{"id":25993,"date":"2022-12-26T10:00:05","date_gmt":"2022-12-26T07:00:05","guid":{"rendered":"https:\/\/www.klimikdergisi.org\/?p=25993"},"modified":"2022-12-26T10:41:04","modified_gmt":"2022-12-26T07:41:04","slug":"covid-asilari-sonrasi-istenmeyen-etkiler","status":"publish","type":"post","link":"https:\/\/www.klimikdergisi.org\/tr\/2022\/12\/26\/covid-asilari-sonrasi-istenmeyen-etkiler\/","title":{"rendered":"COVID-19 Ge\u00e7irenlerde BNT162b2 mRNA ve \u0130naktif SARS-CoV-2 A\u015f\u0131s\u0131 Sonras\u0131 Akut \u0130stenmeyen Etkilerin \u0130ncelenmesi"},"content":{"rendered":"

G\u0130R\u0130\u015e\u00a0<\/span><\/h2>\n

A\u015f\u0131lar modern t\u0131bb\u0131n en \u00f6nemli silahlar\u0131ndan biridir. Tarih boyunca g\u00f6r\u00fclen di\u011fer b\u00fcy\u00fck salg\u0131nlarda oldu\u011fu gibi COVID-19 pandemisinde de a\u015f\u0131, en etkili \u00e7\u0131k\u0131\u015f yolu olarak g\u00f6r\u00fclm\u00fc\u015f ve h\u0131zla a\u015f\u0131 \u00e7al\u0131\u015fmalar\u0131 ba\u015flat\u0131lm\u0131\u015ft\u0131r (1). A\u015f\u0131 geli\u015ftirme \u00e7al\u0131\u015fmalar\u0131nda COVID-19 a\u015f\u0131lar\u0131n\u0131n bir k\u0131sm\u0131n\u0131n etkili ve kabul edilebilir bir g\u00fcvenlik profiline sahip oldu\u011fu g\u00f6sterilmi\u015ftir (<\/span>2, 3).<\/span> Bu a\u015f\u0131lardan ikisi, Pfizer-BioNTech ortakl\u0131\u011f\u0131 ile geli\u015ftirilen COVID-19 mRNA a\u015f\u0131s\u0131 (BNT162b2) ve Sinovac taraf\u0131ndan geli\u015ftirilen inaktif SARS-CoV-2 a\u015f\u0131s\u0131 (CoronaVac) olup \u00fclkemizde acil kullan\u0131m onay\u0131 alarak yayg\u0131n a\u015f\u0131lamada kullan\u0131lmaktad\u0131r (4). Her ne kadar klinik \u00e7al\u0131\u015fmalarda bu a\u015f\u0131lar\u0131n etkinli\u011fi ve g\u00fcvenli\u011fi kan\u0131tlanm\u0131\u015f olsa da \u00f6zel gruplarla ilgili veriler eksik kalmaktad\u0131r. Daha \u00f6nceden COVID-19 ge\u00e7irmi\u015f bireyler, a\u015f\u0131lar\u0131n ruhsatland\u0131rma \u00f6ncesi de\u011ferlendirildi\u011fi klinik \u00e7al\u0131\u015fmalara dahil edilmemi\u015ftir (2, 3). Ayr\u0131ca hen\u00fcz az say\u0131da \u00e7al\u0131\u015fmada bu iki a\u015f\u0131 t\u00fcr\u00fcn\u00fcn etkinli\u011fi ve g\u00fcvenli\u011fi kar\u015f\u0131la\u015ft\u0131rmal\u0131 olarak incelenmi\u015ftir (5). Toplumda a\u015f\u0131lama oranlar\u0131n\u0131n hedeflenen d\u00fczeye ula\u015fmas\u0131n\u0131 sa\u011flamak ve COVID-19\u2019a kar\u015f\u0131 geli\u015ftirilen yeni a\u015f\u0131lar hakk\u0131nda daha fazla bilimsel veriye ula\u015fmak i\u00e7in, yeni a\u015f\u0131lar\u0131n ger\u00e7ek ya\u015famdaki istenmeyen etkilerinin insidans\u0131 ve ciddiyeti hakk\u0131nda ara\u015ft\u0131rmalara ihtiya\u00e7 vard\u0131r.\u00a0<\/span><\/p>\n

\u00c7al\u0131\u015fmam\u0131zda, COVID-19 ge\u00e7iren ve ge\u00e7irmeyen bireylerde a\u015f\u0131 dozlar\u0131 ve t\u00fcrleri aras\u0131nda akut istenmeyen etki insidans\u0131n\u0131n belirlenmesi ve kar\u015f\u0131la\u015ft\u0131r\u0131lmas\u0131 ama\u00e7land\u0131.\u00a0<\/span><\/p>\n

Y\u00d6NTEMLER<\/h2>\n

\u00c7al\u0131\u015fma,\u00a0 <\/span>01 Temmuz – 31 Ekim 2021 tarihleri aras\u0131nda prospektif olarak y\u00fcr\u00fct\u00fcld\u00fc. Hastanemizin a\u015f\u0131 poliklini\u011finde BNT162b2 veya inaktif SARS-CoV-2 a\u015f\u0131s\u0131 uygulanan bireyler kohortu olu\u015fturdu. Gebeler, emzirenler, 18 ya\u015f alt\u0131 bireyler, \u015fahsen olur veremeyecek ki\u015filer ve a\u015f\u0131 uygulamas\u0131 sonras\u0131 sekiz g\u00fcn i\u00e7inde COVID-19 ge\u00e7irmi\u015f olanlar \u00e7al\u0131\u015fma d\u0131\u015f\u0131 tutuldu. Kohort; kendi i\u00e7inde iki a\u015f\u0131 grubuna ve her bir a\u015f\u0131 grubu da COVID-19 ge\u00e7irmi\u015f ve ge\u00e7irmemi\u015f olanlar olmak \u00fczere iki alt gruba ayr\u0131ld\u0131. Alt gruplarda da ayn\u0131 g\u00fcn BNT162b2 a\u015f\u0131s\u0131 veya inaktif SARS-CoV-2 a\u015f\u0131s\u0131 uygulananlar e\u015fle\u015ftirildi. \u00c7al\u0131\u015fmaya dahil edilen t\u00fcm kat\u0131l\u0131mc\u0131lardan a\u015f\u0131n\u0131n uyguland\u0131\u011f\u0131 g\u00fcn bilgilendirilmi\u015f g\u00f6n\u00fcll\u00fc onam\u0131 yaz\u0131l\u0131 olarak al\u0131nd\u0131; ya\u015f\u0131, cinsiyeti, daha \u00f6nce COVID-19 ge\u00e7irip ge\u00e7irmedi\u011fi bilgisi, hangi a\u015f\u0131lar\u0131n uyguland\u0131\u011f\u0131, ka\u00e7\u0131nc\u0131 doz a\u015f\u0131s\u0131 uyguland\u0131\u011f\u0131 ve kronik hastal\u0131k bilgileri kay\u0131t alt\u0131na al\u0131nd\u0131. Kohorttaki t\u00fcm bireyler a\u015f\u0131lanma tarihinden sekiz g\u00fcn sonra telefonla aranarak \u0130stenmeyen Etki De\u011ferlendirme Anketi<\/i> yoluyla a\u015f\u0131 sonras\u0131 ilk yedi g\u00fcn i\u00e7inde ortaya \u00e7\u0131kan akut istenmeyen etkiler belirlendi.\u00a0<\/span><\/p>\n

\u00c7al\u0131\u015fma i\u00e7in Ankara \u015eehir Hastanesi 1 No\u2019lu Klinik Ara\u015ft\u0131rmalar Etik Kurulu\u2019ndan 07 Temmuz 2021 tarih ve E1-21-1933 karar numaras\u0131yla onay al\u0131nd\u0131.\u00a0<\/span><\/p>\n

\u0130stenmeyen Etki De\u011ferlendirme Anketi\u00a0<\/span><\/h3>\n

Anket ara\u015ft\u0131rmac\u0131lar\u0131m\u0131z taraf\u0131ndan haz\u0131rlanm\u0131\u015f olup akut istenmeyen etki sorgulamas\u0131, genel semptomlar, lokal semptomlar, kardiyovask\u00fcler sistem semptomlar\u0131, solunum sistemi semptomlar\u0131, gastrointestinal sistem semptomlar\u0131, n\u00f6rolojik ve psikiyatrik semptomlar, solunum sistemi semptomlar\u0131, kulak\/burun\/ bo\u011faz\/g\u00f6z semptomlar\u0131 ve alerjik semptomlar olmak \u00fczere dokuz ana ba\u015fl\u0131k alt\u0131nda 46 maddeden olu\u015fan sistem sorgusundan olu\u015fmaktayd\u0131. Kat\u0131l\u0131mc\u0131lardan her bir maddeyi \u201cevet \/ hay\u0131r<\/i>\u201d \u015feklinde cevaplamalar\u0131 istendi. Bildirilen istenmeyen etkilerin g\u00fcnl\u00fck aktivitelere etkisi; \u201cge\u00e7ici olarak g\u00fcnl\u00fck d\u00fczenli aktivitelerimi ger\u00e7ekle\u015ftiremedim<\/i>\u201d, \u201cge\u00e7ici olarak i\u015fe gidemedim<\/i>\u201d, \u201cevde ayaktan tedavi ald\u0131m<\/i>\u201d, \u201cacil servise ba\u015fvurup, tedavi oldum<\/i>\u201d ve \u201chastanede yatarak tedavi oldum<\/i>\u201d \u015feklinde be\u015f madde ile sorguland\u0131. \u0130stenmeyen etkinin \u015fiddet derecesi belirlenmeye \u00e7al\u0131\u015f\u0131ld\u0131. Herhangi bir nedenle anketi tamamlayamayan ya da kendi iste\u011fi ile \u00e7al\u0131\u015fmadan ayr\u0131lanlar \u00e7al\u0131\u015fma d\u0131\u015f\u0131 b\u0131rak\u0131ld\u0131.\u00a0<\/span><\/p>\n

\u00d6rneklem<\/h3>\n

Minimum \u00f6rnek b\u00fcy\u00fckl\u00fc\u011f\u00fc, Epi Info versiyon 3.01 (CDC, Atlanta, ABD) bilgisayar program\u0131nda; %95 g\u00fcven d\u00fczeyinde ve 0.90 g\u00fc\u00e7, COVID-19 ge\u00e7irmeyenlerde istenmeyen etki insidans\u0131 %50, COVID-19 ge\u00e7iren ve ge\u00e7irmeyenlerin birbirine oran\u0131 1 ve r\u00f6latif risk (\u201crisk ratio\u201d – RR) oran\u0131 1.8 kabul edilerek her bir alt kolda 317 ki\u015fi olmak \u00fczere toplam 1268 olarak hesapland\u0131. \u00c7al\u0131\u015fma i\u00e7in \u00f6rnek se\u00e7imi yap\u0131lmad\u0131 ve a\u015f\u0131lanan t\u00fcm bireyler \u00e7al\u0131\u015fmaya al\u0131nd\u0131.<\/p>\n

\u0130statistiksel Analiz<\/h3>\n

Kategorik de\u011fi\u015fkenler; say\u0131, y\u00fczde ve %95 g\u00fcven aral\u0131\u011f\u0131 ile \u00f6zetlenip, kar\u015f\u0131la\u015ft\u0131rmalarda \u03c72<\/sup> testi kullan\u0131ld\u0131. Ya\u015f, aktiviteye etki ve istenmeyen etki s\u00fcresi de\u011fi\u015fkeni ortalama, standart sapma, minimum ve maksimum de\u011fer ile \u00f6zetlenip, normallik varsay\u0131m\u0131 kar\u015f\u0131lanan durumlarda kar\u015f\u0131la\u015ft\u0131rmalarda ba\u011f\u0131ms\u0131z gruplarda Student t testi kullan\u0131ld\u0131. Normallik varsay\u0131m\u0131 kar\u015f\u0131lanm\u0131yorsa Mann-Whitney U testi kullan\u0131ld\u0131. \u0130stenmeyen etki s\u00fcresi <1 g\u00fcn olanlar analize 0.5 g\u00fcn olarak al\u0131nd\u0131. A\u015f\u0131 dozlar\u0131, a\u015f\u0131 t\u00fcrleri aras\u0131nda ve COVID-19 ge\u00e7irme durumuna g\u00f6re insidans (istenmeyen etki geli\u015fen ki\u015fi say\u0131s\u0131\/toplam ki\u015fi say\u0131s\u0131 x100) ve %95 g\u00fcven aral\u0131klar\u0131 hesapland\u0131. Gruplar aras\u0131nda istenmeyen etki geli\u015fimi i\u00e7in risk \u00f6l\u00e7\u00fct\u00fc olarak RR ve %95 g\u00fcven aral\u0131\u011f\u0131 (GA) hesapland\u0131. \u0130stenmeyen etki geli\u015fiminde etkili fakt\u00f6rler \u00e7ok de\u011fi\u015fkenli lojistik regresyon analizi ile incelendi. Veriler \u201cIBM SPSS Statistics for Windows, Version 20.0\u201d (Armonk, NY, ABD) program\u0131 kullan\u0131larak analiz edildi ve t\u00fcm istatistiksel testler i\u00e7in \u00f6nemlilik s\u0131n\u0131r\u0131 0.05 olarak al\u0131nd\u0131.<\/p>\n

BULGULAR<\/h2>\n
\"\"<\/a>

Tablo 1.<\/strong> A\u015f\u0131 Dozu ve A\u015f\u0131 T\u00fcr\u00fcne G\u00f6re Ya\u015f Da\u011f\u0131l\u0131m\u0131<\/p><\/div>\n

\"\"<\/a>

Tablo 2.<\/strong> A\u015f\u0131 Dozu ve A\u015f\u0131 T\u00fcr\u00fcne G\u00f6re Cinsiyet, COVID-19 Ge\u00e7irme \u00d6yk\u00fcs\u00fc ve Ek Hastal\u0131k Varl\u0131\u011f\u0131n\u0131n
Da\u011f\u0131l\u0131m\u0131<\/p><\/div>\n

\"\"<\/a>

Tablo 3.<\/strong> COVID-19 Ge\u00e7irme Durumuna G\u00f6re A\u015f\u0131 Dozlar\u0131 Sonras\u0131 \u0130stenmeyen Etki Geli\u015fme \u0130nsidans\u0131n\u0131n
Kar\u015f\u0131la\u015ft\u0131r\u0131lmas\u0131<\/p><\/div>\n

\"\"<\/a>

Tablo 4.<\/strong> A\u015f\u0131 T\u00fcr\u00fcne G\u00f6re A\u015f\u0131 Dozlar\u0131 Sonras\u0131 \u0130stenmeyen Etki Geli\u015fme \u0130nsidans\u0131n\u0131n COVID-19 Ge\u00e7iren
ve Ge\u00e7irmeyenler Aras\u0131nda Kar\u015f\u0131la\u015ft\u0131r\u0131lmas\u0131<\/p><\/div>\n

\"\"<\/a>

Tablo 5.<\/strong> A\u015f\u0131 Dozlar\u0131 Sonras\u0131 \u0130stenmeyen Etki Geli\u015fme \u0130nsidans\u0131n\u0131n Ek Hastal\u0131k Varl\u0131\u011f\u0131, Say\u0131s\u0131 ve A\u015f\u0131
T\u00fcr\u00fcne G\u00f6re Kar\u015f\u0131la\u015ft\u0131r\u0131lmas\u0131<\/p><\/div>\n

\"\"<\/a>

Tablo 6.<\/strong> A\u015f\u0131 Sonras\u0131 \u0130stenmeyen Etki T\u00fcrlerinin Da\u011f\u0131l\u0131m\u0131<\/p><\/div>\n

\u00c7al\u0131\u015fmada toplam 1607 a\u015f\u0131 uygulamas\u0131 izlenmi\u015f olup bunlar\u0131n 807 (%50.2)\u2019si erkek ve 800 (%49.8)\u2019\u00fc kad\u0131nd\u0131. A\u015f\u0131 dozlar\u0131n\u0131n 301 (%18.7)\u2019i inaktif SARS-CoV-2 a\u015f\u0131s\u0131, 1306 (%81.3)\u2019s\u0131 BNT162b2 a\u015f\u0131s\u0131 olup %62.2\u2019si 1. doz, %29.8\u2019i 2. doz ve %8\u2019i 3. doz a\u015f\u0131yd\u0131. \u00c7al\u0131\u015fmaya dahil edilen bireylerin a\u015f\u0131 \u015femas\u0131nda ayn\u0131 a\u015f\u0131 t\u00fcr\u00fc ile a\u015f\u0131lamaya (homolog a\u015f\u0131 \u015femas\u0131) devam edildi\u011fi g\u00f6zlendi; farkl\u0131 a\u015f\u0131 t\u00fcrleri ile a\u015f\u0131lanma (heterolog a\u015f\u0131lama) g\u00f6zlenmedi. A\u015f\u0131 uygulanan ki\u015filerin ya\u015f ortalamas\u0131, ka\u00e7\u0131nc\u0131 doz oldu\u011funa bak\u0131lmaks\u0131z\u0131n 43.9\u00b114.5 (minimum=18 \u2013 maksimum=91) olarak tespit edildi (Tablo 1). A\u015f\u0131 dozu \u00f6ncesi COVID-19 ge\u00e7irme \u00f6yk\u00fcs\u00fc olan birey say\u0131s\u0131 743 (%46.2)\u2019t\u00fc. A\u015f\u0131 uygulanan ki\u015filerin 379 (%23.6)\u2019unda en az bir ek hastal\u0131k \u00f6yk\u00fcs\u00fc olup 75 (%4.7)\u2019inde birden fazla ek hastal\u0131k \u00f6yk\u00fcs\u00fc bulunmaktayd\u0131. A\u015f\u0131 dozu ve t\u00fcr\u00fcne g\u00f6re; cinsiyet, COVID-19 ge\u00e7irme \u00f6yk\u00fcs\u00fc ve ek hastal\u0131k varl\u0131\u011f\u0131n\u0131n da\u011f\u0131l\u0131m\u0131 Tablo 2\u2019de verildi.\u00a0<\/span><\/p>\n

A\u015f\u0131 uygulamas\u0131 sonras\u0131nda yedi g\u00fcn i\u00e7inde herhangi bir istenmeyen etki g\u00f6r\u00fclme oran\u0131 BNT162b2 a\u015f\u0131s\u0131 i\u00e7in %64.1 [%95 GA: %61.2-%66.4], inaktif SARS-CoV-2 a\u015f\u0131s\u0131 i\u00e7in %24.6 (%95 GA: %20.1-%29.8) olarak tespit edildi [\u201codds ratio\u201d (OR)<\/i>: 1.975; %95 GA: 1.60-2.44]. A\u015f\u0131 dozu, a\u015f\u0131 t\u00fcr\u00fc, COVID-19 ge\u00e7irme \u00f6yk\u00fcs\u00fc, ek hastal\u0131k varl\u0131\u011f\u0131 ve say\u0131s\u0131na g\u00f6re istenmeyen etki da\u011f\u0131l\u0131m\u0131 Tablo 3, 4, ve 5\u2019te verildi. BNT162b2 a\u015f\u0131s\u0131 sonras\u0131 istenmeyen etki geli\u015fme riski, ek hastal\u0131\u011f\u0131 olanlarda olmayanlara g\u00f6re anlaml\u0131 d\u00fczeyde daha y\u00fcksek bulundu (p<\/i><0.001). Birden fazla ek hastal\u0131k olmas\u0131 riski art\u0131rmad\u0131. A\u015f\u0131 dozlar\u0131 sonras\u0131 istenmeyen etki geli\u015fme insidans\u0131 COVID-19 ge\u00e7iren ve ge\u00e7irmeyenlerde a\u015f\u0131 t\u00fcr\u00fcne g\u00f6re kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda, COVID-19 ge\u00e7irenlerde BNT162b2 a\u015f\u0131s\u0131 sonras\u0131 istenmeyen etki geli\u015fme riski 3. doz i\u00e7in 1. ve 2. doza g\u00f6re anlaml\u0131 \u00f6l\u00e7\u00fcde y\u00fcksek bulundu (p<\/i>=0. 039; OR: 1.43; %95 GA: 1.35-1.52). Her iki a\u015f\u0131 t\u00fcr\u00fcnde a\u015f\u0131 dozundan ba\u011f\u0131ms\u0131z olarak, a\u015f\u0131 sonras\u0131 en s\u0131k g\u00f6zlenen istenmeyen etkiler s\u0131ras\u0131yla; kolda a\u011fr\u0131 [BNT162b2 grubunda 653 (%50) ki\u015fi ve inaktif SARS-CoV-2 a\u015f\u0131 grubunda 52 (%17.3) ki\u015fi; p<<\/i>0.001], halsizlik\/yorgunluk [BNT162b2 grubunda 237 (%18.1) ki\u015fi ve inaktif SARS-CoV-2 a\u015f\u0131 grubunda 20 (%6.6) ki\u015fi; p<<\/i>0.001] ve ba\u015f a\u011fr\u0131s\u0131 [BNT162b2 grubunda 120 (%9.2) ki\u015fi ve inaktif SARS-CoV-2 a\u015f\u0131 grubunda 10 (%3.3); p<<\/i>0.001] idi (Tablo 6). \u00c7al\u0131\u015fmaya dahil edilen hi\u00e7bir bireyde \u00f6l\u00fcm ve hayat\u0131 tehdit eden ciddi istenmeyen etki (anafilaksi vb.) g\u00f6zlenmedi. \u0130stenmeyen etki geli\u015fen a\u015f\u0131 dozlar\u0131nda inaktif SARS-CoV-2 a\u015f\u0131s\u0131 ile %28.4 ve BNT162b2 a\u015f\u0131s\u0131 ile %36.2 oran\u0131nda istenmeyen etkinin g\u00fcnl\u00fck aktiviteye etkisi bulunurken (p<\/i>=0.359); a\u015f\u0131 t\u00fcrleri aras\u0131nda ortalama g\u00fcnl\u00fck aktiviteye etki (p=<\/i>0.359) ve ortalama istenmeyen etki s\u00fcresi (p=<\/i>0.520) de benzer bulundu. \u00c7ok de\u011fi\u015fkenli lojistik regresyon analizinde, BNT162b2 a\u015f\u0131s\u0131 ile istenmeyen etki geli\u015fme riski; ya\u015f, cinsiyet, a\u015f\u0131 dozu, COVID-19 ge\u00e7irme \u00f6yk\u00fcs\u00fc ve ek hastal\u0131k varl\u0131\u011f\u0131na g\u00f6re d\u00fczeltildi\u011finde inaktif SARS-CoV-2 a\u015f\u0131s\u0131na g\u00f6re 5.8 kat daha y\u00fcksek bulundu (OR: 5.83; %95 GA: 4.34-7.84). COVID-19 ge\u00e7irenlerde COVID-19 ge\u00e7irmeyenlere g\u00f6re istenmeyen etki geli\u015fme riski; a\u015f\u0131 dozu, a\u015f\u0131 t\u00fcr\u00fc, ya\u015f, cinsiyet ve ek hastal\u0131k varl\u0131\u011f\u0131na g\u00f6re d\u00fczeltildi\u011finde 1.6 kat fazla bulundu (OR: 1.60; %95 GA: 1.29-2.00).<\/p>\n

\u0130RDELEME<\/h2>\n

A\u015f\u0131lar\u0131n yayg\u0131n kullan\u0131ma sunulmas\u0131ndan sonra genel pop\u00fclasyonun a\u015f\u0131 g\u00fcvenli\u011fi a\u00e7\u0131s\u0131ndan izlenmesi gerekir. T\u00fcm d\u00fcnyada COVID-19 a\u015f\u0131lar\u0131n\u0131n \u00e7e\u015fitli gruplarda, ger\u00e7ek ya\u015famdaki etkinli\u011fini ve g\u00fcvenli\u011fini de\u011ferlendirmek i\u00e7in \u00e7al\u0131\u015fmalar y\u00fcr\u00fct\u00fclmektedir (6). \u00dclkemizde de a\u015f\u0131 sonras\u0131 istenmeyen etkiler, yap\u0131lan bildirimlere dayal\u0131 olarak, T.C. Sa\u011fl\u0131k Bakanl\u0131\u011f\u0131 taraf\u0131ndan izlenmektedir (7). Ancak s\u00f6z konusu bildirimlerde eksiklikler ve bilgi k\u0131s\u0131tl\u0131l\u0131\u011f\u0131 olabilir. COVID-19 a\u015f\u0131lar\u0131, nispeten s\u0131n\u0131rl\u0131 klinik veriyle h\u0131zland\u0131r\u0131lm\u0131\u015f bir onay s\u00fcreci sonunda kullan\u0131ma sunuldu\u011fu i\u00e7in ger\u00e7ek ya\u015fam verileri, bu a\u015f\u0131lar\u0131n etkinli\u011finin ve g\u00fcvenli\u011finin izlenmesinde ve toplumun g\u00fcveninin korunmas\u0131nda kritik \u00f6neme sahiptir. \u00c7al\u0131\u015fmam\u0131zda, \u00fclkemizde kullan\u0131mda olan BNT162b2 ve inaktif SARS-CoV-2 a\u015f\u0131lar\u0131n\u0131n ger\u00e7ek ya\u015fam verileri, a\u015f\u0131 g\u00fcvenli\u011fi a\u00e7\u0131s\u0131ndan incelendi.<\/p>\n

\u0130naktif SARS-CoV-2 a\u015f\u0131s\u0131, ger\u00e7ekle\u015ftirilen klinik \u00e7al\u0131\u015fmalarda tolere edilebilir advers etki profiline sahip olarak bildirilmi\u015ftir. CoronaVac a\u015f\u0131s\u0131n\u0131n faz 1 ve 2 \u00e7al\u0131\u015fmalar\u0131nda, farkl\u0131 dozlama ve a\u015f\u0131lama \u015femalar\u0131 uygulansa da en s\u0131k g\u00f6zlenen advers etkilerin lokal reaksiyonlar oldu\u011fu ve a\u015f\u0131 uygulanan grupta advers etki s\u0131kl\u0131\u011f\u0131 s\u0131ras\u0131yla %29 ve %33 olarak bildirilmi\u015ftir (8). \u00dclkemizden bildirilen faz 3 \u00e7al\u0131\u015fma sonu\u00e7lar\u0131nda, lokal reaksiyonlar daha s\u0131k g\u00f6zlenmi\u015f ve advers etki g\u00f6r\u00fclme oran\u0131 a\u015f\u0131lanan grupta %18.9 olarak raporlanm\u0131\u015ft\u0131r. Ciddi advers etki g\u00f6r\u00fclme oran\u0131 %0.1 olarak bulunmu\u015f ve sadece bir kat\u0131l\u0131mc\u0131da ciddi sistemik alerjik reaksiyon geli\u015fti\u011fi bildirilmi\u015ftir (3). A\u015f\u0131n\u0131n uyguland\u0131\u011f\u0131 bir di\u011fer \u00fclke olan \u015eili\u2019de yap\u0131lan \u00e7al\u0131\u015fmada ise hi\u00e7bir ciddi advers etki g\u00f6zlenmedi\u011fi bildirilmi\u015ftir (9). Di\u011fer taraftan ger\u00e7ek ya\u015fam verileri ile sa\u011fl\u0131k \u00e7al\u0131\u015fanlar\u0131 aras\u0131nda inaktif SARS-CoV-2 a\u015f\u0131s\u0131n\u0131n g\u00fcvenli\u011fini de\u011ferlendiren bir \u00e7al\u0131\u015fmada; 1. ve 2.\u00a0 <\/span>doz sonras\u0131 advers etki g\u00f6r\u00fclme insidans\u0131 s\u0131ras\u0131yla %15.6 ve %14.6 olarak bulunmu\u015ftur (10). Bir di\u011fer \u00e7al\u0131\u015fmada da daha \u00f6nceden COVID-19 ge\u00e7irmi\u015f ve ge\u00e7irmemi\u015f sa\u011fl\u0131k \u00e7al\u0131\u015fanlar\u0131 aras\u0131nda inaktif SARS-CoV-2 a\u015f\u0131s\u0131 sonras\u0131 advers etki insidans\u0131n\u0131n benzer oldu\u011fu bildirilmi\u015ftir (11). \u00dclkemizde inaktif SARS-CoV-2 a\u015f\u0131s\u0131 olan 4040 sa\u011fl\u0131k \u00e7al\u0131\u015fan\u0131n\u0131n incelendi\u011fi bir \u00e7al\u0131\u015fmada 1. ve 2. dozlar sonras\u0131 en s\u0131k g\u00f6r\u00fclen yan etkiler enjeksiyon b\u00f6lgesinde a\u011fr\u0131, ba\u015f a\u011fr\u0131s\u0131 ve halsizliktir (12). Sa\u011fl\u0131k \u00e7al\u0131\u015fanlar\u0131 toplumda kronik hastal\u0131k insidans\u0131n\u0131n d\u00fc\u015f\u00fck oldu\u011fu nispeten gen\u00e7 pop\u00fclasyonu temsil edebilece\u011finden, sonu\u00e7lar bu durum g\u00f6z \u00f6n\u00fcnde bulundurularak yorumlanmal\u0131d\u0131r. \u0130naktif SARS-CoV-2 a\u015f\u0131s\u0131n\u0131n otoimm\u00fcn romatolojik hastal\u0131\u011f\u0131 olan grupta g\u00fcvenlik ve etkinli\u011finin de\u011ferlendirildi\u011fi bir \u00e7al\u0131\u015fmada, a\u015f\u0131 sonras\u0131 istenmeyen etki insidans\u0131 \u00f6nceki klinik \u00e7al\u0131\u015fma sonu\u00e7lar\u0131yla benzer bulunmu\u015ftur (13). \u00dclkemizde kanser hastalar\u0131nda inaktif SARS-CoV-2 a\u015f\u0131s\u0131n\u0131n etkinlik ve g\u00fcvenli\u011fini de\u011ferlendiren \u00e7ok merkezli bir kohort \u00e7al\u0131\u015fmada, kanser hastalar\u0131na g\u00f6re kontrol grubunda ilk a\u015f\u0131 dozu sonras\u0131 yan etki oran\u0131 y\u00fcksek bulunmu\u015ftur. Bunun nedeni, ara\u015ft\u0131rmac\u0131lar taraf\u0131ndan, kanser hastalar\u0131n\u0131n hastal\u0131k seyrinde ve daha \u00f6nceki tedavilerinde benzer yan etkiler ile kar\u015f\u0131la\u015ft\u0131klar\u0131ndan yan etki bildiriminin d\u00fc\u015f\u00fck bulundu\u011fu \u015feklinde yorumlanm\u0131\u015ft\u0131r. \u0130kinci a\u015f\u0131 dozu sonras\u0131 yan etki oran\u0131 ise her iki grupta benzer bulunmu\u015ftur (14).\u00a0<\/span><\/p>\n

Genetik temelli bir a\u015f\u0131 olan BNT162b2 a\u015f\u0131s\u0131 i\u00e7in 6 \u00fclkeden 43 548 kat\u0131l\u0131mc\u0131 ile ger\u00e7ekle\u015ftirilen faz 3 \u00e7al\u0131\u015fma sonu\u00e7lar\u0131nda, 16-55 ya\u015flar\u0131 aras\u0131 yeti\u015fkinlerin yakla\u015f\u0131k %80\u2019inde (1. doz: %83; 2. doz: %78) a\u015f\u0131lama sonras\u0131 lokal reaksiyon bildirilmi\u015ftir. En s\u0131k bildirilen sistemik reaksiyonlar ise %59 oran\u0131nda yorgunluk ve %52 oran\u0131nda ba\u015f a\u011fr\u0131s\u0131 olarak raporlanm\u0131\u015ft\u0131r. Advers etkiler gen\u00e7 ya\u015f grubunda (16-55 ya\u015f) ve 2. dozdan sonra daha s\u0131k g\u00f6r\u00fclm\u00fc\u015ft\u00fcr (2). 600 000\u2019den fazla a\u015f\u0131lanm\u0131\u015f ki\u015finin anket verilerine dayal\u0131 bir \u00e7al\u0131\u015fman\u0131n sonucunda, BNT162b2 a\u015f\u0131s\u0131 sonras\u0131 akut istenmeyen etkiler faz 3 \u00e7al\u0131\u015fmas\u0131nda bildirilen oranlardan daha d\u00fc\u015f\u00fck bulunmu\u015ftur (15). Her ne kadar BNT162b2 a\u015f\u0131s\u0131n\u0131n ger\u00e7ek ya\u015fam verileri ile etkinli\u011fi ve g\u00fcvenli\u011fi do\u011frulanm\u0131\u015f olsa da faz 3 \u00e7al\u0131\u015fmalar\u0131nda bildirilmemi\u015f fakat yayg\u0131n a\u015f\u0131lama s\u0131ras\u0131nda nadir g\u00f6r\u00fclen advers etkiler a\u015f\u0131 ile ili\u015fkili bulunmu\u015ftur (16). \u00c7al\u0131\u015fmam\u0131zda, a\u015f\u0131 sonras\u0131 istenmeyen etki g\u00f6r\u00fclme oran\u0131 BNT162b2 a\u015f\u0131s\u0131nda %64.1 (%95 GA: %61.2-%66.4), inaktif SARS-CoV-2 a\u015f\u0131s\u0131nda %24.6 (%95 GA: %20.1-%29.8) olarak tespit edildi (OR: 1.97; %95 GA: 1.60-2.44). Bu oranlar, a\u015f\u0131lar\u0131n klinik \u00f6ncesi \u00e7al\u0131\u015fmalar\u0131nda bulunan oranlardan daha d\u00fc\u015f\u00fck olup di\u011fer ger\u00e7ek ya\u015fam verileri ile benzerdir.\u00a0<\/span><\/p>\n

Mart 2022 itibariyle d\u00fcnya genelinde, BNT162b2 a\u015f\u0131s\u0131 141 \u00fclkede, inaktif SARS-CoV-2 a\u015f\u0131s\u0131 54 \u00fclkede acil kullan\u0131m onay\u0131 alm\u0131\u015f olup bir\u00e7ok \u00fclkede yayg\u0131n olarak a\u015f\u0131lamada kullan\u0131lmaktad\u0131r (17). Bu a\u015f\u0131lar\u0131n her biri ile ilgili olarak \u00e7e\u015fitli ara\u015ft\u0131rmalar\u0131n klinik \u00f6ncesi \u00e7al\u0131\u015fmalar\u0131 ve ger\u00e7ek ya\u015fam verileri sunulmu\u015f olmakla birlikte yaln\u0131zca bir prospektif kohort \u00e7al\u0131\u015fmada BNT162b2 ve inaktif SARS-CoV-2 a\u015f\u0131s\u0131 g\u00fcvenlik a\u00e7\u0131s\u0131ndan kar\u015f\u0131la\u015ft\u0131r\u0131lm\u0131\u015ft\u0131r (5). \u00c7al\u0131\u015fmam\u0131zda, her iki a\u015f\u0131da da a\u015f\u0131 dozundan ba\u011f\u0131ms\u0131z olarak g\u00f6zlenen istenmeyen etkilerin genellikle lokal ve ciddi olmayan sistemik advers etkiler oldu\u011funu saptad\u0131k. BNT162b2 a\u015f\u0131s\u0131 ile istenmeyen etki geli\u015fme riski inaktif SARS-CoV-2 a\u015f\u0131s\u0131na g\u00f6re 5.8 kat daha y\u00fcksekti. Bununla birlikte istenmeyen etki s\u00fcresi ve istenmeyen etkinin g\u00fcnl\u00fck ya\u015fama etkisi iki a\u015f\u0131 aras\u0131nda benzer bulundu. Lai ve arkada\u015flar\u0131n\u0131n (5) \u00e7al\u0131\u015fmas\u0131ndan farkl\u0131 olarak \u00e7al\u0131\u015fmam\u0131zda, a\u015f\u0131 sonras\u0131 istenmeyen etkiler COVID-19 ge\u00e7irip ge\u00e7irmeme durumuna g\u00f6re de incelendi. COVID-19 ge\u00e7iren ki\u015filerde zamanla n\u00f6tralize edici antikorlar\u0131n azald\u0131\u011f\u0131 ve tekrarlayan infeksiyonlar\u0131n giderek artan oranda g\u00f6r\u00fcld\u00fc\u011f\u00fc bildirilmektedir (18). SARS-CoV-2 varyantlar\u0131, \u00f6zellikle delta ve omicron, daha bula\u015f\u0131c\u0131d\u0131r ve \u00f6nceki infeksiyondan kaynaklanan n\u00f6tralize edici antikorlar\u0131n \u00f6nemli bir k\u0131sm\u0131ndan ka\u00e7abilme yetene\u011fine sahiptir. Bu nedenle \u00f6nceden COVID-19 ge\u00e7iren ki\u015filerin de tekrar a\u015f\u0131lanmas\u0131 makul g\u00f6r\u00fcnmektedir (19). \u00c7al\u0131\u015fmam\u0131zda COVID-19 ge\u00e7irenlerde a\u015f\u0131 sonras\u0131 istenmeyen etki g\u00f6r\u00fclme riski COVID-19 ge\u00e7irmeyenlere g\u00f6re 1.6 kat fazla bulundu (OR: 1.61; %95 GA: 1.29-2.00). A\u015f\u0131 t\u00fcrlerine g\u00f6re inceledi\u011fimizde BNT162b2 a\u015f\u0131s\u0131 sonras\u0131 advers etki geli\u015fme riski hastal\u0131\u011f\u0131 ge\u00e7irenlerde anlaml\u0131 derecede y\u00fcksek bulundu. \u0130naktif SARS-CoV-2 a\u015f\u0131s\u0131 sonras\u0131 hastal\u0131\u011f\u0131 ge\u00e7irenlerde istenmeyen etki insidans\u0131n\u0131n say\u0131sal olarak daha y\u00fcksek oldu\u011fu g\u00f6zlenmekle birlikte kontrol grubuyla kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda istatistiksel olarak anlaml\u0131 d\u00fczeyde bir fark saptanmad\u0131. COVID-19 infeksiyonu \u00f6yk\u00fcs\u00fc olanlarda BNT162b2 a\u015f\u0131s\u0131n\u0131n advers etkiler a\u00e7\u0131s\u0131ndan de\u011ferlendirildi\u011fi bir \u00e7al\u0131\u015fmada, a\u015f\u0131n\u0131n genellikle iyi tolere edildi\u011fi fakat hastal\u0131\u011f\u0131 ge\u00e7irenlerde advers etki riskinin daha y\u00fcksek oldu\u011fu bildirilmi\u015ftir. S\u00f6z konusu \u00e7al\u0131\u015fmada, yaln\u0131zca 1. doz sonras\u0131 g\u00f6zlenen istenmeyen etkiler incelenmi\u015f, 2. doz ve hat\u0131rlatma dozuna ait veriler de\u011ferlendirilmemi\u015ftir (20). Birle\u015fik Krall\u0131k\u2019ta \u00e7ok say\u0131da kat\u0131l\u0131mc\u0131n\u0131n mobil uygulama \u00fczerinden verilerini olu\u015fturdu\u011fu a\u015f\u0131 sonras\u0131 akut istenmeyen etkilerin de\u011ferlendirildi\u011fi bir \u00e7al\u0131\u015fmada, COVID-19 ge\u00e7irenlerde mRNA a\u015f\u0131lar\u0131 sonras\u0131 hem 1. doz hem de 2. doz sonras\u0131 sistemik ve lokal reaksiyonlar\u0131n kontrol grubuna g\u00f6re daha s\u0131k g\u00f6zlendi\u011fi raporlanm\u0131\u015ft\u0131r (15). Bizim \u00e7al\u0131\u015fmam\u0131zda COVID-19 ge\u00e7irenlerde BNT162b2 a\u015f\u0131s\u0131 sonras\u0131 advers etki s\u0131kl\u0131\u011f\u0131n\u0131n 3. dozda, 1. ve 2. doza k\u0131yasla daha fazla oldu\u011fu g\u00f6r\u00fcld\u00fc. COVID-19 ge\u00e7irenlerde her bir a\u015f\u0131 dozu, daha y\u00fcksek bir h\u00fcmoral ve h\u00fccresel yan\u0131ta sahip ikinci bir doza kar\u015f\u0131l\u0131k gelerek a\u015f\u0131 sonras\u0131 reaktojeniteye yol a\u00e7\u0131yor olabilir. Bununla birlikte, a\u015f\u0131 sonras\u0131 reaktojenitenin h\u00fcmoral veya h\u00fccresel yan\u0131t\u0131n yo\u011funlu\u011fu ile ili\u015fkili olup olmad\u0131\u011f\u0131n\u0131 anlamak i\u00e7in daha fazla \u00e7al\u0131\u015fmaya ihtiya\u00e7 vard\u0131r.\u00a0<\/span><\/span><\/p>\n

\u00c7al\u0131\u015fmam\u0131zda yaln\u0131zca a\u015f\u0131 sonras\u0131 akut istenmeyen etkiler de\u011ferlendirilmi\u015f olup ciddi advers reaksiyonlar g\u00f6zlenmedi. Rapor edilen istenmeyen etkiler telefon g\u00f6r\u00fc\u015fmesi ile de\u011ferlendirildi\u011fi ve ayr\u0131nt\u0131l\u0131 bir vizit ve fizik muayene yap\u0131lmad\u0131\u011f\u0131ndan min\u00f6r reaksiyonlar g\u00f6zden ka\u00e7m\u0131\u015f veya ger\u00e7ekte olandan daha \u015fiddetli saptanm\u0131\u015f olabilir. Di\u011fer taraftan genel olarak anket bazl\u0131 \u00e7al\u0131\u015fmalarda verilerin s\u00fcbjektif olarak yans\u0131d\u0131\u011f\u0131, ya\u015fl\u0131lar gibi anketi yan\u0131tlayamayacak engeli bulunan gruplar\u0131n \u00e7al\u0131\u015fmaya dahil edilememesinin \u201cbias\u201d olas\u0131l\u0131\u011f\u0131n\u0131 art\u0131raca\u011f\u0131 ak\u0131lda tutulmal\u0131d\u0131r. COVID-19 ge\u00e7iren bireylerde akut infeksiyondan sonra devam eden ve bazen aylarca s\u00fcrebilen uzam\u0131\u015f COVID-19 ile ili\u015fkili semptomlar a\u015f\u0131 sonras\u0131 g\u00f6r\u00fclen yan etkiler ile benzer olabilir (21). \u00c7al\u0131\u015fmam\u0131zda, COVID-19 ge\u00e7iren baz\u0131 bireylerde a\u015f\u0131 sonras\u0131 g\u00f6zlenen yan etkilerin g\u00f6zden ka\u00e7an bir uzam\u0131\u015f COVID-19 klini\u011fine ait olabilece\u011fini de d\u00fc\u015f\u00fcnmekteyiz. COVID-19 a\u015f\u0131lar\u0131 sonras\u0131 uzun d\u00f6nem istenmeyen etkilerin ve daha nadir g\u00f6r\u00fclen advers etkilerin s\u0131kl\u0131\u011f\u0131n\u0131 belirlemek i\u00e7in daha geni\u015f \u00e7apl\u0131, randomize, kontroll\u00fc \u00e7al\u0131\u015fmalara ihtiya\u00e7 vard\u0131r.<\/p>\n

Sonu\u00e7 olarak; BNT162b2 a\u015f\u0131 uygulamas\u0131nda inaktif SARS-CoV-2 a\u015f\u0131s\u0131na k\u0131yasla ve COVID-19 ge\u00e7irenlerde ge\u00e7irmeyenlere k\u0131yasla a\u015f\u0131 sonras\u0131 akut istenmeyen etki daha s\u0131k g\u00f6r\u00fclmesine ra\u011fmen, s\u00f6z konusu etkilerin \u00e7o\u011fu hafif, ge\u00e7ici ve y\u00f6netilebilirdir. Yeni ortaya \u00e7\u0131kan varyantlarla birlikte tekrarlayan doz gereksinimlerinin istenmeyen etki insidans\u0131nda art\u0131\u015fa yol a\u00e7\u0131p\u00a0 <\/span>a\u00e7mayaca\u011f\u0131 hen\u00fcz bilinmese de toplumun a\u015f\u0131 g\u00fcvenli a\u00e7\u0131s\u0131ndan s\u00fcrekli izlemi \u00e7ok \u00f6nemlidir.<\/p>\n","protected":false},"excerpt":{"rendered":"

G\u0130R\u0130\u015e\u00a0 A\u015f\u0131lar modern t\u0131bb\u0131n en \u00f6nemli silahlar\u0131ndan biridir. Tarih boyunca g\u00f6r\u00fclen di\u011fer b\u00fcy\u00fck salg\u0131nlarda oldu\u011fu gibi COVID-19 pandemisinde de a\u015f\u0131, en etkili \u00e7\u0131k\u0131\u015f yolu olarak g\u00f6r\u00fclm\u00fc\u015f ve h\u0131zla a\u015f\u0131 \u00e7al\u0131\u015fmalar\u0131 ba\u015flat\u0131lm\u0131\u015ft\u0131r (1). A\u015f\u0131 geli\u015ftirme \u00e7al\u0131\u015fmalar\u0131nda COVID-19 a\u015f\u0131lar\u0131n\u0131n bir k\u0131sm\u0131n\u0131n etkili ve kabul edilebilir bir g\u00fcvenlik profiline sahip oldu\u011fu g\u00f6sterilmi\u015ftir (2, 3). Bu a\u015f\u0131lardan ikisi, Pfizer-BioNTech […]<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[5129],"tags":[5577,5578,5174,5579],"class_list":["post-25993","post","type-post","status-publish","format-standard","hentry","category-ozgun-arastirma","tag-advers-etki","tag-bnt162b2-asisi","tag-covid-19","tag-inaktif-sars-cov-2-asisi"],"acf":[],"_links":{"self":[{"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/posts\/25993","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/comments?post=25993"}],"version-history":[{"count":3,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/posts\/25993\/revisions"}],"predecessor-version":[{"id":26151,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/posts\/25993\/revisions\/26151"}],"wp:attachment":[{"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/media?parent=25993"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/categories?post=25993"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/tags?post=25993"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}