Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Ανίχνευση προγνωστικών βιολογικών δεικτών στο μεταστατικό καρκίνο του παχέος εντέρου και τοπικώς προχωρημένο καρκίνο του ορθού

Colorectal cancer (CRC) is the third most common type of cancer for both sexes and one of the leading causes of cancer-related mortality worldwide. These characteristics have attracted numerous research teams across the globe, creating the right conditions for significant advances on unveiling the underlying molecular biology, identifying new diagnostic tests and expanding treatment options while introducing personalized ones. However, despite numerous attempts to identify effective prognostic and predictive tools only little progress has been made. This is because in most studies the size of patient sets is rather small which prevents safe conclusions to be drawn. At the same time, the relatively high cost and complexity of the proposed techniques makes the implementation of these tools deterrent. Therefore, current practice in CRC management continues to evaluate patient response after completion of their treatment. This is of great importance, since patients who develop chemoresistance will be identified with substantial delay, leaving both them and health care systems challenging with the unnecessary side effects and increased cost of ineffective treatments. Thus, in order to optimize clinical practice, the identification of sensitive and easy-to-use tools that will provide valuable information about the prognosis of each patient is emerging as crucial. Such tools are expected to benefit patients with CRC and clinicians directly (as they will be able to discontinue ineffective treatment at an early stage) but also indirectly the health care system given the more efficient management of resources to treat these patients. In addition, it should be noted the possibility of expanding the validation of the prognostic value of these tools to other types of cancer. It is well established that molecular biomarkers can serve as promising candidates for this purpose. In view of the above, the present study focused on validating the clinical value of two new biomarkers: a) micronuclei frequency (MNf) in 55 metastatic CRC (mCRC) and 21 locally advanced rectal cancer (laRC) patients using cytokinesis block micronucleus assay (CBMN assay) and b) telomerase activity (TA) in 23 mCRC and 5 laRC patients using TRAP-ELISA. These biomarkers were chosen on the basis of their close relationship to chromosomal instability (CIN) and aberrant genetic function, both major hallmarks in colorectal carcinogenesis. All biomarkers were evaluated in peripheral blood lymphocytes (PBLs) before, in the middle and at the end of treatment (approximately 0, 3 and 6 months) for mCRC patients and before, at the end of treatment and after surgery for patients with laRC. Overall, MNf demonstrated significant prognostic value, since a reduction of <29% between middle and initial MNf measurements can discriminate between progressive and stable/responsive disease with a sensitivity of 36% and a specificity of 87.0%. It also appeared to be able to identify responsive disease with sensitivity of 72.7% and specificity 59.3%. Regarding TA, no statistically significant difference was found between the disease response groups in any of the sampling points (before the beginning of chemotherapy p = 0.256, in the middle of the chemotherapy p = 0.072, at the end of the chemotherapy p = 0.096). However, it was observed that in the middle and last sampling points, the patients with progressive disease had an increase in TA while the concomitant comparison between groups (disease progression vs stable disease, disease progression vs partial response, disease progression vs complete response) revealed a significant trend to increase TA in patients with disease progression (middle sampling point p = 0.072, final sampling point p = 0.096). However, it was not possible to further statistically compare TA values of patients with progressive disease between the three sampling points due to the absence of a normal distribution of TA values, possibly due to the small sample we studied. In conclusion, the findings of this study demonstrate the value of MN frequency as a promising prognostic biomarker for monitoring the response to treatment of patients with CRC, while TA should be evaluated in a larger group of patients to document its possible change during chemotherapy and its related clinical significance.Ο κολοορθικός καρκίνος (ΚΟΚ) είναι ο τρίτος πιο κοινός τύπος καρκίνου και για τα δύο φύλα και μία από τις κύριες αιτίες θανάτου σχετιζόμενο με καρκίνο παγκοσμίως. Αυτά τα χαρακτηριστικά έχουν προσελκύσει πολλές ερευνητικές ομάδες σε όλο τον κόσμο δημιουργώντας τις κατάλληλες προϋποθέσεις για την επίτευξη σημαντικής προόδου στην αποκάλυψη της υποκείμενης μοριακής βιολογίας, στον εντοπισμό νέων διαγνωστικών test και στην εισαγωγή νέων και εξατομικευμένων θεραπευτικών επιλογών. Ωστόσο, παρά τις πολυάριθμες προσπάθειες για τον εντοπισμό αποτελεσματικών προγνωστικών εργαλείων, τα αποτελέσματα δεν είναι ιδιαίτερα ενθαρρυντικά. Αυτό συμβαίνει γιατί στις περισσότερες μελέτες ο μικρός αριθμός των υπό μελέτη ασθενών δεν επιτρέπει την ασφαλή εξαγωγή συμπερασμάτων. Παράλληλα, το σχετικά υψηλό κόστος αλλά και η πολυπλοκότητα των προτεινόμενων τεχνικών καθιστά αποτρεπτική την εφαρμογή των εν λόγω εργαλείων. Ως εκ τούτου, η τρέχουσα πρακτική στη διαχείριση του ΚΟΚ εξακολουθεί να αξιολογεί την ανταπόκριση των ασθενών κατόπιν ολοκλήρωσης της θεραπείας τους. Αυτό έχει μεγάλη σημασία, καθώς οι ασθενείς που αναπτύσσουν χημειοανθεκτικότητα, θα αναγνωριστούν με μεγάλη καθυστέρηση, αφήνοντας τόσο αυτούς όσο και τα συστήματα υγείας εκτεθειμένους να αντιμετωπίσουν τις περιττές παρενέργειες και το αυξημένο κόστος των αναποτελεσματικών θεραπειών. Έτσι, προκειμένου να βελτιστοποιηθεί η κλινική πρακτική, αναδεικνύεται ως ζωτικής σημασίας η ταυτοποίηση ευαίσθητων και εύχρηστων εργαλείων που θα παρέχουν πολύτιμες πληροφορίες σχετικά με την πρόγνωση της πορείας κάθε ασθενούς. Τέτοια εργαλεία αναμένεται να ωφελήσουν άμεσα τους ασθενείς με ΚΟΚ και τους κλινικούς ιατρούς (αφού θα είναι σε θέση να διακόψουν μια αναποτελεσματική θεραπεία σε πρώιμο στάδιο) αλλά έμμεσα και το σύστημα υγείας δεδομένης της αποδοτικότερης διαχείρισης των πόρων για την θεραπεία αυτών των ασθενών. Επί πλέον πρέπει να σημειωθεί η δυνατότητα επέκτασης της αξιολόγησης της προγνωστικής αξίας των εργαλείων αυτών και σε άλλους τύπου καρκίνου. Ένας μεγάλος αριθμός δεδομένων δείχνει ότι οι μοριακοί βιοδείκτες είναι πολλά υποσχόμενοι υποψήφιοι για αυτόν τον σκοπό. Έχοντας τα ανωτέρω υπ όψιν, η παρούσα μελέτη επικεντρώθηκε στην διερεύνηση της κλινικής αξίας δύο νέων βιοδεικτών: α) της συχνότητας μικροπυρήνων (ΣΜ) σε 55 ασθενείς με μεταστατικό ΚΟΚ (μΚΟΚ) και 21 με τοπικά προχωρημένο καρκίνο του ορθού (τπΚΟ) χρησιμοποιώντας την τεχνική cytokinesis block micronucleus assay (CBMN) και β) της ενεργότητας τελομεράσης (ΕΤ) σε 23 μΚΟΚ και 5 τπΚΟ ασθενείς χρησιμοποιώντας την τεχνική της TRAP-ELISA. Αυτοί οι βιοδείκτες επιλέχθηκαν βάσει της στενής τους σχέσης με τη χρωμοσωμική αστάθεια και τη διαταραγμένη γενετική λειτουργία, αμφότερα ουσιαστικά γνωρίσματα στην καρκινογένεση του παχέος εντέρου. Όλοι οι βιοδείκτες αξιολογήθηκαν σε λεμφοκύτταρα περιφερικού αίματος πριν, στο μέσο και στο τέλος της θεραπείας (περίπου 0, 3 και 6 μήνες) για ασθενείς με μΚΟΚ και πριν, στο τέλος της θεραπείας και μετά από χειρουργική επέμβαση για ασθενείς με τπΚΟ. Συνολικά, η ΣΜ έδειξε σημαντική προγνωστική αξία, καθώς μια μείωσή <29% μεταξύ των μεσαίων και των αρχικών μετρήσεων μπορεί να διακρίνει μεταξύ εξελισσόμενης και σταθερής / ανταποκρινόμενης νόσου με ευαισθησία 36% και ειδικότητα 87,0%. Ακόμα φάνηκε να είναι σε θέση να αναγνωρίσει την ανταπόκριση νόσου με ευαισθησία 72,7 % και ειδικότητα 59,3%. Αναφορικά δε με την ΕΤ, δεν αποδείχθηκε στατιστικά σημαντική διαφορά μεταξύ των ομάδων ανταπόκρισης νόσου σε καμία από τις μετρήσεις (προ της έναρξης της χημειοθεραπείας p = 0.256, στη μέση της χημειοθεραπείας p=0.072, στο τέλος της χημειοθεραπείας p=0.096). Ωστόσο, παρατηρήθηκε ότι στη μέση και τελευταία μέτρηση οι ασθενείς με πρόοδο νόσου είχαν αύξηση της ΕΤ ενώ η σύγκριση των υπολοίπων ομάδων με αυτή την ομάδα (πρόοδος νόσου vs σταθερή νόσος, πρόοδος νόσου vs μερική ανταπόκριση, πρόοδος νόσου vs πλήρης ανταπόκριση) ανέδειξε μια σημαντική τάση στην αύξηση της ΕΤ στους ασθενείς με πρόοδο νόσου (μέση μέτρηση p=0.072, τελική μέτρηση p=0.096). Παρ’ όλα αυτά, δεν κατέστη δυνατή η περαιτέρω στατιστική μελέτη των ασθενών με πρόοδο νόσου στις τρεις φάσεις της χημειοθεραπείας εξ’ αιτίας της απουσίας κανονικής κατανομής των τιμών της ΕΤ πιθανά λόγω του μικρού δείγματος που μελετήσαμε. Συνοπτικά, τα ευρήματα της μελέτης αυτής καταδεικνύουν την αξία της συχνότητας των μικροπυρήνων ως προγνωστικού βιοδείκτη για την παρακολούθηση της ανταπόκρισης στη θεραπεία ασθενών με ΚΟΚ, ενώ η ΕΤ πρέπει να αξιολογηθεί σε μια μεγαλύτερη ομάδα ασθενών για να τεκμηριωθεί η πιθανή μεταβολή της κατά τη διάρκεια της χημειοθεραπείας οπότε και η κλινική της σημασία

Oral Bacteria and Intestinal Dysbiosis in Colorectal Cancer

The human organism coexists with its microbiota in a symbiotic relationship. These polymicrobial communities are involved in many crucial functions, such as immunity, protection against pathogens, and metabolism of dietary compounds, thus maintaining homeostasis. The oral cavity and the colon, although distant anatomic regions, are both highly colonized by distinct microbiotas. However, studies indicate that oral bacteria are able to disseminate into the colon. This is mostly evident in conditions such as periodontitis, where specific bacteria, namely Fusobacterium nucrelatum and Porphyromonas gingivalis project a pathogenic profile. In the colon these bacteria can alter the composition of the residual microbiota, in the context of complex biofilms, resulting in intestinal dysbiosis. This orally-driven disruption promotes aberrant immune and inflammatory responses, eventually leading to colorectal cancer (CRC) tumorigenesis. Understanding the exact mechanisms of these interactions will yield future opportunities regarding prevention and treatment of CRC

Current and Future Trends in Molecular Biomarkers for Diagnostic, Prognostic, and Predictive Purposes in Non-Melanoma Skin Cancer

Skin cancer represents the most common type of cancer among Caucasians and presents in two main forms: melanoma and non-melanoma skin cancer (NMSC). NMSC is an umbrella term, under which basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and Merkel cell carcinoma (MCC) are found along with the pre-neoplastic lesions, Bowen disease (BD) and actinic keratosis (AK). Due to the mild nature of the majority of NMSC cases, research regarding their biology has attracted much less attention. Nonetheless, NMSC can bear unfavorable characteristics for the patient, such as invasiveness, local recurrence and distant metastases. In addition, late diagnosis is relatively common for a number of cases of NMSC due to the inability to recognize such cases. Recognizing the need for clinically and economically efficient modes of diagnosis, staging, and prognosis, the present review discusses the main etiological and pathological features of NMSC as well as the new and promising molecular biomarkers available including telomere length (TL), telomerase activity (TA), CpG island methylation (CIM), histone methylation and acetylation, microRNAs (miRNAs), and micronuclei frequency (MNf). The evaluation of all these aspects is important for the correct management of NMSC; therefore, the current review aims to assist future studies interested in exploring the diagnostic and prognostic potential of molecular biomarkers for these entities

Investigation of the miRNA levels changes to acceptable daily intake dose pesticide mixture exposure on rat mesentery and pancreas

Consumers are constantly exposed to a variety of chemical mixtures as part of their everyday activities and lifestyle. Food, water and commercial products are only some examples of the possible ways people get exposed to these mixtures. However, following federal and local guidelines for risk assessment related to chemical exposure, risk analysis focuses on a single substance exposure scenario and not on a mixture, as in real life. Realizing the pronounced gap of this methodology, the real-life risk simulation scenario approach tries to address this problem by investigating the possible effect of long-term exposure to chemical mixtures closely resembling the actual circumstances of modern life. As part of this effort, this study aimed to identify the cumulative effects of pesticides belonging to different classes and commonly used commercial products on long-term exposure with realistic doses. Sprague Dawley rats were given a pesticide mix of active ingredients and formulation chemicals in a daily acceptable dose (ADI) and 10xADI for 90 days. Following thorough everyday documentation of possible side-effects, after 90 days all animals were sacrificed and their organs were examined. Exposure to pesticides particularly affects the miRNA levels at that point will provide us with more information about whether they can be potential biomarkers

Challenges and Scientific Prospects of the Newest Generation of mRNA-Based Vaccines against SARS-CoV-2

In the context of the current COVID-19 pandemic, traditional, complex and lengthy methods of vaccine development and production would not have been able to ensure proper management of this global public health crisis. Hence, a number of technologies have been developed for obtaining a vaccine quickly and ensuring a large scale production, such as mRNA-based vaccine platforms. The use of mRNA is not a new concept in vaccine development but has leveraged on previous knowledge and technology. The great number of human resources and capital investements for mRNA vaccine development, along with the experience gained from previous studies on infectious diseases, allowed COVID-19 mRNA vaccines to be developed, conditionally approved and commercialy available in less than one year, thanks to decades of basic research. This review critically presents and discusses the COVID-19 mRNA vaccine-induced immunity, and it summarizes the most common anaphylactic and autoimmune adverse effects that have been identified until now after massive vaccination campaigns

Challenges and Scientific Prospects of the Newest Generation of mRNA-Based Vaccines against SARS-CoV-2

In the context of the current COVID-19 pandemic, traditional, complex and lengthy methods of vaccine development and production would not have been able to ensure proper management of this global public health crisis. Hence, a number of technologies have been developed for obtaining a vaccine quickly and ensuring a large scale production, such as mRNA-based vaccine platforms. The use of mRNA is not a new concept in vaccine development but has leveraged on previous knowledge and technology. The great number of human resources and capital investements for mRNA vaccine development, along with the experience gained from previous studies on infectious diseases, allowed COVID-19 mRNA vaccines to be developed, conditionally approved and commercialy available in less than one year, thanks to decades of basic research. This review critically presents and discusses the COVID-19 mRNA vaccine-induced immunity, and it summarizes the most common anaphylactic and autoimmune adverse effects that have been identified until now after massive vaccination campaigns.publishe