{"id":24200,"date":"2022-02-22T14:43:58","date_gmt":"2022-02-22T11:43:58","guid":{"rendered":"https:\/\/www.klimikdergisi.org\/?p=24200"},"modified":"2022-03-28T12:32:30","modified_gmt":"2022-03-28T09:32:30","slug":"covid-19-ve-immunsupresif-tedaviler","status":"publish","type":"post","link":"https:\/\/www.klimikdergisi.org\/tr\/2022\/02\/22\/covid-19-ve-immunsupresif-tedaviler\/","title":{"rendered":"\u00dc\u00e7\u00fcnc\u00fc Basamak Bir Hastanede Takip Edilen COVID-19 Olgular\u0131nda \u0130mm\u00fcnos\u00fcpresif Tedavi Uygulanan Hastalar\u0131n De\u011ferlendirilmesi"},"content":{"rendered":"

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

\u015eiddetli akut solunum sendromu virusu (SARS-CoV-2) ile ili\u015fkili<\/span> infeksiyon ilk kez Aral\u0131k 2019\u2019da \u00c7in\u2019in Hubei eyaletinde bulunan Vuhan \u015fehrinde saptanm\u0131\u015f olup alt\u0131 aydan daha k\u0131sa bir s\u00fcrede d\u00fcnya geneline yay\u0131larak k\u00fcresel bir salg\u0131na sebep olmu\u015ftur (1). Virusun infektivitesinin y\u00fcksek olmas\u0131, tedavide etkili bir antiviral ajan\u0131n bulunmamas\u0131 ve infeksiyonun y\u00fcksek oranda asemptomatik seyretmesi nedenlerinden dolay\u0131 koronavirus hastal\u0131\u011f\u0131 2019 (COVID-19)\u2019un tedavi y\u00f6netimi ve pandeminin kontrol alt\u0131na al\u0131nmas\u0131 olduk\u00e7a g\u00fc\u00e7 olmaktad\u0131r (2). \u00c7e\u015fitli klinik tablolarla kar\u015f\u0131m\u0131za \u00e7\u0131kan COVID-19\u2019un \u00f6zellikle risk fakt\u00f6r\u00fc y\u00fcksek hastalarda; \u015fiddetli sitokin f\u0131rt\u0131nas\u0131 sendromuna, akut solunum yetmezli\u011fi sendromuna (\u201cacute respiratory distress syndrome\u201d, ARDS), doku perf\u00fczyon bozukluklar\u0131na, septik \u015foka ve \u00e7oklu organ yetmezli\u011fine ve hatta \u00f6l\u00fcme neden oldu\u011fu g\u00f6r\u00fclmektedir (3, 4). Sekonder hemofagositik lenfohistiyositoz (sHLH) sendromu, \u00e7oklu organ yetmezli\u011fine yol a\u00e7an f\u00fclminan ve fatal hipersitokinemiyle karakterize hiperinflamasyon sendromu olup COVID-19 infeksiyonu gibi viral infeksiyonlarla tetiklenebilmektedir (5). \u015eiddetli COVID-19 geli\u015fen hastalar i\u00e7in bildirilen olgu serileri ve g\u00f6zlemler sonucunda potansiyel patogenezin sitokin sal\u0131n\u0131m sendromu oldu\u011fu d\u00fc\u015f\u00fcn\u00fclmekte olup \u015fiddetli tablonun sHLH ile karakterize oldu\u011fu \u00f6ne s\u00fcr\u00fclmektedir (6). Sitokin sal\u0131n\u0131m sendromu; abart\u0131lm\u0131\u015f ve kontrols\u00fcz inflamatuar sitokin \u00fcretimi [ba\u015fl\u0131ca interl\u00f6kin-6 (IL-6), interl\u00f6kin-10 (IL-10) ve t\u00fcm\u00f6r nekroz fakt\u00f6r-\u03b1 (TNF- \u03b1)] olarak tan\u0131mlanmaktad\u0131r (2, 7). Bu durum, her ne kadar g\u00fcvenlik ve etkinli\u011fi kesin olarak belirlenmi\u015f olmasa da COVID-19 hasta grubunda anti-sitokin ve kortikosteroid tedavilerinin tercih edilmesine yol a\u00e7m\u0131\u015ft\u0131r (3). \u0130nterl\u00f6kin-6 resept\u00f6r antagonistleri, Amerikan G\u0131da ve \u0130la\u00e7 Dairesi\u00a0 <\/span>(\u201cU.S. Food and Drug Administration\u201d, FDA) taraf\u0131ndan sitokin f\u0131rt\u0131nas\u0131 sendromu tedavisinde onaylanm\u0131\u015ft\u0131r (8). COVID-19 infeksiyonunun ind\u00fckledi\u011fi sitokin f\u0131rt\u0131nas\u0131nda, interl\u00f6kin-6\u2019n\u0131n anahtar rol\u00fc oldu\u011fu d\u00fc\u015f\u00fcn\u00fcld\u00fc\u011f\u00fcnden, tedavide tosilizumab kullan\u0131lmas\u0131 g\u00fcndeme gelmi\u015ftir (9). Bir\u00e7ok \u00fclkenin COVID-19 tedavi rehberinde, sitokin f\u0131rt\u0131nas\u0131 ve\/veya ARDS geli\u015fen kritik hastalar\u0131n tedavisinde kortikosteroid ve IL-6 antagonistleri yer almaktad\u0131r<\/span> (10-12). Buna kar\u015f\u0131n, COVID-19 tedavisinde immu\u0308nosu\u0308presif tedavilerin ba\u015flanma zaman\u0131 hakk\u0131nda farkl\u0131 g\u00f6r\u00fc\u015fler bulunmakta ve HLH skorlamalar\u0131n\u0131n COVID-19 olgular\u0131 i\u00e7in her zaman yeterli olamayaca\u011f\u0131 d\u00fc\u015f\u00fcn\u00fclmektedir (12). \u00c7al\u0131\u015fmam\u0131zda klini\u011fimizde yat\u0131rmak suretiyle takip etti\u011fimiz COVID-19 olgular\u0131nda immu\u0308nosu\u0308presif tedavi alan ve almayan hasta gruplar\u0131n\u0131n kar\u015f\u0131la\u015ft\u0131rmal\u0131 olarak de\u011ferlendirilmesi ama\u00e7lanm\u0131\u015ft\u0131r. Bunun yan\u0131nda, hastal\u0131\u011f\u0131n \u015fiddetini saptamada T.C. Sa\u011fl\u0131k Bakanl\u0131\u011f\u0131 COVID-19 Eri\u015fkin Hasta Tedavisi Rehberi\u2019nde belirtilen k\u00f6t\u00fc prognostik fakt\u00f6rler ve HLH skorlamas\u0131nda kullan\u0131lan parametrelerden se\u00e7ilen 13 k\u00f6t\u00fc prognostik parametreden olu\u015fan bir skorlama algoritmas\u0131n\u0131n, imm\u00fcnos\u00fcpresif tedavi alan ve almayan hastalar ile mortalite geli\u015fen ve geli\u015fmeyen hastalarda kar\u015f\u0131la\u015ft\u0131r\u0131lmas\u0131 ve mortaliteyi tahmin ettirmedeki duyarl\u0131l\u0131k ve \u00f6zg\u00fcll\u00fc\u011f\u00fc ara\u015ft\u0131r\u0131lm\u0131\u015ft\u0131r (12).\u00a0<\/span><\/p>\n

<\/b>Y\u00d6NTEMLER<\/h2>\n

\u00c7al\u0131\u015fma 01 Mart -31 May\u0131s 2020 tarihleri aras\u0131nda, \u00fc\u00e7\u00fcnc\u00fc basamak bir e\u011fitim ara\u015ft\u0131rma hastanesinde y\u00fcr\u00fct\u00fcld\u00fc. Hastane, 1500 yatak kapasiteli olup 62 eri\u015fkin yo\u011fun bak\u0131m yatak kapasitesine sahiptir. \u00c7al\u0131\u015fmaya T.C. Sa\u011fl\u0131k Bakanl\u0131\u011f\u0131 COVID-19 Eri\u015fkin Hasta Tedavisi Rehberi\u2019ne g\u00f6re COVID-19 tan\u0131s\u0131 koyularak yo\u011fun bak\u0131m \u00fcnitesi (YB\u00dc) ve servislerde takip edilen 18 ya\u015f \u00fczeri 263 hasta dahil edildi. COVID-19 tan\u0131s\u0131n\u0131n laboratuvar do\u011frulamas\u0131, hastalar\u0131n nazofaringeal s\u00fcr\u00fcnt\u00fc \u00f6rneklerinde SARS-CoV-2 \u201creal-time\u201d polimeraz zincir reaksiyon testi (RT-PCR) pozitifli\u011finin g\u00f6sterilmesiyle yap\u0131ld\u0131. Hastalar\u0131n tamam\u0131 yat\u0131r\u0131larak tedavi edilmi\u015f olup tedavi s\u00fcresince Sa\u011fl\u0131k Bakanl\u0131\u011f\u0131\u2019n\u0131n yay\u0131nlad\u0131\u011f\u0131 rehberde \u00f6nerilen standard tedavi algoritmalar\u0131 uyguland\u0131 (12).<\/p>\n

Standard tedavi verilen hasta gruplar\u0131nda antiviral tedavi olarak; hidroksiklorokin ve\/veya favipravir kullan\u0131ld\u0131. Pn\u00f6moni saptanan olgularda bakteriyel infeksiyonun e\u015flik etti\u011fi d\u00fc\u015f\u00fcn\u00fcld\u00fc\u011f\u00fcnde, infeksiyonun \u015fiddetine g\u00f6re ampirik olarak levofloksasin, azitromisin ve sefalosporin t\u00fcrevleriyle monoterapi veya kombinasyon tedavisi (sefalosporin + levofloksason \/ sefalosporin + azitromisin) antiviral tedaviye eklendi. Antimikrobiyal ve antiviral tedaviye ek olarak antikoag\u00fclan, mukolitik ve antiasit tedavileri T.C. Sa\u011fl\u0131k Bakanl\u0131\u011f\u0131 COVID-19 Eri\u015fkin Hasta Tedavisi Rehberi\u2019nde belirtilen doz ve endikasyonlarda uyguland\u0131.<\/p>\n

Karantina servisi veya YB\u00dc\u2019nde takip edilen hastalarda, diren\u00e7li ate\u015f (>37.8 0<\/sup>C), CRP y\u00fcksekli\u011fi, normalin \u00fcst s\u0131n\u0131rlar\u0131n\u0131n \u00fczerinde ve art\u0131\u015f e\u011filiminde olan ferritin de\u011ferleri (>500\u03bcg\/L), D-dimer y\u00fcksekli\u011fi, lenfopeni (<0.800×103\/<\/sup>uL), trombositopeni (<150 x103\/<\/sup>uL), karaci\u011fer fonksiyon testlerinde (ALT, AST, LDH) patoloji olmas\u0131 durumunda, klinisyen tercihine g\u00f6re tek ba\u015f\u0131na steroid, steroid ve tosilizumab ard\u0131\u015f\u0131k olarak yada sadece tosilizumab olacak \u015fekilde standard tedavilere, imm\u00fcnos\u00fcpresif tedaviler eklendi. Hastalarda ko-infeksiyon ve sekonder infeksiyonun d\u0131\u015flanmas\u0131nda; kan k\u00fclt\u00fcr\u00fc negatifli\u011finin olmas\u0131, spontan balgam \u00e7\u0131karan hastalarda balgam k\u00fclt\u00fcr\u00fcnde \u00fcreme olmamas\u0131 ve normal prokalsitonin de\u011ferleri esas al\u0131nd\u0131. Sitokin f\u0131rt\u0131nas\u0131 ya da hemofogositoz d\u00fc\u015f\u00fcn\u00fclen hastalar\u0131n standard tedavilerine klinisyenin tercihine g\u00f6re ek olarak kortikosteorid (metilprednizolon 1 mg\/kg dozunda 5-7 g\u00fcn) ve\/veya IL-6 blok\u00f6r\u00fc (tosilizumab 8 mg\/kg, maks. 800 mg) ard\u0131\u015f\u0131k iki doz \u015feklinde intraven\u00f6z olarak uyguland\u0131.<\/p>\n

Tocilizumab tedavisi, \u015f\u00fcpheli ya da do\u011frulanm\u0131\u015f bakteriyel infeksiyon varl\u0131\u011f\u0131, aktif divertik\u00fclit varl\u0131\u011f\u0131 ya da gastrointestinal perforasyon varl\u0131\u011f\u0131, n\u00f6tropeni (0.500×103<\/sup> h\u00fccre\/uL) ve trombositopeni (50×103<\/sup> h\u00fccre\/uL) varl\u0131\u011f\u0131 durumlar\u0131nda uygulanmad\u0131. ARDS tan\u0131s\u0131 konulan hastalar\u0131n tedavilerine, kortikosteorid tedavisi <\/i><\/b>eklendi. Kan \u015fekeri reg\u00fclasyonu sa\u011flanamayan diabetes mellitus (DM) varl\u0131\u011f\u0131, kontrols\u00fcz hipertansiyon, kalp yetmezli\u011fi ve periferal \u00f6dem, katarakt, glokom, peptik \u00fclser hastal\u0131\u011f\u0131, bakteriyel infeksiyon varl\u0131\u011f\u0131, d\u00fc\u015f\u00fck kemik dansitesi ve\/veya osteoporozu bulunan hastalara kortikosteroid tedavisi uygulanmad\u0131 (13).<\/p>\n

ARDS, a\u015fa\u011f\u0131da belirtilen \u00fc\u00e7 patolojik kriterin bir arada olmas\u0131 olarak tan\u0131mland\u0131 (12):<\/p>\n

    \n
  1. Son bir haftada ortaya \u00e7\u0131kan veya k\u00f6t\u00fcle\u015fen solunum s\u0131k\u0131nt\u0131s\u0131,<\/li>\n
  2. Radyolojik olarak plevral ef\u00fczyon, kollaps ile a\u00e7\u0131klanamayan bilateral multilober buzlu cam dansiteleri,<\/li>\n
  3. Kalp yetmezli\u011fi veya vol\u00fcm fazlal\u0131\u011f\u0131 ile a\u00e7\u0131klanamayan solunum yetmezli\u011fi (transtorasik ekokardiyografi ile sol ventrik\u00fcl disfonksiyonunun olmad\u0131\u011f\u0131n\u0131n g\u00f6sterilmesi).<\/li>\n<\/ol>\n

    ARDS \u015fiddeti; hafif [200<PaO2\/FiO2 \u2264 300 (PEEP \u2265 5 cmH20)], orta [100<PaO2\/FiO2 \u2264 200 (PEEP \u2265 5 cmH20)] ve a\u011f\u0131r [PaO2\/FiO2 \u2264 100 (PEEP \u2265 5 cmH20)] olarak s\u0131n\u0131fland\u0131r\u0131ld\u0131.<\/p>\n

    \u201cQuick\u201d SOFA (qSOFA) Skoru<\/h3>\n

    \u201cQuick\u201d SOFA (qSOFA) skoru, YB\u00dc d\u0131\u015f\u0131ndaki hastalar\u0131 de\u011ferlendirmek ve sepsis a\u00e7\u0131s\u0131ndan \u00f6l\u00fcm riski olan hastalar\u0131 erken belirlemek amac\u0131yla; solunum say\u0131s\u0131, sistolik kan bas\u0131nc\u0131 <\/i>ve mental durum de\u011fi\u015fikli\u011fi<\/i> \u015feklinde \u00fc\u00e7 parametreden olu\u015fan bir skorlama sistemidir. \u201cSequential Organ Failure Assessment Score\u201d (SOFA)\u2019un modifiye \u015fekli olup hastalarda daha h\u0131zl\u0131 septik tablo varl\u0131\u011f\u0131n\u0131 belirlemek amac\u0131yla \u201cQuick\u201d SOFA (qSOFA) olarak adland\u0131r\u0131lan skorlama sistemi kullan\u0131lm\u0131\u015ft\u0131r (14). Hastalar yatak ba\u015f\u0131nda kolayl\u0131kla belirlenebilen, solunum say\u0131s\u0131 \u226522\/dk., mental durumda bozulma-Glaskow Koma Skalas\u0131 \u226413 ve sistolik kan bas\u0131nc\u0131 \u2264100 mmHg \u00f6zelliklerinin her biri i\u00e7in birer puan al\u0131r.<\/p>\n

    Hastalara, klinisyenlerin tercihlerine g\u00f6re farkl\u0131 etki mekanizmalar\u0131 olan immu\u0308nosu\u0308presif tedaviler uyguland\u0131. Hastalar etki mekanizmalar\u0131ndan ba\u011f\u0131ms\u0131z olarak, imm\u00fcnos\u00fcpresif tedavi verilen ve verilmeyen olarak iki gruba ayr\u0131ld\u0131 ve analizler bu gruplamaya g\u00f6re yap\u0131ld\u0131. T.C. Sa\u011fl\u0131k Bakanl\u0131\u011f\u0131 COVID-19 Eri\u015fkin Hasta Tedavisi Rehberi\u2019nde belirtilen k\u00f6t\u00fc prognostik fakt\u00f6rlerin yan\u0131 s\u0131ra HLH skorlamas\u0131nda kullan\u0131lan parametrelerle 13 k\u00f6t\u00fc prognostik parametrelik bir skorlama algoritmas\u0131 olu\u015fturuldu. Prognostik fakt\u00f6rlerin ortalama de\u011ferleri, imm\u00fcnos\u00fcpresif tedavi alan ve almayan hastalar ile mortalite geli\u015fen ve geli\u015fmeyen hastalarda kar\u015f\u0131la\u015ft\u0131r\u0131larak hastal\u0131\u011f\u0131n \u015fiddeti ve mortaliteyi tahmin ettirmedeki duyarl\u0131l\u0131k ve \u00f6zg\u00fcll\u00fc\u011f\u00fc ara\u015ft\u0131r\u0131ld\u0131.<\/p>\n

    Mortalitenin \u00f6ng\u00f6r\u00fclebilmesinde kullan\u0131labilecek skorlama sisteminde a\u015fa\u011f\u0131daki parametreler kullan\u0131ld\u0131 ve her bir parametreye birer puan verilerek toplam skor hesapland\u0131:<\/p>\n

      \n
    1. Antiviral tedaviye ra\u011fmen tedavinin 48. ve 72. saatleri aras\u0131nda 37.8 0<\/sup>C ve \u00fczeri ate\u015fin devam etmesi,<\/li>\n
    2. Bilgisayarl\u0131 tomografi (BT)\u2019de bilateral yayg\u0131n buzlu cam g\u00f6r\u00fcn\u00fcm\u00fc varl\u0131\u011f\u0131,<\/li>\n
    3. C-reaktif protein (CRP) de\u011ferinin 48-72 saatlik d\u00f6nemde progresyonu,<\/li>\n
    4. Ferritin de\u011ferinin 500 ng\/ml ve \u00fczerinde olmas\u0131,<\/li>\n
    5. D-dimer de\u011ferinde yat\u0131\u015fa g\u00f6re 2 kat art\u0131\u015f olmas\u0131,<\/li>\n
    6. Takiplerde derinle\u015fen lenfopeni (<0.800×103\/uL),<\/li>\n
    7. Trombositopeni (<150 x103\/uL) e\u015flik etmesi,<\/li>\n
    8. Troponin y\u00fcksekli\u011fi saptanmas\u0131,<\/li>\n
    9. Tedaviye ra\u011fmen solunum say\u0131s\u0131n\u0131n 30\/dk. \u00fczerinde olmas\u0131,<\/li>\n
    10. Oksijen sat\u00fcrasyonunun %75-85 aras\u0131nda seyretmesi,<\/li>\n
    11. En az iki komorbid fakt\u00f6r\u00fcn e\u015flik ediyor olmas\u0131,<\/li>\n
    12. 40 ya\u015f ve \u00fczeri olmak,<\/li>\n
    13. Erkek cinsiyet.<\/li>\n<\/ol>\n

      \u0130statistiksel Analizler<\/h3>\n

      \u0130statistiksel analiz, \u201cIBM SPSS Statistics for Windows. Version 22.0 (Statistical Package for the Social Sciences\u201d (IBM Corp., Armonk, NY, ABD)\u201d program\u0131 kullan\u0131larak ger\u00e7ekle\u015ftirildi. Verilerin normal da\u011f\u0131l\u0131ma uygunlu\u011fu Kolmogorov-Smirnov testi ile de\u011ferlendirildi. Gruplar aras\u0131ndaki farkl\u0131l\u0131klar\u0131n kar\u015f\u0131la\u015ft\u0131r\u0131lmas\u0131 kapsam\u0131nda; kategorik de\u011fi\u015fkinlerden ba\u011f\u0131ms\u0131z grup oranlar\u0131n\u0131n kar\u015f\u0131la\u015ft\u0131r\u0131lmas\u0131 i\u00e7in \u03c72 ve Fisher kesin olas\u0131l\u0131k testleri, ba\u011f\u0131ml\u0131 grup oranlar\u0131n\u0131n kar\u015f\u0131la\u015ft\u0131r\u0131lmas\u0131 i\u00e7in McNemar testi kullan\u0131ld\u0131. Say\u0131sal de\u011fi\u015fkenlerden ba\u011f\u0131ms\u0131z iki grup ortalamas\u0131n\u0131n kar\u015f\u0131la\u015ft\u0131r\u0131lmas\u0131 kapsam\u0131nda; normal da\u011f\u0131l\u0131m g\u00f6steren gruplar i\u00e7in Student t testi ve normal da\u011f\u0131l\u0131m g\u00f6stermeyen gruplar i\u00e7in Mann-Whitney U testi kullan\u0131ld\u0131. Skorlama sisteminin mortaliteyi tahmin ettirmedeki duyarl\u0131l\u0131k ve \u00f6zg\u00fcll\u00fc\u011f\u00fc ROC (\u201cReceiver Operating Characteristics\u201d) analizi ile de\u011ferlendirildi.<\/p>\n

      P de\u011ferinin 0.05\u2019ten k\u00fc\u00e7\u00fck olmas\u0131 istatistiksel olarak anlaml\u0131 kabul edilmi\u015f olup p=0.000 olan de\u011ferler p<0.001 olarak raporland\u0131.<\/p>\n

      \u00c7al\u0131\u015fmam\u0131z i\u00e7in Sa\u011fl\u0131k Bakanl\u0131\u011f\u0131\u2019ndan 30 Nisan 2020 tarihinde izin ve Sa\u011fl\u0131k Bilimleri \u00dcniversitesi Van E\u011fitim Ara\u015ft\u0131rma Hastanesi Etik Kurulu\u2019ndan 18 Haziran 2020 tarih ve 2020\/11 karar numaras\u0131yla onay al\u0131nd\u0131.<\/p>\n

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

      Tablo 1.<\/strong> \u0130mm\u00fcns\u00fcpresif Tedavi Uygulanan ve Uygulanmayan Hastalar\u0131n Kar\u015f\u0131la\u015ft\u0131r\u0131lmas\u0131<\/p><\/div>\n

      \"\"<\/a>

      Tablo 2.<\/strong> \u0130mm\u00fcns\u00fcpresif Tedavi Gereklili\u011finde \u00d6nemli Risk Fakt\u00f6rlerinin Da\u011f\u0131l\u0131m\u0131<\/p><\/div>\n

      \"\"<\/a>

      \u015eekil 1a.<\/strong> Risk skorlamas\u0131n\u0131n mortaliteyi tahmin ettirmedeki etkinli\u011fi. Skor>4 mortaliteyi tahmin etmede Duyarl\u0131l\u0131k %93, \u00d6zg\u00fcll\u00fck %84.<\/p><\/div>\n

      \"\"<\/a>

      \u015eekil 1b.<\/strong> E\u011fri alt\u0131nda kalan alan.<\/p><\/div>\n

      \"\"<\/a>

      Tablo 3.<\/strong> Hastalar\u0131n \u00d6l\u00fcm ve Ya\u015fam Oranlar\u0131<\/p><\/div>\n

      \u0130mm\u00fcnos\u00fcpresif tedavi uygulanan hastalar\u0131n ya\u015f ortalamas\u0131 60.74\u00b11.96 olup %90.6\u2019s\u0131n\u0131n 40 ya\u015f \u00fczerinde oldu\u011fu g\u00f6r\u00fcld\u00fc. \u0130mm\u00fcnos\u00fcpresif tedavi grubunda 40 ya\u015f \u00fczerinde hastalar\u0131n istatistiksel olarak anlaml\u0131 oranda y\u00fcksek oldu\u011fu g\u00f6r\u00fcld\u00fc (p<\/i><0.05). \u0130mm\u00fcnos\u00fcpresif tedavi uygulanan hastalar\u0131n % 39.6\u2019s\u0131 kad\u0131nd\u0131. \u0130mm\u00fcns\u00fcpresif tedavi uygulanmas\u0131 ve cinsiyet aras\u0131nda anlaml\u0131 bir ili\u015fki bulunamad\u0131 (p<\/i>>0.05). \u0130mm\u00fcns\u00fcpresif tedavi alan hastalar\u0131n hastaneye ba\u015fvuru an\u0131ndaki semptom s\u00fcreleri ortalama 4.68\u00b10.28 g\u00fcn olup ba\u015fvuru an\u0131nda ortalama l\u00f6kosit say\u0131s\u0131 7400.94 \u00b1 524.02, trombosit say\u0131s\u0131 190 037.74\u00b18525.33, lenfosit say\u0131s\u0131 1140.94\u00b167.48 ve n\u00f6trofil\/lenfosit oran\u0131 (NLO) 6.27\u00b10.79 olarak saptand\u0131 (Tablo 1). \u0130mmu\u0308nosu\u0308presif tedavi alan ve alamayan gruplar aras\u0131nda; ba\u015fvuru an\u0131ndaki trombosit say\u0131s\u0131, lenfosit say\u0131s\u0131, NLO, C-reaktif protein (CRP) de\u011feri, ferritin de\u011feri, kan oksijen sat\u00fcrasyonu, solunum say\u0131s\u0131, antiviral tedaviye ra\u011fmen y\u00fckselen ate\u015f (>37.8 0<\/sup>C), qSOFA skoru ve toplam yat\u0131\u015f s\u00fcreleri aras\u0131nda anlaml\u0131 fark bulundu\u011fu tespit edildi (Tablo 1). \u0130mm\u00fcns\u00fcpresif tedavi uygulanan hastalar\u0131n toraks BT g\u00f6r\u00fcnt\u00fclemelerinde daha yayg\u0131n tutulum oldu\u011fu g\u00f6r\u00fcld\u00fc (p<\/i><0.05). YB\u00dc takip gereklili\u011fi, 40 ya\u015f \u00fczerinde olma, toraks BT g\u00f6r\u00fcnt\u00fclemesinde yayg\u0131n tutulum varl\u0131\u011f\u0131, kronik hastal\u0131k varl\u0131\u011f\u0131, troponin y\u00fcksekli\u011fi varl\u0131\u011f\u0131, trombositopeni ve lenfopeni bulunmas\u0131 gibi parametrelerin imm\u00fcnos\u00fcpresif tedavi ihtiyac\u0131n\u0131 art\u0131rd\u0131\u011f\u0131 saptand\u0131 (Tablo 2). T\u00fcm \u00e7al\u0131\u015fma grubunda mortalite oran\u0131 %5.3 iken bu oran\u0131n immunos\u00fcpresif tedavi uygulanan hasta grubunda %22.6 (12\/53) oldu\u011fu ve anlaml\u0131 bir \u015fekilde mortalitenin daha y\u00fcksek oldu\u011fu g\u00f6r\u00fcld\u00fc (p<\/i><0.05) (Tablo 1). \u00c7al\u0131\u015fma grubunda \u00f6l\u00fcm\u00fcn \u00f6n g\u00f6r\u00fclebilmesinde olu\u015fturdu\u011fumuz skorlama sisteminde imm\u00fcnos\u00fcpresif tedavi uygulanan hastalardan elde edilen ortalama skorun 6.09\u00b10.29 oldu\u011fu belirlendi ve imm\u00fcnos\u00fcpresif tedavi almayan gruba g\u00f6re elde etti\u011fimiz de\u011fer istatistiki olarak anlaml\u0131 \u015fekilde imm\u00fcnos\u00fcpresif tedavi uygulanan hasta grubunda daha y\u00fcksek bulundu (p<<\/i>0.05). Ayr\u0131ca yap\u0131lan ROC analizlerinde Skor >4 olmas\u0131n\u0131n mortaliteyi tahmin etmede %93 duyarl\u0131l\u0131k ve %84 \u00f6zg\u00fcll\u00fckte oldu\u011fu saptand\u0131 (\u015eekil 1).<\/p>\n

      \u0130RDELEME<\/h2>\n

      COVID-19 hastalar\u0131nda imm\u00fcnos\u00fcpresif tedavinin etkinli\u011fi ve \u00f6nemi halen ara\u015ft\u0131r\u0131lmaya devam eden konulardan biridir. Hekimler aras\u0131nda COVID-19 infeksiyonu tedavisinde imm\u00fcn sistem \u00fczerine etkili tedavilerin yeri tart\u0131\u015fmal\u0131 konular aras\u0131nda yer almaktad\u0131r. Sa\u011fl\u0131kl\u0131 bir bireyde olu\u015fan imm\u00fcn yan\u0131t, \u00e7e\u015fitli proinflamatuar sitokinler \u00fcreterek T h\u00fccrelerinin (CD4 ve CD8 T h\u00fccreler) aktivasyonunun sa\u011flanmas\u0131n\u0131, mikroorganizma ile infekte h\u00fccrelerin temizlenmesini, inflamasyonu, virusun yay\u0131l\u0131m\u0131n\u0131n k\u0131s\u0131tlanmas\u0131n\u0131 ve viral replikasyonun kontrol\u00fcn\u00fc sa\u011flamaktad\u0131r (4). SARS-CoV-2 infeksiyonunda olu\u015fan disreg\u00fcle sitokin\/kemokin yan\u0131t\u0131 ve y\u00fcksek virus titresi, imm\u00fcno patolojik akci\u011fer hasar\u0131na yol a\u00e7arak inflamatuar sitokin f\u0131rt\u0131nas\u0131na neden olmaktad\u0131r (15). Uzun ink\u00fcbasyon periyoduna sahip olan koronaviruslerin, bu s\u00fcre zarf\u0131nda, \u00f6zellikle dalak lenf nodlar\u0131n\u0131, k\u00fc\u00e7\u00fck kan damarlar\u0131n\u0131, kalp, karaci\u011fer ve b\u00f6brek gibi organlar\u0131 etkileyerek \u00e7oklu organ hasar\u0131na sebep oldu\u011fu bilinmektedir (16). SARS-CoV-2 infeksiyonunda olu\u015fan bu proinflamatuar yan\u0131t, influenza dahil bir\u00e7ok viral infeksiyon taraf\u0131ndan taklit edilen ve hayat\u0131 tehdit eden otoimm\u00fcn hastal\u0131klarda g\u00f6r\u00fclen klinik durum olan makrofaj aktivasyonu sendromuna (MAS) benzetilmektedir (17\u201319). COVID-19 hastalar\u0131nda da ana \u00f6l\u00fcm nedeninin MAS ve ARDS oldu\u011fu bilinmektedir (20). <\/span><\/p>\n

      Huang ve arkada\u015flar\u0131 (7), SARS ve MERS\u2019de raporlanan sitokin f\u0131rt\u0131nas\u0131na benzeyen bir y\u00fcksek sitokin profilinin, kritik COVID-19 hastalar\u0131nda da g\u00f6r\u00fcld\u00fc\u011f\u00fcn\u00fc bildirmi\u015ftir.\u00a0 <\/span>Zhou ve arkada\u015flar\u0131 (21), 191 COVID-19 olgusundan olu\u015fan \u00e7al\u0131\u015fmalar\u0131nda \u00f6len hastalar\u0131n %93 (50\/54)\u2019\u00fcnde ARDS geli\u015fti\u011fini ve ARDS geli\u015fiminin semptom ba\u015flang\u0131c\u0131ndan 8-12 g\u00fcn sonra oldu\u011funu bildirmi\u015ftir (21). Xu ve arkada\u015flar\u0131n\u0131n (22), 239 kritik COVID-19 hastas\u0131ndan olu\u015fan \u00e7al\u0131\u015fmas\u0131nda, semptomlar ba\u015flad\u0131ktan 13.5 g\u00fcn sonra t\u00fcm olgular\u0131n %68.6\u2019s\u0131nda ARDS geli\u015fti\u011fi tespit edilmi\u015ftir (22). Guan ve arkada\u015flar\u0131n\u0131n (23) yapt\u0131\u011f\u0131 \u00e7al\u0131\u015fmada; t\u00fcm olgularda %3.4 oran\u0131nda ARDS geli\u015fti\u011fi, bu oran\u0131n ciddi olgularda %15.6\u2019y\u0131 buldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. Ayr\u0131ca ciddi COVID-19 olgular\u0131nda y\u00fcksek qSOFA de\u011feri saptand\u0131\u011f\u0131 ve bu hastalar\u0131n ileri ya\u015fta oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr (21, 22). COVID-19 olgular\u0131nda akci\u011ferde olu\u015fan patolojinin yan\u0131 s\u0131ra; COVID-19 olgu serilerinde ciddi hasta grubunda l\u00f6kositoz ve l\u00f6kopeni, n\u00f6tropeni ve lenfopeni, CRP art\u0131\u015f\u0131, ferritin y\u00fcksekli\u011fi, D-dimer art\u0131\u015f\u0131, kardiyak troponin y\u00fcksekli\u011fi saptanm\u0131\u015ft\u0131r (24\u201326). \u00c7al\u0131\u015fmam\u0131zda di\u011fer \u00e7al\u0131\u015fmalarla benzer \u015fekilde imm\u00fcnos\u00fcpresif tedavi uygulamalar\u0131na ihtiya\u00e7 duydu\u011fumuz kritik hasta grubunda; lenfopeni, y\u00fcksek NLO, ferritin ve CRP de\u011ferlerinde saptanan y\u00fckseklik, tedavinin \u00fc\u00e7\u00fcnc\u00fc g\u00fcn\u00fcnde saptanan D-dimer de\u011ferinin y\u00fcksekli\u011finin istatistiki olarak anlaml\u0131 \u015fekilde imm\u00fcnos\u00fcpresif tedavi uygulanmayan hasta grubundan farkl\u0131 oldu\u011fu ortaya kondu (p<<\/i>0.05) (Tablo 1). Standard tedavi alan grubun hastaneye daha erken ba\u015fvurdu\u011fu, hastanede yat\u0131\u015f s\u00fcresinin daha k\u0131sa oldu\u011fu, qSOFA de\u011ferlerinin daha d\u00fc\u015f\u00fck oldu\u011fu ve kan oksijenasyonunun imm\u00fcnos\u00fcpresif tedavi grubundan daha iyi oldu\u011fu saptand\u0131 (p<<\/i>0.05). Ayr\u0131ca imm\u00fcns\u00fcpresif tedavi ihtiyac\u0131n\u0131n >40 ya\u015f \u00fczerinde 15.9 kat, toraks BT\u2019de yayg\u0131n tutulum varl\u0131\u011f\u0131nda 15.6 kat, kronik hastal\u0131k e\u015flik etti\u011finde 6.6 kat, lenfopeni varl\u0131\u011f\u0131nda 1.7 kat ve trombositopeni varl\u0131\u011f\u0131nda 2.7 kat artt\u0131\u011f\u0131 belirlendi (Tablo 2).<\/p>\n

      SARS-CoV-2 infeksiyonunda sitokin f\u0131rt\u0131nas\u0131n\u0131 destekleyen \u00e7al\u0131\u015fmalar \u0131\u015f\u0131\u011f\u0131nda; imm\u00fcnos\u00fcpresif tedaviler klinisyenler taraf\u0131ndan COVID-19 standard tedavilerine eklenmektedir. Sistemik kortikosteroidler, IL-1 blok\u00f6r\u00fc, IL-6 blok\u00f6rleri, intraven\u00f6z imm\u00fcnglobulinler, Janus kinaz inhibit\u00f6rleri gibi daha bir\u00e7ok imm\u00fcn sistem \u00fczerinden etki g\u00f6steren ila\u00e7 COVID-19 hastal\u0131\u011f\u0131nda g\u00f6r\u00fclen sitokin f\u0131rt\u0131nas\u0131n\u0131n tedavisinde denenmi\u015f olup halen kullan\u0131lmaya devam etmektedir (10, 27). COVID-19 d\u0131\u015f\u0131 kritik ARDS hastalar\u0131 ile ger\u00e7ekle\u015ftirilen \u00e7e\u015fitli \u00e7al\u0131\u015fmalarda steroidler denenmi\u015f olup plasebo kontroll\u00fc \u00e7al\u0131\u015fmalar da dahil olmak \u00fczere steroid uygulanan gruplarda, t\u00fcm nedenlere ba\u011fl\u0131 mortalite oranlar\u0131n\u0131n ve mekanik ventilasyon s\u00fcresinin azalmakta oldu\u011fu bildirilmi\u015ftir (28\u201330). COVID -19 hastalar\u0131nda da sitokin f\u0131rt\u0131nas\u0131 e\u015fli\u011finde olu\u015fan akci\u011fer hasar\u0131nda, glukokortikoidlerin kullan\u0131m\u0131 \u00f6nerilmektedir (10\u201312). Kortikosteroidler, kanser imm\u00fcnoterapisi gibi durumlarda da sitokin f\u0131rt\u0131nas\u0131n\u0131n kontrol\u00fcnde kullan\u0131labilmekte olup deksametazon sitokin f\u0131rt\u0131nas\u0131n\u0131n y\u00f6netiminde etkili bir ajand\u0131r (31). COVID-19 olgular\u0131nda bir glukokortikoid olan deksametazonun etkinli\u011fini ara\u015ft\u0131ran \u00e7al\u0131\u015fmada, oksijen deste\u011fi alan hastalarda deksametazon uygulamalar\u0131n\u0131n, invazif mekanik ventilasyon ihtiyac\u0131n\u0131 ve mortalite oranlar\u0131n\u0131 standard tedavi grubuna g\u00f6re anlaml\u0131 \u015fekilde azaltt\u0131\u011f\u0131 g\u00f6sterilmi\u015ftir (32). COVID-19 infeksiyonunda hiperinflamasyon ile ili\u015fkili sitokinlerin blokaj\u0131 ise kortikosteroid kullan\u0131m\u0131na kar\u015f\u0131 daha hedefe y\u00f6nelik bir yakla\u015f\u0131m olarak g\u00f6r\u00fclmekte ve bunun umut verici bir tedavi yolu oldu\u011fu d\u00fc\u015f\u00fcn\u00fclmektedir (20). Xu ve arkada\u015flar\u0131n\u0131n (33), ciddi COVID-19 hastalar\u0131 ile yapt\u0131klar\u0131 retrospektif \u00e7al\u0131\u015fmada, tosilizumab uyguland\u0131ktan sonra hastalar\u0131n CRP de\u011ferinin geriledi\u011fi, lenfopeninin d\u00fczeldi\u011fi, ate\u015fin d\u00fc\u015ft\u00fc\u011f\u00fc ve oksijen ihtiyac\u0131n\u0131n azal\u0131p kan oksijen sat\u00fcrasyonunun oksijen deste\u011fi olmadan artt\u0131\u011f\u0131 ortaya konmu\u015ftur. Toniati ve arkada\u015flar\u0131n\u0131n (34), tosilizumab uygulanan 100 COVID-19 pn\u00f6monili hastay\u0131 inceledikleri \u00e7al\u0131\u015fmada, ila\u00e7 uyguland\u0131ktan 24-72 saat sonra hastalar\u0131n %58\u2019inin klinik ve respiratuar durumlar\u0131nda iyile\u015fme oldu\u011fu; uygulaman\u0131n 10. g\u00fcn\u00fcnde hastalar\u0131n %77\u2019sinde respiratuar durumda stabilizasyon ya da iyile\u015fmenin yan\u0131 s\u0131ra lenfosit say\u0131s\u0131, CRP, fibrinojen, ferritin ve IL-6 dahil olmak \u00fczere infeksiyon parametrelerinin normale d\u00f6nd\u00fc\u011f\u00fc bildirilmi\u015ftir. \u00c7al\u0131\u015fmam\u0131za kat\u0131lan hastalar\u0131n %20.1\u2019ine imm\u00fcnos\u00fcpresif tedavi uyguland\u0131 ve bu hastalar\u0131n klinik, radyolojik ve laboratuvar olarak di\u011fer gruptan daha k\u00f6t\u00fc hastalar oldu\u011fu g\u00f6r\u00fcld\u00fc (Tablo 1). \u0130mm\u00fcnos\u00fcpresif tedavi uygulanan hasta grubu daha uzun s\u00fcren semptomlar\u0131 olan, hastanede daha uzun takip edilmi\u015f ve ileri ya\u015fa sahip hastalardan olu\u015fmaktad\u0131r (p<<\/i>0.05) (Tablo 1). Bu hasta grubunun; hastaneye daha ge\u00e7 ba\u015fvuran, radyolojide patolojik tutulumu daha fazla ve yayg\u0131n olan, akut faz reaktanlar\u0131 y\u00fcksek, SPO2 de\u011feri d\u00fc\u015f\u00fck ve birden fazla kronik hastal\u0131\u011f\u0131 olan hastalardan olu\u015ftu\u011fu g\u00f6zlendi. Hastalar\u0131n \u00f6l\u00fcm oran\u0131 incelendi\u011finde >40 ya\u015f \u00fczeri olman\u0131n, trombositopeni ve lenfopeni varl\u0131\u011f\u0131n\u0131n, toraks BT\u2019de yayg\u0131n tutulum varl\u0131\u011f\u0131n\u0131n, kronik hastal\u0131\u011f\u0131n e\u015flik etmesinin, YB\u00dc\u2019nde takip edilmesinin ve imm\u00fcns\u00fcpresif tedavi gereklili\u011finin mortalite ile ili\u015fkili oldu\u011fu g\u00f6r\u00fcld\u00fc (Tablo 3). COVID-19 olgular\u0131nda mortaliteyi \u00f6ng\u00f6rmede kullan\u0131lmak amac\u0131yla risk fakt\u00f6rlerini g\u00f6z \u00f6n\u00fcne alarak d\u00fczenledi\u011fimiz skorlamada, skorun >4 olmas\u0131n\u0131n mortaliteyi \u00f6ng\u00f6rmede y\u00fcksek \u00f6zg\u00fcll\u00fck ve duyarl\u0131l\u0131kta oldu\u011fu belirlendi (Resim 1). Verilerimiz \u0131\u015f\u0131\u011f\u0131nda COVID-19 hastal\u0131\u011f\u0131n\u0131n ciddiyeti artt\u0131k\u00e7a sitokin f\u0131rt\u0131nas\u0131 riskinin de artmakta oldu\u011fu ve bu durumun mortaliteyi art\u0131rd\u0131\u011f\u0131 d\u00fc\u015f\u00fcn\u00fclmektedir. Sitokin f\u0131rt\u0131nas\u0131 durumunun daha ciddi tablolara sebep olmas\u0131n\u0131n \u00f6n\u00fcne ge\u00e7ilmesi i\u00e7in standard tedavilerin imm\u00fcnos\u00fcpresif tedavilerle yeniden d\u00fczenlenmesine ihtiya\u00e7 duyulabilece\u011fi sonucuna ula\u015f\u0131ld\u0131.<\/p>\n

      Sonu\u00e7 olarak; kritik COVID-19 hastalar\u0131 laboratuvar ve klinik parametrelerle sitokin f\u0131rt\u0131nas\u0131 a\u00e7\u0131s\u0131ndan mutlaka de\u011ferlendirilmelidir. Standard tedavilere ek olarak imm\u00fcnos\u00fcpresif tedavilerin uygun hastaya, uygun zamanda ve uygun dozda eklenmesinin, mortalite ve morbidite \u00fczerine olumlu y\u00f6nde etkisinin olaca\u011f\u0131 \u00e7ok a\u00e7\u0131kt\u0131r. Bunun yan\u0131nda mortaliteyi tahmin etmede 13 parametreden olu\u015fan skorlama sistemimin kullan\u0131lmas\u0131 faydal\u0131 olabilir. Bu t\u00fcr skorlama sistemlerinin valide edilebilmesi i\u00e7in hasta say\u0131s\u0131n\u0131n daha y\u00fcksek oldu\u011fu geni\u015f \u00e7apl\u0131 \u00e7al\u0131\u015fmalara ihtiya\u00e7 vard\u0131r.<\/p>\n","protected":false},"excerpt":{"rendered":"

      G\u0130R\u0130\u015e \u015eiddetli akut solunum sendromu virusu (SARS-CoV-2) ile ili\u015fkili infeksiyon ilk kez Aral\u0131k 2019\u2019da \u00c7in\u2019in Hubei eyaletinde bulunan Vuhan \u015fehrinde saptanm\u0131\u015f olup alt\u0131 aydan daha k\u0131sa bir s\u00fcrede d\u00fcnya geneline yay\u0131larak k\u00fcresel bir salg\u0131na sebep olmu\u015ftur (1). Virusun infektivitesinin y\u00fcksek olmas\u0131, tedavide etkili bir antiviral ajan\u0131n bulunmamas\u0131 ve infeksiyonun y\u00fcksek oranda asemptomatik seyretmesi nedenlerinden dolay\u0131 […]<\/p>\n","protected":false},"author":5,"featured_media":24715,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[5129],"tags":[5174,5371,5372,3717],"class_list":["post-24200","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-ozgun-arastirma","tag-covid-19","tag-immunsupresyon","tag-sitokin-firtinasi","tag-tedavi"],"acf":[],"_links":{"self":[{"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/posts\/24200","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\/5"}],"replies":[{"embeddable":true,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/comments?post=24200"}],"version-history":[{"count":4,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/posts\/24200\/revisions"}],"predecessor-version":[{"id":24784,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/posts\/24200\/revisions\/24784"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/media\/24715"}],"wp:attachment":[{"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/media?parent=24200"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/categories?post=24200"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.klimikdergisi.org\/tr\/wp-json\/wp\/v2\/tags?post=24200"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}