Vaccines and allergic reactions: The past,the current COVID-19 pandemic,and future perspectives

Vaccines are essential public health tools with a favorable safety profile and prophylactic effectiveness that have historically played significant roles in reducing infectious disease burden in populations, when the majority of individuals are vaccinated. The COVID-19 vaccines are expected to have similar positive impacts on health across the globe. While serious allergic reactions to vaccines are rare, their underlying mechanisms and implications for clinical management should be considered to provide individuals with the safest care possible. In this review, we provide an overview of different types of allergic adverse reactions that can potentially occur after vaccination and individual vaccine components capable of causing the allergic adverse reactions. We present the incidence of allergic adverse reactions during clinical studies and through post-authorization and post-marketing surveillance and provide plausible causes of these reactions based on potential allergenic components present in several common vaccines. Additionally, we review implications for individual diagnosis and management and vaccine manufacturing overall. Finally, we suggest areas for future research.     

Multidisciplinary consensus on sputum induction biosafety during the COVID-19 pandemic

Sputum induction (SI) is the gold standard approach to the non-invasive study of airway inflammation. The differential count of inflammatory cells for SI allows patients with asthma to be classified according to inflammatory phenotypes and predicted therapeutic responses. Since SI involves the generation of aerosols, there is a need to establish a protocol to ensure biosafety in clinical practice during the current COVID-19 pandemic. The multidisciplinary consensus on SI described in this article was developed by 22 experts in SI from different Spanish hospitals who drew on available scientific evidence in achieving consensuated opinions, compiled by means of an electronic survey. We hope that these unified criteria and recommendations will guide health professionals in implementing SI sampling and processing procedures as safely as possible during the COVID-19 pandemic.     

Caring for older adults during the COVID-19 pandemic

BackgroundElderly patients represent a high-risk group with increased risk of death from COVID-19. Despite the number of published studies, several unmet needs in care for older adults exist.ObjectivesTo discuss unmet needs of COVID-19 in this special population.SourcesA literature review for studies on COVID-19 in elderly patients published between December 2019 and November 2021 was performed. Clinical questions were formulated to guide the literature search. The search was conducted in the MEDLINE database, combining specific search terms. Two reviewers independently conducted the search and selected the studies according to the prespecified clinical questions.ContentElderly patients with COVID-19 have peculiar characteristics. They may have atypical clinical presentation, with no fever and with delirium or neurological manifestations as the most common signs, with potential delayed diagnosis and increased risk of death. The reported fatality rates among elderly patients with COVID-19 are extremely high. Several factors, including comorbidities, atypical presentation, and exclusion from intensive care unit care, contribute to this excess of mortality. Age alone is frequently used as a key factor to exclude the elderly from intensive care, but there is evidence that frailty rather than age better predicts the risk of poor outcome in this category. Durability of vaccine efficacy in the elderly remains debated, and the need for a third booster dose is becoming increasingly evident. Finally, efforts to care for elderly patients who have survived after acute COVID-19 should be implemented, considering the high rates of long COVID sequelae and the risk of longitudinal functional and cognitive decline.ImplicationsWe highlight peculiar aspects of COVID-19 in elderly patients and factors contributing to high risk of poor outcome in this category. We also illuminated gaps in current evidence, suggesting future research directions and underlining the need for further studies on the optimal management of elderly patients with COVID-19.     

Discriminating promiscuous from target-specific autoantibodies in COVID-19

Diverse autoantibodies were suggested to contribute to severe outcomes of COVID-19, but their functional implications are largely unclear. ACE2, the SARS-CoV-2 receptor and a key regulator of blood pressure, was described to be one of many targets of autoantibodies in COVID-19. ACE2 in its soluble form (sACE2) is highly elevated in the blood of critically ill patients, raising the question of whether sACE2:spike complexes induce ACE2 reactivity. Screening 247 COVID-19 patients, we observed elevated sACE2 and anti-ACE2 IgG that were poorly correlated. Interestingly, levels of IgGs recognizing ACE2, IFNα2, and CD26 strongly correlated in severe COVID-19, with 15% of sera showing polyreactivity versus 4.1% exhibiting target-directed autoimmunity. Promiscuous autoantibodies failed to impair the activity of ACE2 and IFNα2, while only specific anti-IFNα2 IgG compromised cytokine function. Our study suggests that the detection of autoantibodies in COVID-19 is often attributed to a promiscuous reactivity, potentially misinterpreted as target-specific autoimmunity with functional impact.     

Editorial commentary on special issue of COVID-19 pandemic

This special issue of The Journal of Biomedical Research presents rigorous empirical analysis related to COVID-19 research in responding to the current global COVID-19 pandemic. Selected articles from different disciplines not only offer broader perspectives on combating the outbreaks, but also disseminate the most updated findings on this new challenge for human being to the field.     

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.     

Immunological map in COVID-19

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by SARS-CoV-2, a newly discovered coronavirus that exhibits many similarities with the severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (SARS-CoV and MERS-CoV, respectively). The definite pathogenesis and immunological influences of SARS-CoV-2 have not been fully elucidated. Therefore, we constructed a brief summary comparison of SARS-CoV-2, SARS-CoV, and MERS-CoV infections regarding their immunological changes. In addition, we further investigated the immunological differences between severe and nonsevere COVID-19 cases, and we searched for possible immunological predictors of the patient outcome by reviewing case series studies to date. Possible immunological predictors of a poor outcome are leukocytosis, neutrophilia, lymphopenia (both CD4 and CD8 T cells), an increased neutrophil-to-lymphocyte ratio (NLR), and increased levels of pro-inflammatory cytokines (IL-6 and TNF-α), Th1 cytokines (IL-2 and IFN-γ), regulatory T cell cytokines (IL-10) and Th17 cytokines (IL-17). A more precise immunological map needs to be established, which may assist in diagnosing this disease and facilitate immunological precision medicine treatment.     

Impact of the COVID-19 pandemic on pathological autopsy practices in Japan

During the coronavirus disease 2019 (COVID-19) pandemic, autopsies have provided valuable insights into the pathogenesis of COVID-19. The precise effect of this pandemic on autopsy procedures in Japan, especially in instances unrelated to COVID-19, has not yet been established. Therefore, we conducted a questionnaire survey from December 2020 to January 2021 regarding the status of pathological autopsy practices in Japan during the first year of the COVID-19 pandemic. The questionnaire was sent to 678 medical facilities with pathologists, of which 227 responded. In cases where a confirmed diagnosis of COVID-19 was not made at the time of autopsy, many facilities counted them as suspected COVID-19 cases if pneumonia was suspected clinically. At around half of the sites, autopsies were prohibited for suspected COVID-19 cases. In addition, the number of autopsies of non-COVID-19 cases during the pandemic period was also investigated, and a significant decrease was observed compared with the incidence in the pre-pandemic period. The COVID-19 pandemic has affected not only the autopsies of COVID-19 cases but also the entire practice of pathological autopsies. It is necessary to establish a system that supports the implementation of pathological autopsy practices during the pandemic of an emerging infectious disease.     

National case fatality rates of the COVID-19 pandemic

ObjectivesThe case fatality rate (CFR) of coronavirus disease 2019 (COVID-19) varies significantly between countries. We aimed to describe the associations between health indicators and the national CFRs of COVID-19.MethodsWe identified for each country health indicators potentially associated with the national CFRs of COVID-19. We extracted data for 18 variables from international administrative data sources for 34 member countries of the Organization for Economic Cooperation and Development (OECD). We excluded the collinear variables and examined the 16 variables in multivariable analysis. A dynamic web-based model was developed to analyse and display the associations for the CFRs of COVID-19. We followed the Guideline for Accurate and Transparent Health Estimates Reporting (GATHER).ResultsIn multivariable analysis, the variables significantly associated with the increased CFRs were percentage of obesity in ages >18 years (β = 3.26; 95%CI = 1.20, 5.33; p 0.003), tuberculosis incidence (β = 3.15; 95%CI = 1.09, 5.22; p 0.004), duration (days) since first death due to COVID-19 (β = 2.89; 95%CI = 0.83, 4.96; p 0.008), and median age (β = 2.83; 95%CI = 0.76, 4.89; p 0.009). The COVID-19 test rate (β = –3.54; 95%CI = –5.60, –1.47; p 0.002), hospital bed density (β = –2.47; 95%CI = –4.54, –0.41; p 0.021), and rural population ratio (β = –2.19; 95%CI = –4.25, –0.13; p 0.039) decreased the CFR.ConclusionsThe pandemic hits population-dense cities. Available hospital beds should be increased. Test capacity should be increased to enable more effective diagnostic tests. Older patients and patients with obesity and their caregivers should be warned about a potentially increased risk.     

COVID-19 vaccines: Knowing the unknown

Vaccine development against SARS-CoV-2 has drawn attention around the globe due to the exploding pandemic. Although COVID-19 is caused by a new coronavirus, SARS-CoV-2, previous research on other coronavirus vaccines, such as FIPV, SARS, and MERS, has provided valuable information for the rapid development of COVID-19 vaccine. However, important knowledge gaps remain — some are specific to SARS-CoV-2, others are fundamental to immunology and vaccinology. Here, we discuss areas that need to be addressed for COVID-19 vaccine development, and what can be learned from examples of vaccine development in the past. Since the beginning of the outbreak, the research progress on COVID-19 has been remarkable. We are therefore optimistic about the rapid development of COVID-19 vaccine.     

Impact of the COVID-19 pandemic on the incidence of dengue fever in Peru

Dengue virus and severe acute respiratory syndrome coronavirus 2 coexist in dengue-endemic countries; therefore, the adoption of preventive measures is essential to control the spread of both viruses. We conducted an ecological study to compare the temporal patterns of the incidence of dengue before and during the Coronavirus disease 2019 (COVID-19) pandemic in Peru. A time-series analysis comparing the incidence of dengue using a Student's t test with variance correction was performed. Poisson regression was applied to determine the incidence rate ratio (IRR) of dengue before and during the COVID-19 pandemic. The incidence of dengue was found to be increased in all endemic regions of Peru during the COVID-19 pandemic, with the highest incidences registered in Ica (IRR = 90.14), Huánuco (IRR = 38.6), and Ucayali (IRR = 23.78), with the exception of Piura (IRR = 0.83). The highest increases in the number of dengue cases per million inhabitants were in Ucayali (393.38), Tumbes (233.19), Ica (166.08), and Loreto (129.93). The gradient of dengue cases was positive in all endemic regions during the COVID-19 pandemic. The number of dengue cases per million increased during the COVID-19 pandemic throughout Peru and in several endemic regions, with the exception of Piura.     

Immune-mediated liver injury following COVID-19 vaccination

Liver injury secondary to vaccination is a rare adverse event that has recently come under attention thanks to the continuous pharmacovigilance following the widespread implementation of coronavirus disease 2019 (COVID-19) vaccination protocols. All three most widely distributed severe acute respiratory syndrome coronavirus 2 vaccine formulations, e.g., BNT162b2, mRNA-1273, and ChAdOx1-S, can induce liver injury that may involve immune-mediated pathways and result in autoimmune hepatitis-like presentation that may require therapeutic intervention in the form of corticosteroid administration. Various mechanisms have been proposed in an attempt to highlight immune checkpoint inhibition and thus establish causality with vaccination. The autoimmune features of such a reaction also prompt an in-depth investigation of the newly employed vaccine technologies. Novel vaccine delivery platforms, e.g., mRNA-containing lipid nanoparticles and adenoviral vectors, contribute to the inflammatory background that leads to an exaggerated immune response, while patterns of molecular mimicry between the spike (S) protein and prominent liver antigens may account for the autoimmune presentation. Immune mediators triggered by vaccination or vaccine ingredients per se, including autoreactive antibodies, cytokines, and cytotoxic T-cell populations, may inflict hepatocellular damage through well-established pathways. We aim to review available data associated with immune-mediated liver injury associated with COVID-19 vaccination and elucidate potential mechanisms underlying its pathogenesis.     

Maternal Outcomes and Clinical Characteristics of COVID-19 in Korean Pregnant Women during the Early Period of the Pandemic

The present study aimed to compare the clinical characteristics and outcomes between pregnant women and non-pregnant women of childbearing age (20–49 years old) diagnosed with coronavirus disease 2019 (COVID-19) during the initial stage of the COVID-19 pandemic in the Republic of Korea. This nationwide observational study included the information of COVID-19 patients collected by the Korea Disease Control and Prevention Agency from January 2020 to April 2021. Among 5,647 COVID-19 patients, 2,444 (43.3%) were women of childbearing age and 19 were pregnant. None of the pregnant women died. However, 4 deaths occurred among non-pregnant women aged 20–49 years. None of the 19 pregnant women with COVID-19 were admitted to the intensive care unit: they were admitted to the general ward, and none of them required supplemental oxygen. In conclusion, none of the pregnant women with COVID-19 experienced severe infection or death, unlike non-pregnant women of childbearing age.