Safety, immunogenicity and protective effectiveness of heterologous boost with a recombinant COVID-19 vaccine (Sf9 cells) in adult recipients of inactivated vaccines.

Vaccines have proven effective in protecting populations against COVID-19, including the recombinant COVID-19 vaccine (Sf9 cells), the first approved recombinant protein vaccine in China. In this positive-controlled trial with 85 adult participants (Sf9 cells group: n = 44; CoronaVac group: n = 41), we evaluated the safety, immunogenicity, and protective effectiveness of a heterologous boost with the Sf9 cells vaccine in adults who had been vaccinated with the inactivated vaccine, and found a post-booster adverse events rate of 20.45% in the Sf9 cells group and 31.71% in the CoronaVac group (p = 0.279), within 28 days after booster injection. Neither group reported any severe adverse events. Following the Sf9 cells vaccine booster, the geometric mean titer (GMT) of binding antibodies to the receptor-binding domain of prototype SARS-CoV-2 on day 28 post-booster was significantly higher than that induced by the CoronaVac vaccine booster (100,683.37 vs. 9,451.69, p < 0.001). In the Sf9 cells group, GMTs of neutralizing antibodies against pseudo SARS-CoV-2 viruses (prototype and diverse variants of concern [VOCs]) increased by 22.23-75.93 folds from baseline to day 28 post-booster, while the CoronaVac group showed increases of only 3.29-10.70 folds. Similarly, neutralizing antibodies against live SARS-CoV-2 viruses (prototype and diverse VOCs) increased by 68.18-192.67 folds on day 14 post-booster compared with the baseline level, significantly greater than the CoronaVac group (19.67-37.67 folds). A more robust Th1 cellular response was observed with the Sf9 cells booster on day 14 post-booster (mean IFN-γ+ spot-forming cells per 2 × 105 peripheral blood mononuclear cells: 26.66 vs. 13.59). Protective effectiveness against symptomatic COVID-19 was approximately twice as high in the Sf9 cells group compared to the CoronaVac group (68.18% vs. 36.59%, p = 0.004). Our study findings support the high protective effectiveness of heterologous boosting with the recombinant COVID-19 vaccine (Sf9 cells) against symptomatic COVID-19 of diverse SARS-CoV-2 variants of concern, while causing no apparent safety concerns.

Effect of inactivated vaccine boosters against severe and critical COVID-19 during the Omicron BA.5 wave: A retrospective analysis of hospitalized patients in China.

Few real-world analyses of the ability of vaccines to protect against severe COVID-19 have been published. In this real-world study, we compared the prevalence of severe or critical COVID-19 between patients at our hospital who were not vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or who had been vaccinated partial, full, or booster course with the CoronaVac, containing inactivated virus propagated in Vero cells. Data from electronic health records were retrospectively analyzed for 4090 inpatients with COVID-19 who were treated at West China Hospital, Chengdu between December 6, 2022 and February 14, 2023. Clinicodemographic characteristics and COVID-19 severity were compared among patients who had been vaccinated 0, 1, 2 or more times with inactivated vaccine CoronaVac. To evaluate vaccine effectiveness over time, we plotted Kaplan-Meier curves with the percentage of patients with the outcome of severe or critical COVID-19 from the time of their last vaccine dose according to vaccination status. Ordinal logistic regression was used to assess associations between vaccination status and COVID-19 severity. Cox regression was used to identify risk factors for severe or critical COVID-19. Among the 4090 patients, 171 had been vaccinated partial and 423 twice with the full CoronaVac regimens, while 905 had been vaccinated three times (boosted). The prevalence of severe or critical COVID-19 among patients was 11 percentage points lower among those vaccinated (40%) at least twice than among those unvaccinated (51%) (p＜0.001), while it was 10% points lower among those who had received a booster (41%) than among those unvaccinated (51%) (p＜0.001). Protection against severe or critical COVID-19 due to vaccination was significantly weakened by being older than 65 years, being male, or having diabetes, chronic heart disease, autoimmune disease, or chronic lung disease. Completing a full course of immunization with inactivated vaccine CoronaVac against SARS-CoV-2 can reduce the risk of severe or critical COVID-19 due to the Omicron BA.5 subvariant.

Azvudine and nirmatrelvir-ritonavir in hospitalized patients with moderate-to-severe COVID-19: Emulation of a randomized target trial.

To examine the effectiveness of azvudine and nirmatrelvir-ritonavir in treating hospitalized patients with moderate-to-severe COVID-19. We emulated a target trial with a multicenter retrospective cohort of hospitalized adults with moderate-to-severe COVID-19 without contraindications for azvudine or nirmatrelvir-ritonavir between December 01, 2022 and January 19, 2023 (during the Omicron BA.5.2 variant wave). Exposures included treatment with azvudine or nirmatrelvir-ritonavir for 5 days versus no antiviral treatment during hospitalization. Primary composite outcome (all-cause death and initiation of invasive mechanical ventilation), and their separate events were evaluated. Of the 1154 patients, 27.2% were severe cases. In the intent-to-treat analyses, azvudine reduced all-cause death (Hazard ratio [HR]: 0.31; 95% CI: 0.12-0.78), and its composite with invasive mechanical ventilation (HR: 0.47; 95% CI: 0.24-0.92). Nirmatrelvir-ritonavir reduced invasive mechanical ventilation (HR: 0.42; 95% CI: 0.17-1.05), and its composite with all-cause death (HR: 0.38; 95% CI: 0.18-0.81). The study did not identify credible subgroup effects. The per-protocol analyses and all sensitivity analyses confirmed the robustness of the findings. Both azvudine and nirmatrelvir-ritonavir improved the prognosis of hospitalized adults with moderate-to-severe COVID-19.