key: cord-0832552-mwfyo4yp authors: Ye, Chanyuan; Lv, Yan; Kuang, Wei; Yang, Lisha; Lu, Yingfeng; Gu, Jueqing; Ding, Feng; Shen, Huajiang; Yang, Yida title: Inactivated vaccines prevent severe COVID‐19 in patients infected with the Delta variant: A comparative study of the Delta and Alpha variants from China date: 2022-04-19 journal: J Med Virol DOI: 10.1002/jmv.27759 sha: 8545dcee5f315155dea50719253f57ae021229ea doc_id: 832552 cord_uid: mwfyo4yp The Delta variant has gradually replaced the Alpha variant as the major strain of SARS‐COV‐2 infection worldwide. We extracted the clinical characteristics and outcomes information about 381 hospitalized patients infected with Delta variant and compared them with 856 patients diagnosed with Alpha variant infection in Zhejiang Province. The majority (85.3%) of patients infected with the Delta variant had received inactivated vaccine. The patients' condition was generally mild. Most of them were mild (35.7%) and common (62.7%) types. Only six patients (1.5%) were severe/critical types. During the follow‐up period, patients infected with the Delta variant had longer hospital stays than the Alpha variant (24 [21–26] vs. 18 [14–24], p < 0.001). In addition, the unvaccinated patients infected with the Delta variant had a higher proportion of severe/critical cases than vaccinated patients (11.11% vs. 0.92%, p = 0.024) and a higher usage rate of glucocorticoids (38.89 vs. 14.77%, p = 0.017) and antibiotics (55.56% vs. 32.31%, p = 0.042) during hospitalization. The vaccine's efficacy against severe COVID‐19 did not diminish over time for patients who received two doses of the inactivated vaccine. The disease types and clinical manifestations were generally mild in patients infected with the Delta variant, possibly associated with widespread vaccination with inactivated vaccines in China. The basic information, epidemiology, laboratory examinations, clinical manifestations, treatments, and prognosis of all patients were extracted from the electronic case database of the Affiliated Hospital of Shaoxing University. The data were entered into a computerized standardized data collection form by several infectious disease physicians specializing in diagnosing and treating COVID-19 and verified by two other experienced clinicians. The follow-up time for outcomes of both groups was 31 days. The Delta cohort was followed until January 10, 2022, and the Alpha cohort was followed until February 16, 2020. All confirmed patients met the diagnostic criteria in the Diagnosis and Treatment of COVID-19 of China (Seventh Edition), 8 according to which COVID-19 patients were classified into mild, common, severe, and critical types. Discharge criteria: (1) temperature returned to normal for more than 3 days; (2) respiratory symptoms improved significantly; (3) the lung imaging absorbed; (4) two consecutive negative nucleic acid tests of respiratory specimens (at least 24 h apart). Those who meet the above conditions can be discharged from the hospital. Vaccination: based on the information on the home page of the patients' electronic medical records, we extracted the information on the type of vaccine, dose, and time of vaccination. Most of the patients were vaccinated with the inactivated vaccine CoronaVac/ BBIBP-CorV. The second dose needs to be completed within 3-8 weeks, and the booster dose can be administered 6 months after the second injection. Continuous measurement data with normal distribution were expressed as mean ± standard deviation, and a t test was applied for comparison between groups. Measurement data with non-normal distribution were expressed as median and quartile (Q1-Q3), and the Mann-Whitney U test was used for comparison. Categorical variables were expressed as percentages (%) and compared using χ 2 tests, taking the results of Pearson χ 2 , continuity correction, or Fisher's exact test as appropriate. Statistical significance was defined as a p value less than 0.05. The figures were drawn using GraphPad Prism 8.0 software. This round of epidemic spread fast. The number of infected people reached nearly 400 in just over 10 days, as shown in Supporting Information: Figure 1 . We collected 381 COVID-19 patients as of December 26, 2021, and each patient was identified as infected with the Delta variant by whole-genome sequencing. Among them, 173 (45.4%) were male, and 208 (54.6%) were female, with a median age of 52 (38-61) years, which was older compared to patients infected with the Alpha variant (p < 0.001). In the Delta group, 26.8% were ≥60 years, and 7.9% were <18 years, which accounted for a higher proportion than those infected with the Alpha variant (p < 0.001). Common clinical manifestations included cough (65.6%), fever (40.9%), expectoration (31.0%), sore throat (22.6%), fatigue (16.3%) and nasal congestion (12.6%), and rare symptoms included muscle aches (7.3%), headache (6.6%), diarrhea (5.0%), and so forth. Most of the Delta 381 cohort patients were common type (62.7%), 35.7% were mild, and only 6 (1.5%) were severe/critical. The proportion of severe/critical type patients was significantly lower than that of the Alpha cohort (18%), p < 0.001. During hospitalization, 65 (17.0%) received glucocorticoid therapy, which was comparable to the Alpha cohort (p = 0.643), but the antibiotic usage rate was significantly lower (41.4% vs. 33.9%, p = 0.013). In the Delta group, 94.2% received antiviral therapy, almost all patients received Abidol antiviral regimen, and 2 (0.5%) patients underwent invasive mechanical ventilation during hospitalization for progressive disease. Both cohorts were followed up for 31 days, and no patients experienced shock or death during the observation period in the Delta group. As of the follow-up date, 48.6% and 59.8% of the Alpha and Delta cohorts were discharged from the hospital, respectively, with p < 0.001. The specific number of daily discharges is shown in Supporting Information: Figure 2 . The median length of hospital stay in the Delta cohort was 24 (21-26) days, which was significantly higher than that in the Alpha cohort of 18 (14) (15) (16) (17) (18) (19) (20) (21) (22) (23) (24) , p < 0.001. (Table 3) By comparison with the Alpha cohort, we found that the Delta cohort was milder in clinical presentations, abnormal laboratory tests, and T A B L E 1 Comparison of demographic and clinical characteristics between patients infected with the Alpha and Delta variants were also significantly lower than those in the unvaccinated group. (Table 4 ). vaccination time was unknown. We found no significant differences in baseline characteristics, clinical outcomes, viral shedding time, and laboratory tests between the two groups ( Table 5 ). The data of this study were all from Zhejiang Province, China, and were collected by the same group of doctors, which greatly reduced the data collection errors and provided good comparability. The Delta variant has been studied by many countries. Many data [9] [10] [11] [12] need to be paid more attention. 13, 14 Many previous studies, 15 have shown that COVID-19 often causes liver damage. In a multicenter retrospective study in China, 16 liver enzyme levels were elevated after admission in 28.2% of patients. Data from a prospective study 17 of 217 COVID-19 patients without previous liver diseases showed that 58% of patients observed any liver biochemical abnormality at admission, with 42% having elevated aspartate aminotransferase, 37% elevated gammaglutamyl-transferase, and 27% elevated alanine aminotransferase. By comparing it to the Alpha group, the proportion of patients with abnormal liver function in the Delta group was significantly lower in our study, which indirectly suggested that the Delta variant had less liver damage. Besides, the Delta cohort had lower rates of abnormalities in other common clinical tests than that of Alpha, which differed from many other studies. 18 Since most patients in the Delta cohort have been vaccinated with inactivated vaccines, we thought it had something to do with the COVID-19 vaccination. By further subgrouping, we found that vaccinated patients did have a lower probability of severe illness and a lower rate of glucocorticoids and antibiotics use, which would explain why the severity of the Delta-infected patients in our study was milder than Alpha ( Figure 1 ). Before that, A study in Scotland 9 showed that the risk of hospital T A B L E 5 Comparison between patients who had been vaccinated for more than 6 months since the second dose and those less than 6 months. Note: Data are presented as medians (interquartile ranges, IQR), mean ± standard deviation, and n (%). Chanyuan Ye designed the study and drafted the manuscript; Yida The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request. http://orcid.org/0000-0002-9673-0969 F I G U R E 1 Study profile. When comparing the characteristics of the vaccinated and unvaccinated cohorts in the Delta group, 38 patients were not included because of the unknown history of COVID-19 vaccination. Of the vaccinated patients, 303 received two doses of the inactivated COVID-19 vaccine, and when comparing vaccine efficacy over time, 69 patients were not included due to a lack of information on the timing of vaccination Clinical features of patients infected with 2019 novel coronavirus in Wuhan COVID-19 vaccine strategies must focus on severe disease and global equity The 2020 race towards SARS-CoV-2 specific vaccines Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: a randomised, double-blind, placebo-controlled, phase 1/2 trial Safety and immunogenicity of an inactivated COVID-19 vaccine, BBIBP-CorV, in people younger than 18 years: a randomised, double-blind, controlled, phase 1/2 trial Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy children and adolescents: a double-blind, randomised, controlled, phase 1/2 clinical trial General office of national health and health commission SARS-CoV-2 Delta VOC in Scotland: demographics, risk of hospital admission, and vaccine effectiveness The biological and clinical significance of emerging SARS-CoV-2 variants Transmission, viral kinetics and clinical characteristics of the emergent SARS-CoV-2 Delta VOC in Guangzhou The global epidemic of the SARS-CoV-2 Delta variant key spike mutations and immune escape Trends in COVID-19 cases, emergency department visits, and hospital admissions among children and adolescents aged 0-17 years-United States Effectiveness of Pfizer-BioNTech and moderna vaccines in preventing SARS-CoV-2 infection among nursing home residents before and during widespread circulation of the SARS-CoV-2 B.1.617.2 (Delta) variant-National Healthcare Safety Network COVID-19 and the liver Liver enzyme elevation in coronavirus disease 2019: a multicenter, retrospective, crosssectional study Liver function test abnormalities at hospital admission are associated with severe course of SARS-CoV-2 infection: a prospective cohort study Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum Immune evasion of SARS-CoV-2 emerging variants: what have we learnt so far? Letter from China: response after the first wave of COVID-19 The Delta SARS-CoV-2 variant has a higher viral load than the Beta and the historical variants in nasopharyngeal samples from newly diagnosed COVID-19 patients Elevation of blood glucose level predicts worse outcomes in hospitalized patients with COVID-19: a retrospective cohort study Association of blood glucose control and outcomes in patients with COVID-19 and pre-existing type 2 diabetes Inactivated vaccines prevent severe COVID-19 in patients infected with the Delta variant: a comparative study of the Delta and Alpha variants from China