Immunogenicity and Safety of the Coronavac Inactivated SARS-CoV-2 Vaccine in People with Underlying Medical Conditions: A Retrospective Study

Background: People living with chronic disease, particularly seniors older than 60 years old, are lagging behind in the national COVID-19 vaccination campaign in China due to uncertainty of safety and effectiveness. However, this special population made up of most severe symptom and death cases among SARS-CoV-2 infected patients and should be prioritized in vaccination program. Safety and immunogenicity data of COVID-19 vaccines in people with underlying medical conditions are needed to address the vaccine hesitation in this special population. Methods: In this cohort study, volunteers aged 40 years and older, had received two doses of CoronaVac inactivated vaccines (3-5 weeks interval), been healthy or with at least one of the six diseases: coronary artery disease (CAD), hypertension, diabetes mellitus (DM), chronic respiratory disease (CRD), obesity and cancer, were recruited from 4 study sites in China. The primary safety outcome was the incidence of adverse events within 14 days after each dose of vaccination. The primary immunogenic outcome was the geometric mean titre (GMT) of neutralising antibodies to live SARS-CoV-2 virus at 14-28 days, 3 months, and 6 months after two-dose vaccination. This study is registered with ChiCTR.org.cn (ChiCTR2200058281).Findings: Among 1,302 volunteers screened between Jul 5 and Dec 30, 2021, 969 were eligible and enrolled in our cohort, including 740 living with underlying medical conditions and 229 as healthy control. All of them formed the safety cohort. The overall incidence of adverse events was 150 (20.27%) of 740 in the comorbidities group versus 32 (13.97%) of 229 in the healthy control, with significant difference (p=0.0334). The difference was mainly contributed by fatigue and injection-site pain in some disease groups. Most adverse events were mild (Grade 1). We did not observe any serious adverse events related to vaccination. By day 14-28 post vaccination, the seroconversion rates and geometric mean titre (GMT) of neutralising antibody showed no significant difference between disease group and healthy control, except CAD group (p=0.03) and CRD group (p=0.04) showed slight reduction. By day 90, the neutralising antibody GMTs were significantly reduced in each group, with no significant difference between diseases and healthy group. By day 180, the neutralising antibody continued to decrease in each group, but with slower declination. Most people showed detectable SARS-CoV-2-specific CD4+ T cell response at day 90 and day 180 without significant difference between disease groups and healthy controls. Similar trend was observed for CD8+ T cell response but with low overall positive rate among all groups. Interpretation: For people living with chronic disease especially seniors older than 60 years, the CoronaVac vaccines are as safe as in healthy people. Although the immunogenicity is slightly different in subgroup of some diseases compared with that of the healthy population, the overall trend was consistent. Our findings highlight the clinical data to address vaccine hesitancy for seniors and people living with chronic diseases.Trial Registration Details: This study is registered with ChiCTR.org.cn, ChiCTR2200058281. Funding Information: This study was supported by the Yunnan Provincial Science and Technology Department (202102AA100051 and 202003AC100010, China) and Sinovac Biotech Ltd (PRO-nCOV-4004).Declaration of Interests: This study is sponsored by Sinovac Biotech Ltd. Z.Z. on behalf of Yunnan University as an investigator has received research funding for this study from Sinovac Biotech Ltd.Ethics Approval Statement: The study protocol and informed consent form were approved by the Committee on Human Subject Research and Ethics of Yunnan University (CHSRE2021021). This study was conducted in accordance with the requirements of Good Clinical Practice of China and the International Conference on Harmonization.