Diagnostic accuracy of vaccine and vaccine excipient testing in the setting of allergic reactions to COVID-19 vaccines: A systematic review and meta-analysis

For persons with immediate allergic reactions to mRNA COVID-19 vaccines, skin testing (ST) to the vaccine/excipients (polyethylene glycol[PEG] and polysorbate 80 [PS]) has been recommended, but has unknown accuracy. To assess vaccine/excipient ST accuracy in predicting all-severity immediate allergic reactions upon re-vaccination, systematic review was performed searching Medline, EMBASE, Web of Science, and the WHO global coronavirus database (inception-Oct 4, 2021) for studies addressing immediate (≤4 h post-vaccination) all-severity allergic reactions to 2nd mRNA COVID-19 vaccination in persons with 1st dose immediate allergic reactions. Cases evaluating delayed reactions, change of vaccine platform, or revaccination without vaccine/excipient ST were excluded. Meta-analysis of diagnostic testing accuracy was performed using Bayesian methods. The GRADE approach evaluated certainty of the evidence, and QUADAS-2 assessed risk of bias. Among 20 studies of mRNA COVID-19 first dose vaccine reactions, 317 individuals underwent 578 ST to any one or combination of vaccine, PEG, or PS, and were re-vaccinated with the same vaccine. Test sensitivity for either mRNA vaccine was 0.2 (95%CrI 0.01–0.52) and specificity 0.97 (95%CrI 0.9–1). PEG test sensitivity was 0.02 (95%CrI 0.00–0.07) and specificity 0.99 (95%CrI 0.96–1). PS test sensitivity was 0.03 (95%CrI 0.00–0.0.11) and specificity 0.97 (95%CrI 0.91–1). Combined for use of any of the 3 testing agents, sensitivity was 0.03 (95%CrI 0.00–0.08) and specificity was 0.98 (95%CrI 0.95–1.00). Certainty of evidence was moderate. ST has low sensitivity but high specificity in predicting all-severity repeat immediate allergic reactions to the same agent, among persons with 1st dose immediate allergic reactions to mRNA COVID-19 vaccines. mRNA COVID-19 vaccine or excipient ST has limited risk assessment utility.     

A survey of mechanisms underlying current and potential COVID-19 vaccines

The emergence of SARS-CoV-2 caught the world off guard resulting in a global health crisis. Even though COVID-19 have caused the death of millions of people and many countries are still battling waves of infections, the odds of the pandemic ending soon have turned significantly in our favor. The key has been the development and distribution of a broad range of vaccines in record time. In this survey, we summarize the immunology required to understand the mechanisms underlying current and potential COVID-19 vaccines. Furthermore, we provide an up to date (according to data from WHO May 27, 2022) overview of the vaccine landscape consisting of 11 approved vaccines in phase 4, and a pipeline consisting of 161 vaccine candidates in clinical development and 198 in preclinical development (World Health Organization, Draft landscape and tracker of COVID-19 candidate vaccines [Internet], WHO, 2022). Our focus is to provide an understanding of the underlying biological mode of action of different vaccine platform designs, their advantages and disadvantages, rather than a deep dive into safety and efficacy data. We further present arguments concerning why a broad range of vaccines are needed and discuss future challenges.     

RNA-Based COVID-19 vaccine candidates with clinical phase trials in progress

Due to the COVID-19 infection, which was recognized as a global pandemic by the WHO on March 11, 2020, the number of cases and disease-related deaths increases day by day globally. For this reason, antiviral agents used in treatment and vaccines, the most effective weapon in prevention, continue to be the most popular topic of the plan. Several situations are expected to affect the course of the pandemic. The loss of the ability of the virus to mutate and cause disease, the fact that those who become immunized by having the disease in the society reach a critical rate and create social immunity (herd immunity), and the provision of social immunity with effective vaccination can be counted as some of these situations.Candidate vaccines in the clinical phase among RNA-based vaccines: This review aimed to examine COVID-19 vaccine candidates using RNA technology and compile its current data. We used PubMed, Google Scholar, and World Health Organization (WHO) databases. Also, we followed up on the latest news and developments on vaccine companies’ websites.Conclusion: Vaccination trials, which started due to the seriousness and urgency of the situation that we are in, continue exceptionally quickly and effectively. As per the WHO›s data on July 9, 2021, there have been 291 vaccine trials, 107 of which are in the clinical phase, and 18 (16%) of the vaccine candidates in the clinical phase are RNA-based vaccines. Also, the number of RNA-based vaccines with ongoing preclinical trials is 2     

Underrepresentation of older adults in clinical trials on COVID-19 vaccines: A systematic review

During the COVID-19 pandemic older subjects have been disproportionately affected by the disease. Vaccination is a fundamental intervention to prevent the negative consequences of COVID-19, but it is not known if the needs and vulnerabilities of older people are adequately addressed by their inclusion in randomized clinical trials (RCTs) evaluating the efficacy of vaccines for COVID-19. Given this background, we aimed to evaluate if current and ongoing phase II-III RCTs evaluating the efficacy of COVID-19 vaccines included a representative sample of older people. A systematic literature search in PubMed and Clinicaltrials.gov was performed until May 01st, 2021. Among 474 abstracts initially retrieved, 20 RCTs (ten already published, ten ongoing) were included. In the ten studies already published, the mean age of participants was 45.2 ± 11.9 years and only 9.83% of the participants were more than 65 years, 1.66% more than 75 years and less than 1% (0.55%) more than 85 years. In the ten ongoing RCTs, many of the studies aimed at including participants older than 18 years, with one study including participants between 18 and 84 years, and two between 21 and 100 years. In conclusion, our systematic review demonstrates that in published and ongoing phase II-III randomized clinical trials evaluating the efficacy of COVID-19 vaccines only a tiny fraction of the most vulnerable group of older people was included, although they clearly were the first population that had to be vaccinated.     

Fewer non-COVID-19 respiratory tract infections and gastrointestinal infections during the COVID-19 pandemic

For preventing the spread of the coronavirus disease 2019 (COVID-19) pandemic, measures like wearing masks, social distancing, and hand hygiene played crucial roles. These measures may also have affected the expansion of other infectious diseases like respiratory tract infections (RTI) and gastro-intestinal infections (GII). Therefore, we aimed to investigate non-COVID-19 related RTI and GII during the COVID-19 pandemic. Patients with a diagnosis of an acute RTI (different locations) or acute GII documented anonymously in 994 general practitioner (GP) or 192 pediatrician practices in Germany were included. We compared the prevalence of acute RTI and GII between April 2019–March 2020 and April 2020–March 2021. In GP practices, 715,440 patients were diagnosed with RTI or GII in the nonpandemic period versus 468,753 in the pandemic period; the same trend was observed by pediatricians (275,033 vs. 165,127). By GPs, the strongest decrease was observed for the diagnosis of influenza (?71%, p < 0.001), followed by acute laryngitis (?64%, p < 0.001), acute lower respiratory infections (bronchitis) (?62%, p < 0.001), and intestinal infections (?40%, p < 0.001). In contrast, the relatively rare viral pneumonia strongly increased by 229% (p < 0.001). In pediatrician practices, there was a strong decrease in infection diagnoses, especially influenza (?90%, p < 0.001), pneumonia (?73%, p < 0.001 viral; ?76%, p < 0.001 other pneumonias), and acute sinusitis (?66%, p < 0.001). No increase was observed for viral pneumonia in children. The considerable limitations concerning social life implemented during the COVID-19 pandemic to combat the spread of SARS-CoV-2 also resulted in an inadvertent but welcome reduction in other non-Covid-19 respiratory tract and gastro-intestinal infections.     

COVID-19 and impairment of mental health: public health perspective

ObjectivesThe objective of the article is to understand the impact of COVID-19 on the mental health of the members of the general population.IntroductionThe coronavirus disease-2019 (COVID-19) pandemic has forced the public health authorities to implement unprecedented public health measures with an intention to control the spread of the infection.MethodsAn extensive search of all materials related to the topic was carried out in the PubMed search engine and World Health Organization website and a total of 27 articles were selected based upon the suitability with the current review objectives.ResultsIn order to reduce the caseload and interrupt the chain of transmission of the novel viral infection, it was envisaged that people should stay indoors unless it is extremely essential. This intervention did play its part in reducing the caseload, but significantly affected the daily routine of the people, which in turn accounted for a significant impact on the mental health of the people. Considering the ongoing development and the impact of COVID-19 infection on the mental health of people, there is an immense need to implement strategies to improve the lifestyle of the general population and the health care professionals.ConclusionTo conclude, the ongoing COVID-19 pandemic has created a state of public health emergency on the global scale. The infection has impacted people from all walks of life and is also responsible for precipitating a number of psychological and mental disorders. Thus, it is the need of the hour to identify those individuals who are prone to psychological disorders, and take urgent steps to ensure the preservation and improvement of the mental health of people.     

Caution in underrepresentation of older adults in clinical trials on COVID-19 vaccines

We read with great interest the article “Underrepresentation of older adults in clinical trials on COVID-19 vaccines: A systematic review” written by Nicola Veronese et al. This important work demonstrated that medications and vaccines commonly used in older adults have not been adequately evaluated. Concerning this systematic review, we shall like to mention some certain points deserved to be attended by the authors.     

新型冠状病毒肺炎疫情对一线临床护士的冲击程度

研究显示[1-2],面对新型冠状病毒肺炎(CO-VID-19)疫情等突发传染性重大公共卫生事件,人们往往会有不同程度的压力反应和创伤后应激障碍等冲击表现,导致不同的心理问题。因此早期识别事件对人们的冲击程度并采取针对性的干预措施具有重要意义。     

Cost-effectiveness analysis of COVID-19 vaccination in Poland

IntroductionThe aim of our study was to assess the potential value of the Comirnaty vaccine (BNT162b2) in Poland. A model was used to estimate patient events, direct medical costs, utilities, and cost-effectiveness for 1 year with and without implementation of the vaccine.Material and methodsThe Markov model with 1-week cycles was used to estimate patient events, direct medical costs, utilities, and cost-effectiveness for 1 year with and without implementing the Comirnaty vaccine in Poland. The incremental cost per quality-adjusted life-year (QALY) gained vs. no vaccine was calculated for the general population and selected age-groups. All costs are reported in PLN (average exchange rate in 2020: 1 EUR = 4.44 PLN).ResultsIn the base case analysis the incremental cost per QALY gained associated with vaccinating the whole population is 6249 PLN. For individuals aged 60–69 years and > 80 years vaccination is less costly and more effective than no vaccination. The incremental cost per QALY gained when vaccinating individuals aged 40–49 and 30–39 years is 28,135 PLN and 67,823 PLN, respectively. In the general population and in younger subpopulations the incremental cost-effectiveness ratio is most sensitive to the vaccine effectiveness, vaccine price, and SARS-CoV-2 infection rates.ConclusionsWhen prioritization is required due to supply constraints, vaccination of the elderly is justified because it gives the highest number of QALY gained and generates savings for the health care system. Continual updates of the model concerning vaccine real-life effectiveness and epidemic course are required to refine the prioritisation scheme in the future.     

Mucosal COVID-19 vaccines: Risks,benefits and control of the pandemic

Based on mucosal immunization to promote both mucosal and systemic immune responses, next-generation coronavirus disease 2019 (COVID-19) vaccines would be administered intranasally or orally. The goal of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines is to provide adequate immune protection and avoid severe disease and death. Mucosal vaccine candidates for COVID-19 including vector vaccines, recombinant subunit vaccines and live attenuated vaccines are under development. Furthermore, subunit protein vac-cines and virus-vectored vaccines have made substantial progress in preclinical and clinical settings, resulting in SARS-CoV-2 intranasal vaccines based on the previously successfully used nasal vaccines. Additional to their ability to trigger stable, protective immune responses at the sites of pathogenic infection, the development of ‘specific’ mucosal vaccines targeting coronavirus antigens could be an excellent option for preventing future pandemics. However, their efficacy and safety should be confirmed.     

The value of clinical parameters in predicting the severity of COVID-19

To study the relationship between clinical indexes and the severity of coronavirus disease 2019 (COVID-19), and to explore its role in predicting the severity of COVID-19. Clinical data of 443 patients with COVID-19 admitted to our hospital were retrospectively analyzed, which were divided into nonsevere group (n = 304) and severe group (n = 139) according to their condition. Clinical indicators were compared between different groups. The differences in sex, age, the proportion of patients with combined heart disease, leukocyte, neutrophil-to-lymphocyte ratio (NLR), neutrophil, lymphocyte, platelet, D-dimer, C-reactive protein (CRP), procalcitonin, lactate dehydrogenase, and albumin on admission between the two groups were statistically significant (P < .05). Multivariate logistic regression analysis showed NLR and CRP were independent risk factors for severe COVID-19. Platelets were independent protective factors for severe COVID-19. The receiver operating characteristic (ROC) curve analysis demonstrated area under the curve of NLR, platelet, CRP, and combination was 0.737, 0.634, 0.734, and 0.774, respectively. NLR, CRP, and platelets can effectively assess the severity of COVID-19, among which NLR is the best predictor of severe COVID-19, and the combination of three clinical indicators can further predict severe COVID-19.     

A comparison of the protective effect of vaccination and clinical features between the SARS-CoV-2 wild-type strain and Delta (B.1.617.2) variant

IntroductionThis study aimed to investigate the clinical features and vaccine effectiveness of patients with the SARS-CoV-2 wild-type strain and the Delta variant.MethodsWe retrospectively evaluated patients with the SARS-CoV-2 wild-type strain and the Delta variant.ResultsThe Delta-variant group showed a higher infection rate in minors, who had higher incidence of anosmia or dysgeusia and shorter incubation period. Unvaccinated patients had a 15.59-fold higher risk of severe classification than vaccinated patients. The viral clearance time was significantly shorter in the Delta-variant group.ConclusionsThe Delta-variant group show higher transmissibility, and vaccination reduces the incidence of severe classification and promotes viral clearance.     

From asymptomatic to critical illness: decoding various clinical stages of COVID-19

The clinical course of COVID-19 is variable, with clinical manifestation ranging from 81% mild course to 14% severe course along with 5% critical course in patients. The asymptomatic course is reported to potentially range between 20% and 70% (avg. 33%). A more severe course is seen in the elderly, those with various chronic diseases, and the immunosuppressed, where the case fatality rate is higher in these risk groups. The disease progresses with various symptoms, such as fever, cough, shortness of breath, malaise, myalgia, taste and smell disorders, diarrhea, sore throat, headache, and conjunctivitis. The disease begins with shortness of breath, indicative of lung damage, after an average of 7 to 10 days, and progresses in ARDS, sepsis, and septic shock. Some patients quickly enter shortness of breath, while others gradually develop shortness of breath and chest tightness and burning. The risk factors for a poor prognosis are age, comorbidities, and changes in laboratory tests. Secondary bacterial and fungal infections frequently develop with steroids and immunosuppressants, especially in the intensive care unit. Frequent complications in hospitalized patients include pneumonia (75%), ARDS (15%), acute renal failure (9%), and acute liver injury (19%). An increased incidence of heart damage is observed, including acute heart failure, arrhythmias, and myocarditis. Of the patients hospitalized due to COVID-19, 10%–25% present with prothrombotic coagulopathy, resulting in venous and arterial thromboembolic events. The most common extrapulmonary symptom is neuropsychiatric involvement, frequently accompanied by insomnia, an impediment to remembering, and an altered state of consciousness. During the course of COVID-19, patients undergo some pathological changes (severe lymphopenia, high levels of C-reactive protein, D-dimer, ferritin, etc.) depending on the condition and exposure level of the affected systems as shown by various laboratory tests. The relevant tests are the guiding elements of risk assessment, clinical monitoring, disease severity, and prognosis setting and therapy decision-making processes.