Impact of a delayed second dose of mRNA vaccine (BNT162b2) and inactivated SARS-CoV-2 vaccine (CoronaVac) on risks of all-cause mortality, emergency department visit, and unscheduled hospitalization

Abstract

Background Safety after the second dose of the SARS-CoV-2 vaccine remains to be elucidated, especially among individuals reporting adverse events after their first dose. This study aims to evaluate the impact of a delayed second dose on all-cause mortality and emergency services. Methods A territory-wide, retrospective cohort of people who had completed two doses of mRNA (BNT162b2) or inactivated SARS-CoV-2 (CoronaVac) vaccine between February 23 and July 3, 2021, in Hong Kong was analyzed, with linkage to electronic health records retrieved from the Hong Kong Hospital Authority. Vaccine recipients were classified as receiving a second dose within recommended intervals (21–28 days for BNT162b2; 14–28 days for CoronaVac) or delayed. Study outcomes were all-cause mortality, emergency department (ED) visits, and unscheduled hospitalizations within 28 days after the second dose of vaccination. Results Among 417,497 BNT162b2 and 354,283 CoronaVac second dose recipients, 3.8% and 28.5% received the second dose beyond the recommended intervals (mean 34.4 and 31.8 days), respectively. During the study period, there were < 5 daily new cases of COVID-19 infections in the community. Delaying the second dose was not associated with all-cause mortality (hazard ratio [HR] = 1.185, 95% CI 0.478–2.937, P = 0.714), risk of ED visit (HR = 0.966, 95% CI 0.926–1.008, P = 0.113), and risk of unscheduled hospitalization (HR = 0.956, 95% CI 0.878–1.040, P = 0.294) compared to that within the recommended interval for CoronaVac recipients. No statistically significant differences in all-cause mortality (HR = 4.438, 95% CI 0.951–20.701, P = 0.058), ED visit (HR = 1.037, 95% CI 0.951–1.130, P = 0.411), and unscheduled hospitalization (HR = 1.054, 95% CI 0.867–1.281, P = 0.597) were identified between people who received a second dose of BNT162b2 within and beyond the recommended intervals. Conclusions No significant association between delayed second dose of BNT162b2 or CoronaVac and all-cause mortality, ED visit, and unscheduled hospitalization was observed in the present cohort. Regardless of the recommended or delayed schedule for SARS-CoV-2 vaccination, a second dose of both vaccines should be administered to obtain better protection against infection and serious disease. The second dose should be administered within the recommended interval following the manufacturer’s product information, until further studies support the benefits of delaying vaccination outweighing the risks.

Effects of spike protein and toxin-like peptides found in COVID-19 patients on human 3D neuronal/glial model undergoing differentiation: Possible implications for SARS-CoV-2 impact on brain development

“…The observed OLIG1 downregulation induced by Spike in short-term differentiated cultures and by Peptides in long-term differentiated cultures, as well as the upregulation of MBP mainly elicited by Peptides in both short- and long-term differentiated cultures, suggest a dysregulation of oligodendrocyte development and maturation. Indeed, OLIG1 controls oligodendrocyte precursor differentiation into myelin-forming oligodendrocytes during development, and together with SOX10, activates MBP transcription [80] .…”

Risk of acute liver injury following the mRNA (BNT162b2) and inactivated (CoronaVac) COVID-19 vaccines

“…Records were linked using a unique de-identified mapping key. These 2 linked sources of data have been extensively used for COVID-19 vaccine pharmacovigilance research [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] and drug-induced liver injury research. 26 …”

“…Conditional Poisson regression models weighted by IPTW were fitted to estimate the incidence rate ratio (IRR) and 95% confidence interval (CI) of ALI risks for BNT162b2 or CoronaVac recipients relative to patients with SARS-CoV-2 infection.The severity of ALI following vaccination and SARS-CoV-2 infection was assessed by the following parameters: peak ALT level, peak AST level, Drug-Induced Liver Injury Network (DILIN) scale(37), the De Ritis ratio (i.e., AST: ALT ratio which has been associated with poor prognosis in SARS-CoV-2 infection(38,39), proportion of patients requiring hospitalization, and intensive care unit (ICU) admission. Follow-up information about the ALI such as the proportion of patients who would had a delayed second dose (>42 days after the first dose of BNT162b2 or >56 days after the first dose of CoronaVac)(24), incident AIH and liver diseases among those with a follow-up period of at least 28 days after their ALI was explored. Differences in ALI severity and follow-up information between the two vaccines were compared using ordered or binary logistic regressions adjusting for baseline characteristics.…”

Adverse events of special interest and mortality following vaccination with mRNA (BNT162b2) and inactivated (CoronaVac) SARS-CoV-2 vaccines in Hong Kong: A retrospective study

“…Various demographic and clinical characteristics of the vaccinated individuals were considered in this analysis. As reported by previous studies [ 40 , 45 , 49 – 51 ], baseline covariates that were potential risk factors of AESIs were chosen. The following covariates were weighted between BNT162b2 and CoronaVac recipients for each dose (as elaborated the “Statistical analyses” section below): age, sex, any previous SARS-CoV-2 infection (defined as ever a positive result on the SARS-CoV-2 reverse transcription polymerase chain reaction [RT-PCR] test before COVID-19 vaccination), pre-existing comorbidities documented from 2018 (myocardial infarction [MI], peripheral vascular disease, cerebrovascular disease, coronary artery disease [CAD], chronic obstructive pulmonary disease, dementia, paralysis, diabetes with and without chronic complications, hypertension, chronic renal failure, mild and moderate-severe liver disease, ulcers, rheumatoid arthritis or other inflammatory polyarthropathy, acquired immune deficiency syndrome, malignancy, and metastatic solid tumor), medication use in the past 90 days (including renin–angiotensin-system agents, beta blockers, calcium channel blockers, diuretics, lipid-lowering agents, insulin, antidiabetic drugs, anticoagulants, antiplatelets, hormonal agents, antidepressants, non-steroidal anti-inflammatory drugs, drugs for gout, antiepileptic drugs, antiviral drugs, antibacterial drugs, and immunosuppressants), venue for vaccination (community vaccination center, clinic, or other), and the time interval between the administration of the first and second doses.…”