| Abstract | Objectives: The aims of this study were to determine whether there are differences in the
frequency of adverse events (AEs) from COVID-19 vaccines compared to widely issued
vaccines and from COVID-19 drugs in contrast to a widely prescribed drug reported to the
FDA Adverse Event Reporting System (FAERS) or EudraVigilance (EV) during the COVID-
19 pandemic.
Materials and methods: The FAERS and EV adverse event databases were searched for
adverse event reports filed in the U.S. and EU from November 2019 to March 2022. We
included all COVID-19 vaccines and drugs which have been approved or emergency use
authorized by both the FDA and EMA as of March 31, 2022. The numbers of AEs (serious or
non-serious) and the numbers of reaction groups of AEs from Comirnaty (Pfizer-BioNTech),
Spikevax (Moderna), or Jcovden (Janssen) COVID-19 vaccines were compared to tetanus and
human papillomavirus (HPV) vaccines from January 2021 to March 2022 separately in FAERS
and EV. The numbers of AEs (serious or non-serious) and the numbers of reaction groups of
AEs from remdesivir, nirmatrelvir/ritonavir, tocilizumab, tixagevimab/cilgavimab,
sotrovimab, or casirivimab/imdevimab were compared to methotrexate during three time
periods: pre-pandemic (November 7, 2019, to January 29, 2020), first wave (January 30, 2020,
to July 15, 2020), and subsequent waves (July 16, 2020, to March 31, 2022).
Results: In both the FAERS and EV databases, there was no statistical difference in the number
of serious or non-serious AEs from the COVID-19 vaccines compared to the tetanus and HPV
vaccines (P=0.406 for both comparisons), although numbers of reported AEs from COVID-19
vaccines are higher in both databases. The median number of serious AEs from COVID-19
vaccines was greater in the FAERS database than in the EV database (94 ([IQR 17-1575]) vs.
11131 ([IQR 120-161077]) although this comparison did not reach statistical significance
(P=0.077). For non-serious AEs from COVID-19 vaccines, the EV database reported a greater
median number (17376 [IQR 209-251219]) compared to the FAERS database (59 [IQR 21-
429]). There were more serious AEs recorded for methotrexate (median 14601 [IQR 8899-
26493]) compared to the COVID-19 drugs (P=0.047) in the FAERS database, while in the EV
database there were more both serious and non-serious AEs for methotrexate (median 5370
[IQR 3868-12883]); P=0.026 and median 754 [IQR 672-1649]; P=0.043, respectively). There
was a median of 1755 (IQR 297-7980) serious and 1191 (IQR 370-1821) non-serious AEs from
COVID-19 drugs in the FAERS database (P=0.018 and P=0.002, respectively) in the
subsequent waves of COVID-19 than in the pre-pandemic and first wave. Similarly, there was a median of 234 (IQR 145-3576) serious and 97 (IQR 45-476) non-serious AEs for COVID-
19 drugs in the EV database (both P=0.002) respectively) in the subsequent waves of COVID-
19 than in the pre-pandemic and first wave.
Conclusions: Adverse event reporting systems are important and beneficial tools for
pharmacovigilance. Reporting of AEs from COVID-19 vaccines has been significantly high,
which may indicate a rise in safety issues and concomitant AEs or a change in reporting
behavior or both, while reporting of AEs from COVID-19 drugs has been low, which may
indicate that the safety profile of the COVID-19 drugs is sufficient, that the overall use of these
drugs is rather low or at least lower than methotrexate, or that reporting behavior is insufficient.
Among the two databases, reporting of AEs from COVID-19 vaccines has been higher in the
EV database than in the FAERS database, and, in contrast, reporting of AEs of COVID-19
drugs has been higher in the FAERS database than in the EV database for the investigated
period. Generally, reporting of AEs has not relevantly changed during the COVID-19
pandemic, although the introduction of COVID-19 vaccines and mass-vaccinations worldwide
likely led to stimulated reporting of vaccine AEs, while general under-reporting likely still
prevails. Our results may indicate a deficit in the U.S. reporting behavior of AEs following
vaccine administration, but this requires further investigation. |
| Abstract (croatian) | Ciljevi: Ciljevi ove studije bili su utvrditi postoje li razlike u učestalosti nuspojava od cjepiva
protiv COVID-19 u usporedbi na obično korištena cjepiva i od lijekova za COVID-19 u
usporedbi na obično propisani lijek koji je prijavljen FDA Adverse Event Reporting System
(FAERS) ili EudraVigilance (EV) tijekom pandemije COVID-19.
Materijali i metode: U bazama podataka o štetnim događajima FAERS i EV pretražene su
prijave štetnih događaja podnesenih u SAD-u i EU od studenog 2019. do ožujka 2022. Uključili
smo sva cjepiva protiv COVID-19 i lijekove koje su FDA i EMA odobrili ili odobrili za hitne
slučajeve od 31. ožujka 2022. Broj nuspojava (ozbiljnih ili neozbiljnih) i brojevi reakcijskih
skupina nuspojava iz Comirnaty (Pfizer-BioNTech), Spikevax (Moderna) ili Jcovden (Janssen)
cjepiva protiv COVID-19 uspoređeni su s cjepivima protiv tetanusa i humanog papiloma virusa
(HPV) od siječnja 2021. do ožujka 2022. zasebno u FAERS-u i EV. Broj nuspojava (ozbiljnih
ili neozbiljnih) i broj reakcijskih skupina nuspojava remdesivira, nirmatrelvira/ritonavira,
tocilizumaba, tixagevimaba/cilgavimaba, sotrovimaba ili casirivimaba/imdevimaba uspoređen
je s metotreksatom tijekom tri vremenska razdoblja: prije pandemije (7. studenog 2019. do 29.
siječnja 2020.), prvi val (30. siječnja 2020. do 15. srpnja 2020.) i sljedeći valovi (16. srpnja
2020. do 31. ožujka 2022.).
Rezultati: U bazama podataka FAERS i EV, nije bilo statističke razlike u broju ozbiljnih ili
neozbiljnih nuspojava od cjepiva protiv COVID-19 u usporedbi s cjepivima protiv tetanusa i
HPV-a (P=0,406 za obje usporedbe), iako je broj prijavljenih nuspojava od cjepiva protiv
COVID-19 viši u obje baze podataka. Medijan broja ozbiljnih nuspojava od cjepiva protiv
COVID-19 bio je veći u bazi podataka FAERS nego u bazi podataka EV (94 ([IQR 17-1575])
naspram 11131 ([IQR 120-161077]) iako ova usporedba nije dosegla statističku značajnost
(P=0,077). Za neozbiljne nuspojave od cjepiva protiv COVID-19, baza podataka EV prijavila
je veći srednji broj (17376 [IQR 209-251219]) u usporedbi s bazom podataka FAERS (59 [IQR
21-429]). Bilo je više ozbiljnih nuspojava zabilježenih za metotreksat (medijan 14601 [IQR
8899-26493]) u usporedbi s lijekovima protiv COVID-19 (P=0,047) u bazi podataka FAERS,
dok je u bazi podataka EV bilo više i ozbiljnih i neozbiljnih nuspojava za metotreksat (medijan
5370 [IQR 3868-12883]); P=0,026 i medijan 754 [IQR 672-1649]; P=0,043, redom). Postojao je medijan od 1755 (IQR 297-7980) ozbiljnih i 1191 (IQR 370-1821) neozbiljnih nuspojava
uzrokovanih lijekovima protiv COVID-19 u bazi podataka FAERS (P=0,018 odnosno
P=0,002) u narednim COVID-19 valovima nego u razdoblju prije pandemije i prvom valu.
Slično tome, postojao je medijan od 234 (IQR 145-3576) ozbiljnih i 97 (IQR 45-476)
neozbiljnih nuspojava za lijekove protiv COVID-19 u EV bazi podataka (oba P=0,002) u
narednim COVID-19 valovima nego u razdoblju prije pandemije i prvom valu.
Zaključci: Sustavi za prijavu nuspojava važni su i korisni alati za farmakovigilanciju.
Prijavljivanje nuspojava od cjepiva protiv COVID-19 bilo je značajno visoko, što može
ukazivati na porast sigurnosnih problema i pratećih nuspojava ili promjenu ponašanja pri
prijavljivanju ili oboje, dok je prijavljivanje nuspojava od lijekova protiv COVID-19 bilo
nisko, što može ukazivati na to da sigurnosni profil lijekova za COVID-19 je dovoljan, da je
ukupna upotreba ovih lijekova prilično niska ili barem niža od metotreksata, ili da je ponašanje
prijavljivanja nedovoljno. Među dvjema bazama podataka, prijava nuspojava od cjepiva protiv
COVID-19 bila je veća u bazi podataka EV nego u bazi podataka FAERS, a, nasuprot tome,
prijava nuspojava lijekova protiv COVID-19 bila je veća u bazi podataka FAERS nego u bazi
podataka EV za istraživano razdoblje. Općenito, prijavljivanje štetnih događaja nije se
značajno promijenilo tijekom pandemije COVID-19, iako je uvođenje cjepiva protiv COVID-
19 i masovnih cijepljenja u cijelom svijetu vjerojatno dovelo do poticanog prijavljivanja štetnih
događaja cjepiva, dok općenito nedovoljno prijavljivanje vjerojatno i dalje prevladava. Naši
rezultati mogu ukazivati na deficit u izvještavanju o ponašanju štetnih događaja nakon primjene
cjepiva u SAD-u, ali to zahtijeva daljnje istraživanje. |
