Of the 357 Delta COVID-19 patients included for analysis, 105 (29.4%), 72 (20.2%), and 180 (50.4%) were unvaccinated, partially vaccinated and fully vaccinated, respectively. The types of inactivated COVID-19 vaccines used were CoronaVac (Sinovac Biotech, Beijing, China), BBIBP-CorV (Sinopharm, Beijing, China), and KCONVAC (BioKangtai, Shenzhen, China), accounting for 73.3%, 26.5%, and 0.2% of the vaccination shots, respectively. The median age was 49 (IQR: 39–65) years old, and 108 (30.3%) of the patients were older than 60 years. There were no significant differences in sex, diabetes, asthma, autoimmune diseases, most clinical symptoms, and levels of C-reactive protein, lymphocytes, LDH, and D-dimer among patients with different vaccination status (Table 1) at the time of admission. Interleukin-6 level was significantly lower in fully vaccinated patients (P < 0.001, Table 1).

There were significant differences in the VOI and POI in whole lung and the chest CT scores in patients with different vaccination status (P < 0.001, P < 0.001, P < 0.001 for three outcomes, respectively, Table 2). For all of the outcomes, the fully vaccinated group had less lung injury than unvaccinated patients (Table 2). Besides, the time from illness onset to most serious lung lesion was shorter in fully vaccinated group compared with unvaccinated group (6.00 days in fully vaccinated Vs 10.00 days in unvaccinated, P < 0.001, Table 2; an unvaccinated patient’s most severe lung lesions was on the 11th day of hospitalization, Fig. 1). There were also significant differences in the distribution of severe/critical and non-severe patients among the three groups (P < 0.001; Table 2).

Illustration of Artificial Intelligence-Assisted CT imaging. Figures A to C were chest CT images of an unvaccinated patient during hospitalization. Chest CT of this patient was normal at admission, and on the third day of hospitalization showed traces of patchy ground-glass opacities on both lungs (A). A repeated chest CT on the 7th of hospitalization demonstrated substantial lesion progression. The most severe lung lesions were demonstrated by the chest CT scan obtained on the 11th day of hospitalization, with large patches of ground-glass opacities on both lungs (B). Follow-up chest CT scans performed on the 15th and 22nd day of hospitalization showed gradually improvement of the lung lesions. The last chest CT was completed on the 29th day of hospitalization, revealing a substantially resolution of lung lesions (C). Figures D–F demonstrated inflammatory areas on three CT scan images that were automatically demarcated by artificial intelligence (AI) software. The lung lesions demarcated by AI software were consistent with those delimited by visual inspection. The extent of lung injuries was presented as VOI and POI in the whole lung. For the three sequential chest CT scans of the patients, VOI (POI)in the whole lung was 47.1 cm3(1.3%); 523.6 cm3 (13.3%); 242.6 cm3 (6.2%), respectively.

In univariable analysis (Table 3), compared with the unvaccinated group, the fully vaccinated group had a significantly decreased risk of lung injury , P < 0.001; Coef(95%CI) = − 190.56 (− 247.4, − 133.72), P < 0.001, and Coef(95%CI) = − 3.58 (− 4.47,− 2.7), P < 0.001 for the POI and VOI in the whole lung, and the chest CT scores, respectively). A trend of less severe lung injuries was also seen in partially vaccinated patients (Coef (95%CI) = − 1.17 (− 3.58,1.24), P = 0.341; Coef (95%CI) = − 9.74 (− 80.56,61.08), P = 0.788; Coef(95%CI) = − 0.84 (− 1.94,0.26), P = 0.136 for three outcomes, respectively), however this was not statistically significant. Other factors that were associated with more lung injuries were older age, with underlying diseases, cough, higher levels of CRP, IL-6 and LDH, and lower levels of Lymphocyte count, SARS-COV-2 antibodies.

In multivariable analysis, the effect of vaccination on pulmonary injuries was adjusted for age, sex, comorbidity, time from illness onset to hospitalization and SARS-COV-2 viral load base on clinical consideration. Since clinical parameters such as lymphocyte counts, CRP, IL-6 and LDH were more appropriate as an index of disease severity rather than risk factors, those variables not included in the multivariable regression analysis.

After adjusted for confounding factors, fully vaccination was still significantly associated with lower extent of lung injuries , P < 0.001; Coefadj(95%CI) = − 106.10(− 167.30, − 44.89), P = 0.001; and Coefadj(95%CI) = − 1.81(− 2.72, − 0.91), P < 0.001 for the three outcomes, respectively; Table 4). Of note, SARS-COV-2 viral load was not associated with the severity of the COVID-19 pneumonia in our patients (P = 0.334, P = 0.161, P = 0.188 for the three outcomes, respectively; Table 4).

Subgroup analyses were performed for the three outcomes stratified by sex, age, and comorbidity status (Additional file 1: Tables S1, S2, S3). Likewise, partially vaccination was not associated with any reduction of pulmonary injuries in the subgroup analyses. In fully vaccinated patients, variation of protection could be found within subgroups. Generally, the extent of reduction of pulmonary injuries was more profound in fully vaccinated patients with older age, having underlying diseases, and being female sex, as demonstrated by relatively larger absolute values of adjusted coefficients (Additional file 1: Tables S1, S2, S3). Nevertheless, for patients with underlying diseases, the reduction of pulmonary injury in fully vaccinated patients was statistically significant only when pulmonary lesions were evaluated by chest CT scores . This suggested that chest CT scores may be more sensitive than POI and VOI in the whole lung, when evaluating different treatment strategies for COVID-19 pneumonia. Finally, when patients with severe/critical COVID-19 diseases were excluded from analysis, fully vaccination was still significantly associated with less pulmonary injuries , P < 0.001; Coefadj(95%CI) = − 97.44(− 147.33, − 47.55), P = 0.001; and Coefadj(95%CI) = − 1.65(− 2.51, − 0.79), P < 0.001 for the POI and VOI in the whole lung, and the chest CT scores, respectively; Additional file 1: Table S4).