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Background: The surge in omicron variants has caused nationwide breakthrough infections in mainland China since the December 2022. In this study, we report the neutralization profiles of serum samples from the patients with breast cancer and the patients with liver cancer who had contracted subvariant breakthrough infections., Methods: In this real-world study, we enrolled 143 COVID-19-vaccinated (81 and 62 patients with breast and liver cancers) and 105 unvaccinated patients with cancer (58 and 47 patients with breast and liver cancers) after omicron infection. Anti-spike receptor binding domain (RBD) IgGs and 50% pseudovirus neutralization titer (pVNT 50 ) for the preceding (wild type), circulating omicron (BA.4-BA.5, and BF.7), and new subvariants (XBB.1.5) were comprehensively analyzed., Results: Patients with liver cancer receiving booster doses had higher levels of anti-spike RBD IgG against circulating omicron (BA.4-BA.5, and BF.7) and a novel subvariant (XBB.1.5) compared to patients with breast cancer after breakthrough infection. Additionally, all vaccinated patients produced higher neutralizing antibody titers against circulating omicron (BA.4-BA.5, and BF.7) compared to unvaccinated patients. However, the unvaccinated patients produced higher neutralizing antibody against XBB.1.5 than vaccinated patients after Omicron infection, with this trend being more pronounced in breast cancer than in liver cancer patients. Moreover, we found that there was no correlation between anti-spike RBD IgG against wildtype virus and the neutralizing antibody titer, but a positive correlation between anti-spike RBD IgG and the neutralizing antibody against XBB.1.5 was found in unvaccinated patients., Conclusion: Our study found that there may be differences in vaccine response and protective effect against COVID-19 infection in patients with liver and breast cancer. Therefore, we recommend that COVID-19 vaccine strategies should be optimized based on vaccine components and immunology profiles of different patients with cancer., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

People living with human immunodeficiency virus (PLWH) are a vulnerable population with a higher risk of severe coronavirus disease 2019 (COVID-19); therefore, vaccination is recommended as a priority. Data on viral reservoirs and immunologic outcomes for PLWH breakthrough infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are currently limited. In this study, we investigated the effects of SARS-CoV-2 breakthrough infection on hematological parameters, human immunodeficiency virus (HIV) reservoir size, and T-cell recovery in PLWH receiving antiretroviral therapy (ART) after SARS-CoV-2 booster vaccination. The results indicated that during breakthrough infection, booster vaccination with homologous and heterologous vaccines was safe in PLWH after receiving two doses of inactivated vaccination. The absolute CD4 counts decreased in the heterologous group, whereas the CD8 counts decreased in the homologous booster group after breakthrough infection in PLWH. Breakthrough infection increased HIV reservoirs and was associated with increased T-cell activation in PLWH who received virally suppressed ART and a 3-dose vaccination. According to our data, the breakthrough infection of SARS-CoV-2 may put PLWH at a greater risk for increased HIV reservoirs, even if these individuals were virally suppressed with ART after 3-dose SARS-CoV-2 vaccination.

Background: The widespread use of vaccines against the novel coronavirus disease (COVID-19) has become one of the most effective means to establish a population immune barrier. Patients with cancer are vulnerable to COVID-19 infection, adverse events, and high mortality, and should be the focus of epidemic prevention and treatment. However, real-world data on the safety of vaccines for patients with breast cancer are still scarce., Objective: This study aims to compare the safety of COVID-19 vaccines between patients vaccinated before or after being diagnosed with breast cancer., Methods: Patients with breast cancer who sought medical advice from October 2021 to December 2021 were screened. Those who received COVID-19 vaccines were enrolled in this study to analyze the safety of the vaccines. The primary outcome was patient-reported adverse events (AEs). All events after vaccine injection were retrospectively documented from the patients., Results: A total of 15,455 patients with breast cancer from 41 hospitals in 20 provinces in China were screened, and 5766 patients who received COVID-19 vaccines were enrolled. Of those enrolled, 45.1% (n=2599) of patients received vaccines before breast cancer diagnosis, 41.3% (n=2379) were vaccinated after diagnosis, and 13.6% (n=784) did not known the accurate date of vaccination or cancer diagnosis. Among the patients vaccinated after diagnosis, 85.4% (n=2032) were vaccinated 1 year after cancer diagnosis and 95.4% (n=2270) were vaccinated during early-stage cancer. Of all 5766 vaccinated patients, 93.9% (n=5415) received an inactivated vaccine, 3.7% (n=213) received a recombinant subunit vaccine, and 2.4% (n=138) received other vaccines, including adenovirus and mRNA vaccines. In the first injection of vaccines, 24.4% (n=10, 95% CI 11.2-37.5) of patients who received an adenovirus vaccine reported AEs, compared to only 12.5% (n=677, 95% CI 11.6-13.4) of those who received an inactivated vaccine. Patients with metastatic breast cancer reported the highest incidence of AEs (n=18, 16.5%, 95% CI 9.5-23.5). Following the second injection, patients who received an inactivated vaccine (n=464, 8.7%, 95% CI 8.0-9.5) and those who received a recombinant vaccine (n=25, 8.7%, 95% CI 5.5-12.0) reported the same incidence of AEs. No significant differences in patient-reported AEs were found between the healthy population and patients with breast cancer (16.4% vs 16.9%, respectively); the most common AEs were local pain (11.1% vs 9.1%, respectively), fatigue (5.5% vs 6.3%, respectively), and muscle soreness (2.3% vs 3.6%, respectively). The type of vaccine and time window of vaccination had little impact on patient-reported AEs., Conclusions: Compared with patients vaccinated before breast cancer diagnosis, there were no significant differences in patient-reported AEs in the patients vaccinated after diagnosis. Thus, it is safe for patients with breast cancer, especially for those in the early stage, to receive COVID-19 vaccines., Trial Registration: Chinese Clinical Trial Registry ChiCTR2200055509; https://tinyurl.com/33zzj882., (©Shaohua Zhang, Jianbin Li, Ruonan Xu, Qianjun Chen, Gang Sun, Ying Lin, Yali Cao, Yiding Chen, Cuizhi Geng, Yuee Teng, Jianyun Nie, Xinzheng Li, Guiying Xu, Xinlan Liu, Feng Jin, Zhimin Fan, Ting Luo, Hong Liu, Fu-sheng Wang, Zefei Jiang. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 07.12.2023.)

Humoral immunity confers protection against COVID-19. The longevity of antibody responses after receiving an inactivated vaccine in individuals with previous SARS-CoV-2 infection is unclear. Plasma samples were collected from 58 individuals with previous SARS-CoV-2 infection and 25 healthy donors (HDs) who had been vaccinated with an inactivated vaccine. The neutralizing antibodies (NAbs) and S1 domain-specific antibodies against the SARS-CoV-2 wild-type and Omicron strains and nucleoside protein (NP)-specific antibodies were measured using a chemiluminescent immunoassay. Statistical analysis was performed using clinical variables and antibodies at different timepoints after SARS-CoV-2 vaccination. NAbs targeting the wild-type or Omicron strain were detected in individuals with previous SARS-CoV-2 infection at 12 months after infection (wild-type: 81%, geometric mean (GM): 20.3 AU/mL; Omicron: 44%, GM: 9.4 AU/mL), and vaccination provided further enhancement of these antibody levels (wild-type: 98%, GM: 53.3 AU/mL; Omicron: 75%, GM: 27.8 AU/mL, at 3 months after vaccination), which were significantly higher than those in HDs receiving a third dose of inactivated vaccine (wild-type: 85%, GM: 33.6 AU/mL; Omicron: 45%, GM: 11.5 AU/mL). The level of NAbs in individuals with previous infection plateaued 6 months after vaccination, but the NAb levels in HDs declined continuously. NAb levels in individuals with previous infection at 3 months post-vaccination were strongly correlated with those at 6 months post-vaccination, and weakly correlated with those before vaccination. NAb levels declined substantially in most individuals, and the rate of antibody decay was negatively correlated with the neutrophil-to-lymphocyte ratio in the blood at discharge. These results suggest that the inactivated vaccine induced robust and durable NAb responses in individuals with previous infection up to 9 months after vaccination.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused a global pandemic since late 2019 that resulted in more than 360 million population infection. Among them, less than 7% of infected individuals develop severe or critical illness. Mass vaccination has been carried out, but reinfection and vaccine breakthrough cases still occur. Besides supportive and antiviral medications, much attention has been paid in immunotherapies that aim at reducing pathological changes in the lungs. Mesenchymal stem cells (MSCs) is used as an option because of their immunomodulatory, anti-inflammatory, and regenerative properties. As of January 16, 2022, when ClinicalTrials.gov was searched for "Mesenchymal stem cells and COVID-19," over 80 clinical trials were registered. MSC therapy was found to be safe and some effective in preclinical and clinical studies. Here, we summarize the major pathological characteristics of COVID-19 and provide scientific and rational evidence for the safety and possible effectiveness of MSCs in COVID-19 treatment., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The long-term consequences of human umbilical cord-derived mesenchymal stem cell (UC-MSC) treatment for COVID-19 patients are yet to be reported. This study assessed the 1-year outcomes in patients with severe COVID-19, who were recruited in our previous UC-MSC clinical trial., Methods: In this prospective, longitudinal, cohort study, 100 patients enrolled in our phase 2 trial were prospectively followed up at 3-month intervals for 1 year to evaluate the long-term safety and effectiveness of UC-MSC treatment. The primary endpoint was an altered proportion of whole-lung lesion volumes measured by high-resolution CT. Other imaging outcomes, 6 min walking distance (6-MWD), lung function, plasma biomarkers, and adverse events were also recorded and analyzed. This trial was registered with ClinicalTrials.gov (NCT04288102)., Findings: MSC administration improved in whole-lung lesion volume compared with the placebo with a difference of -10.8% (95% CI: -20.7%, -1.5%, p = 0.030) on day 10. MSC also reduced the proportion of solid component lesion volume compared with the placebo at each follow-up point. More interestingly, 17.9% (10/56) of patients in the MSC group had normal CT images at month 12, but none in the placebo group (p = 0.013). The incidence of symptoms was lower in the MSC group than in the placebo group at each follow-up time. Neutralizing antibodies were all positive, with a similar median inhibition rate (61.6% vs. 67.6%) in both groups at month 12. No difference in adverse events at the 1-year follow-up and tumor markers at month 12 were observed between the two groups., Interpretation: UC-MSC administration achieves a long-term benefit in the recovery of lung lesions and symptoms in COVID-19 patients., Funding: The National Key R&D Program of China, the Innovation Groups of the National Natural Science Foundation of China, and the National Science and Technology Major Project., Competing Interests: Declaration of interests YZ is a current employee of Vcanbio Cell & Gene Engineering Co., Ltd. All authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has placed a global public burden on health authorities. Although the virological characteristics and pathogenesis of COVID-19 has been largely clarified, there is currently no specific therapeutic measure. In severe cases, acute SARS-CoV-2 infection leads to immune disorders and damage to both the adaptive and innate immune responses. Having roles in immune regulation and regeneration, mesenchymal stem cells (MSCs) serving as a therapeutic option may regulate the over-activated inflammatory response and promote recovery of lung damage. Since the outbreak of the COVID-19 pandemic, a series of MSC-therapy clinical trials has been conducted. The findings indicate that MSC treatment not only significantly reduces lung damage, but also improves patient recovery with safety and good immune tolerance. Herein, we summarize the recent progress in MSC therapy for COVID-19 and highlight the challenges in the field., (© 2021. The Author(s).)

Treatment of severe Coronavirus Disease 2019 (COVID-19) is challenging. We performed a phase 2 trial to assess the efficacy and safety of human umbilical cord-mesenchymal stem cells (UC-MSCs) to treat severe COVID-19 patients with lung damage, based on our phase 1 data. In this randomized, double-blind, and placebo-controlled trial, we recruited 101 severe COVID-19 patients with lung damage. They were randomly assigned at a 2:1 ratio to receive either UC-MSCs (4 × 10 7 cells per infusion) or placebo on day 0, 3, and 6. The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28. Other imaging outcomes, 6-minute walk test (6-MWT), maximum vital capacity, diffusing capacity, and adverse events were recorded and analyzed. In all, 100 COVID-19 patients were finally received either UC-MSCs (n = 65) or placebo (n = 35). UC-MSCs administration exerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo (the median difference was -13.31%, 95% CI -29.14%, 2.13%, P = 0.080). UC-MSCs significantly reduced the proportions of solid component lesion volume compared with the placebo (median difference: -15.45%; 95% CI -30.82%, -0.39%; P = 0.043). The 6-MWT showed an increased distance in patients treated with UC-MSCs (difference: 27.00 m; 95% CI 0.00, 57.00; P = 0.057). The incidence of adverse events was similar in the two groups. These results suggest that UC-MSCs treatment is a safe and potentially effective therapeutic approach for COVID-19 patients with lung damage. A phase 3 trial is required to evaluate effects on reducing mortality and preventing long-term pulmonary disability. (Funded by The National Key R&D Program of China and others. ClinicalTrials.gov number, NCT04288102.