COVID-19 疫苗：我們正在做些什麼，我們應該做些什麼？

資料來源：http://www.thelancet.com/infection Vol 22 May 2022；財團法人台灣紅絲帶基金會編譯

圖：Flickr – Erdonzello

疫苗是預防感染和對抗 COVID-19 大流行的最重要武器。現在已經確定疫苗會隨著時間的推移而失去效力。出於這個原因，一些國家的衛生當局和藥物監管機構已批准在疫苗接種週期完成後 3-5 個月向個人施用額外劑量的疫苗（稱為追加劑）。這種方法似乎可以有效地維持對 SARS-CoV-2 的免疫力。

在《刺胳針傳染病》中，Giovanni Corrao 及其同事發表了一項真實世界研究的結果，該研究檢視了超過 5,000,000 名接種了疫苗並進行了9 個月追蹤之個體的感染率。本研究證實了過去已有之較短追蹤期的數據，這些數據顯示，自第二劑疫苗接種以來，對感染的保護作用隨著時間的推移而降低。然而，他們亦證明了使用腺病毒載體和 mRNA疫苗仍然對嚴重形式的 COVID- 19的保護，儘管減弱了。從這些信息中可以得出什麼結論？首先，在尚未獲得疫苗保護的人群中繼續接種疫苗非常重要，特別是如果他們感染可能會導致嚴重疾病風險的人（老年人、體弱、免疫功能低下和有合併症的人）。因此有必要去確定導致這些高危人群不接種疫苗的主要因素。對疫苗之猶豫肯定是最重要的，首先是由於媒體過分強調了疫苗接種反對者的抗議和所謂的疫苗嚴重副作用，其次是由於 COVID-19 科學訊息的引人注目，這導致所任命的專家散佈彼此矛盾的觀點和訊息，讓公眾對科學失去信心。其次，隨著 omicron 變異株 (B.1.1.529) 等新的高度傳染性變異株的出現，似乎有必要對高風險個體在第二劑接種後 3-5 個月鼓勵接種加強劑，並為所有 5 歲及以上以及尚未接種第一劑的個體接種疫苗。疫苗對感染的保護作用之喪失以及高度傳播變異株的出現阻止了單獨使用疫苗足以控制大流行。衛生和社交距離措施（經常洗手、盡可能避免身體接觸、在室內戴口罩）和其他非藥物措施必須與疫苗接種策略相結合。

並提出了三個假設來解釋 omicron 變異株的發生，它在幾個方面（大約 30 個突變）與 SARS-CoV-2 的其他變異株不同。第一個是它在免疫功能低下的人慢性感染 SARS-CoV-2 過程中演化，第二個是它在世界上那些缺乏或不經常進行病毒測序的地區演化，第三個是它在跨越物種傳播到人類前在一個動物宿主中演化。不管假設是否正確，教訓都是一樣的：免疫功能低下人群數量眾多、變異追踪很少進行、有機會與可能感染冠狀病毒之動物接觸的國家需要迅速參與在疫苗接種運動中。非洲是一個巨大的大陸，具有所有這些特徵，同時疫苗接種率非常低。如果我們不讓非洲和所有發展中國家參與疫苗接種運動，以防止更多更危險變異株的出現和傳播，而這些變異株可以逃避自然和疫苗觸發的免疫反應，並具有更高的死亡率。如發生與 omicron變異株具有相似傳染性且死亡率高的變異株的情況那將是災難性的，必須不惜一切的代價來避免。然而，重要的是要考慮到，即使在致死或住院率並沒有變化的情況下增加傳染性，也可能導致醫院急診部門和醫療保健系統之崩潰，並導致異常高的死亡人數。此外，有希望和有效的新療法還不能產生實質性的效果，因為它們的缺稀、昂貴，而且在短期內不太可能產生可衡量的效果。與病毒的鬥爭必須在許多開放戰線上付諸實施：積極的全球疫苗接種運動（同時還需考慮將強制性疫苗接種從某些類別族群擴展到整個人群）、非藥物介入措施、加強急診和重症監護系統，並尋找在疾病的每個階段都有效的療法。邁向正常的路其實還很長遠。

Marcello Candelli/ marcello.candelli@policlinicogemelli.it/ 急診科， Policlinico A Gemelli–IRCCS大學基金會，羅馬聖心天主教大學，00168 羅馬，意大利

COVID-19 vaccine: what are we doing and what should we do? 

Flickr – Erdonzello 

Vaccines are the most important weapon for preventing infections and fighting the COVID-19 pandemic. It is now well established that vaccines lose effectiveness over time. For this reason, health authorities and drug regulatory agencies in several countries have approved the administration of an additional dose of vaccine (called a booster) to individuals 3–5 months after the completion of the vaccination cycle. This approach appears to be effective in maintaining immunity against SARS-CoV-2. 

In The Lancet Infectious Diseases, Giovanni Corrao and colleagues published the results of a real-world study that examined the infection rate of more than 5000000 vaccinated individuals with a follow-up of 9 months. This study confirms data already available for shorter follow-up periods, which showed a decrease in protection against infection that increased with time since the second dose of vaccine. However, they documented that protection against severe forms of COVID-19 remained, albeit attenuated, with both adenoviral and mRNA vector vaccines. What conclusions can be drawn from this information? First, it is extremely important to continue the vaccination campaign in people who do not yet have vaccine protection, especially if they are at risk of developing severe forms of the disease (elderly, frail, immunocompromised, and people with comorbidities). It is therefore necessary to ascertain the main factors that lead these high-risk individuals to not be vaccinated. Vaccine hesitancy is certainly the most important and is due, first, to the media overemphasising the protests of vaccination opponents and the alleged serious side effects of vaccines, and second, to the spectacularisation of scientific information on COVID-19, which has led to appointed experts spreading contradictory opinions and messages and the public losing confidence in science. Second, with the emergence of new highly contagious variants such as the omicron variant (B.1.1.529), it seems necessary to encourage the administration of booster doses to high-risk individuals 3–5 months after the second dose and to vaccinate all individuals aged 5 years and older who have not yet received the first dose. The loss of protection against infection by the vaccines and the emergence of the highly transmissible variants prevent the vaccine alone from controlling the pandemic. Hygienic and social distancing measures (frequent hand washing, avoiding physical contact as much as possible, wearing a face mask indoors) and other nonpharmacological measures must be combined with the vaccination strategy. 

Three hypotheses have been proposed to explain the occurrence of the omicron variant, which differs in several respects (about 30 mutations) from the other variants of SARS-CoV-2. The first is that it evolved in an immunocompromised human chronically infected with SARS-CoV-2, the second that it evolved in an area of the world where viral sequencing is absent or infrequent, and the third that it evolved in an animal reservoir before a spillover to humans. Regardless of the correct hypothesis, the lesson is the same: countries with high numbers of immunocompromised people, where tracing of variants is rarely done, and where contact with animals potentially susceptible to coronaviruses is possible, need to be quickly involved in vaccination campaigns. Africa is a huge continent that has all these characteristics and at the same time has a very low vaccination rate. We cannot think of getting out of the pandemic emergency if we do not include Africa and all developing countries in a capillary vaccination campaign to prevent the emergence and spread of further and more dangerous variants that can evade both natural and vaccine-triggered immune responses and have higher mortality. The scenario of a variant that is similarly transmissible to the omicron variant and has high mortality would be catastrophic and must be avoided at all costs. However, it is important to consider that even an increase in transmissibility with no change in lethality or hospitalisation rates could lead to the collapse of hospital emergency departments and health-care systems and an exceptionally high number of deaths. Moreover, promising and effective new therapies cannot yet have a substantial effect because they are scarce, expensive, and unlikely to have a measurable effect in the short term. The fight against the virus must be waged on numerous open fronts: aggressive global vaccination campaigns (while also considering extending mandatory vaccination from some categories to the entire population), nonpharmacological interventions, strengthening emergency and critical care systems, and finding therapies that are effective at every stage of the disease. The road to normality is still very long.

Marcello Candelli marcello.candelli@policlinicogemelli.it Emergency Department, Fondazione Universitaria Policlinico A Gemelli–IRCCS, Catholic University of Sacred Heart of Rome, 00168 Rome, Italy