Advances of mRNA vaccine in tumor: a maze of opportunities and challenges.

High-frequency mutations in tumor genomes could be exploited as an asset for developing tumor vaccines. In recent years, with the tremendous breakthrough in genomics, intelligence algorithm, and in-depth insight of tumor immunology, it has become possible to rapidly target genomic alterations in tumor cell and rationally select vaccine targets. Among a variety of candidate vaccine platforms, the early application of mRNA was limited by instability low efficiency and excessive immunogenicity until the successful development of mRNA vaccines against SARS-COV-2 broken of technical bottleneck in vaccine preparation, allowing tumor mRNA vaccines to be prepared rapidly in an economical way with good performance of stability and efficiency. In this review, we systematically summarized the classification and characteristics of tumor antigens, the general process and methods for screening neoantigens, the strategies of vaccine preparations and advances in clinical trials, as well as presented the main challenges in the current mRNA tumor vaccine development.

Impact of prior bariatric surgery on risk and severity of COVID-19 infection: A meta-analysis of observational studies.

BACKGROUND: The association of prior bariatric surgery (BS) with infection rate and prognosis of coronavirus disease 2019 (COVID-19) remains unclear. We conducted a meta-analysis of observational studies to address this issue. METHODS: We searched databases including MEDLINE, Embase, and CENTRAL from inception to May, 2022. The primary outcome was risk of mortality, while secondary outcomes included risk of hospital/intensive care unit (ICU) admission, mechanical ventilation, acute kidney injury (AKI), and infection rate. RESULTS: Eleven studies involving 151,475 patients were analyzed. Meta-analysis showed lower risks of mortality [odd ratio (OR)= 0.42, 95% CI: 0.27-0.65, p < 0.001, I2 = 67%; nine studies; 151,113 patients, certainty of evidence (COE):moderate], hospital admission (OR=0.56, 95% CI: 0.36-0.85, p = 0.007, I2 =74.6%; seven studies; 17,810 patients; COE:low), ICU admission (OR=0.5, 95% CI: 0.37-0.67, p < 0.001, I2 =0%; six studies; 17,496 patients, COE:moderate), mechanical ventilation (OR=0.52, 95% CI: 0.37-0.72, p < 0.001, I2 =57.1%; seven studies; 137,992 patients, COE:moderate) in patients with prior BS (BS group) than those with obesity without surgical treatment (non-BS group). There was no difference in risk of AKI (OR=0.74, 95% CI: 0.41-1.32, p = 0.304, I2 =83.6%; four studies; 129,562 patients, COE: very low) and infection rate (OR=1.05, 95% CI: 0.89-1.22, p = 0.572, I2 =0%; four studies; 12,633 patients, COE:low) between the two groups. Subgroup analysis from matched cohort studies demonstrated associations of prior BS with lower risks of mortality, ICU admission, mechanical ventilation, and AKI. CONCLUSION: Our results showed a correlation between prior BS and less severe COVID-19, which warrants further investigations to verify.

Safety, immunogenicity and antibody persistence of a bivalent Beta-containing booster vaccine against COVID-19: a phase 2/3 trial.

Updated immunization strategies are needed to address multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Here we report interim results from an ongoing, open-label phase 2/3 trial evaluating the safety and immunogenicity of the bivalent Coronavirus Disease 2019 (COVID-19) vaccine candidate mRNA-1273.211, which contains equal mRNA amounts encoding the ancestral SARS-CoV-2 and Beta variant spike proteins, as 50-µg (n = 300) and 100-µg (n = 595) first booster doses administered approximately 8.7-9.7 months after the mRNA-1273 primary vaccine series ( NCT04927065 ). The primary objectives were to evaluate the safety and reactogenicity of mRNA-1273.211 and to demonstrate non-inferior antibody responses compared to the mRNA-1273 100-µg primary series. Additionally, a pre-specified immunogenicity objective was to demonstrate superior antibody responses compared to the previously authorized mRNA-1273 50-µg booster. The mRNA-1273.211 booster doses (50-µg or 100-µg) 28 days after immunization elicited higher neutralizing antibody responses against the ancestral SARS-CoV-2 and Beta variant than those elicited 28 days after the second mRNA­1273 dose of the primary series ( NCT04470427 ). Antibody responses 28 days and 180 days after the 50-µg mRNA-1273.211 booster dose were also higher than those after a 50-µg mRNA-1273 booster dose ( NCT04405076 ) against the ancestral SARS-CoV-2 and Beta, Omicron BA.1 and Delta variants, and all pre-specified immunogenicity objectives were met. The safety and reactogenicity profile of the bivalent mRNA-1273.211 booster (50-µg) was similar to the booster dose of mRNA-1273 (50-µg). Immunization with the primary series does not set a ceiling to the neutralizing antibody response, and a booster dose of the bivalent vaccine elicits a robust response with titers that are likely to be protective against COVID-19. These results indicate that bivalent booster vaccines can induce potent, durable and broad antibody responses against multiple variants, providing a new tool in response to emerging variants.

A Bivalent Omicron-Containing Booster Vaccine against Covid-19.

BACKGROUND: The safety and immunogenicity of the bivalent omicron-containing mRNA-1273.214 booster vaccine are not known. METHODS: In this ongoing, phase 2-3 study, we compared the 50-µg bivalent vaccine mRNA-1273.214 (25 µg each of ancestral Wuhan-Hu-1 and omicron B.1.1.529 [BA.1] spike messenger RNAs) with the previously authorized 50-µg mRNA-1273 booster. We administered mRNA-1273.214 or mRNA-1273 as a second booster in adults who had previously received a two-dose (100-µg) primary series and first booster (50-µg) dose of mRNA-1273 (≥3 months earlier). The primary objectives were to assess the safety, reactogenicity, and immunogenicity of mRNA-1273.214 at 28 days after the booster dose. RESULTS: Interim results are presented. Sequential groups of participants received 50 µg of mRNA-1273.214 (437 participants) or mRNA-1273 (377 participants) as a second booster dose. The median time between the first and second boosters was similar for mRNA-1273.214 (136 days) and mRNA-1273 (134 days). In participants with no previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the geometric mean titers of neutralizing antibodies against the omicron BA.1 variant were 2372.4 (95% confidence interval [CI], 2070.6 to 2718.2) after receipt of the mRNA-1273.214 booster and 1473.5 (95% CI, 1270.8 to 1708.4) after receipt of the mRNA-1273 booster. In addition, 50-µg mRNA-1273.214 and 50-µg mRNA-1273 elicited geometric mean titers of 727.4 (95% CI, 632.8 to 836.1) and 492.1 (95% CI, 431.1 to 561.9), respectively, against omicron BA.4 and BA.5 (BA.4/5), and the mRNA-1273.214 booster also elicited higher binding antibody responses against multiple other variants (alpha, beta, gamma, and delta) than the mRNA-1273 booster. Safety and reactogenicity were similar with the two booster vaccines. Vaccine effectiveness was not assessed in this study; in an exploratory analysis, SARS-CoV-2 infection occurred in 11 participants after the mRNA-1273.214 booster and in 9 participants after the mRNA-1273 booster. CONCLUSIONS: The bivalent omicron-containing vaccine mRNA-1273.214 elicited neutralizing antibody responses against omicron that were superior to those with mRNA-1273, without evident safety concerns. (Funded by Moderna; ClinicalTrials.gov number, NCT04927065.).

Cytomegalovirus Proctitis Developed after COVID-19 Vaccine: A Case Report and Literature Review.

(1) Background: We describe a case of a 58-year-old Chinese woman, without obvious cause of immunosuppression, who developed cytomegalovirus (CMV) proctitis three days after a second COVID-19 vaccination. Electronic colonoscopy revealed a new lesion that was circumferential at the anorectal junction, with an uneven surface and ulceration, which mimicked rectal carcinoma. This is the first case of CMV proctitis following vaccination since the invention of the COVID-19 vaccine, suggesting that the COVID-19 vaccine may cause disorders of immune homeostasis, including not only immune hyperactivity but also immune deficiency. We report this case to increase readers' awareness of the risks after COVID-19 vaccination and to provide new ideas for the diagnosis and treatment of similar cases. (2) Methods: In this case, we used laboratory biochemical examinations, colonoscopy, immunohistochemistry, and a biochemical index to confirm the existence of CMV proctitis. (3) Results: In this case, the vaccine-induced CMV proctitis had a similar endoscopic appearance to rectal neoplastic lesions, which could be confirmed by biopsy and quickly relieved by ganciclovir treatment. Ganciclovir was used to treat the patient, and a good effect was observed. (4) Conclusions: COVID-19 vaccination may cause immune disorders, not just immune hyperactivity as previously reported, but also immune deficiency, such as CMV proctitis in this case. The clinical course of CMV proctitis secondary to COVID-19 vaccination was favorable with ganciclovir therapy.

Work Stress and Willingness of Nursing Aides during the COVID-19 Pandemic.

OBJECTIVES: During the coronavirus disease 2019 (COVID-19) pandemic, nursing aides (NAs) experienced greater work stress than they do typically because they worked in highly contagious environments. This may have influenced their work morale and willingness to work, which can reduce patient satisfaction, influence their physical and mental health, and even endanger patient safety or cause medical system collapse. DESIGN: A cross-sectional survey with a structured self-report questionnaire was conducted. SETTING AND PARTICIPANTS: 144 NAs from a medical center in Central Taiwan participated. METHODS: We recruited NAs through convenience sampling to discuss their work stress, willingness to work, and patients' satisfaction with them during the COVID-19 pandemic. RESULT: Of the 144 recruited NAs, 115 (79.9%) were women and 29 (20.1%) were men, and 89 (61.8%) had completed COVID-19 training courses. NAs with different work tenure lengths exhibited significant differences in work stress (p = 0.022), willingness to work (p = 0.029), and patient satisfaction (p = 0.029) scores during the pandemic. CONCLUSION: The study findings provide crucial data for the management of NAs during pandemics to prevent them from neglecting patients due to excessive work stress or losing their willingness to work, which may cause the medical system to collapse.

Association between Fibrinogen-to-Albumin Ratio and Prognosis of Hospitalized Patients with COVID-19: A Systematic Review and Meta-Analysis.

Although the fibrinogen-to-albumin ratio (F/R ratio) has been used as an inflammation marker to predict clinical outcomes in patients with cardiovascular diseases, its association with the prognosis of patients with coronavirus disease 2019 (COVID-19) remains unclear. Electronic databases including EMBASE, MEDLINE, Google Scholar, and Cochrane Library were searched from inception to 20 June 2022. The associations of F/R ratio with poor prognosis (defined as the occurrence of mortality or severe disease) were investigated in patients with COVID-19. A total of 10 studies (seven from Turkey, two from China, one from Croatia) involving 3675 patients published between 2020 and 2022 were eligible for quantitative syntheses. Merged results revealed a higher F/R ratio in the poor prognosis group (standardized mean difference: 0.529, p < 0.001, I2 = 84.8%, eight studies) than that in the good prognosis group. In addition, a high F/R ratio was associated with an increased risk of poor prognosis (odds ratio: 2.684, I2 = 59.5%, five studies). Pooled analysis showed a sensitivity of 0.75, specificity of 0.66, and area under curve of 0.77 for poor prognosis prediction. In conclusion, this meta-analysis revealed a positive correlation between F/A ratio and poor prognostic outcomes of COVID-19. Because of the limited number of studies included, further investigations are warranted to support our findings.

Immune response to SARS-CoV-2 after a booster of mRNA-1273: an open-label phase 2 trial.

Rising breakthrough infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in previously immunized individuals have raised concerns for the need for a booster vaccine dose to combat waning antibody levels and new variants. Here we report the results of the open-label, non-randomized part B of a phase 2 trial in which we evaluated the safety and immunogenicity of a booster injection of 50 µg of the coronavirus disease 2019 (COVID-19) vaccine mRNA-1273 in 344 adult participants immunized 6-8 months earlier with a primary series of two doses of 50 µg or 100 µg of mRNA-1273 ( NCT04405076 ). Neutralizing antibody (nAb) titers against wild-type SARS-CoV-2 at 1 month after the booster were 1.7-fold (95% confidence interval (CI): 1.5, 1.9) higher than those at 28 days after the second injection of the primary series, which met the pre-specified non-inferiority criterion (primary immunogenicity objective) and might indicate a memory B cell response. The nAb titers against the Delta variant (B.1.617.2) (exploratory objective) at 1 month after the booster were 2.1-fold (95% CI: 1.8, 2.4) higher than those at 28 days after the second injection of the primary series. The seroresponse rate (95% CI (four-fold rise from baseline)) was 100% (98.7, 100.0) at 28 days after the booster compared to 98.3% (96.0, 99.4) after the primary series. The higher antibody titers at 28 days after the booster dose compared to 28 days after the second dose in the phase 3 COVE study were also observed in two assays for anti-spike IgG antibody measured by ELISA and by Meso Scale Discovery (MSD) Multiplex. The frequency of solicited local and systemic adverse reactions after the booster dose was similar to that after the second dose in the primary two-dose series of mRNA-1273 (50 µg or 100 µg); no new signals were observed in the unsolicited adverse events; and no serious adverse events were reported in the 1-month follow-up period. These results show that a booster injection of mRNA-1273 more than 6 months after completing the primary two-dose series is safe and elicited nAb titers that were statistically significantly higher than the peak titers detected after the primary vaccination series, suggesting that a booster dose of mRNA-1273 might result in increased vaccine effectiveness against infection and disease caused by SARS-CoV-2.

Challenges of Using Instant Communication Technology in the Emergency Department during the COVID-19 Pandemic: A Focus Group Study.

A record outbreak of community-spread COVID-19 started on 10 May 2021, in Taiwan. In response to the COVID-19 pandemic, care facilities have adopted various protocols using instant communication technology (ICT) to provide remote yet timely healthcare while ensuring staff safety. The challenges of patient evaluation in the emergency department (ED) using ICT are seldom discussed in the literature. The objective of this study was to investigate the factors influencing the utility of ICT for patient assessment in emergency settings during the pandemic. The patient flow protocol and the ED layout were modified and regionalized into different areas according to the patient's risk of COVID-19 infection. Nine iPads were stationed in different zones to aid in virtual patient assessment and communication between medical personnel. A focus group study was performed to assess and analyze the utility of the ICT module in the ED. Eight emergency physicians participated in the study. Of them, four (50%) had been directly involved in the development of the ICT module in the study hospital. Three main themes that influenced the application of the ICT module were identified: setting, hardware, and software. The setting theme included six factors: patient evaluation, subspecialty consultation, patient privacy and comfortableness, sanitation, cost, and patient acceptability. The hardware theme included six factors: internet connection, power, quality of image and voice, public or personal mode, portable or fixed mode, and maintenance. The software theme included six factors: platform choices, security, ICT accounts, interview modes, video/voice recording, and time limitation. Future studies should focus on quantifying module feasibility, user satisfaction, and protocol adjustment for different settings.

Mortality and risk factors associated with pulmonary embolism in coronavirus disease 2019 patients: a systematic review and meta-analysis.

To determine, in patients with coronavirus disease 2019 (COVID-19) infection, the associations of pulmonary embolism (PE) with mortality and risk factors for PE as well as the therapeutic benefit of anticoagulant prophylaxis. Embase, PubMed, Cochrane controlled trials register, and Web of Science databases were searched from inception to October 10, 2020. We included all published trials on PE in patients diagnosed with COVID-19 with eligibility of the trials assessed following the PRISMA guidelines. Sixteen clinical trials with 5826 patients were eligible. There were significant associations of PE with the male gender [odd ratio (OR) = 1.59, 95% CI 1.28-1.97], mechanical ventilation (OR = 3.71, 95% CI 2.57-5.36), intensive care unit admission (OR = 2.99, 95% CI 2.11-4.23), circulating D-dimer [mean difference (MD) = 5.04 µg/mL, 95% CI 3.67-6.42) and CRP (MD = 1.97 mg/dL, 95% CI 0.58- 3.35) concentrations without significant correlation between PE and mortality (OR = 1.31, 95% CI 0.82-2.08) as well as other parameters or comorbidities. After omitting one trial with strict patient selection criteria for anticoagulant prophylaxis, significant prophylactic benefit was noted (OR = 0.31, 95% CI 0.1-0.91). Our findings identified the risk factors associated with PE in COVID-19 patients and supported the therapeutic benefit of anticoagulant prophylaxis against PE in this patient population.

A Scoring System for Predicting the Prognosis of Late-Onset Severe Pneumonia after Allogeneic Hematopoietic Stem Cell Transplantation.

Late-onset severe pneumonia (LOSP) is defined as severe pneumonia developing during the late phase of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Because of the high mortality in patients with LOSP, it is important to identify prognostic factors. In this study, we aimed to develop a risk score system with broad applicability that can help predict the risk of LOSP-associated mortality. We retrospectively analyzed 100 patients with LOSP after allo-HSCT between June 2009 and July 2017. The assessment variables included immune, nutritional, and metabolic parameters at the onset of LOSP. Of these 100 patients, 45 (45%) eventually died, and 55 (55%) were positive for organisms, most commonly viruses. In the multivariate analysis, higher monocyte count (≥0.20 × 109/L versus <0.20 × 109/L; P = .001), higher albumin level (≥30.5 g/L versus <30.5 g/L; P = .044), lower lactic dehydrogenase level (<250 U/L versus ≥250 U/L; P = .008) and lower blood urea nitrogen concentration (<7.2 mmol/L versus ≥7.2 mmol/L; P = .026) at the onset of LOSP were significantly associated with better 60-day survival. A risk score system based on the foregoing results showed that the probability of 60-day survival decreased with increasing risk factors, from 96.3% in the low-risk group to 49.1% in the intermediate-risk group and 12.5% in the high-risk group. Our results indicate that this scoring system using 4 variables can stratify patients with different probabilities of survival after LOSP, which suggests that patients' immune, nutritional, and metabolic status are crucial factors in determining outcome.

Clinical Factors and Quantitative CT Parameters Associated With ICU Admission in Patients of COVID-19 Pneumonia: A Multicenter Study.

The clinical spectrum of COVID-19 pneumonia is varied. Thus, it is important to identify risk factors at an early stage for predicting deterioration that require transferring the patients to ICU. A retrospective multicenter study was conducted on COVID-19 patients admitted to designated hospitals in China from Jan 17, 2020, to Feb 17, 2020. Clinical presentation, laboratory data, and quantitative CT parameters were also collected. The result showed that increasing risks of ICU admission were associated with age > 60 years (odds ratio [OR], 12.72; 95% confidence interval [CI], 2.42-24.61; P = 0.032), coexisting conditions (OR, 5.55; 95% CI, 1.59-19.38; P = 0.007) and CT derived total opacity percentage (TOP) (OR, 8.0; 95% CI, 1.45-39.29; P = 0.016). In conclusion, older age, coexisting conditions, larger TOP at the time of hospital admission are associated with ICU admission in patients with COVID-19 pneumonia. Early monitoring the progression of the disease and implementing appropriate therapies are warranted.