key: cord-0289670-6p3rmhyt
authors: Wang, J.; Huang, P.; Yi, Y.; Zhu, M.; Li, J.; Yi, C.; Song, Y.; Li, Z.; Tao, B.; Hu, Z.
title: Effectiveness of inactive COVID-19 vaccines against severe illness in B.1.617.2 (Delta) variant-infected patients in Jiangsu, China
date: 2021-09-05
journal: nan
DOI: 10.1101/2021.09.02.21263010
sha: 41a4a120cd777825999e432001b4c950b5069a24
doc_id: 289670
cord_uid: 6p3rmhyt

The SARS-CoV-2 B.1.617.2 (Delta) variant has caused a new surge in the number of COVID-19 cases. The effectiveness of vaccines against this variant is not fully understood. Using data from a recent large-scale outbreak of COVID-19 in China, we conducted a real-world study to explore the effect of inactivated vaccine immunization on the course of disease in patients infected with Delta variants. We recruited 476 confirmed cases over the age of 18, of which 42 were severe. After adjusting for age, gender, and comorbidities, patients who received two doses of inactivated vaccine (fully vaccinated) had an 88% reduced risk in progressing to the severe stage (adjusted OR: 0.12, 95% CI: 0.02- 0.45). However, this protective effect was not observed in patients who only received only one dose of the vaccine(adjusted OR: 1.11, 95% CI: 0.51- 2.36). The full immunization offered 100% protection from a severe illness among women. The effect of the vaccine was potentially affected by underlying medical conditions (OR: 0.26, 95% CI: 0.03-1.23). This is the largest real-world study confirming the effectiveness of inactive COVID-19 vaccines against severe illness in Delta variant-infected patients in Jiangsu, China.

interval between the second shot and disease onset was at least 14 days. We categorized 105 patients into three groups: unvaccinated, partially vaccinated, and fully vaccinated 106 according to the immunization history. Patients would also be considered unvaccinated 107 if they had received one dose but the time interval between the first shot and illness 108 onset was less than 14 days. Likewise, patients, who had received two vaccine shots, 109 however, the time interval between the second shot and illness onset was less than 14 110 days, would be considered partially vaccinated [22] . 111

Outcomes 113

The primary outcome of interest was the progression to severe illness in patients 114 All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted September 5, 2021. ; https://doi.org/10.1101 https://doi.org/10. /2021 infected with the Delta variant. As defined by the "Guideline of and Treatment (trial version 8)" in China, severe illness of COVID-19 for adult patients 116 should meet one of the following criteria: 1) respiratory rate ≥30 breaths/min, 2) at 117 rest, the oxygen saturation of fingers during air inhalation is ≤93%, 3) arterial partial 118 pressure of oxygen (PaO2) / oxygen uptake concentration (FiO2) ≤300 mmHg, 4) 119 clinical symptoms were aggravated, and the pulmonary imaging showed that the lesion 120 progressed more than 50% within 24-48 hours. Patients with critical COVID-19 were 121 those who had developed respiratory failure requiring mechanical ventilation or had 122 evidence of shock or other organ dysfunctions that needed transferring to the intensive 123 care unit (ICU) [23] . The most severe condition of the patients during the hospitalization 124 was recorded. In this study, we analyzed severe and critical cases together. 125

Covariates 127

Covariates that have been confirmed to or possibly have a role in disease progression 128 were considered, including age, gender, comorbidities, vaccination status, baseline 129 SARS-CoV-2 viral load, and therapies (corticosteroids, intravenous immunoglobulin, 130 and aerosol interferon-a). Age was categorized into two groups: 18-59 years and >=60 131 years. Clinical parameters such as blood lymphocyte counts, C-reactive protein (CRP) , 132

Interleukin-6 (IL-6), D-dimer, lactate dehydrogenase (LDH), and pulmonary 133 involvement were more appropriate to an index of disease severity rather than the risk 134 factors, thereby were not included in the multivariable regression analysis. All cases 135 involved in this study were vaccinated with the inactivated vaccine. 136 137

All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in severe illness, the proportion of unvaccinated, partially vaccinated, and fully vaccinated 162 All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted September 5, 2021. ; https://doi.org/10.1101/2021.09.02.21263010 doi: medRxiv preprint was 64.29%, 0.95%, and 4.76%, respectively. (Table 1) . 163 164

Initial symptoms were fever, dry cough, sputum production, chest tightness or shortness 166 of breath, nausea or vomiting, abdominal pain or diarrhea, loss of smell or taste, 167 myalgia, stuffy or runny nose, headache or dizziness, fatigue, and pharyngeal 168 discomfort. Patients with severe illness had a higher proportion of fever (61.90% vs. 169 31.87%) and shortness of breath (19.05% vs. 3.46%) than those without severe illness. 170

Besides, the patients with severe illness were commonly cough, sputum production, 171 nausea or vomiting, abdominal pain or diarrhea, myalgia, headache, or dizziness, but 172 the difference was not statistically significant (Table 1) . 173 174

As shown in Table 1 , patients who progressed to severe illness had relatively higher 176 levels of baseline CRP, procalcitonin, IL-6, aspartate aminotransferase, alanine 177 aminotransferase, urea nitrogen, creatinine, creatine kinase, myoglobin, troponin I, 178 LDH, prothrombin time, and D-dimer. Baseline levels of the white blood cell count, 179 lymphocyte count, neutrophil count, hemoglobin, total bilirubin, CK-MB, and 180 fibrinogen degradation products were similar between the two groups. Patients without 181 severe illness had a higher IgG and IgM antibody to SARS-CoV-2. There were no 182 significant differences in viral load threshold cycle value (Ct) detecting ORF1ab and O 183 gene. 184 185

Severe illness occurred in 14.7% (27/184), 12.4% (13/105), and 1.1% (2/187) of the 187 All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in 

The risk of progressing to severe illness reached 0 in fully vaccinated persons without 211 underlying medical conditions, age≥60 years or female. Only 14 elderly patients were 212 All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted September 5, 2021. ; https://doi.org/10.1101/2021.09.02.21263010 doi: medRxiv preprint substantially decreased in fully vaccinated patients. After adjusting for age, sex, and 238 underlying medical conditions, the risk reduction remained significant, with an 88% 239 risk reduction. This is the largest real-world study to confirm the effectiveness of 240 inactivated vaccines in preventing severe illness caused by Delta variants in China. 241 242 It is well known that underlying comorbidities and old age are risk factors for severe 243 illness in SARS-CoV-2 infected patients [30] . This is consistent with findings from our 244 study. Severe illness did not occur in fully vaccinated patients without underlying 245 medical conditions (100% protection). Both of the two fully vaccinated patients who 246 developed severe illness had underlying diseases. Interestingly, 100% protection was 247 also found in elderly patients that had been fully vaccinated. Since only 14 elderly 248 patients were fully vaccinated, the protective effect of inactive vaccines might be 249 overestimated in this study. Fully vaccinated women were 100% prevented from 250 progressing to severe illness, while fully vaccinated men had only 81% reduced risk. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted September 5, 2021. ; https://doi.org/10.1101/2021.09.02.21263010 doi: medRxiv preprint relatively higher immunity may be necessary, which generally would be achieved after 263 a full vaccination [8] . perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted September 5, 2021. ; https://doi.org/10.1101 https://doi.org/10. /2021 2. COPD, chronic obstructive pulmonary disease; CK-MB, creatine kinase-myocardial band; eGFR, estimated glomerular filtration rate; FDPs, fibrinogen degradation products; Ct, cycle threshold; SARS-COV-2, severe acute respiratory syndrome coronavirus 2.

3. the Ct value from quantitative reverse transcription polymerase chain reaction was used to represent the viral load of SARS-COV-2 in the upper respiratory tract. 

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