysis of infection cases at Indraprastha Apollo Hospitals in New Delhi, India, found that SARS-CoV-2 infection occurred in 2.63% of vaccinated healthcare workers within three months of observation. [19] In our study, the infection rate among red-zone frontline workers over a 12-week period was 9.9%, which was higher than that of the Indian cohort.\u003c/p\u003e\n\u003cp\u003eWe noted an increased risk of infection and hospitalization in pregnant women who were between 12 and 36 weeks of pregnancy at the time of their initial vaccination, during the first 12 weeks following vaccination. Pregnant women face heightened risks during the pandemic due to cardiovascular, pulmonary, hormonal, and immunological changes. These factors increase susceptibility to infections and reduce tolerance to hypoxia and dyspnea. Consequently, infections with SARS-CoV-2 in pregnant women are associated with a severe disease.[20]\u003c/p\u003e\n\u003cp\u003eWe identified age cut points adjusted for sex, showing that COVID-19 significantly affected females who are under 56. A meta-analysis conducted by Pijls BG et al. (2021), which included 59 studies, found that males have a higher overall relative risk (RR) compared to females, with an RR of 1.18 (95% CI: 1.10 – 1.27). Specifically, out of the 35 studies examined, nine reported a higher risk in females (RR ranging from 0.74 to 0.99), while the remaining studies indicated an increased risk for males, with an RR ranging from 1.01 to 2.38.[21] A variation in sex steroid levels in men and women might, to some extent, explain the sex disparities in susceptibility to SARS-CoV-2, however, the underlying mechanisms are still open to speculation.[22]\u003c/p\u003e\n\u003cp\u003eIn this study, recipients of the Pfizer BioNTech or Sputnik V vaccines demonstrated a significantly lower RR and HR for new infections compared to those who received the AstraZeneca ChadOX1-S or Sinopharm vaccines after a 24-week observation period. Furthermore, individuals who received the Sinopharm vaccine showed a significantly increased risk and hazard for hospitalization. According to the Vaccine Updates document issued by the University of Melbourne in December 2022 [23], the Pfizer BioNTech vaccine demonstrated an effectiveness of 47% to 65% in preventing any new COVID-19 infections. It provided 87% to 92% effectiveness in preventing hospitalization or severe disease, and 92% effectiveness in preventing COVID-related deaths for 3 to 6 months following vaccination. However, the vaccine's effectiveness decreased after 6 months, showing only 0% to 64% prevention of new infections, 68% to 81% prevention of hospitalization or severe disease, and 70% to 84% prevention of COVID-related deaths.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe did not observe any association between the seroconversion status after the initial vaccine series and the risk of new infection or hospitalization. The hospitalization rate within the first 12 weeks among seropositive individuals was lower than that of seronegative individuals; however, no significant difference was found. The interim guideline from the Ministry of Health [14]was issued on March 18, 2021, but it has not been consistently implemented. For example, among 150 hospitalized patients observed by Batmunkh et al. [10] from October 11, 2020, to June 30, 2021, 80 were diagnosed with mild to moderate COVID-19.\u003c/p\u003e\n\u003cp\u003eThe case-fatality rate (CFR) in our cohort (0.12) was found lower than the country’s CFR (0.21), however, it was close to the findings of Chimiddorj et al. (0.100).[6] \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOur findings indicate that healthcare professionals on the frontlines of pandemics face heightened risks and hazards, particularly in resource-limited rural areas. Both the Pfizer BioNTech and Sputnik V vaccines demonstrated greater effectiveness in preventing new infections and subsequent hospitalizations, while the Sinopharm BBIBP vaccine showed lower preventive effects of hospitalization.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStudy limitations\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this study, we were unable to investigate the unvaccinated population; therefore, we did not establish the effectiveness of the initial vaccine series. The registration of hospitalizations in the country does not indicate the severity of cases, making it difficult to assess the severity of COVID-19 through hospitalization data, especially during the initial stages of the outbreak.\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eData availability statement\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe original contributions presented in the study are included in the Supplementary Material. Further inquiries can be directed to the corresponding author, or requested from the Division of Science and Technology, Mongolian National University of Medical Sciences via email ([email protected]), or via phone (+976-7775-7575 (1010)), for researchers who meet the criteria for access to confidential data.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthics Statement\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the principles of the Declaration of Helsinki. Ethical approval was obtained from the Ethical Review Committee of the Ministry of Health, Mongolia (resolutions 216, 217, and 219 dated April 6, 2021). All participants were informed about the purpose, procedures, potential risks, and benefits of the study. Written informed consent was obtained from all participants prior to data collection.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFunding statement\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eDeclaration of competing interest\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAcknowledgment\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe appreciate the Ministry of Health and the State Emergency Commission for their assistance in conducting the study. We also thank the Health Development Agency of Mongolia for providing the necessary data.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMongolia: Coronavirus Pandemic Country Profile. https://ourworldindata.org/grapher/share-people-vaccinated-covid?time=2021-04-15..latest\u0026amp;country=~MNG.\u003c/li\u003e\n\u003cli\u003eNguyen LH, Drew DA, Graham MS, Joshi AD, Guo C-G, Ma W, et al. Risk of COVID-19 among front-line health-care workers and the general community: a prospective cohort study. The Lancet Public Health. 2020;5(9):e475-e83.\u003c/li\u003e\n\u003cli\u003eAlshamrani MM, El-Saed A, Al Zunitan M, Almulhem R, Almohrij S. Risk of COVID-19 morbidity and mortality among healthcare workers working in a Large Tertiary Care Hospital. International Journal of Infectious Diseases. 2021;109:238-43.\u003c/li\u003e\n\u003cli\u003eBedston S, Akbari A, Jarvis CI, Lowthian E, Torabi F, North L, et al. COVID-19 vaccine uptake, effectiveness, and waning in 82,959 health care workers: A national prospective cohort study in Wales. Vaccine. 2022;40(8):1180-9.\u003c/li\u003e\n\u003cli\u003eGaio V, Santos AJ, Amaral P, Viana JF, Antunes I, Pacheco V, et al. COVID-19 vaccine effectiveness among healthcare workers: a hospital-based cohort study. BMJ Open. 2023;13(5):e068996.\u003c/li\u003e\n\u003cli\u003eUnderlying Medical Conditions Associated with Higher Risk for Severe COVID-19: Information for Healthcare Professionals. Centers for Disease Control and Prevention. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html; Feb. 2023.\u003c/li\u003e\n\u003cli\u003eMongolia At-A-Glance. World bank in Mongolia. World bank group. https://www.worldbank.org/en/country/mongolia [\u003c/li\u003e\n\u003cli\u003eWorld Health Organization. Country profile. Mongolia. https://www.who.int/countries/mng/ [\u003c/li\u003e\n\u003cli\u003eBatmunkh B, Otgonbayar D, Shaarii S, Khaidav N, Shagdarsuren O-E, Boldbaatar G, et al. RBD-specific antibody response after two doses of different SARS-CoV-2 vaccines during the mass vaccination campaign in Mongolia. Plos one. 2023;18(12):e0295167.\u003c/li\u003e\n\u003cli\u003eBatmunkh MU, Ravjir O, Lkhagvasuren E, Dambaa N, Boldoo T, Ganbold S, et al. Sex-adjusted approach to baseline variables demonstrated some improved predictive capabilities for disease severity and survival in patients with Coronavirus Disease 19. Inform Med Unlocked. 2022;31:100982.\u003c/li\u003e\n\u003cli\u003eHolland C, Hammond C, Richmond MM. COVID-19 and Pregnancy: Risks and Outcomes. Nursing for women's health. 2023;27(1):31-41. https://doi.org./10.1016/j.nwh.2022.11.004.\u003c/li\u003e\n\u003cli\u003eNguyen NN, Houhamdi L, Hoang VT, Delerce J, Delorme L, Colson P, et al. SARS-CoV-2 reinfection and COVID-19 severity. Emerging microbes \u0026amp; infections. 2022;11(1):894-901.\u003c/li\u003e\n\u003cli\u003eInterim guidelines for the diagnosis and treatment of coronavirus infections (Covid-19). Attachment to the order of minister of health (in Mongolian language). Ulaanbaatar: Ministry of Health; https://moh.gov.mn/uploads/files/15dc7d190950e661137e5e2707b7fd3ea31fdc22.pdf. 21 August 2020.\u003c/li\u003e\n\u003cli\u003eInterim guidelines for the diagnosis and treatment of coronavirus infections (Covid-19). Attachment to the order of Minister of Health (in Mongolian language). https://moh.gov.mn/uploads/files/15dc7d190950e661137e5e2707b7fd3ea31fdc22.pdf. In: Ministry of Health M, editor. UlaanbaatarAugust 21, 2020.\u003c/li\u003e\n\u003cli\u003eWilkinson P. Risk and Hazard. 2009. In: Public Health Textbook in Faculty of Public Health [Internet]. Health Knowledge, Faculty of Public Health. https://www.healthknowledge.org.uk/public-health-textbook/disease-causation-diagnostic/2f-environment/risk-hazard.\u003c/li\u003e\n\u003cli\u003eA User\u0026rsquo;s Guide to U.S. Vaccine Breakthrough Rates [press release]. The Rockefeller Foundation. https://www.rockefellerfoundation.org/insights/perspective/a-users-guide-to-u-s-vaccine-breakthrough-rates/2022.\u003c/li\u003e\n\u003cli\u003eChimeddorj B, Bailie CR, Mandakh U, Price DJ, Bayartsogt B, Meagher N, et al. SARS-CoV-2 seroepidemiology in Mongolia, 2020\u0026amp;#x2013;2021: a\u0026amp;#xa0;longitudinal national study. The Lancet Regional Health \u0026ndash; Western Pacific. 2023;36.\u003c/li\u003e\n\u003cli\u003eGuedes AR, Oliveira MS, Tavares BM, Luna-Muschi A, Lazari CdS, Montal AC, et al. Reinfection rate in a cohort of healthcare workers over 2 years of the COVID-19 pandemic. Scientific Reports. 2023;13(1):712.\u003c/li\u003e\n\u003cli\u003eVaishya R, Sibal A, Malani A, Prasad KH. SARS-CoV-2 infection after COVID-19 immunization in healthcare workers: A retrospective, pilot study. The Indian journal of medical research. 2021;153(5\u0026amp;6):550-4.\u003c/li\u003e\n\u003cli\u003eNtounis T, Prokopakis I, Koutras A, Fasoulakis Z, Pittokopitou S, Valsamaki A, et al. Pregnancy and COVID-19. Journal of clinical medicine. 2022;11(22).\u003c/li\u003e\n\u003cli\u003ePijls BG, Jolani S, Atherley A, Derckx RT, Dijkstra JIR, Franssen GHL, et al. Demographic risk factors for COVID-19 infection, severity, ICU admission and death: a meta-analysis of 59 studies. BMJ Open. 2021;11(1):e044640.\u003c/li\u003e\n\u003cli\u003eLott N, Gebhard CE, Bengs S, Haider A, Kuster GM, Regitz-Zagrosek V, et al. Sex hormones in SARS-CoV-2 susceptibility: key players or confounders? Nature Reviews Endocrinology. 2023;19(4):217-31.\u003c/li\u003e\n\u003cli\u003eCOVID-19. Vaccine Updates. Number 54, 22\u003csup\u003end\u003c/sup\u003e December 2022. Melbourne, Australia: The University of Melbourne; December 2022.\u003c/li\u003e\n\u003cli\u003eDeng L, Li P, Zhang X, Jiang Q, Turner D, Zhou C, et al. Risk of SARS-CoV-2 reinfection: a systematic review and meta-analysis. Scientific Reports. 2022;12(1):20763.\u003c/li\u003e\n\u003cli\u003eRahman MO, Kamigaki T, Thandar MM, Haruyama R, Yan F, Shibamura-Fujiogi M, et al. Protection of the third-dose and fourth-dose mRNA vaccines against SARS-CoV-2 Omicron subvariant: a systematic review and meta-analysis. BMJ Open. 2023;13(12):e076892.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"COVID-19 mass vaccination, relative risk, hazard function, hazard ratio","lastPublishedDoi":"10.21203/rs.3.rs-6660450/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6660450/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this study, we aimed to compare the risks and hazards of new infection and hospitalization in seronegative before-vaccination population groups and its association with sociodemographic, initial, and booster vaccination patterns.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials and Methods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe enrolled a total of 1,709 vaccinees who tested negative for anti-SARS-CoV-2 receptor binding domain (RBD) specific antibodies before receiving two doses of one of four COVID-19 vaccines. Data on vaccinations, new infections, hospitalizations and fatal outcomes during the 80-weeks follow-up were obtained from national health registry operators using participants' national registration IDs.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe observed a new infection rate of 49.1% among the antibody-naïve population over an 80-week follow-up period. We found frontline workers (FWs), especially those who worked in rural health facilities and those who worked in direct contact with infected patients (red-zone FWs) at increased risk and hazard for new infections and followed hospitalizations beginning with milestone of 24 weeks compared to rest population groups prioritized for mass immunization. Both the Pfizer BioNTech and Sputnik V vaccines demonstrated greater effectiveness in preventing new infections while the Sinopharm BBIBP vaccine showed lower preventive effects of hospitalization. We identified age cut points adjusted for sex, showing that COVID-19 significantly affected younger females.\u003c/p\u003e","manuscriptTitle":"Risks and Hazards of Post-Vaccine SARS-CoV-2 Infection in Antibody Naive Populations during the Mass Vaccination Campaign Against COVID-19 in Mongolia","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-29 14:47:40","doi":"10.21203/rs.3.rs-6660450/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewersInvited","content":"","date":"2025-06-24T04:48:07+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-18T15:58:47+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-05-30T19:27:31+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-29T00:23:06+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2025-05-29T00:21:58+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"67468df8-9c3a-4105-896f-e9f0d77125e6","owner":[],"postedDate":"June 29th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-06-29T14:47:40+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-29 14:47:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6660450","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6660450","identity":"rs-6660450","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}