➥【重點摘要】：
為什麼兒童與成人感染新冠病毒的疾病嚴重度迥異，作者針對兩種可能性做探討: 腎素-血管張力素系統(Renin angiotensin (RAS) system)的受體(receptors)差異及對病原體的發炎反應(inflammatory responses)改變。


新冠病毒(COVID-19)與嚴重急性呼吸道症候群的冠狀病毒(SARS-CoV)都是藉由血管張力素轉化酶2受體(angiotension-convereting enzyme (ACE)2 receptor)入侵宿主細胞並主要通過呼吸道傳播。


這些受體存在體內多種不同型態的細胞包含免疫細胞如單核球、嗜中性球和淋巴球等。RAS系統與發炎有關，藉由血管張力素II 和血管張力素轉化酶2改變RAS 活性，可使促炎症反應轉為消炎反應。


相關實證列舉如下: 在敗血症休克的動物模組可觀察血管張力素II第一型受體的抑制劑有部分緩解效果；在小鼠模組研究，血管張力素轉化酶2的濃度過高或過低都可能產生不正常的免疫反應和肺部發炎。


成人與兒童的發炎反應不同且隨著生命週期而變異。研究顯示年齡與急性呼吸窘迫症候群(acute respiratory distress syndrome，ARDS)的嚴重度有關，嗜中性球功能所涉及的促炎因子之增加也與年齡相關。


而在利用phytohemaggluttinin (PHA)刺激探討細胞激素生成(cytokine production)的個體發生學(Ontogeny)時，觀察到新生兒時期升高的IL-10在生命早期即轉變為IL-10 / Th1 / Th2 / Th17細胞激素的平衡。這有助於防止病原體的侵襲但改善細胞激素風暴(cytokine storm)。


嚴重新冠病毒感染的特徵在於大量的促炎反應或是細胞激素風暴導致ARDS和多器官功能障礙 (Multiorgan dysfunction)。因此建議對於重症病患進行是否過度發炎(hyperinflammation)的篩檢，藉由趨勢變化例如鐵蛋白(ferritin)增加、血小板減少或紅血球沉降率(erythrocyte sedimentation rate)下降，來辨識那些患者可能可使用抗炎治療以改善死亡率。


治療的選擇包括類固醇 (steroids)、靜脈注射免疫球蛋白(Intravenous immunoglobulin)、選擇性細胞激素的阻斷劑 (selective cytokine blockade) 如anakinra或tocilizumab、瑞德西韋(Remdesivir)、羥氯奎寧(hydroxychloroquine) 和JAK 抑制劑 (Janus kinase inhibition)。


Remdesivir (GS-5734)的結構為核苷酸類似物(nucleotide analog)，作用在阻斷RNA依賴性聚合酶(RNA dependent RNA polymerase)，是一種前驅藥物(prodrug，需於生物體內轉化才具有藥理作用)，目前使用於治療伊波拉病毒(Ebola virus)感染的臨床試驗，具有廣泛抗RNA病毒的活性包括SARS-CoV和中東呼吸症候群冠狀病毒(Middle East respiratory syndrome coronavirus [MERS-CoV]。


氯奎寧(Chloroquine)可阻止病毒進入胞內體(Endosome)。在一個開放性(Open-label)、非隨機(non-randomized clinical trial)的臨床試驗，合併使用羥氯奎寧加抗黴漿菌藥物日舒(Azithromycin)帶來治療新冠病毒感染的曙光。系統性回顧亦顯示氯奎寧能抑制SARS-CoV-2在體外的複製。


中國正在進行一項臨床試驗，對於感染新冠病毒且IL-6升高的重症患者投予tocilizumab，目前的成果是正向的(ChiCTR2000029765)。Tocilizumab是一種抗IL-6受體之單株抗體，被核准用於巨細胞動脈炎(giant cell arteritis)和類風濕關節炎(rheumatoid arthritis)，但對幼年型免疫性關節炎似乎無法單用阻斷IL-6去控制發炎反應。


類固醇可抑制發炎，但由於缺乏有效的證據及存在免疫抑制和次發性細菌或真菌感染的傷害風險，世界衛生組織目前的臨時指南並不建議使用。


敗血症可分為兩個階段，第一階段是強烈的初始促炎期和細胞激素風暴，接者是潛在的長期免疫抑制期，這個免疫抑制和調節異常是敗血症相關致死的主因。若在此階段進行抗炎治療可能是有害的。


個人化的免疫反應資訊將有助於啟動抗IL-6等治療，且全程監測促炎和抗炎反應是必要的。此外，敗血症的定義和反應在兒童及新生兒是不同的。兒童感染新冠病毒的預後較佳可能有多種原因，進一步了解在不同年齡層的免疫反應差異，對於標靶免疫治療 (targeted immunotherapies)是很有價值。


*關於羥氯奎寧、抗黴漿菌藥物日舒及瑞德西韋對新冠病毒感染的治療成效已陸續有新的成果發表，包含可能的副作用等。請參考更新的實證。(「財團法人國家衛生研究院」陳美惠醫師 摘要整理)


📋 CIVID-19 in Children and Altered Inflammatory Responses(2020/04/03)+中文摘要轉譯

➥Author：Eleanor J. Molloy and Cynthia F. Bearer
➥Link： Pediatric Research (Nature)
https://www.nature.com/articles/s41390-020-0881-y


#2019COVID19Academic
衛生福利部
疾病管制署 - 1922防疫達人
疾病管制署
國家衛生研究院-論壇

“Let him cry”

What Love means to a 4-8 year old

A group of professional people posed this question to a group of 4 to 8 year-olds, ’What does love mean?’ The answers they got were broader and deeper than anyone could have imagined

See what you think:

‘When my grandmother got arthritis , she couldn’t bend over and paint her toenails anymore.. So my grandfather does it for her all the time , even when his hands got arthritis too. That’s love.’ – Rebecca, age 8

‘When someone loves you, the way they say your name is different. You just know that your name is safe in their mouth.’ – Billy, age 4

‘Love is when a girl puts on perfume and a boy puts on shaving cologne and they go out and smell each other.’ – Karl, age 5

‘Love is when you go out to eat and give somebody most of your French fries without making them give you any of theirs.’ –Chrissy, age 6

‘Love is what makes you smile when you’re tired.’ -Terri, age 4

‘Love is when my mommy makes coffee for my daddy and she takes a sip before giving it to him , to make sure the taste is OK.’ – Danny, age 7

‘Love is when you kiss all the time. Then when you get tired of kissing , you still want to be together and you talk more. My Mommy and Daddy are like that.
They look gross when they kiss’ – Emily, age 8

‘Love is what’s in the room with you at Christmas if you stop opening presents
and listen.’ –Bobby, age 7

‘If you want to learn to love better , you should start with a friend who you hate” –Nikka, age 6

‘Love is when you tell a guy you like his shirt , then he wears it everyday..’ –Noelle, age 7

‘Love is like a little old woman and a little old man who are still friends even after they know each other so well.’ –Tommy, age 6

‘During my piano recital , I was on a stage and I was scared. I looked at all the people watching me and saw my daddy waving and smiling. He was the only one doing that. I wasn’t scared anymore.’ – Cindy, age 8

‘My mommy loves me more than anybody. You don’t see anyone else kissing me to sleep at night.’ –Clare, age 6

‘Love is when Mommy gives Daddy the best piece of chicken.’ –Elaine, age 5

‘Love is when Mommy sees Daddy smelly and sweaty and still says he is handsomer than Robert Redford.’ –Chris, age 7

‘Love is when your puppy licks your face even after you left him alone all day.’ -Mary Ann, age 4

‘I know my older sister loves me because she gives me all her old clothes and has to go out and buy new ones.’ –Lauren, age 4

‘When you love somebody , your eyelashes go up and down and little stars come out of you.’ - Karen, age 7

‘Love is when Mommy sees Daddy on the toilet and she doesn’t think it’s gross..’ –Mark, age 6

‘You really shouldn’t say ‘I love you’ unless you mean it. But if you mean it, you should say it a lot. People forget.’ –Jessica, age 8

And the final one -- Author and lecturer Leo Buscaglia once talked about a contest he was asked to judge.

The purpose of the contest was to find the most caring child.

The winner was a four year old child whose next door neighbor was an elderly gentleman who had recently lost his wife. Upon seeing the man cry, the little boy went into the old gentleman’s yard, climbed onto his lap, and just sat there. When his Mother asked what he had said to the neighbor, the little boy said, ‘Nothing , I just helped him cry’.

(So now, what love means to you? May you post your own answers here? If you have a kid, ask him/her and post his/her answer here too. Thanks!)

中文版︰http://www.facebook.com/photo.php?fbid=559953077356745&set=a.500783563273697.117817.500762883275765&type=1&theater

‘When someone loves you, the way they say your name is different.You just know that your name is safe in their mouth.’ – Billy, age 4

What Love means to a 4-8 year old

A group of professional people posed this question to a group of 4 to 8 year-olds, ’What does love mean?’ The answers they got were broader and deeper than anyone could have imagined

See what you think:

‘When my grandmother got arthritis , she couldn’t bend over and paint her toenails anymore.. So my grandfather does it for her all the time , even when his hands got arthritis too. That’s love.’ – Rebecca, age 8

‘When someone loves you, the way they say your name is different. You just know that your name is safe in their mouth.’ – Billy, age 4

‘Love is when a girl puts on perfume and a boy puts on shaving cologne and they go out and smell each other.’ – Karl, age 5

‘Love is when you go out to eat and give somebody most of your French fries without making them give you any of theirs.’ –Chrissy, age 6

‘Love is what makes you smile when you’re tired.’ -Terri, age 4

‘Love is when my mommy makes coffee for my daddy and she takes a sip before giving it to him , to make sure the taste is OK.’ – Danny, age 7

‘Love is when you kiss all the time. Then when you get tired of kissing , you still want to be together and you talk more. My Mommy and Daddy are like that.
They look gross when they kiss’ – Emily, age 8

‘Love is what’s in the room with you at Christmas if you stop opening presents
and listen.’ –Bobby, age 7

‘If you want to learn to love better , you should start with a friend who you hate” –Nikka, age 6

‘Love is when you tell a guy you like his shirt , then he wears it everyday..’ –Noelle, age 7

‘Love is like a little old woman and a little old man who are still friends even after they know each other so well.’ –Tommy, age 6

‘During my piano recital , I was on a stage and I was scared. I looked at all the people watching me and saw my daddy waving and smiling. He was the only one doing that. I wasn’t scared anymore.’ – Cindy, age 8

‘My mommy loves me more than anybody. You don’t see anyone else kissing me to sleep at night.’ –Clare, age 6

‘Love is when Mommy gives Daddy the best piece of chicken.’ –Elaine, age 5

‘Love is when Mommy sees Daddy smelly and sweaty and still says he is handsomer than Robert Redford.’ –Chris, age 7

‘Love is when your puppy licks your face even after you left him alone all day.’ -Mary Ann, age 4

‘I know my older sister loves me because she gives me all her old clothes and has to go out and buy new ones.’ –Lauren, age 4

‘When you love somebody , your eyelashes go up and down and little stars come out of you.’ - Karen, age 7

‘Love is when Mommy sees Daddy on the toilet and she doesn’t think it’s gross..’ –Mark, age 6

‘You really shouldn’t say ‘I love you’ unless you mean it. But if you mean it, you should say it a lot. People forget.’ –Jessica, age 8

And the final one -- Author and lecturer Leo Buscaglia once talked about a contest he was asked to judge.

The purpose of the contest was to find the most caring child.

The winner was a four year old child whose next door neighbor was an elderly gentleman who had recently lost his wife. Upon seeing the man cry, the little boy went into the old gentleman’s yard, climbed onto his lap, and just sat there. When his Mother asked what he had said to the neighbor, the little boy said, ‘Nothing , I just helped him cry’.

(So now, what love means to you? May you post your own answers here? If you have a kid, ask him/her and post his/her answer here too. Thanks!)

中文版︰http://www.facebook.com/photo.php?fbid=559953077356745&set=a.500783563273697.117817.500762883275765&type=1&theater