Immunoloji ve COVID-19

.: PREFACE
ÖN SÖZ
PREFACE
Prof. Dr. Ayşegül ATAK YÜCEL
Gazi Üniversitesi Tıp Fakültesi, İmmünoloji ABD, Ankara
Article Language: TR
Koronavirüsler (Orthocoronavirinae) Coronaviridae familyasının Sarbecovirus altcinsinin (beta-CoV soy B) üyesidir, bugüne kadar tespit edilmiş en büyük RNA genomuna sahip bu virüsler pozitif polariteli, tek iplikçikli RNA içerirler. En belirgin özellikleri olan çeperlerindeki değneğe benzeyen çıkıntılar nedeni ile virüs mikroskop altında güneşin taç küresine (corona) benzediği için 'koronavirüs' olarak adlandırılmıştır.

Koronavirüsler kuşlarda ve memelilerde hastalık yapabilir. İnsanda sıklıkla soğuk algınlığı, nezle ve grip benzeri şikâyetlere yola açsa da son yıllarda bu ailenin üyelerinden SARS-CoV ve MERS-CoV, insanlarda ağır ölümcül solunum yolu enfeksiyonu salgınlarına yol açmıştır.

Çin'in Guangdong Eyaleti'nde 2002'de başlayan SARS-CoV virüsü salgını dünya genelinde 17 ülkeye yayılmış, 8.098 kişi hastalığa yakalanmış ve 774 kişi hayatını kaybetmiştir. Suudi Arabistan'da 2012 yılında başlayan MERS-CoV virüsü salgını ise dünya genelinde 27 ülkeyi etkilemiş, salgına yakalanan 2.499 kişiden 861'i hayatını kaybetmiştir. 2019 yılında Aralık ayının son günlerinde Çin'in Hubei Eyaleti'ne bağlı Wuhan şehrinde hastaneye başvuran pnömoni vakalarında bir artış olduğu fark edildi ve hastalık hızla yayılmaya başladı. ABD Hastalık Koruma ve Korunma Merkezi'nin (CDC), 1 Ocak 2020'de virüsün Wuhan'daki bir deniz ürünleri pazarından kaynaklanıyor olabileceğini açıklamasının ardından bu pazar kapatıldı. Çinli yetkililer söz konusu virüsün zatürreye neden olan bir virüs olmayıp yeni bir virüs çeşidi olduğunu 7 Ocak 2020'de resmen açıkladı ve doğrudan solunum yollarını etkileyen, tıpkı SARS-CoV ve MERS-CoV gibi koronavirüs familyasından olan bu yeni virüse '2019-nCoV' adını verdiler. Çin'de bu virüse bağlı ilk ölüm 11 Ocak 2020'de gerçekleşti. ABD'de ise ilk vaka 30 Ocak 2020'de görüldü. Aynı gün Dünya Sağlık Örgütü (DSÖ) Genel Direktörü Tedros Adhanom Ghebreyesus, Çin dışında 18 ülkede 98 vaka tespit edildiğini, 'Çin'de değil, diğer ülkelerde yaşananlar' nedeni ile küresel ölçekte acil durum ilan edildiğini açıkladı ve asıl endişenin virüsün sağlık sistemleri zayıf ülkelere yayılması olduğunu belirtti. Şubat ayı içerisinde Çin dışında da ölüm vakaları bildirilmeye başlandı ve 9 Şubat'a gelindiğinde 813 ölümle yeni koronavirüs, 2002 ve 2003 yılları arasında 8 bin kişide görülen ve 774 kişinin toplam ölümüne yol açan SARS'ı geride bırakmıştı.

Uluslararası Virüs Taksonomi Komitesi (ICTV), SARS'a neden olan virüs ile olan genetik benzerliği nedeni ile, bu yeni virüsün bilimsel adının 11 Şubat'ta 'SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2)' olması hususunda fikir birliğine ulaşıldığını açıklarken, DSÖ bu virüsün neden olduğu hastalığı, 2019'da başlayan koronavirüs hastalığı anlamında 'COVID-19' olarak adlandırdı ve virüsü de 'COVID-19 virüsü' olarak isimlendirmeye karar verdi.
Mart ayında COVID-19'un merkezi Avrupa olmuştu, en yüksek vaka sayısı ve ölüm İtalya'daydı, yine bu ay içinde İran'da da vakalar tırmanışa geçti. 10 Mart'ta koronavirüsün tespit edildiği ülkeler arasına Türkiye de katıldı. DSÖ, 14 Mart'ta Avrupa'nın salgının yeni merkezi hâline geldiğini açıkladı. ABD ise 'ulusal acil durum' ilan etti. Türkiye'de yeni koronavirüs kaynaklı ilk ölüm 18 Mart'ta 89 yaşında bir hastada gerçekleşti.

Temmuz ayına kadar dünya genelinde 10.700.000'in üzerinde tespit edilmiş vaka, 5.500.000 dolayında iyileşen vaka ve 500.000'in üzerinde ölüm; üllkemizde ise 200.000'in üzerinde tespit edilen vaka ve 5.000'in üzerinde ölüm görülmüştü.

Diğer koronavirüsler gibi SARS-CoV-2 de S (spike), E (envelope: zarf), M (membran) ve N (nükleokapsid) proteinleri olarak bilinen dört yapısal proteine sahiptir. N proteini RNA genomunu tutar ve S, E ve M proteinleri birlikte viral zarfı oluşturur. S proteini virüsün konakçının hücre zarına yapışmasına neden olmaktadır. SARS-CoV-2'nin diğer beta koronavirüslerde olmayan bir özelliği polibazik ayrılma alanı ile birleşmesidir ki bu virüsün patojenitesini ve bulaşabilirliğini arttırmaktadır. Ancak hâlen virüsün hastalık yapma mekanizmaları tamamı ile aydınlatılmış, virüse karşı özgül etkin tedavi veya aşı bulunmuş değildir. COVID-19 hastalığının patogenezinde, özellikle daha geç evrede ve ağır vakalarda görülen sitokin fırtınasında immün sistemin cevabının çok önemli olduğuna dair veriler her geçen gün artmakta, verilen tedavilerin büyük bir bölümünde immün hücreler veya immün cevap hedef alınmaktadır. Çocuklarda ve gençlerde genellikle daha hafif seyirli geçen COVID-19'da bunun nedeninin, hastalığın farklı aşamalarında ve başka hastalıkları olan kişilerde immün sistemin ne yönde çalıştığının henüz izahı kesin olarak yapılamamıştır.

Biz hazırladığımız bu kitapta bir şekilde immünoloji ile uğraşan farklı disiplinlerdeki bilim insanlarımızı bir araya toplayarak, 'İMMÜNOLOJİ VE COVID-19'u hem adaptif (humoral ve hücresel) ve doğal immün cevaplar, sitokin fırtınası, koagülasyon sistemi, oksidatif metabolizma, hücre içi sinyalizasyon, HLA ve COVID-19 ilişkisi gibi temel bilim açısından; hem de alt ve üst solunum yollarında virüse karşı çocuk ve erişkindeki cevap, transplantasyon ve COVID-19, immün yetmezlik ve COVID-19, aşı çalışmaları, plazma tedavisi, sürü bağışıklığı, destekleyici tıp, immünoloji ve COVID-19 gibi klinik açıdan; hem de hücre akış ölçer, nükleik asit ve antijen-antikor tabanlı tanısal testler gibi laboratuvar testleri açıdan şu an için eldeki son güncel bilgileri derleyip, bilimsel akıl süzgecinden geçirerek sizlere topluca güvenilir bir şekilde vermeyi hedefledik. Dileriz tıbbın ve biyolojik bilimlerin tüm alanları ile ilgilenen herkesin yaralanabileceği bir kaynak kitap sunabilmişizdir sizlere. Hijyen, maske ve sosyal mesafe kurallarına her zaman uyarak sağlıcakla ve mutlu kalın, keyifli okumalar...

Prof. Dr. Ayşegül ATAK YÜCEL
Editör
Coronaviruses (Orthocoronavirinae) are members of the Sarbecovirus subspecies (betaCoV lineage B) of the Coronaviridae family. With the largest RNA genome ever detected, these viruses contain single-stranded RNA with positive polarity. These viruses are named as 'coronavirus' because, under a microscope, they resemble the sun's crown sphere (corona) due to the wand-like bulges on their walls, which are the most distinctive features.

Coronaviruses can cause diseases in birds and mammals. Despite often causing common cold, rhinitis and flu-like complaints in humans; recently, SARS-CoV and MERSCoV, members of this family, have led to outbreaks of severe lethal respiratory infections in humans.

The SARS-CoV outbreak, which began in 2002 in China's Guangdong Province, spread to 17 countries around the world, with 8098 people infected and 774 people lost their lives. The MERS-CoV outbreak, which started in Saudi Arabia in 2012, affected 27 countries around the world and killed 861 of the 2499 infected people. In 2019, an increase in pneumonia cases drew attention on the last days of December in Wuhan city, Hubei Province, China; and the disease began to spread rapidly. The seafood market in Wuhan was closed after the US Center for Disease Control and Prevention (CDC) announced on January 1, 2020 that the virus might have originated from this market. On January 7 of 2020, Chinese authorities officially announced that the virus in question is not one of the known viruses causing pneumonia, but rather, it is a new type of virus and they named the virus '2019-nCoV', which directly affects the respiratory tract, such as SARS-CoV and MERS-CoV, from the coronavirus family. The first death linked to this virus in China occurred on January 11, 2020. In the US, the first case was seen on January 30, 2020. On the same day, World Health Organization (WHO) Director General Tedros Adhanom Ghebreyesus announced that 98 cases were identified in 18 countries other than China, and WHO declared a 'global emergency' state due to 'the happenings in other countries other than China' and that the main concern was the spread of the virus to countries with poor health systems. In February, death cases have began to be reported outside of China, and by February 9, with 813 deaths, the new coronavirus left SARS behind, which occurred in 8,000 people between 2002 and 2003, leading to the total death of 774 people.

On February 11, the International Virus Taxonomy Committee (ICTV), announced that the consensus has been reached regarding the scientific name of this new virus as 'SARSCoV-2 (severe acute respiratory syndrome coronavirus 2)' due to its genetic similarity to the virus that caused the SARS. WHO decided to name the disease caused by this virus as 'COVID-19' in terms of its outbreak in 2019 and decided to continue to call the virus as 'COVID-19 virus'. In March, the center of COVID-19 had shifted to Europe. Highest number of cases and deaths were in Italy. Again, in March, cases were on the rise in Iran. On March 10, Turkey joined the countries where coronavirus was detected. On March 14, WHO announced that Europe had become the new center of the pandemic. The United States has declared a 'state of national emergency'. The first recent coronavirus-induced death in Turkey occurred on March 18 in an 89-year-old patient.

By July, there were over 10,700,000 cases detected, around 5,500,000 recovered cases and over 500,000 deaths worldwide; and in our country, there were over 200,000 cases and over 5000 deaths. Like other coronaviruses, SARS-CoV-2 has four structural proteins known as S (spike), E (envelope), M (membrane), and N (nucleocapsid) proteins. The N protein holds the RNA genome, and with the S, E, and M proteins, forms the viral envelope, and the S protein causes the virus to adhere to the host's cell membrane. One feature of SARS-CoV-2 that is not present in other beta coronaviruses is its incorporation with the polybasic separation site, which increases the pathogenicity and transmissibility of the virus. However, the disease-making mechanisms of the virus haven't been fully clarified and no specific effective treatment or vaccine have been found against the virus. In the pathogenesis of COVID-19 disease, data regarding the response of the immune system in cytokine storm that is especially seen in the later stage and severe cases are increasing day by day, and immune cells or immune responses are targeted in most treatments. COVID-19 generally has a milder course in children and adolescents and the reason for this and precisely how the immune system works in different stages of the disease and in people with other diseases have not been explained definitively yet.

We prepared this study by gathering scientists from different disciplines dealing in a way with immunology, we aimed to compile the most up-to-date information available and pass it through a scientific mind filter to give you COVID-19 and IMMUNOLOGY collectively reliably in terms of basic science such as adaptive (humoral and cellular) and innate immune responses, cytokine storm, the coagulation system, oxidative metabolism, intracellular signaling, and HLA and COVID-19 relation; clinically such as response of the virus in the child and adult body in the lower and upper respiratory tract, transplantation and COVID-19, vaccine studies, plasma treatment, herd immunity, supportive medicine, immunology and COVID-19; and also in terms of laboratory tests such as cell flow meter, nucleic acid and antigen-antibody based diagnostic tests.

We hope that we have been able to provide you with a source book that anyone interested in all fields of medicine and biological sciences can benefit from. Follow the rules of hygiene, mask and social distance, stay healthy and happy, and enjoy reading...

Prof. Dr. Ayşegül ATAK YÜCEL
Editor

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