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超兩千萬(wàn)美國(guó)人或患“長(zhǎng)期新冠”,癥狀超200種

ERIN PRATER
2022-06-01

一個(gè)陽(yáng)性患者甚至出現(xiàn)了幻覺(jué),而且保存新的記憶,語(yǔ)言功能也出現(xiàn)了障礙。

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你聽(tīng)說(shuō)過(guò)“長(zhǎng)期新冠”嗎?簡(jiǎn)而言之,就是得了新冠久治不愈,感染過(guò)后好幾周,仍然有疲勞、喪失嗅覺(jué)、持續(xù)咳嗽等癥狀。

還有一個(gè)陽(yáng)性患者甚至出現(xiàn)了幻覺(jué),而且保存新的記憶,語(yǔ)言功能也出現(xiàn)了障礙。

新冠疫情持續(xù)到現(xiàn)在,它的癥狀也變得越來(lái)越奇怪了。據(jù)英國(guó)醫(yī)學(xué)期刊《柳葉刀》發(fā)表的一項(xiàng)重磅研究稱,到目前為止,新冠病毒感染者出現(xiàn)的癥狀已經(jīng)達(dá)到200多種,其中包括耳朵麻痹,出現(xiàn)“大腦著火”感,男性勃起功能障礙,女性月經(jīng)失調(diào),便秘,皮膚脫皮和視力重影,等等。

這項(xiàng)研究指出,新冠病毒感染者出現(xiàn)的癥狀涵蓋了10個(gè)人體的主要器官系統(tǒng)——而人體總共只有11個(gè)主要器官系統(tǒng)。

現(xiàn)在,美國(guó)已經(jīng)迎來(lái)了第六波疫情高峰,很多美國(guó)人再次得了新冠。幾千萬(wàn)美國(guó)人都迫切地想要知道,當(dāng)自己出現(xiàn)久治不愈的癥狀時(shí)該怎么辦。

專家表示,他們正在盡最大努力尋找這個(gè)問(wèn)題的答案。

新冠病毒專家、倫敦帝國(guó)理工學(xué)院兒童免疫學(xué)教授、兒科醫(yī)生彼得·布羅丁對(duì)《財(cái)富》表示:“我也希望我能知道‘長(zhǎng)期新冠’到底是怎么回事?!?/p>

不過(guò)有一件事是確定的:“‘長(zhǎng)期新冠’絕對(duì)不簡(jiǎn)單?!?/p>

如何定義是難題

雖然‘長(zhǎng)期新冠’的癥狀已不鮮見(jiàn),但學(xué)界對(duì)它的發(fā)病機(jī)制仍不甚了解,對(duì)它的定義也各不相同。

世界衛(wèi)生組織對(duì)長(zhǎng)期新冠的定義是:新冠肺炎確診病例出現(xiàn)了持續(xù)兩個(gè)月以上的長(zhǎng)期癥狀,而且這些癥狀無(wú)法用其他原因解釋。這些癥狀可能在感染后便一直存在,也有可能間隙性反復(fù)發(fā)作。世衛(wèi)組織還建議,醫(yī)療機(jī)構(gòu)應(yīng)在患者出現(xiàn)急性癥狀三個(gè)月以上,再考慮給出“長(zhǎng)期新冠”的診斷。

梅奧診所則將“長(zhǎng)期新冠”定義為由新冠病毒引起的、確診后持續(xù)四周以上的一系列癥狀。

布羅丁表示:“這充分說(shuō)明了診斷有多不靠譜。關(guān)于‘長(zhǎng)期新冠’究竟是什么,你問(wèn)不同的人,就會(huì)得到不同的答案?!?/p>

根據(jù)來(lái)自美國(guó)政府問(wèn)責(zé)署的數(shù)據(jù),預(yù)計(jì)有700萬(wàn)到2300萬(wàn)美國(guó)人可能遭受過(guò)“長(zhǎng)期新冠”的困擾,也就是說(shuō)最多7%的美國(guó)人口都可能出現(xiàn)過(guò)“長(zhǎng)期新冠”的癥狀。有研究推測(cè),在所有感染過(guò)新冠病毒的人中,出現(xiàn)“長(zhǎng)期新冠”癥狀的人口比例可能在5%到80%之間。

美國(guó)疾控中心上周二發(fā)表的一項(xiàng)研究顯示,有五分之一的美國(guó)成年人在感染新冠病毒的幾周至幾個(gè)月內(nèi),出現(xiàn)了至少一種可能與“長(zhǎng)期新冠”有關(guān)的癥狀。而在老年人中,這一比例更是提高到了四分之一。

新冠病毒專家、藥品開(kāi)發(fā)公司Fractal Therapeutics的首席執(zhí)行官阿利吉特·查克拉瓦提認(rèn)為,“長(zhǎng)期新冠”可能短短幾年就會(huì)影響全球10億人。有專家認(rèn)為,“長(zhǎng)期新冠”正在迅速變成一個(gè)重大公共衛(wèi)生問(wèn)題,而且它也讓廣大初級(jí)保健醫(yī)生不堪重負(fù),因?yàn)樗麄儾⒉恢廊绾味x或治療它。

布羅丁指出,在“長(zhǎng)期新冠”的患者中,有些只是感到疲勞始終揮之不去,這種情況對(duì)于很多病毒都比較常見(jiàn)。不過(guò)其他患者則可能出現(xiàn)更復(fù)雜的癥狀。

他表示:“這其中有些癥狀是較為常見(jiàn)的——比如嗅覺(jué)遲遲無(wú)法恢復(fù),此外還有一定程度的疲勞。我覺(jué)得多數(shù)成年人在嚴(yán)重感染感冒或者其他病毒后,都有可能出現(xiàn)持續(xù)性的疲勞。所以你問(wèn)80%的新冠患者,他們也會(huì)表示自己有這種疲勞感,這是可以理解的。”

“不過(guò)就其他一些癥狀而言,它確實(shí)是比較罕見(jiàn)的?!?/p>

五種類型的“長(zhǎng)期新冠”

華盛頓特區(qū)國(guó)立兒童醫(yī)院的傳染病專家、兒科新冠項(xiàng)目負(fù)責(zé)人亞歷山德拉·布魯格·揚(yáng)茨醫(yī)生表示,“長(zhǎng)期新冠”癥狀基本可以分為五大類。

第一種就是新冠病毒本身造成的長(zhǎng)期影響,包括直接性的肺損傷。其他患者則基本上屬于以下四類的某一類或某幾類:炎癥、自主神經(jīng)功能障礙、病毒持續(xù)活動(dòng),以及免疫反應(yīng)改變。

首先,新冠病毒一旦引發(fā)炎癥,病毒就會(huì)觸發(fā)人體釋放炎性因子來(lái)殺滅染毒細(xì)胞,但炎性反應(yīng)也會(huì)損害多個(gè)器官系統(tǒng),尤其是如果炎性反應(yīng)一直持續(xù)的話。

自主神經(jīng)功能異常(POTS)又稱體位性心動(dòng)過(guò)速,是指自主神經(jīng)系統(tǒng)受到了直接損傷。這種病本質(zhì)上可能是一種自體免疫疾病,它會(huì)導(dǎo)致患者的心率和血壓隨著體位的變化(如立、坐、臥)而出現(xiàn)紊亂。

持續(xù)性病毒活動(dòng)則可能是由所謂的“幽靈病毒”細(xì)胞引起的,這些病毒細(xì)胞可能在感染數(shù)月后仍然保持活性。最近有研究發(fā)現(xiàn),這種病毒細(xì)胞一旦進(jìn)入腸道,就有可能導(dǎo)致腹瀉等非典型癥狀。

最后是免疫反應(yīng)改變,它有可能單獨(dú)出現(xiàn),也有可能與其他類型的癥狀合并出現(xiàn)。在感染新冠病毒后,為了讓身體盡快康復(fù),人體免疫系統(tǒng)有可能會(huì)“過(guò)度反應(yīng)”,甚至對(duì)一些平時(shí)無(wú)關(guān)痛養(yǎng)的病毒也反應(yīng)過(guò)度。比如有的年僅20多歲的患者在感染新冠肺炎后,在很短的時(shí)間里相繼感染了一系列其他疾病,比如單核細(xì)胞增多癥和鏈球菌感染等。

一些相關(guān)研究

專家表示,雖然有些人可能被確診為“長(zhǎng)期新冠”,或者疑心自己得了“長(zhǎng)期新冠”,但他們未必真的就得了這種病。

有些患者出現(xiàn)了新冠急性期后后遺癥,比如咳嗽和氣短等持續(xù)性癥狀。不過(guò)人體感染很多病毒后都會(huì)出現(xiàn)持續(xù)性癥狀,比如人類皰疹病毒4型(EB病毒)就會(huì)導(dǎo)致單核細(xì)胞增多癥和埃博拉病。

有些患者在感染新冠病毒后,可能需要住院治療,這部分患者容易患上“重癥監(jiān)護(hù)后綜合癥”,也就是插管和長(zhǎng)時(shí)間臥床等因素造成的不良反應(yīng)。潛在癥狀包括持續(xù)性肌無(wú)力、記憶問(wèn)題和創(chuàng)傷后應(yīng)激障礙等。

但不管是以上哪種情況,雖然恢復(fù)時(shí)間可能較長(zhǎng),但患者最終都會(huì)康復(fù)。華盛頓特區(qū)國(guó)立兒童醫(yī)院的傳染病專家、兒科新冠項(xiàng)目負(fù)責(zé)人亞歷山德拉·布魯格·揚(yáng)茨醫(yī)生表示,新冠病毒的感染和后續(xù)癥狀之間并不會(huì)有明顯間隔。

還有一些是遲發(fā)性的后遺癥,比如MIS,又稱多系統(tǒng)炎癥綜合征。這些新冠肺炎患者已經(jīng)完全康復(fù)了,有的甚至沒(méi)有明顯癥狀,在接下來(lái)的4到12周內(nèi)也基本沒(méi)事,但是后來(lái)卻突然出現(xiàn)了罕見(jiàn)的炎性疾病。這種情況往往出現(xiàn)在確診或密接病例上。這種情況發(fā)生在兒童身上的,叫做MIS-C;發(fā)生在成年人身上的,叫做MIS-A。這種癥狀有時(shí)甚至是致命的。

神奇的反轉(zhuǎn)

布羅丁也認(rèn)同揚(yáng)茨醫(yī)生的觀點(diǎn),即有些所謂的“長(zhǎng)期新冠”病例實(shí)質(zhì)上是重癥監(jiān)護(hù)后綜合征,或者是MIS-C和MIS-A。

布羅丁重點(diǎn)研究的是那些起初癥狀輕微,但突然出現(xiàn)“神奇反轉(zhuǎn)”,在后期出現(xiàn)持續(xù)癥狀的患者。他認(rèn)為這些患者可能屬于以下三種類型:一是由新冠病毒引發(fā)的自體免疫性疾病,二是由新冠病毒觸發(fā)的代謝性疾病,三是病毒的長(zhǎng)期存在。

布羅丁的“自體免疫說(shuō)”與揚(yáng)茨的“自主神經(jīng)功能障礙說(shuō)”大同小異,指的都是人體的自身免疫問(wèn)題。他的“病毒長(zhǎng)期存在說(shuō)”與揚(yáng)茨的“病毒持續(xù)活動(dòng)說(shuō)”一致。至于“代謝說(shuō)”,則是指在發(fā)生新冠病毒感染時(shí),人體的代謝會(huì)適應(yīng)感染過(guò)程,導(dǎo)致持續(xù)性的代謝紊亂。

“我們還在研究每一個(gè)類別?!辈剂_丁說(shuō):“到目前為止,每種說(shuō)法都有一些零散的數(shù)據(jù)支持,但也都沒(méi)有確鑿的證據(jù)?!?/p>

研究人員已經(jīng)在給“長(zhǎng)期新冠”對(duì)癥分類了,不過(guò)在他們找到確切的生物學(xué)依據(jù)之前,我們對(duì)“長(zhǎng)期新冠”的治療,仍將僅限于緩解癥狀。

揚(yáng)茨表示:“‘長(zhǎng)期新冠’的背后可能有多個(gè)病理機(jī)制在起作用,我不相信所有人的‘長(zhǎng)期新冠’癥狀都是同一病理機(jī)制引起的。一旦我們能夠更扎實(shí)地梳理出這些問(wèn)題,就能想出更好的辦法來(lái)管理這些病人,并且更加靶向地進(jìn)行藥物治療?!保ㄘ?cái)富中文網(wǎng))

譯者:樸成奎

你聽(tīng)說(shuō)過(guò)“長(zhǎng)期新冠”嗎?簡(jiǎn)而言之,就是得了新冠久治不愈,感染過(guò)后好幾周,仍然有疲勞、喪失嗅覺(jué)、持續(xù)咳嗽等癥狀。

還有一個(gè)陽(yáng)性患者甚至出現(xiàn)了幻覺(jué),而且保存新的記憶,語(yǔ)言功能也出現(xiàn)了障礙。

新冠疫情持續(xù)到現(xiàn)在,它的癥狀也變得越來(lái)越奇怪了。據(jù)英國(guó)醫(yī)學(xué)期刊《柳葉刀》發(fā)表的一項(xiàng)重磅研究稱,到目前為止,新冠病毒感染者出現(xiàn)的癥狀已經(jīng)達(dá)到200多種,其中包括耳朵麻痹,出現(xiàn)“大腦著火”感,男性勃起功能障礙,女性月經(jīng)失調(diào),便秘,皮膚脫皮和視力重影,等等。

這項(xiàng)研究指出,新冠病毒感染者出現(xiàn)的癥狀涵蓋了10個(gè)人體的主要器官系統(tǒng)——而人體總共只有11個(gè)主要器官系統(tǒng)。

現(xiàn)在,美國(guó)已經(jīng)迎來(lái)了第六波疫情高峰,很多美國(guó)人再次得了新冠。幾千萬(wàn)美國(guó)人都迫切地想要知道,當(dāng)自己出現(xiàn)久治不愈的癥狀時(shí)該怎么辦。

專家表示,他們正在盡最大努力尋找這個(gè)問(wèn)題的答案。

新冠病毒專家、倫敦帝國(guó)理工學(xué)院兒童免疫學(xué)教授、兒科醫(yī)生彼得·布羅丁對(duì)《財(cái)富》表示:“我也希望我能知道‘長(zhǎng)期新冠’到底是怎么回事?!?/p>

不過(guò)有一件事是確定的:“‘長(zhǎng)期新冠’絕對(duì)不簡(jiǎn)單?!?/p>

如何定義是難題

雖然‘長(zhǎng)期新冠’的癥狀已不鮮見(jiàn),但學(xué)界對(duì)它的發(fā)病機(jī)制仍不甚了解,對(duì)它的定義也各不相同。

世界衛(wèi)生組織對(duì)長(zhǎng)期新冠的定義是:新冠肺炎確診病例出現(xiàn)了持續(xù)兩個(gè)月以上的長(zhǎng)期癥狀,而且這些癥狀無(wú)法用其他原因解釋。這些癥狀可能在感染后便一直存在,也有可能間隙性反復(fù)發(fā)作。世衛(wèi)組織還建議,醫(yī)療機(jī)構(gòu)應(yīng)在患者出現(xiàn)急性癥狀三個(gè)月以上,再考慮給出“長(zhǎng)期新冠”的診斷。

梅奧診所則將“長(zhǎng)期新冠”定義為由新冠病毒引起的、確診后持續(xù)四周以上的一系列癥狀。

布羅丁表示:“這充分說(shuō)明了診斷有多不靠譜。關(guān)于‘長(zhǎng)期新冠’究竟是什么,你問(wèn)不同的人,就會(huì)得到不同的答案?!?/p>

根據(jù)來(lái)自美國(guó)政府問(wèn)責(zé)署的數(shù)據(jù),預(yù)計(jì)有700萬(wàn)到2300萬(wàn)美國(guó)人可能遭受過(guò)“長(zhǎng)期新冠”的困擾,也就是說(shuō)最多7%的美國(guó)人口都可能出現(xiàn)過(guò)“長(zhǎng)期新冠”的癥狀。有研究推測(cè),在所有感染過(guò)新冠病毒的人中,出現(xiàn)“長(zhǎng)期新冠”癥狀的人口比例可能在5%到80%之間。

美國(guó)疾控中心上周二發(fā)表的一項(xiàng)研究顯示,有五分之一的美國(guó)成年人在感染新冠病毒的幾周至幾個(gè)月內(nèi),出現(xiàn)了至少一種可能與“長(zhǎng)期新冠”有關(guān)的癥狀。而在老年人中,這一比例更是提高到了四分之一。

新冠病毒專家、藥品開(kāi)發(fā)公司Fractal Therapeutics的首席執(zhí)行官阿利吉特·查克拉瓦提認(rèn)為,“長(zhǎng)期新冠”可能短短幾年就會(huì)影響全球10億人。有專家認(rèn)為,“長(zhǎng)期新冠”正在迅速變成一個(gè)重大公共衛(wèi)生問(wèn)題,而且它也讓廣大初級(jí)保健醫(yī)生不堪重負(fù),因?yàn)樗麄儾⒉恢廊绾味x或治療它。

布羅丁指出,在“長(zhǎng)期新冠”的患者中,有些只是感到疲勞始終揮之不去,這種情況對(duì)于很多病毒都比較常見(jiàn)。不過(guò)其他患者則可能出現(xiàn)更復(fù)雜的癥狀。

他表示:“這其中有些癥狀是較為常見(jiàn)的——比如嗅覺(jué)遲遲無(wú)法恢復(fù),此外還有一定程度的疲勞。我覺(jué)得多數(shù)成年人在嚴(yán)重感染感冒或者其他病毒后,都有可能出現(xiàn)持續(xù)性的疲勞。所以你問(wèn)80%的新冠患者,他們也會(huì)表示自己有這種疲勞感,這是可以理解的?!?/p>

“不過(guò)就其他一些癥狀而言,它確實(shí)是比較罕見(jiàn)的?!?/p>

五種類型的“長(zhǎng)期新冠”

華盛頓特區(qū)國(guó)立兒童醫(yī)院的傳染病專家、兒科新冠項(xiàng)目負(fù)責(zé)人亞歷山德拉·布魯格·揚(yáng)茨醫(yī)生表示,“長(zhǎng)期新冠”癥狀基本可以分為五大類。

第一種就是新冠病毒本身造成的長(zhǎng)期影響,包括直接性的肺損傷。其他患者則基本上屬于以下四類的某一類或某幾類:炎癥、自主神經(jīng)功能障礙、病毒持續(xù)活動(dòng),以及免疫反應(yīng)改變。

首先,新冠病毒一旦引發(fā)炎癥,病毒就會(huì)觸發(fā)人體釋放炎性因子來(lái)殺滅染毒細(xì)胞,但炎性反應(yīng)也會(huì)損害多個(gè)器官系統(tǒng),尤其是如果炎性反應(yīng)一直持續(xù)的話。

自主神經(jīng)功能異常(POTS)又稱體位性心動(dòng)過(guò)速,是指自主神經(jīng)系統(tǒng)受到了直接損傷。這種病本質(zhì)上可能是一種自體免疫疾病,它會(huì)導(dǎo)致患者的心率和血壓隨著體位的變化(如立、坐、臥)而出現(xiàn)紊亂。

持續(xù)性病毒活動(dòng)則可能是由所謂的“幽靈病毒”細(xì)胞引起的,這些病毒細(xì)胞可能在感染數(shù)月后仍然保持活性。最近有研究發(fā)現(xiàn),這種病毒細(xì)胞一旦進(jìn)入腸道,就有可能導(dǎo)致腹瀉等非典型癥狀。

最后是免疫反應(yīng)改變,它有可能單獨(dú)出現(xiàn),也有可能與其他類型的癥狀合并出現(xiàn)。在感染新冠病毒后,為了讓身體盡快康復(fù),人體免疫系統(tǒng)有可能會(huì)“過(guò)度反應(yīng)”,甚至對(duì)一些平時(shí)無(wú)關(guān)痛養(yǎng)的病毒也反應(yīng)過(guò)度。比如有的年僅20多歲的患者在感染新冠肺炎后,在很短的時(shí)間里相繼感染了一系列其他疾病,比如單核細(xì)胞增多癥和鏈球菌感染等。

一些相關(guān)研究

專家表示,雖然有些人可能被確診為“長(zhǎng)期新冠”,或者疑心自己得了“長(zhǎng)期新冠”,但他們未必真的就得了這種病。

有些患者出現(xiàn)了新冠急性期后后遺癥,比如咳嗽和氣短等持續(xù)性癥狀。不過(guò)人體感染很多病毒后都會(huì)出現(xiàn)持續(xù)性癥狀,比如人類皰疹病毒4型(EB病毒)就會(huì)導(dǎo)致單核細(xì)胞增多癥和埃博拉病。

有些患者在感染新冠病毒后,可能需要住院治療,這部分患者容易患上“重癥監(jiān)護(hù)后綜合癥”,也就是插管和長(zhǎng)時(shí)間臥床等因素造成的不良反應(yīng)。潛在癥狀包括持續(xù)性肌無(wú)力、記憶問(wèn)題和創(chuàng)傷后應(yīng)激障礙等。

但不管是以上哪種情況,雖然恢復(fù)時(shí)間可能較長(zhǎng),但患者最終都會(huì)康復(fù)。華盛頓特區(qū)國(guó)立兒童醫(yī)院的傳染病專家、兒科新冠項(xiàng)目負(fù)責(zé)人亞歷山德拉·布魯格·揚(yáng)茨醫(yī)生表示,新冠病毒的感染和后續(xù)癥狀之間并不會(huì)有明顯間隔。

還有一些是遲發(fā)性的后遺癥,比如MIS,又稱多系統(tǒng)炎癥綜合征。這些新冠肺炎患者已經(jīng)完全康復(fù)了,有的甚至沒(méi)有明顯癥狀,在接下來(lái)的4到12周內(nèi)也基本沒(méi)事,但是后來(lái)卻突然出現(xiàn)了罕見(jiàn)的炎性疾病。這種情況往往出現(xiàn)在確診或密接病例上。這種情況發(fā)生在兒童身上的,叫做MIS-C;發(fā)生在成年人身上的,叫做MIS-A。這種癥狀有時(shí)甚至是致命的。

神奇的反轉(zhuǎn)

布羅丁也認(rèn)同揚(yáng)茨醫(yī)生的觀點(diǎn),即有些所謂的“長(zhǎng)期新冠”病例實(shí)質(zhì)上是重癥監(jiān)護(hù)后綜合征,或者是MIS-C和MIS-A。

布羅丁重點(diǎn)研究的是那些起初癥狀輕微,但突然出現(xiàn)“神奇反轉(zhuǎn)”,在后期出現(xiàn)持續(xù)癥狀的患者。他認(rèn)為這些患者可能屬于以下三種類型:一是由新冠病毒引發(fā)的自體免疫性疾病,二是由新冠病毒觸發(fā)的代謝性疾病,三是病毒的長(zhǎng)期存在。

布羅丁的“自體免疫說(shuō)”與揚(yáng)茨的“自主神經(jīng)功能障礙說(shuō)”大同小異,指的都是人體的自身免疫問(wèn)題。他的“病毒長(zhǎng)期存在說(shuō)”與揚(yáng)茨的“病毒持續(xù)活動(dòng)說(shuō)”一致。至于“代謝說(shuō)”,則是指在發(fā)生新冠病毒感染時(shí),人體的代謝會(huì)適應(yīng)感染過(guò)程,導(dǎo)致持續(xù)性的代謝紊亂。

“我們還在研究每一個(gè)類別?!辈剂_丁說(shuō):“到目前為止,每種說(shuō)法都有一些零散的數(shù)據(jù)支持,但也都沒(méi)有確鑿的證據(jù)?!?/p>

研究人員已經(jīng)在給“長(zhǎng)期新冠”對(duì)癥分類了,不過(guò)在他們找到確切的生物學(xué)依據(jù)之前,我們對(duì)“長(zhǎng)期新冠”的治療,仍將僅限于緩解癥狀。

揚(yáng)茨表示:“‘長(zhǎng)期新冠’的背后可能有多個(gè)病理機(jī)制在起作用,我不相信所有人的‘長(zhǎng)期新冠’癥狀都是同一病理機(jī)制引起的。一旦我們能夠更扎實(shí)地梳理出這些問(wèn)題,就能想出更好的辦法來(lái)管理這些病人,并且更加靶向地進(jìn)行藥物治療?!保ㄘ?cái)富中文網(wǎng))

譯者:樸成奎

One Long COVID patient complains of fatigue, loss of smell, and a persistent cough weeks after his initial COVID infection.

Another experiences hallucinations and an inability to record new memories, and begins speaking unrecognizable words.

It gets stranger. Among the 200-plus symptoms identified so far are ear numbness, a sensation of “brain on fire,” erectile dysfunction, irregular menstrual periods, constipation, peeling skin, and double vision, according to a landmark July study published in British medical journal The Lancet.

The study identified symptoms involving 10 major organ systems—and the body only has 11.

With the U.S. in a sixth COVID wave and many Americans catching COVID yet again, millions are hungry to know just what they’re experiencing when it comes to persistent symptoms.

Experts say they’re working as hard as they can to find out.

“I wish I knew the full answer” as to exactly what Long COVID is, Dr. Petter Brodin—a COVID researcher, professor of pediatric immunology, and pediatrician at the Imperial College of London—tells Fortune.

But one thing is definitely certain: “Long COVID is not one thing.”

Defining an enigma

While researchers are making strides in understanding what has become a common condition, Long COVID is still poorly understood, and definitions vary.

The World Health Organization defines Long COVID as a condition that occurs in someone who had COVID, with symptoms that cannot be explained by another diagnosis, that last for two months or more. The symptoms can persist following the initial onset, or come and go over time, the organization says, adding that a diagnosis of long COVID usually wouldn't be made until three months after acute illness.

The Mayo Clinic defines long COVID as a set of symptoms stemming from COVID that persist for more than four weeks after diagnosis.

“This just shows you how uncertain the diagnosis is,” Brodin says. “Depending on whom you ask, you’ll get a different answer as to what Long COVID is.”

Whatever it is, it may already affect between 7 million and 23 million Americans who previously had the virus, or up to 7% of the U.S. population, according to the U.S. Government Accountability Office. Studies have hypothesized that between 5% and 80% of those who’ve had COVID end up with Long COVID.

A study released Tuesday by the U.S. Centers for Disease Prevention and Control found that one in five U.S. adults with a history of COVID—of the millions whose records were examined—experienced at least one medical condition potentially attributable to Long COVID in the weeks and months following infection.The rate rose to one in four among seniors.

Long COVID could potentially impact over a billion worldwide in just a few years, says Arijit Chakravarty, a COVID researcher and CEO of Fractal Therapeutics, a drug development firm. Experts say that it’s quickly growing into a major public health concern and already overwhelming primary-care physicians, who are unsure of how to define or treat it.

Of those who identify as having Long COVID, some may just have the kind of lingering fatigue you see after many viruses, while others likely have a more complex condition, Brodin says.

“We know some symptoms are more common than others—like a persistent lack of smell is pretty common, and also fatigue, to some level,” Brodin says. “I think most adults can relate to some degree of persistent fatigue after a serious infection, the flu or some other thing. If you ask people if they have Long COVID and that’s the kind of fatigue they’re describing, I can understand why 80% say yes.

“If it’s something else, it would be more rare.”

5 types of Long COVID

Those who have Long COVID can likely be divided into five categories, according to Dr. Alexandra Brugler Yonts, an infectious disease specialist at Children's National Hospital in Washington, D.C., and the head of its new Pediatric Post-COVID Program.

There are patients who simply have long-term effects of COVID, including direct lung damage. She believes the rest of the patients likely belong in one or more of four categories: inflammation, dysautonomia, ongoing viral activity, and altered immune response.

In the case of inflammation, the virus triggers the body’s release of inflammasomes that kill infected cells—but the fallout can wreak havoc in various organ systems, especially if the process continues.

In dysautonomia—also known as POTS, or Postural Orthostatic Tachycardia Syndrome—patients experience direct damage to the autonomic nervous system. Potentially autoimmune in nature, the syndrome causes disruptions in heart rate and blood pressure in response to changes in position, like sitting or standing or laying.

Ongoing viral activity could be caused by “ghost” virus cells that can linger for months after initial infection. Recent research has found that such cells, when located in the gut, can cause ongoing gastrointestinal symptoms like diarrhea that aren’t typical of a respiratory virus.

Altered immune response may be seen alone or in combination with the other categories, she says. In order to bring itself back to normal, the immune system overcorrects, resulting in susceptibility to a number of viruses the body might usually fight off. Anecdotally, she’s heard of patients in their 20s who had COVID and then came down with a slew of other illnesses in short order, like mono and strep.

Red herrings abound

Not everyone who has been diagnosed with Long COVID, or who thinks they have it, actually does, experts say.

There are those who have post-acute sequelae of COVID, or persistent symptoms like a cough or shortness of breath. Symptoms after an infection can be seen with a number of viruses, like the Epstein-Barr virus, which causes mono, and ebola.

Some patients whose COVID required hospitalization may have post-intensive care syndrome due to a traumatic and debilitating ICU stay that may have included intubation and prolonged bed confinement. Potential symptoms can include persistent muscle weakness, memory problems, and post-traumatic stress disorder.

In both cases, patients become sick with COVID and take a while to recover, but eventually do. There isn’t a break between COVID and symptoms that persist, she says.

Then there are those with late-onset sequelae, like MIS, or multisystem inflammatory syndrome. These patients fully recover from COVID, if they even had symptoms, and are fine for four to 12 weeks before developing the rare, inflammatory-based illness that can occur in those who have had COVID or been exposed. MIS-C occurs in children, MIS-A in adults. It’s fatal in some cases.

A puzzling plot twist

Brodin agrees with Brugler Yonts that some cases described as having Long COVID actually have post intensive care syndrome, MIS-C, or MIS-A.

His research has focused on those who had milder COVID initially but, in a puzzling plot twist, later developed persistent symptoms. He sees those patients as belonging in one or more of three categories: autoimmune disease triggered by COVID, metabolic disease triggered by COVID, and long-term persistence of the virus.

Brodin’s autoimmune category aligns with Brugler Yonts’ dysautonomia category, as the disorder has been hypothesized to be autoimmune. And his long-term persistence of the virus category aligns with her ongoing viral activity category. In metabolic disease triggered by COVID, the body’s metabolism adapts during infection, leading to metabolic disturbance that persists.

“We’re looking at each and every one” of the categories,” Brodin said. “As of now, there is scattered data supporting each, but nothing conclusive.”

Researchers are beginning to refine nebulous Long COVID categories. But until they can nail down the biological causes, treatments will be limited to management of symptoms.

“There are different pathologies at play,” Brugler Yonts says. “I don’t think there’s one process that is ‘Long COVID’ in every single person. There are multiple processes going on, and once we can more solidly tease that out, it will lead to better ways to manage those patients and more focused pharmaceutical treatments.”

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