Risk-based cost-benefit analysis of alternative vaccines against COVID-19 in Brazil: Coronavac vs. Astrazeneca vs. Pfizer

We propose a probabilistic model to quantify the cost-benefit of mass Vaccination Scenarios (VSs) against COVID-19. Through this approach, we conduct a six-month simulation, from August 31st, 2021 to March 3rd, 2022, of nine VSs, i.e., the three primary vaccine brands in Brazil (CoronaVac, AstraZeneca and Pfizer), each with three different vaccination rates (2nd doses per week). Since each vaccine has different individual-level effectiveness, we measure the population-level benefit as the probability of reaching herd immunity (HI). We quantify and categorize the cost-benefit of VSs through risk graphs that show: (i) monetary cost vs. probability of reaching HI; and (ii) number of new deaths vs. probability of reaching HI. Results show that AstraZeneca has the best cost-benefit when prioritizing acquisition costs, while Pfizer is the most cost-beneficial when prioritizing the number of deaths. This work provides helpful information that can aid public health authorities in Brazil to better plan VSs. Furthermore, our approach is not restricted to Brazil, the COVID-19 pandemic, or the mentioned vaccine brands. Indeed, the method is flexible so that this study can be a valuable reference for future cost-benefit analyses in other countries and pandemics, especially in the early stages of vaccination, when data is scarce and uncertainty is high.     

新型冠状病毒肺炎出院患者生活质量及影响因素研究

目的:了解新型冠状病毒肺炎(COVID-19)患者出院后的生活质量及其影响因素,为优化早期干预方案,预防社区生活受限,制定相应社区康复措施提供依据。方法:选择2020年3—4月在武汉华润武钢总医院治愈出院的COVID-19患者57例,于2020年4—5月通过"问卷星"平台采用简明健康状况调查量表(SF-12V2)调查患者的生活质量;采用焦虑自评量表(SAS)调查患者的焦虑状态;采用抑郁自评量表(SDS)调查患者的抑郁状态;采用呼吸困难指数量表(mMRC)调查患者的呼吸困难程度。比较不同特征COVID-19患者生活质量的差异;分析患者生活质量与焦虑、抑郁和呼吸困难程度的相关性及其相关的影响因素。结果:共发放57份调查问卷,剔除重复及无效问卷3份,获得有效问卷54份,问卷有效率达94.74%。(1)COVID-19出院后患者生活质量情况:生理总评分和心理总评分分别为(37.02±12.32)分、(38.46±14.42)分;呼吸困难等级0~3级的分别为3例(5.56%)、45例(83.33%)、5例(9.26%)、1例(1.85%);有19例(35.19%)存在焦虑情绪(SAS≥50分)和抑郁情绪(SDS≥53分)。(2)不同特征COVID-19患者生活质量比较:不同疾病分型的患者在生理总评分方面差异有统计学意义(P<0.05)。(3)生活质量与焦虑、抑郁和呼吸困难程度的相关性分析:Pearson相关分析结果显示,SF-12V2生理总评分与焦虑程度(r=-0.34,P=0.011)和呼吸困难程度(r=-0.39,P=0.003)之间存在负相关性,SF-12V2心理总评分与焦虑程度(r=-0.46,P=0.001)和抑郁程度(r=-0.40,P=0.002)之间存在负相关性。(4)COVID-19患者生活质量的影响因素分析:多元线性回归分析显示,性别(β=8.27)、抑郁程度(β=-0.34)和疾病分型(β=-11.68)是患者SF-12V2生理总评分的重要决定因素(P<0.05);焦虑程度(β=-0.62)是患者SF-12V2心理总评分的重要决定因素(P<0.05)。结论:COVID-19出院患者存在呼吸困难、焦虑抑郁情绪和生活质量下降的问题;性别、疾病分型、抑郁程度和焦虑程度是COVID-19患者生活质量下降的重要因素。COVID-19患者(特别是女性患者和重型患者)出院后要尽早进行抑郁症和焦虑症的筛查和干预,减少患者负性情绪,鼓励患者适当参与康复训练,提高呼吸功能,从而促进生活质量提高。     

Development of an IgG-Fc fusion COVID-19 subunit vaccine,AKS-452

AKS-452 is a biologically-engineered vaccine comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain antigen (Ag) and human IgG1 Fc (SP/RBD-Fc) in clinical development for the induction and augmentation of neutralizing IgG titers against SARS-CoV-2 viral infection to address the COVID-19 pandemic. The Fc moiety is designed to enhance immunogenicity by increasing uptake via Fc-receptors (FcγR) on Ag-presenting cells (APCs) and prolonging exposure due to neonatal Fc receptor (FcRn) recycling. AKS-452 induced approximately 20-fold greater neutralizing IgG titers in mice relative to those induced by SP/RBD without the Fc moiety and induced comparable long-term neutralizing titers with a single dose vs. two doses. To further enhance immunogenicity, AKS-452 was evaluated in formulations containing a panel of adjuvants in which the water-in-oil adjuvant, Montanide™ ISA 720, enhanced neutralizing IgG titers by approximately 7-fold after one and two doses in mice, including the neutralization of live SARS-CoV-2 virus infection of VERO-E6 cells. Furthermore, ISA 720-adjuvanted AKS-452 was immunogenic in rabbits and non-human primates (NHPs) and protected from infection and clinical symptoms with live SARS-CoV-2 virus in NHPs (USA-WA1/2020 viral strain) and the K18 human ACE2-trangenic (K18-huACE2-Tg) mouse (South African B.1.351 viral variant). These preclinical studies support the initiation of Phase I clinical studies with adjuvanted AKS-452 with the expectation that this room-temperature stable, Fc-fusion subunit vaccine can be rapidly and inexpensively manufactured to provide billions of doses per year especially in regions where the cold-chain is difficult to maintain.     

Supraclavicular lymphadenopathy following COVID-19 vaccination: an increasing presentation to the two-week wait neck lump clinic?

The first COVID-19 vaccination was given in December 2020 and there is an effort to vaccinate the international population on a massive scale. Common side effects from the vaccine include headache and tiredness. Regional lymphadenopathy has been described in relation to other vaccines. We describe two cases of supraclavicular reactive lymphadenopathy presenting in patients who had the COVID vaccination in the ipsilateral arm. Awareness of this diagnosis is important for patients presenting to the neck lump clinic.     

Diffuse skin rash in tropical areas: Dengue fever or COVID-19?

There have been several clinical manifestations associated with SARS-CoV-2 infection since 2019, including dermatological signs and symptoms. In this article, the authors report a case of a previously healthy patient with COVID-19 who was mistakenly diagnosed with dengue fever due to a skin rash. By the time the patient's investigation was initiated, Joinville (Santa Catarina, Brazil) had approximately 5,000 confirmed cases of dengue fever and 1,700 cases of COVID-19 in 2020. Thus, the authors emphasize that in endemic regions such as Brazil, the two diseases must be considered until proven otherwise. Finally, the authors warn of the possibility of co-infection with these two viruses in regions that are facing both epidemics at the same time.     

Dipeptidyl peptidase 4 inhibitors in COVID-19: Beyond glycemic control

Coronavirus disease 2019 (COVID-19) is associated with a high risk of mortality and complications in patients with diabetes mellitus. Achieving good glycemic control is very important in diabetic patients to reduce complications and mortality due to COVID-19. Recent studies have shown the mortality benefit and anti-inflammatory effects of Dipeptidyl-peptidase-4 inhibitors (DPP-4i) in diabetic patients with COVID-19. DPP-4i may have a beneficial role in halting the severity of infection primarily by three routes, namely viral entry inhibition, anti-inflammatory and anti-fibrotic effects and glycemic control. This has raised the pro-mising hypothesis that DPP-4i might be an optimal strategy for treating COVID-19 in patients with diabetes. This review aims to summarise the possible therapeutic non-glycemic effects of DPP-4i in diabetic patients diagnosed with COVID-19 in the light of available evidence.     

Lipase elevation on admission predicts worse clinical outcomes in patients with COVID-19

Background and objectivesHyperlipasemia is highly prevalent among coronavirus disease 2019 (COVID-19) patients. The aim of this study was to assess the effect of lipase activity, measured at the time of admission, on the clinical course and mortality in COVID-19 patients.MethodsThe population of this study comprised 12,139 patients who were hospitalized due to COVID-19 between June 2020 and June 2021 in a pandemic hospital. Of these, 8819 patients were excluded from the study due to missing data, four patients were excluded due to a diagnosis of acute pancreatitis (according to the revised Atlanta criteria), and 72 patients were excluded due to alcohol use or having a history of chronic pancreatitis. The final study sample consisted of the remaining 3244 COVID-19 patients. Laboratory results, intensive care unit (ICU) follow-up periods, the need for mechanical ventilation, and mortality rates were compared between the normal lipase activity and high lipase activity groups.ResultsThere were 968 (29.8%) patients with high lipase activity at the time of admission. The rate of ICU admission was 36.1% vs. 9.9% (p < 0.001), mechanical ventilation requirement rates were 33.7% vs. 8.3% (p < 0.001), and mortality rates were as 24.6% vs. 6.4% (p < 0.001) in the high lipase activity group compared to the normal lipase activity group. Multivariate regression analysis revealed that high lipase activity was an independent factor in predicting mortality in hospitalized COVID-19 patients (odds ratio [OR]: 3.191, p < 0.001).ConclusionElevated lipase activity without acute pancreatitis at the time of admission in COVID-19 patients was determined as an independent predictor of poor prognosis.     

Vaccines and autoimmunity during the COVID-19 pandemic

To control the pandemic, efficient vaccines must be applied to the population, including patients with autoimmune diseases. Therefore, one can expect that coronavirus disease 2019 (COVID-19) vaccines may influence the underlying autoimmune processes in these patients. Additionally, it is essential to understand whether COVID-19 vaccines would be effective, safe, and provide long-lasting immunological protection and memory. However, the currently available and approved COVID-19 vaccines turned out to be safe, effective, and reliable in patients with autoimmune inflammatory and rheumatic diseases. Furthermore, most patients said they felt safer after getting vaccinations for COVID-19 and reported enhanced overall quality of life and psychological wellbeing. In general, the COVID-19 vaccines have been highly tolerated by autoimmune patients. Such findings might comfort patients who are reluctant to use COVID-19 vaccines and assist doctors in guiding their patients into receiving vaccinations more easily and quickly.