Review Cureus. 2022 Aug 11;14(8):e27883. doi: 10.7759/cureus.27883. eCollection 2022 Aug.
Kateholamini so ključni sprožilec miokarditisa mRNA COVID-19, ki ga povzroči cepivo: prepričljiva hipoteza, podprta z epidemiološkimi, anatomopatološkimi, molekularnimi in fiziološkimi ugotovitvami (Catecholamines Are the Key Trigger of COVID-19 mRNA Vaccine-Induced Myocarditis: A Compelling Hypothesis Supported by Epidemiological, Anatomopathological, Molecular, and Physiological Findings)
Povzetek (Googletranslate)
Miokarditis, ki ga povzroča mRNA cepivo proti hudemu akutnemu respiratornemu sindromu koronavirus 2 (SARS-CoV-2), je redek, a dobro dokumentiran zaplet pri mladih moških. Poročali so o povečani pojavnosti nenadne smrti med športniki po cepljenju, kar zahteva nadaljnje preiskave. Ni znano, ali se tveganje za miokarditis, ki je znani glavni vzrok nenadne smrti pri mladih moških športnikih, poveča tudi po okužbi s koronavirusom 2019 (COVID-19). Resnost in posledice teh kritičnih škodljivih učinkov zahtevajo temeljito analizo, da se pojasnijo njihovi ključni sprožilni mehanizmi. Namen tega pregleda je bil oceniti, ali obstaja utemeljitev za domnevo, da so kateholamini v “hiperkateholaminergičnem” stanju ključni sprožilec miokarditisa, povzročenega s cepivom SARS-CoV-2 mRNA, in s tem povezanih izidov ter ali so podobna tveganja prisotna tudi po COVID-19 okužbah.
Izveden je bil temeljit, strukturiran pregled literature, da se hipoteza zgradi na treh stebrih: odkrivanje tveganja za miokarditis, morebitne spremembe in nenormalnosti, ugotovljene po cepljenju z mRNA SARS-CoV-2 ali okužbi s COVID-19 in posledični dogodki ter fiziološke značilnosti najbolj prizadeto prebivalstvo. Naslednji izrazi so bili iskani v indeksiranih in neindeksiranih strokovnih pregledih in nedavnih prednatisih (<12 mesecev): agent, “SARS-CoV-2” ali “COVID-19”; dogodek, “miokarditis” ali “nenadna smrt(-e)” ali “miokarditis+nenadna smrt(-e)” ali “srčni dogodek(-i)”; osnovni vzrok, “mRNA” ali “protein s konico” ali “okužba” ali “cepivo”; predlagani sprožilec, “kateholamin(i)” ali “adrenalin” ali “epinefrin” ali “noradrenalin” ali “norepinefrin” ali “testosteron”; in prizadeto prebivalstvo, “mladi moški” ali “športniki”.
Utemeljitev in podatki, ki so podprli hipotezo, so bili naslednji: miokarditis, povzročen s cepivom SARS-CoV-2 mRNA, je prizadel predvsem mlade moške, medtem ko tveganje po okužbi s COVID-19 ni bilo opaženo; neodvisne obdukcije ali biopsije bolnikov, ki so imeli miokarditis mRNA po cepljenju s SARS-CoV-2 v različnih geografskih regijah, so omogočile sklep, da je bilo primarno hiperkateholaminergično stanje ključni sprožilec teh dogodkov; mRNA SARS-CoV-2 je bila gosto prisotna, koničasti protein SARS-CoV-2 pa se je postopoma proizvajal v kromafinskih celicah medule nadledvične žleze, ki so odgovorne za proizvodnjo kateholamina; encim dihidroksifenilalanin dekarboksilaza, ki pretvori dopamin v noradrenalin, je bil prekomerno izražen v prisotnosti mRNA SARS-CoV-2, kar je povzročilo povečano aktivnost noradrenalina; odzivi na kateholamine so bili fiziološko višji pri mladih odraslih in moških kot pri drugih populacijah; kateholaminski odzivi in proizvodnja kateholaminov v mirovanju so bili večji pri moških športnikih kot pri nešportnikih; kateholaminski odzivi na stres in njegova občutljivost so bili povečani v prisotnosti androgenov; in izražanje kateholamina pri mladih moških športnikih je bilo že na začetku visoko, višje je bilo po cepljenju in višje od tistih pri necepljenih športnikih. Epidemiološke, obdukcijske, molekularne in fiziološke ugotovitve soglasno in močno kažejo, da je hiperkateholaminergično stanje kritični sprožilec redkih primerov miokarditisa zaradi komponent SARS-CoV-2, kar lahko poveča nenadne smrti med vrhunskimi moškimi športniki.
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine-induced myocarditis is a rare but well-documented complication in young males. The increased incidence of sudden death among athletes following vaccination has been reported and requires further investigation. Whether the risk of myocarditis, a known major cause of sudden death in young male athletes, also increases after coronavirus disease 2019 (COVID-19) infection is unknown. The severity and implications of these critical adverse effects require a thorough analysis to elucidate their key triggering mechanisms. The present review aimed to evaluate whether there is a justification to hypothesize that catecholamines in a “hypercatecholaminergic” state are the key trigger of SARS-CoV-2 mRNA vaccine-induced myocarditis and related outcomes and whether similar risks are also present following COVID-19 infection. A thorough, structured scoping review of the literature was performed to build the hypothesis through three pillars: detection of myocarditis risk, potential alterations and abnormalities identified after SARS-CoV-2 mRNA vaccination or COVID-19 infection and consequent events, and physiological characteristics of the most affected population. The following terms were searched in indexed and non-indexed peer review articles and recent preprints (<12 months): agent, “SARS-CoV-2” or “COVID-19”; event, “myocarditis” or “sudden death(s)” or “myocarditis+sudden death(s)” or “cardiac event(s)”; underlying cause, “mRNA” or “spike protein” or “infection” or “vaccine”; proposed trigger, “catecholamine(s)” or “adrenaline” or “epinephrine” or “noradrenaline” or “norepinephrine” or “testosterone”; and affected population, “young male(s)” or “athlete(s).” The rationale and data that supported the hypothesis were as follows: SARS-CoV-2 mRNA vaccine-induced myocarditis primarily affected young males, while the risk was not observed following COVID-19 infection; independent autopsies or biopsies of patients who presented post-SARS-CoV-2 mRNA vaccine myocarditis in different geographical regions enabled the conclusion that a primary hypercatecholaminergic state was the key trigger of these events; SARS-CoV-2 mRNA was densely present, and SARS-CoV-2 spike protein was progressively produced in adrenal medulla chromaffin cells, which are responsible for catecholamine production; the dihydroxyphenylalanine decarboxylase enzyme that converts dopamine into noradrenaline was overexpressed in the presence of SARS-CoV-2 mRNA, leading to enhanced noradrenaline activity; catecholamine responses were physiologically higher in young adults and males than in other populations; catecholamine responses and resting catecholamine production were higher in male athletes than in non-athletes; catecholamine responses to stress and its sensitivity were enhanced in the presence of androgens; and catecholamine expressions in young male athletes were already high at baseline, were higher following vaccination, and were higher than those in non-vaccinated athletes. The epidemiological, autopsy, molecular, and physiological findings unanimously and strongly suggest that a hypercatecholaminergic state is the critical trigger of the rare cases of myocarditis due to components from SARS-CoV-2, potentially increasing sudden deaths among elite male athletes.
Povezava Pub.Med.gov:
https://pubmed.ncbi.nlm.nih.gov/35971401/