{"id":26001,"date":"2022-12-26T10:00:07","date_gmt":"2022-12-26T07:00:07","guid":{"rendered":"https:\/\/www.klimikdergisi.org\/?p=26001"},"modified":"2022-12-26T18:26:41","modified_gmt":"2022-12-26T15:26:41","slug":"heterolog-asilama-sonrasi-yan-etkiler","status":"publish","type":"post","link":"https:\/\/www.klimikdergisi.org\/tr\/2022\/12\/26\/heterolog-asilama-sonrasi-yan-etkiler\/","title":{"rendered":"\u0130ki Doz \u0130naktif COVID-19 A\u015f\u0131s\u0131 Uygulanm\u0131\u015f Sa\u011fl\u0131k \u00c7al\u0131\u015fanlar\u0131nda BNT162b2 A\u015f\u0131s\u0131 ile Ger\u00e7ekle\u015ftirilen Heterolog A\u015f\u0131lama Sonras\u0131 Yan Etkilerin De\u011ferlendirilmesi"},"content":{"rendered":"

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

SARS-CoV-<\/span>2\u2019nin neden oldu\u011fu COVID-19 hastal\u0131\u011f\u0131, ba\u015fta akci\u011ferler olmak \u00fczere bir\u00e7ok sistemi tutan, mortalitesi ve morbiditesi nedeniyle toplumlar\u0131n g\u00fcndelik ya\u015fam\u0131n\u0131 etkileyen bula\u015f\u0131c\u0131 bir hastal\u0131kt\u0131r. Mart 2020\u2019de ba\u015flayan pandemi nedeniyle t\u00fcm d\u00fcnyada h\u0131zl\u0131 bir \u015fekilde a\u015f\u0131 geli\u015ftirme \u00e7al\u0131\u015fmalar\u0131 ba\u015flat\u0131lm\u0131\u015ft\u0131r. Tarih boyunca t\u00fcm pandemilerin kontrol\u00fcnde en etkili yol a\u015f\u0131 uygulamalar\u0131 olmu\u015ftur. COVID-19 pandemisinde inaktif, canl\u0131 aten\u00fce, protein alt u\u0308nitesi, virus benzeri par\u00e7ac\u0131klar, viral vekt\u00f6r ve mRNA olmak \u00fczere 130\u2019dan fazla a\u015f\u0131 geli\u015ftirilmi\u015f olup pre-klinik \u00e7al\u0131\u015fmalar\u0131 da devam eden y\u00fczlerce a\u015f\u0131 bulunmaktad\u0131r (1). Aral\u0131k 2020\u2019de, Pfizer-BioNTech ortakl\u0131\u011f\u0131 ile geli\u015ftirilen COVID-19 mRNA a\u015f\u0131s\u0131 (BNT162b2), Amerikan G\u0131da ve \u0130la\u00e7 Dairesi (\u201cU.S. Food and Drug Administration \u2013 FDA\u201d) taraf\u0131ndan acil kullan\u0131m onay\u0131 verilen ilk COVID-19 as\u0327\u0131s\u0131 olmu\u015ftur (2). Faz 3 \u00e7al\u0131\u015fmas\u0131nda etkinli\u011fi %95 olarak saptanan BNT162b2 a\u015f\u0131s\u0131n\u0131n, y\u00fcksek SARS-CoV-2 n\u00f6tralize edici antikor titreleri ve g\u00fc\u00e7l\u00fc antijene \u00f6zg\u00fc CD8+ yan\u0131t\u0131 ortaya \u00e7\u0131kard\u0131\u011f\u0131 g\u00f6sterilmi\u015ftir (3, 4). Yap\u0131lan \u00e7e\u015fitli klinik \u00e7al\u0131\u015fmalarda, faz 3 \u00e7al\u0131\u015fmalar\u0131na k\u0131yasla daha d\u00fc\u015f\u00fck \u015fiddet ve oranda yan etkiler g\u00f6r\u00fclm\u00fc\u015ft\u00fcr (5, 6). \u00dclkemizde T.C. Sag\u0306l\u0131k Bakanl\u0131g\u0306\u0131\u2019n\u0131n a\u015f\u0131lama program\u0131 kapsam\u0131nda sa\u011fl\u0131k \u00e7al\u0131\u015fanlar\u0131na, Ocak 2021\u2019den itibaren inaktif SARS-CoV-2 a\u015f\u0131s\u0131 olan CoronaVac (Sinovac Life Sciences, Pekin, \u00c7in) uygulanmaya ba\u015flanm\u0131\u015f olup daha sonra ortaya c\u0327\u0131kan endi\u015fe verici varyantlara kars\u0327\u0131 s\u00f6z konusu a\u015f\u0131n\u0131n etkinlig\u0306inin du\u0308s\u0327mesi nedeniyle, \u00fc\u00e7\u00fcnc\u00fc doz olarak BNT162b2 as\u0327\u0131s\u0131 tercihe sunulmu\u015ftur. Farkl\u0131 a\u015f\u0131 kombinasyonlar\u0131 ile uygulanan heterolog a\u015f\u0131laman\u0131n imm\u00fcnojenisitesi ve ba\u011f\u0131\u015f\u0131kl\u0131\u011fa nas\u0131l katk\u0131 sa\u011flad\u0131\u011f\u0131na dair elde edilecek bilgiler, a\u015f\u0131lama politikalar\u0131na rehberlik etmek i\u00e7in b\u00fcy\u00fck \u00f6nem ta\u015f\u0131maktad\u0131r.<\/p>\n

Kohort olarak planlanan bu \u00e7al\u0131\u015fman\u0131n amac\u0131, hastanemizde iki doz CoronaVac ile a\u015f\u0131lanm\u0131\u015f sa\u011fl\u0131k \u00e7al\u0131\u015fanlar\u0131nda hat\u0131rlatma dozu olarak uygulanan BNT162b2 a\u015f\u0131s\u0131 sonras\u0131 antikor titrelerinde meydana gelen de\u011fi\u015fim ile a\u015f\u0131 yan etkileri aras\u0131ndaki ili\u015fkiyi incelemektir.<\/p>\n

Y\u00d6NTEMLER<\/h2>\n

\u00c7al\u0131\u015fma Grubu<\/h3>\n

\u00c7al\u0131\u015fmam\u0131za, Sanko \u00dcniversitesi T\u0131p Fak\u00fcltesi Sani Konuko\u011flu Uygulama ve Ara\u015ft\u0131rma Hastanesi\u2019nde g\u00f6rev yapan ve COVID-19 ge\u00e7iren\/ge\u00e7irmeyen 428 sa\u011fl\u0131k \u00e7al\u0131\u015fan\u0131 g\u00f6n\u00fcll\u00fc olarak kat\u0131ld\u0131. Kat\u0131l\u0131mc\u0131lar\u0131n tamam\u0131 2021 y\u0131l\u0131 Ocak ve S\u0327ubat aylar\u0131nda iki doz CoronaVac ile as\u0327\u0131land\u0131ktan alt\u0131 ay sonra, u\u0308c\u0327u\u0308ncu\u0308 doz olarak BNT162b2 a\u015f\u0131s\u0131n\u0131 tercih etmi\u015fti. \u00dcc\u0327u\u0308ncu\u0308 dozunda BNT162b2 a\u015f\u0131s\u0131n\u0131 tercih eden 55 ki\u015fi ise bir ay sonra d\u00f6rd\u00fcnc\u00fc doz olarak yine BNT162b2 a\u015f\u0131s\u0131 yapt\u0131rm\u0131\u015flard\u0131. T\u00fcm kat\u0131l\u0131mc\u0131lar bilgilendirilmi\u015f onam formu doldurduktan sonra \u00e7al\u0131\u015fmaya kat\u0131lm\u0131\u015ft\u0131r. \u00a0<\/span><\/p>\n

\u00c7al\u0131\u015fmaya, T.C. Sa\u011fl\u0131k Bakanl\u0131\u011f\u0131 Sag\u0306l\u0131k Hizmetleri Genel Mu\u0308du\u0308rlu\u0308g\u0306u\u0308 Bilimsel C\u0327al\u0131s\u0327ma Platformu\u2019na yap\u0131lan 2022-01-04T11_20_02 ba\u015fvuru numaras\u0131yla 07 Ocak 2022 tarihinde ve Sanko \u00dcniversitesi T\u0131p Fak\u00fcltesi Klinik Ara\u015ft\u0131rmalar Etik Kurulu taraf\u0131ndan \u015eubat 2021\u2019de 2021\/02\/01 karar numaras\u0131yla onay verilmi\u015ftir. \u00a0<\/span><\/p>\n

Laboratuvar Analizleri<\/h3>\n

SARS-CoV-2\u2019ye kar\u015f\u0131 a\u015f\u0131ya ba\u011fl\u0131 ba\u011f\u0131\u015f\u0131kl\u0131\u011f\u0131 anlamak amac\u0131yla, iki doz CoronaVac a\u015f\u0131s\u0131 uygulanm\u0131\u015f sa\u011fl\u0131k \u00e7al\u0131\u015fanlar\u0131ndan ikinci doz uygulamas\u0131ndan sonra 4. ayda ve \u00fc\u00e7\u00fcnc\u00fc doz olarak BNT162b2 a\u015f\u0131s\u0131 yapt\u0131ranlardan ise \u00fc\u00e7 hafta sonra serum \u00f6rne\u011fi al\u0131narak antikor d\u00fczeylerine bak\u0131ld\u0131. T\u00fcm \u00f6rneklerin antikor de\u011ferleri Sanko \u00dcniversitesi T\u0131p Fak\u00fcltesi Sani Konuko\u011flu Uygulama ve Ara\u015ft\u0131rma Hastanesi Merkez Laboratuvar\u0131 Mikrobiyoloji B\u00f6l\u00fcm\u00fc\u2019nde kemil\u00fcminesans mikropartik\u00fcl imm\u00fcnoassay (CMIA) y\u00f6ntemle \u00e7al\u0131\u015fan Architect i2000SR (Abbott Diagnostics, ABD) analiz\u00f6r\u00fc ve SARS-CoV-2 IgG II Quant (CoV-2 IgG II; Abbott Laboratories, \u0130rlanda) kiti kullan\u0131larak belirlendi. \u00dcretici firman\u0131n \u00f6nerileri do\u011frultusunda sonu\u00e7lar \u2265<\/span>50.0 AU\/ml ise pozitif olarak de\u011ferlendirildi; >40.000 AU\/ml\u2019nin \u00fczerinde \u00e7\u0131kan \u00f6rnekler 1:2 oran\u0131nda dil\u00fce edildikten sonra tekrar \u00e7al\u0131\u015f\u0131ld\u0131. Semptomu olan sa\u011fl\u0131k \u00e7al\u0131\u015fanlar\u0131nda SARS-CoV-2 infeksiyonu tan\u0131s\u0131, nazofarengeal su\u0308ru\u0308ntu\u0308 o\u0308rneklerinden CoronaGen RT-qPCR SARS-CoV2 variants detection kit V1.0 (Gensutek Sa\u011fl\u0131k Teknolojileri A.\u015e., T\u00fcrkiye) ile \u00e7al\u0131\u015f\u0131larak do\u011fruland\u0131.<\/p>\n

A\u015f\u0131 Protokol\u00fc\u00a0<\/span><\/h3>\n

BNT162b2 a\u015f\u0131s\u0131, in vitro<\/i> olarak SARS-CoV-2\u2019nin \u201cspike\u201d (S) proteinini kodlayan ilgili RNA dizisinin c\u0327og\u0306alt\u0131lmas\u0131yla elde edilen yu\u0308ksek derecede saflas\u0327t\u0131r\u0131lm\u0131s\u0327 tek zincirli (5\u2019 ucundan bas\u0327layan) \u201cmessenger\u201d RNA (mRNA) a\u015f\u0131s\u0131d\u0131r; 0.3 ml\u2019lik bir doz 30 \u03bcg SARS-CoV-2 mRNA ic\u0327ermektedir. As\u0327\u0131 kullan\u0131lmadan o\u0308nce %0.9 NaCl c\u0327o\u0308zeltisinden 1.8 ml al\u0131n\u0131r ve suland\u0131r\u0131larak seyreltilir; 0.3 ml olarak 90\u00b0 ac\u0327\u0131 ile deltoid kasa intramu\u0308sku\u0308ler olarak uygulan\u0131r.<\/span><\/p>\n

Anket \u00c7al\u0131\u015fmas\u0131<\/h3>\n

Kat\u0131l\u0131mc\u0131lardan, BNT162b2 a\u015f\u0131s\u0131n\u0131n ilk hat\u0131rlatma dozu yap\u0131ld\u0131ktan \u00fc\u00e7 hafta sonra antikor d\u00fczeyi bakmak i\u00e7in serum \u00f6rne\u011fi al\u0131n\u0131rken, a\u015f\u0131n\u0131n yan etkilerini belirlemek amac\u0131yla anket uyguland\u0131. Anket sorular\u0131yla; cinsiyet, ya\u015f gibi demografik verilerin d\u0131\u015f\u0131nda, COVID-19 ge\u00e7irme \u00f6yk\u00fcs\u00fc, a\u015f\u0131 sonras\u0131 yan etki ya\u015fan\u0131p ya\u015fanmad\u0131\u011f\u0131 ve ya\u015fand\u0131 ise ne kadar s\u00fcrd\u00fc\u011f\u00fc hakk\u0131nda bilgiler sorguland\u0131. A\u015f\u0131 sonras\u0131 yan etki s\u0131kl\u0131\u011f\u0131, cinsiyet ve ya\u015f gruplar\u0131na g\u00f6re incelenerek kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131. BNT162b2 a\u015f\u0131s\u0131n\u0131n ikinci dozunu yapt\u0131ranlardan bir hafta sonra tekrar bir anket formu doldurmalar\u0131 istendi ve ikinci doz sonras\u0131 yan etkiler sorguland\u0131. BNT162b2 a\u015f\u0131s\u0131n\u0131n ilk dozu ile ikinci dozu aras\u0131ndaki yan etki oranlar\u0131 kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131.<\/p>\n

\u0130statistiksel Analiz<\/h3>\n

Verilerin analizinde SPSS (\u201cStatistical Package for the Social Sciences\u201d) versiyon 23.0 program\u0131 (IBM Corp., Armonk, NY, ABD) kullan\u0131ld\u0131.\u00a0\u00d6l\u00e7\u00fcmle belirtilen s\u00fcrekli de\u011fi\u015fkenler medyan ve minimum-maksimum de\u011ferleri ile, nitel de\u011fi\u015fkenler frekans ve y\u00fczde de\u011ferleri ile sunuldu. Yan etki olan ve olmayan gruplar\u0131n kar\u015f\u0131la\u015ft\u0131rmalar\u0131nda; \u00f6l\u00e7\u00fcmle belirtilen s\u00fcrekli de\u011fi\u015fkenler i\u00e7in Mann-Whitney U testi, nitel de\u011fi\u015fkenler i\u00e7in \u03c72 <\/sup>testi kullan\u0131ld\u0131. Birinci ve ikinci doz a\u015f\u0131 sonras\u0131 14., 30. ve 60. g\u00fcn k\u00fcm\u00fclatif insidans oranlar\u0131 ve %95 g\u00fcven aral\u0131\u011f\u0131 de\u011ferleri Microsoft Excel program\u0131nda hesapland\u0131. \u0130ki grubun antikor d\u00fczeylerinin grafiksel g\u00f6sterimi i\u00e7in kutu grafi\u011fi (\u201cbox plot\u201d) kullan\u0131ld\u0131. T\u00fcm de\u011ferlendirmelerde p<\/i><0.05 istatistiksel olarak anlaml\u0131 d\u00fczey olarak kabul edildi.\u00a0<\/span><\/p>\n

BULGULAR\u00a0<\/span><\/h2>\n
\"\"<\/a>

\u015eekil 1.<\/strong> Tek Doz BNT162b2 Hat\u0131rlatma A\u015f\u0131s\u0131 Sonras\u0131 Yan Etki
Durumu ve Antikor D\u00fczeyleri<\/p><\/div>\n

\"\"<\/a>

\u015eekil 2.<\/strong> \u0130ki Doz BNT162b2 Hat\u0131rlatma A\u015f\u0131s\u0131 Sonras\u0131 Yan Etki Duru-
mu ve Antikor D\u00fczeyleri<\/p><\/div>\n

\"\"<\/a>

Tablo 1.<\/strong> \u0130lk Hat\u0131rlatma Dozu Sonras\u0131 \u00dc\u00e7\u00fcnc\u00fc Hafta SARS-CoV-2
IgG Antikor D\u00fczeyleri ve Yan Etki Oranlar\u0131<\/p><\/div>\n

\u00c7al\u0131\u015fmaya kat\u0131lan 428 sa\u011fl\u0131k \u00e7al\u0131\u015fan\u0131n\u0131n 373 (%87.1)\u2019\u00fc iki doz CoronaVac sonras\u0131 hat\u0131rlatma dozu olarak BNT162b2, 55 (%12.9)\u2019i ise iki doz CoronaVac sonras\u0131nda iki doz BNT162b2 a\u015f\u0131s\u0131n\u0131 tercih etmi\u015ftir.\u00a0<\/span><\/p>\n

Sa\u011fl\u0131k \u00e7al\u0131\u015fanlar\u0131n\u0131n iki doz CoronaVac a\u015f\u0131s\u0131 sonras\u0131 4. aydaki SARS-CoV-2 IgG titreleri de\u011ferlendirildi\u011finde, seropozitiflik oran\u0131 %95 iken (minimum:10, maksimum: 14 739.5; medyan: 292.10), bir doz BNT162b2 hat\u0131rlatma dozu sonras\u0131 seropozitiflik oran\u0131 %100 (minimum:151.10, maksimum: 117 170.40; medyan: 17 625.3) olarak bulundu.<\/p>\n

BNT162b2 a\u015f\u0131s\u0131 sonras\u0131 ilk 48 saatte g\u00f6r\u00fclen yan etkiler de\u011ferlendirildi\u011finde; tek dozda 148 (%34.6) sa\u011fl\u0131k \u00e7al\u0131\u015fan\u0131nda, iki dozda ise 21 (%38.2) sa\u011fl\u0131k \u00e7al\u0131\u015fan\u0131nda herhangi bir yan etki saptanmad\u0131.<\/p>\n

BNT162b2 a\u015f\u0131s\u0131 sonras\u0131 ilk 48 saatte g\u00f6r\u00fclen yan etkiler de\u011ferlendirildi\u011finde; 104 (%39.7)\u2019\u00fc erkek, 176 (%60.3)\u2019s\u0131 kad\u0131n olmak \u00fczere toplam 280 (%65.4) kat\u0131l\u0131mc\u0131da yan etki tespit edildi (p<\/i><0.001).<\/p>\n

Tek doz BNT162b2 a\u015f\u0131s\u0131 sonras\u0131 yan etki g\u00f6r\u00fclme s\u0131kl\u0131\u011f\u0131 ile kohort ya\u015f da\u011f\u0131l\u0131m\u0131 aras\u0131ndaki ili\u015fki incelendi\u011finde, 18-40 ya\u015f aras\u0131 yan etki oran\u0131n\u0131n istatiksel a\u00e7\u0131dan daha y\u00fcksek oldu\u011fu g\u00f6r\u00fcld\u00fc (p<\/i><0.001).<\/p>\n

Tek doz BNT162b2 a\u015f\u0131s\u0131 sonras\u0131 olu\u015fan yan etkiler cinsiyete g\u00f6re kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda; kad\u0131nlarda erkeklere g\u00f6re daha s\u0131k olarak yan etki g\u00f6r\u00fcld\u00fc\u011f\u00fc ve yorgunluk-halsizlik, ate\u015f, \u00fc\u015f\u00fcme-titreme gibi sistemik semptomlar\u0131n kad\u0131nlarda daha fazla oldu\u011fu tespit edildi (p<\/i><0.001).<\/p>\n

A\u015f\u0131 sonras\u0131 en s\u0131k kar\u015f\u0131la\u015f\u0131lan yan etkiler, %59.6 oran\u0131yla enjeksiyon yerinde k\u0131zar\u0131kl\u0131k, \u015fi\u015flik ve a\u011fr\u0131d\u0131r. Sistemik reaksiyonlardan ise en s\u0131k g\u00f6r\u00fclenlerin s\u0131ras\u0131yla; yorgunluk-halsizlik (%58.6), kas-eklem a\u011fr\u0131s\u0131 (%51.1), ba\u015f a\u011fr\u0131s\u0131 (%40.7), ate\u015f-\u00fc\u015f\u00fcme-titreme (%27.5), mide bulant\u0131s\u0131 (%12.9) ve kusma-ishal (%3.2) oldu\u011fu belirlendi. Bunlar\u0131n d\u0131\u015f\u0131nda, \u00fc\u00e7 (%1.1) sa\u011fl\u0131k \u00e7al\u0131\u015fan\u0131nda istenmeyen yan etki olarak aksiller lenfadenopati g\u00f6r\u00fcld\u00fc. Tek doz BNT162b2 a\u015f\u0131s\u0131 sonras\u0131 yan etki g\u00f6r\u00fclme s\u0131kl\u0131\u011f\u0131 ile ge\u00e7irilmi\u015f COVID-19 \u00f6yk\u00fcs\u00fc aras\u0131nda anlaml\u0131 d\u00fczeyde bir ili\u015fki bulunmad\u0131 (p<\/i>=0.250).\u00a0<\/span><\/span><\/p>\n

Tek doz BNT162b2 a\u015f\u0131s\u0131 sonras\u0131 yan etki g\u00f6r\u00fclme s\u0131kl\u0131\u011f\u0131 ile CoronaVac a\u015f\u0131s\u0131 sonras\u0131 4. aydaki SARS-CoV-2 IgG titreleri kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda, yan etki g\u00f6r\u00fclenlerin medyan de\u011ferinin daha y\u00fcksek oldu\u011fu tespit edildi (minimum:10, maksimum: 8830.2; medyan: 255.1) (p<\/i><0.001) (\u015eekil 1). Tek doz BNT162b2 a\u015f\u0131s\u0131 sonras\u0131 yan etki g\u00f6r\u00fclme s\u0131kl\u0131\u011f\u0131 ile BNT162b2 a\u015f\u0131s\u0131 sonras\u0131 3. haftadaki SARS-CoV-2 IgG titreleri kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda, yan etki g\u00f6r\u00fclenlerin medyan de\u011ferinin bu grupta da yan etki g\u00f6r\u00fclmeyenlere oranla daha y\u00fcksek oldu\u011fu saptand\u0131 (minimum: 151.1, maksimum: 117 170.4; medyan: 19 466.3) (p<\/i><0.001). BNT162b2 a\u015f\u0131s\u0131 sonras\u0131 3. haftadaki SARS-CoV-2 IgG titreleri d\u00f6rt gruba ayr\u0131larak incelendi\u011finde, yan etki g\u00f6r\u00fclen sa\u011fl\u0131k \u00e7al\u0131\u015fanlar\u0131n\u0131n b\u00fcy\u00fck \u00e7o\u011funlu\u011funun 40 000 AU\/ml ve \u00fczeri de\u011ferlere sahip olduklar\u0131 g\u00f6r\u00fcld\u00fc (p<\/i><0.001) (Tablo 1).\u00a0<\/span><\/p>\n

\u0130ki doz BNT162b2 a\u015f\u0131s\u0131 olan 55 kat\u0131l\u0131mc\u0131n\u0131n 21 (%38.2)\u2019inde ilk 48 saat i\u00e7erisinde yan etki g\u00f6r\u00fclmedi. Yan etki g\u00f6r\u00fclen 34 (%61.8) kat\u0131l\u0131mc\u0131n\u0131n 22 (%64.7)\u2019sinin kad\u0131n, 11 (%35.3)\u2019inin ise erkek oldu\u011fu belirlendi.\u00a0<\/span><\/p>\n

\u0130ki doz BNT162b2 a\u015f\u0131s\u0131 sonras\u0131 yan etki g\u00f6r\u00fclme s\u0131kl\u0131\u011f\u0131, kohortun ya\u015f da\u011f\u0131l\u0131m\u0131na (p<\/i>=0.929) ve antikor titrelerinin medyan de\u011ferlerine (p<\/i>=0.585) (\u015eekil 2) g\u00f6re kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda istatistiksel olarak anlaml\u0131 d\u00fczeyde fark bulunmad\u0131. \u0130ki doz BNT162b2 a\u015f\u0131s\u0131 sonras\u0131 yan etki ile cinsiyet aras\u0131ndaki ili\u015fki incelendi\u011finde ise kad\u0131nlar ve erkeklerde yan etki g\u00f6r\u00fclme oran\u0131 e\u015fit olup en s\u0131k izlenen yan etki a\u015f\u0131 uygulanan yerde a\u011fr\u0131d\u0131r.\u00a0<\/span><\/p>\n

K\u00fcm\u00fclatif insidans oran\u0131 hesaplamas\u0131, 389 sa\u011fl\u0131k \u00e7al\u0131\u015fan\u0131n\u0131n verileri \u00fczerinden ger\u00e7ekle\u015ftirildi. BNT162b2 a\u015f\u0131s\u0131 birinci hat\u0131rlatma dozu sonras\u0131nda 14. ve 30. g\u00fcnlerde hi\u00e7 olgu g\u00f6r\u00fclmezken, 60 g\u00fcn i\u00e7inde 48. g\u00fcn tek bir olgu g\u00f6r\u00fcld\u00fc. Semptomatik SARS-CoV-2 infeksiyonunun k\u00fcm\u00fclatif insidans oran\u0131, 100 000 ki\u015fi-g\u00fcnde 4.3 [%95 g\u00fcven aral\u0131\u011f\u0131 (GA); 4.26-4.31] olarak tespit edildi. BNT162b2 a\u015f\u0131s\u0131n\u0131n ikinci hat\u0131rlatma dozu sonras\u0131nda ilk 14 g\u00fcnde \u00fc\u00e7 olgu g\u00f6r\u00fclm\u00fc\u015f olup semptomatik SARS-CoV-2 infeksiyonunun insidans oran\u0131 10 000 ki\u015fi-g\u00fcnde 5.5 (%95 GA; 5.43-5.65); 30 g\u00fcn i\u00e7inde 6 olgu g\u00f6r\u00fclm\u00fc\u015f olup insidans oran\u0131 10 000 ki\u015fi-g\u00fcnde 5.2 (%95 GA, 5.08-5.28) ve 60 g\u00fcn i\u00e7inde 9 olgu g\u00f6r\u00fclm\u00fc\u015f olup insidans oran\u0131 10 000 ki\u015fi-g\u00fcnde 3.9 (%95 GA, 5.43-5.65) olarak tespit edildi.<\/p>\n

\u0130RDELEME<\/h2>\n

Halen pek \u00e7ok \u00fclkede etkili tedavi ve profilaksi sa\u011flayan ila\u00e7lar\u0131n bulunmamas\u0131 nedeniyle COVID-19 pandemisi kapsam\u0131nda geli\u015ftirilen a\u015f\u0131lar kritik o\u0308neme sahiptir. \u00d6zellikle a\u015f\u0131lar\u0131n olu\u015fturdu\u011fu ba\u011f\u0131\u015f\u0131k yan\u0131t\u0131n antikor titreleri ile korelasyonunun anla\u015f\u0131lmas\u0131, COVID-19 pandemisini daha iyi kontrol alt\u0131na almada ve a\u015f\u0131 etkisinin de\u011ferlendirilmesinde yol g\u00f6sterici olmaktad\u0131r (7). Ancak, a\u015f\u0131 sonras\u0131 SARS-CoV-2\u2019ye o\u0308zgu\u0308l antikor arac\u0131l\u0131 humoral yan\u0131t\u0131n koruyuculu\u011funun ne kadar s\u00fcrece\u011fi ve varyantlara kar\u015f\u0131 de\u011fi\u015fkenli\u011fi gibi sorulara halen yan\u0131t bulunamam\u0131\u015ft\u0131r. Heterolog a\u015f\u0131lama, ilk olarak vekt\u00f6r bazl\u0131 ChAdOx1 (Oxford-AstraZeneca) a\u015f\u0131s\u0131na kar\u015f\u0131 geli\u015fen trombositopenili tromboz sendromu sonras\u0131 g\u00fcndeme gelmi\u015f olup adenoviral vekt\u00f6r a\u015f\u0131lama ile a\u015f\u0131 reaksiyonunun daha da tetiklenebilece\u011fi, bu nedenle de hat\u0131rlatma dozu olarak farkl\u0131 t\u00fcr a\u015f\u0131lama ile yan etki riskinin azalt\u0131labilece\u011fi d\u00fc\u015f\u00fcn\u00fclm\u00fc\u015ft\u00fcr (8). \u00c7e\u015fitli a\u015f\u0131 e\u015fle\u015ftirmeleri sonras\u0131nda olu\u015fan ba\u011f\u0131\u015f\u0131kl\u0131k yan\u0131t\u0131n\u0131n artmas\u0131yla daha y\u00fcksek antikor titrelerinin ve g\u00fc\u00e7l\u00fc T-h\u00fccre cevab\u0131n\u0131n olu\u015ftu\u011fu g\u00f6sterilmi\u015ftir (9, 10). \u00a0<\/span><\/p>\n

\u00dclkemizde sa\u011fl\u0131k \u00e7al\u0131\u015fanlar\u0131nda ba\u015flat\u0131lan a\u015f\u0131lama program\u0131 inaktif bir as\u0327\u0131 olan CoronaVac ile devam ederken, yeni varyantlara kar\u015f\u0131 etkinlik ve korumada g\u00f6r\u00fclen eksiklik nedeniyle T.C. Sa\u011fl\u0131k Bakanl\u0131\u011f\u0131 taraf\u0131ndan BNT162b2 a\u015f\u0131s\u0131 hat\u0131rlatma dozu se\u00e7ene\u011fi olarak sunulmu\u015ftur. Daha \u00f6nce yapt\u0131\u011f\u0131m\u0131z bir \u00e7al\u0131\u015fmada, 18-59 ya\u015f aras\u0131ndaki sa\u011fl\u0131k \u00e7al\u0131\u015fanlar\u0131nda iki doz CoronaVac sonras\u0131 \u00fc\u00e7\u00fcnc\u00fc hafta seropozitiflik oran\u0131 %99.6 (minimum10.1, maksimum: 66 923.7; medyan: 1022.4 AU\/ml) olarak bulunmu\u015ftur (11).\u00a0 <\/span>Bu \u00e7al\u0131\u015fmada ise sa\u011fl\u0131k \u00e7al\u0131\u015fanlar\u0131n\u0131n iki doz CoronaVac a\u015f\u0131s\u0131 sonras\u0131 4. aydaki seropozitiflik oran\u0131 %95 (minimum: 10, maksimum: 14 739.5; medyan: 292.10 AU\/ml) olarak saptand\u0131. A\u015f\u0131 sonras\u0131 3. hafta ile 4. ayda saptanan SARS-CoV-2 IgG titrelerinin medyan de\u011ferleri kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda antikor titrelerinde olduk\u00e7a ciddi bir d\u00fc\u015f\u00fc\u015f oldu\u011fu g\u00f6zlendi. Sa\u011fl\u0131k \u00e7al\u0131\u015fanlar\u0131nda iki doz CoronaVac sonras\u0131 antikor titrelerinin de\u011ferlendirildi\u011fi ba\u015fka bir \u00e7al\u0131\u015fmada ise birinci ayda seropozitiflik oran\u0131 %98.9 (medyan: 473.6 AU\/ml) iken d\u00f6rd\u00fcnc\u00fc ayda seropozitiflik oran\u0131 %89.1 (medyan: 166.5 AU\/ml) olarak bulunmu\u015ftur (12).\u00a0<\/span><\/p>\n

\u00dclkemizde ve CoronaVac ile a\u015f\u0131lama yap\u0131lan di\u011fer \u00fclkelerde ger\u00e7ekle\u015ftirilen \u00e7al\u0131\u015fmalarda, iki doz CoronaVac a\u015f\u0131s\u0131 sonras\u0131ndaki takiplerde ayn\u0131 d\u00f6nemlerde antikor titrelerinde g\u00f6r\u00fclen azalma ve olgu say\u0131lar\u0131ndaki h\u0131zl\u0131 art\u0131\u015f hat\u0131rlatma dozu gereklili\u011fi \u00fczerine dikkatleri \u00e7ekmi\u015ftir (13-15). SARS-CoV-2 varyantlar\u0131na kar\u015f\u0131 tam olarak koruyucu antikor titresinin ne kadar oldu\u011fu bilinmese de n\u00f6tralize antikor titresindeki azalman\u0131n a\u015f\u0131 ba\u011f\u0131\u015f\u0131kl\u0131k yan\u0131t\u0131nda da azalmaya neden oldu\u011fu g\u00f6sterilmi\u015ftir (16, 17). D\u00fcnya Sa\u011fl\u0131k \u00d6rg\u00fct\u00fc (DSO\u0308) taraf\u0131ndan endi\u015fe edici varyantlar (\u201cvariants of concern \u2013 VOCs\u201d) olarak tan\u0131mlanan be\u015f varyant i\u00e7inde yer alan delta (B.1.617.2) ve omicron (B.1.526) su\u015flar\u0131na kar\u015f\u0131 \u00f6zellikle inaktif a\u015f\u0131lar\u0131n ki\u015filerde olu\u015fturdu\u011fu seropozitifli\u011fe ra\u011fmen n\u00f6tralize etme kapasitesinde azalma oldu\u011fu \u00e7al\u0131\u015fmalarla saptanm\u0131\u015ft\u0131r (18, 19). \u00c7al\u0131\u015fmam\u0131zda, iki doz inaktif a\u015f\u0131 ile a\u015f\u0131lanm\u0131\u015f sa\u011fl\u0131k \u00e7al\u0131\u015fanlar\u0131nda BNT162b2 a\u015f\u0131s\u0131 hat\u0131rlatma dozu sonras\u0131nda \u00f6nemli \u00f6l\u00e7\u00fcde y\u00fcksek IgG titrelerinin elde edildi\u011fi belirlendi. \u0130ki doz inaktif a\u015f\u0131 sonras\u0131 hat\u0131rlatma dozu olarak BNT162b2 a\u015f\u0131s\u0131n\u0131n daha y\u00fcksek oranda antikor titrelerinde art\u0131\u015fa neden oldu\u011fu farkl\u0131 \u00e7al\u0131\u015fmalarda da g\u00f6sterilmi\u015ftir (10, 17). Can ve arkada\u015flar\u0131n\u0131n (20) \u00e7al\u0131\u015fmalar\u0131nda, hat\u0131rlatma dozu olarak BNT162b2 a\u015f\u0131s\u0131 sonras\u0131 antikor titrelerinde 3.38 kat art\u0131\u015f oldu\u011fu, IFN-gamma, IL-2 seviyelerinde ve CD8+ T h\u00fccre yan\u0131t\u0131nda da art\u0131\u015f g\u00f6r\u00fcld\u00fc\u011f\u00fcn\u00fc bildirilmi\u015ftir. \u0130naktif a\u015f\u0131lar daha d\u00fc\u015f\u00fck titrede antikor yan\u0131t\u0131na neden olmakla birlikte y\u00fcksek bir IgG2a\/IgG1 oran\u0131n\u0131 ind\u00fckledi\u011fi, mRNA temelli a\u015f\u0131lar\u0131n ise Th1 tipi T h\u00fccre yan\u0131t\u0131n\u0131 y\u00fcksek oranda art\u0131rd\u0131\u011f\u0131 g\u00f6sterilmi\u015ftir (21). \u0130naktif a\u015f\u0131 sonras\u0131 hat\u0131rlatma dozu olarak BNT162b2 a\u015f\u0131s\u0131 uygulanmas\u0131n\u0131n, homolog a\u015f\u0131lamaya k\u0131yasla \u201cspike-specific\u201d CD4+ ve CD8+ T h\u00fccre yan\u0131tlar\u0131n\u0131 art\u0131rd\u0131\u011f\u0131, y\u00fcksek titrede n\u00f6tralizan antikor olu\u015fturdu\u011fu ve IFN-gamma salg\u0131layan T h\u00fccre yan\u0131t\u0131n\u0131 da art\u0131rd\u0131\u011f\u0131 tespit edilmi\u015ftir (22, 23).\u00a0<\/span><\/p>\n

T\u00fcm a\u015f\u0131 gruplar\u0131n\u0131n faz 3 \u00e7al\u0131\u015fmalar\u0131n\u0131 i\u00e7eren bir meta analiz \u00e7al\u0131\u015fmas\u0131na g\u00f6re; a\u015f\u0131lanm\u0131\u015f ve a\u015f\u0131lanmam\u0131\u015f bireyler aras\u0131nda yan etki g\u00f6r\u00fclme riski 1.7 kat; CoronaVac a\u015f\u0131s\u0131 i\u00e7in 0.89 kat; mRNA a\u015f\u0131lar\u0131ndan Moderna COVID-19 a\u015f\u0131s\u0131 (mRNA1273) i\u00e7in 1.83 kat ve BNT162b2 a\u015f\u0131s\u0131 i\u00e7inse \u00e7ok daha y\u00fcksek olarak 4.1 kat fazla oldu\u011fu bildirilmi\u015ftir (24). \u00c7al\u0131\u015fmam\u0131zla benzer \u015fekilde FDA raporunda BNT162b2 a\u015f\u0131s\u0131n\u0131n yan etki s\u0131kl\u0131\u011f\u0131n\u0131n hem lokal (%88.7) hem de sistemik yan etkiler (%82.8) bak\u0131m\u0131ndan 18-55 ya\u015f aral\u0131\u011f\u0131nda daha s\u0131k oldu\u011fu bildirilmi\u015ftir (25). \u00c7al\u0131\u015fmam\u0131zda, kat\u0131l\u0131mc\u0131lar\u0131n 280 (%65.4)\u2019inde tek doz BNT162b2 uygulanmas\u0131ndan sonra en az bir yan etki g\u00f6r\u00fcld\u00fc; yan etki g\u00f6r\u00fclen 176 (%60.3) kad\u0131n sa\u011fl\u0131k \u00e7al\u0131\u015fan\u0131nda %64.2 oran\u0131nda yorgunluk-halsizlik ve %31.8 oran\u0131nda ate\u015f-\u00fc\u015f\u00fcme-titreme gibi sistemik yan etkilerin erkeklere g\u00f6re daha yayg\u0131n \u015fekilde g\u00f6r\u00fcld\u00fc\u011f\u00fc belirlendi (p<\/i><0.001).\u00a0<\/span><\/p>\n

Menni ve arkada\u015flar\u0131 (5) \u00e7al\u0131\u015fmalar\u0131nda, sa\u011fl\u0131k \u00e7al\u0131\u015fanlar\u0131 aras\u0131nda BNT162b2 a\u015f\u0131s\u0131n\u0131n ilk dozunu takiben en az bir yan etki g\u00f6r\u00fclme s\u0131kl\u0131\u011f\u0131n\u0131 %71.9 oran\u0131yla daha y\u00fcksek bulmu\u015ftur. Ayn\u0131 \u00e7al\u0131\u015fmada, \u00e7al\u0131\u015fmam\u0131za benzer \u015fekilde kad\u0131nlarda daha yayg\u0131n olarak yan etki g\u00f6r\u00fcld\u00fc\u011f\u00fc bildirilmi\u015ftir. \u00c7al\u0131\u015fmam\u0131zda, BNT162b2 a\u015f\u0131s\u0131n\u0131n faz 3 \u00e7al\u0131\u015fmalar\u0131nda raporlanan yan etkilere k\u0131yasla yan etki s\u0131kl\u0131\u011f\u0131 daha az bulundu ve lokal yan etkilerin sistemik yan etkilere g\u00f6re daha fazla oranda oldu\u011fu g\u00f6r\u00fcld\u00fc (4). Kohort olarak ger\u00e7ekle\u015ftirilen \u00e7al\u0131\u015fmam\u0131zda, sa\u011fl\u0131k \u00e7al\u0131\u015fanlar\u0131nda tek doz BNT162b2 a\u015f\u0131s\u0131 uygulanmas\u0131ndan sonra %59.6 oran\u0131yla enjeksiyon yerinde k\u0131zar\u0131kl\u0131k, \u015fi\u015flik ve a\u011fr\u0131 en s\u0131k g\u00f6r\u00fclen yan etkiydi. Yap\u0131lan \u00e7e\u015fitli \u00e7al\u0131\u015fmalarda ve BNT162b2 a\u015f\u0131s\u0131n\u0131n faz 3 \u00e7al\u0131\u015fmas\u0131nda, enjeksiyon yerinde a\u011fr\u0131 \u00e7al\u0131\u015fmam\u0131zla benzer \u015fekilde en s\u0131k yan etki olarak saptanm\u0131\u015ft\u0131r (4, 26, 27).<\/p>\n

\u00c7al\u0131\u015fmam\u0131zda, %58.6 oran\u0131yla yorgunluk-halsizlik en s\u0131k g\u00f6r\u00fclen sistemik reaksiyon oldu. S\u0131k g\u00f6r\u00fclen yan etkiler a\u00e7\u0131s\u0131ndan bunu %51.1 oran\u0131yla kas-eklem a\u011fr\u0131s\u0131, %40.7 oran\u0131yla ba\u015f a\u011fr\u0131s\u0131 ve %27.5 oran\u0131yla ate\u015f-\u00fc\u015f\u00fcme-titreme izledi. Kat\u0131l\u0131mc\u0131lar\u0131n18-55 ya\u015f aral\u0131\u011f\u0131nda oldu\u011fu bir ba\u015fka \u00e7al\u0131\u015fmada, sistemik reaksiyonlardan yorgunluk-halsizlik benzer \u015fekilde en s\u0131k g\u00f6r\u00fclen yan etki olup ba\u015f a\u011fr\u0131s\u0131, ikinci g\u00fcnden itibaren >38\u00b0C ate\u015f, titreme, kas a\u011fr\u0131s\u0131 ve eklem a\u011fr\u0131s\u0131 da s\u0131k yan etkiler olarak rapor edilmi\u015ftir (27). \u00c7e\u015fitli kohort ara\u015ft\u0131rmalar\u0131nda, tek doz BNT162b2 a\u015f\u0131s\u0131 sonras\u0131nda sistemik yan etkilerin s\u0131kl\u0131\u011f\u0131 di\u011fer mRNA a\u015f\u0131lar\u0131na k\u0131yasla ve faz 3 \u00e7al\u0131\u015fmas\u0131na g\u00f6re daha az oranda g\u00f6r\u00fclm\u00fc\u015ft\u00fcr (4, 5, 28). \u00c7al\u0131\u015fmam\u0131zda iki doz BNT162b2 a\u015f\u0131s\u0131 uygulanm\u0131\u015f 55 sa\u011fl\u0131k \u00e7al\u0131\u015fan\u0131 de\u011ferlendirildi\u011finde, a\u015f\u0131 uygulanan yerde a\u011fr\u0131 en s\u0131k izlenen yan etki oldu.<\/p>\n

\u00c7al\u0131\u015fmam\u0131zda lokal ve sistemik yan etkilerin d\u0131\u015f\u0131nda \u00fc\u00e7 (%1.1) sa\u011fl\u0131k \u00e7al\u0131\u015fan\u0131nda aksiller lenfadenopati saptand\u0131. Faz 3 \u00e7al\u0131\u015fmas\u0131nda BNT162b2 a\u015f\u0131s\u0131 sonras\u0131nda %0.3 pop\u00fclasyonda b\u00f6lgesel lenfadenopati geli\u015fti\u011fi bildirilmi\u015ftir (4). \u00d6zellikle a\u015f\u0131 sonras\u0131 2-4 g\u00fcn i\u00e7erisinde g\u00f6r\u00fclen aksiller ve servikal lenfadenopatiler, \u00e7e\u015fitli \u00e7al\u0131\u015fmalarda BNT162b2 a\u015f\u0131s\u0131 sonras\u0131 bildirilen %16 oran\u0131nda ortak ve %44.1 oran\u0131nda yayg\u0131n istenmeyen etki olarak tan\u0131mlanm\u0131\u015ft\u0131r (28, 29).\u00a0<\/span><\/p>\n

\u00c7al\u0131\u015fmam\u0131zda sa\u011fl\u0131k \u00e7al\u0131\u015fanlar\u0131nda tek doz BNT162b2 a\u015f\u0131s\u0131 sonras\u0131 yan etki g\u00f6r\u00fclme s\u0131kl\u0131\u011f\u0131 ve ge\u00e7irilmi\u015f COVID-19 \u00f6yk\u00fcs\u00fc aras\u0131nda anlaml\u0131 d\u00fczeyde bir ili\u015fki bulunmad\u0131 (p<\/i>=0.250). Benzer \u015fekilde bir \u00fcniversite hastanesinde g\u00f6rev yapan 3659 sa\u011fl\u0131k \u00e7al\u0131\u015fan\u0131n\u0131n dahil edildi\u011fi bir \u00e7al\u0131\u015fmada ge\u00e7irilmi\u015f COVID-19 \u00f6yk\u00fcs\u00fcn\u00fcn yan etki riskini art\u0131rmad\u0131\u011f\u0131 g\u00f6sterilmi\u015ftir (30). Randomize yap\u0131lan klinik \u00e7al\u0131\u015fmalarda ge\u00e7irilmi\u015f COVID-19 \u00f6yk\u00fcs\u00fc ile a\u015f\u0131 sonras\u0131 g\u00f6r\u00fclen yan etki aras\u0131nda kesin bir ili\u015fki g\u00f6sterilmemi\u015f olmak birlikte \u00e7e\u015fitli kohort \u00e7al\u0131\u015fmalar\u0131nda COVID-19 \u00f6yk\u00fcs\u00fc ile a\u015f\u0131 sonras\u0131 g\u00f6r\u00fclen yan etki aras\u0131nda anlaml\u0131 d\u00fczeyde ili\u015fki bulunmu\u015ftur (31-33).\u00a0<\/span><\/p>\n

\u00c7al\u0131\u015fmam\u0131z\u0131n kat\u0131l\u0131mc\u0131lar\u0131nda, tek doz BNT162b2 a\u015f\u0131s\u0131 sonras\u0131 yan etki g\u00f6r\u00fclme s\u0131kl\u0131\u011f\u0131 ile CoronaVac a\u015f\u0131s\u0131 sonras\u0131 4. aydaki SARS-CoV-2 IgG titreleri ve BNT162b2 a\u015f\u0131s\u0131 sonras\u0131 3. haftadaki SARS-CoV-2 IgG titreleri kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda yan etki g\u00f6r\u00fclenlerin medyan de\u011ferinin yan etki g\u00f6r\u00fclmeyenlere g\u00f6re daha y\u00fcksek ve \u2265 40.000 AU\/ml oldu\u011fu g\u00f6r\u00fcld\u00fc (p<\/i><0.001). Coggins ve arkada\u015flar\u0131n\u0131n (34) \u00e7al\u0131\u015fmalar\u0131nda, BNT162b2 a\u015f\u0131s\u0131n\u0131n yan etkileri ile antikor titreleri aras\u0131nda anlaml\u0131 d\u00fczeyde bir ili\u015fki olmad\u0131\u011f\u0131 bildirilmi\u015ftir.\u00a0<\/span><\/p>\n

\u00c7al\u0131\u015fmam\u0131zda, iki doz CoronaVac a\u015f\u0131s\u0131 sonras\u0131 hat\u0131rlatma dozu olarak uygulanan BNT162b2 a\u015f\u0131lamas\u0131nda, gerek birinci gerekse ikinci dozda g\u00f6r\u00fclen yan etkiler hafif-orta derecede olup tolere edilebilir d\u00fczeyde olarak de\u011ferlendirildi. Birinci hat\u0131rlatma dozunda %65.4 oran\u0131yla yan etkilerin g\u00f6r\u00fclme s\u0131kl\u0131\u011f\u0131 %61.8 oran\u0131nda olan ikinci hat\u0131rlatma dozuna g\u00f6re daha s\u0131kt\u0131. BNT162b2 heterolog a\u015f\u0131lama sonras\u0131nda yan etkilerin \u00f6zellikle 18-40 ya\u015f aral\u0131\u011f\u0131nda, kad\u0131nlarda ve \u00f6ncesinde daha y\u00fcksek titrede antikora sahip ki\u015filerde anlaml\u0131 olarak daha s\u0131k g\u00f6r\u00fcld\u00fc\u011f\u00fc saptand\u0131.\u00a0<\/span><\/span><\/p>\n

Sonu\u00e7 olarak, \u00f6zellikle y\u00fcksek riskli ortamda bulunan sa\u011fl\u0131k \u00e7al\u0131\u015fanlar\u0131 ve ya\u015fl\u0131 pop\u00fclasyonda hat\u0131rlatma dozu olarak mRNA a\u015f\u0131lar\u0131 y\u00fcksek koruyucu etkisi nedeniyle tercih edilebilir.<\/p>\n","protected":false},"excerpt":{"rendered":"

G\u0130R\u0130\u015e SARS-CoV-2\u2019nin neden oldu\u011fu COVID-19 hastal\u0131\u011f\u0131, ba\u015fta akci\u011ferler olmak \u00fczere bir\u00e7ok sistemi tutan, mortalitesi ve morbiditesi nedeniyle toplumlar\u0131n g\u00fcndelik ya\u015fam\u0131n\u0131 etkileyen bula\u015f\u0131c\u0131 bir hastal\u0131kt\u0131r. Mart 2020\u2019de ba\u015flayan pandemi nedeniyle t\u00fcm d\u00fcnyada h\u0131zl\u0131 bir \u015fekilde a\u015f\u0131 geli\u015ftirme \u00e7al\u0131\u015fmalar\u0131 ba\u015flat\u0131lm\u0131\u015ft\u0131r. Tarih boyunca t\u00fcm pandemilerin kontrol\u00fcnde en etkili yol a\u015f\u0131 uygulamalar\u0131 olmu\u015ftur. COVID-19 pandemisinde inaktif, canl\u0131 aten\u00fce, protein […]<\/p>\n","protected":false},"author":4,"featured_media":26242,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[5129],"tags":[5587,5578,5586,3675,5588],"class_list":["post-26001","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-ozgun-arastirma","tag-antikor-titresi","tag-bnt162b2-asisi","tag-heterolog-asilama","tag-saglik-calisanlari","tag-yan-etki"],"acf":[],"_links":{"self":[{"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/posts\/26001","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=26001"}],"version-history":[{"count":3,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/posts\/26001\/revisions"}],"predecessor-version":[{"id":26177,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/posts\/26001\/revisions\/26177"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/media\/26242"}],"wp:attachment":[{"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/media?parent=26001"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/categories?post=26001"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/tags?post=26001"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}