既感染者にもワクチン接種は推奨される

2021年3月にNEJMへの報告によると、既感染者にもワクチン接種は推奨されます。但し、ワクチン不足の中では1回で十分のようです。

3回目接種によって、高齢者(65歳以上)の感染は更に減ると報告されていますが、これもまだ先の話でしょう。

また下図の一番左の「Before First Dose」のSeropositive（既感染者・オレンジ色）と、下図中央辺りの「9-12 Days after First Vaccine Dose 」のSeronegative（未感染者・青色）を比べると分かるように、

mRNAワクチンは1回打つだけで抗体上昇は既感染者のワクチン接種前の抗体価を上回っています。

2回目の接種後ともなると、感染防止効果も、CoVID-19罹患者より上回っています。

不活化ワクチンよりも免疫が強く付くと言われていた生ワクチンですら、次の感染防止効果では自然感染に劣り、麻疹ワクチンや水痘ワクチンを打っても麻疹や水痘になる人はいましたが、mRNAワクチンは自然感染をも上回っているのです。

（2021/08/22 管理者記載）

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＜1回目の接種後＞

未感染者に対してmRNAワクチンを接種すると、9〜12日程度でIgG抗体が有意に上昇する。2週間で多くの人が上昇するが、時間が経つほど上昇する人の割合は増える。

一方、既感染者にワクチン接種を行うと、5〜8日で有意にIgG抗体が上昇する。2週間で最大値に達する。

上昇の速度も既感染者の方が速く、抗体価も10〜45倍高い。

＜2回目の接種後＞

未感染者は2回目の接種後、更に抗体は3倍上昇した。

一方、既感染者への2回目のワクチン接種後の抗体上昇は無かった。

最終的に既感染者の方が未感染者より6倍抗体が高くなった。

＜ワクチンの種類＞

Pfizer と Modernaでは抗体上昇のダイナミクスに有意な差は無かった。

Antibody Responses in Seropositive Persons after a Single Dose of SARS-CoV-2 mRNA Vaccine

Florian Krammer, Ph.D.

Komal Srivastava, M.S.

Hala Alshammary, M.S.

Angela A. Amoako, M.S.

Mahmoud H. Awawda, M.S.

Katherine F. Beach, B.S.

Maria C. Bermúdez-González, M.P.H.

Dominika A. Bielak, B.A.

Juan M. Carreño, Ph.D.

Rachel L. Chernet, B.A.

Lily Q. Eaker, B.A.

Emily D. Ferreri, B.S.

Daniel L. Floda, B.A.

Charles R. Gleason, B.S.

Joshua Z. Hamburger, M.D.

Kaijun Jiang, M.S.

Giulio Kleiner, Ph.D.

Denise Jurczyszak, Ph.D.

Julia C. Matthews, B.A.

Wanni A. Mendez, A.A.S.

Ismail Nabeel, M.D.

Lubbertus C.F. Mulder, Ph.D.

Ariel J. Raskin, B.A.

Kayla T. Russo, B.S.

Ashley-Beathrese T. Salimbangon, B.A.

Miti Saksena, M.B., B.S.

Amber S. Shin, B.S.

Gagandeep Singh, Ph.D.

Levy A. Sominsky, B.A.

Daniel Stadlbauer, Ph.D.

Ania Wajnberg, M.D.

Viviana Simon, M.D., Ph.D.

Icahn School of Medicine at Mount Sinai, New York, NY

florian.krammer@mssm.edu, viviana.simon@mssm.edu

N Engl J Med 2021; 384:1372-1374

DOI: 10.1056/NEJMc2101667

https://www.nejm.org/doi/full/10.1056/NEJMc2101667

The efficacy of two injections of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike messenger RNA (mRNA) vaccines (BNT162b2 [Pfizer] and mRNA-1273 [Moderna])1 in preventing symptomatic SARS-CoV-2 infection in persons without previous coronavirus disease 2019 (Covid-19) has been shown to be high.2,3 We wondered what the response would be to the first vaccine dose in persons with previous Covid-19.

We took advantage of our ongoing institutional review board–approved, longitudinal PARIS (Protection Associated with Rapid Immunity to SARS-CoV-2) study to provide a limited snapshot of the antibody responses in 110 study participants with or without documented preexisting SARS-CoV-2 immunity (mean age overall, 40.0 years [range, 24 to 68; ≥60 years, 8%]; 67 seronegative participants [64% female] with a mean age of 41.3 years and 43 seropositive participants [59% female] with a mean age of 41.4 years) (Table S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org) who received their first spike mRNA vaccine dose in 2020 (88 received the Pfizer vaccine and 22 the Moderna vaccine). SARS-CoV-2 spike IgG was measured with the use of a previously described two-step enzyme-linked immunosorbent assay and expressed as area under the curve (AUC).

Repeated sampling after the first dose indicates that the majority of seronegative participants had variable and relatively low SARS-CoV-2 IgG responses within 9 to 12 days after vaccination (median AUC before vaccination, 1 [67 participants]; at 0 to 4 days, 1 [12 participants]; at 5 to 8 days, 1 [22 participants]; at 9 to 12 days, 439 [13 participants]; at 13 to 16 days, 1016 [18 participants]; at 17 to 20 days, 1037 [21 participants]; at 21 to 27 days, 1293 [19 participants]; and after the second dose, 3316 [36 participants]) (Figure 1A). In contrast, participants with SARS-CoV-2 antibodies at baseline before the first vaccine injection rapidly developed uniform, high antibody titers within days after vaccination (median AUC before vaccination, 90 [43 participants]; at 0 to 4 days, 133 [7 participants]; at 5 to 8 days, 14,208 [15 participants]; at 9 to 12 days, 20,783 [8 participants]; at 13 to 16 days, 25,927 [20 participants]; at 17 to 20 days, 11,755 [4 participants]; at 21 to 27 days, 19,534 [14 participants]; and after the second dose, 22,509 [19 participants]) (Figure 1A).

The antibody titers of vaccinees with preexisting immunity were 10 to 45 times as high as those of vaccinees without preexisting immunity at the same time points after the first vaccine dose (e.g., 25 times as high at 13 to 16 days)

and also exceeded the median antibody titers measured in participants without preexisting immunity after the second vaccine dose by more than a factor of 6.

Although the antibody titers of the vaccinees without preexisting immunity increased by a factor of 3 after the second vaccine dose, no increase in antibody titers was observed in the Covid-19 survivors who received the second vaccine dose.

No substantial difference was noted in the dynamics of antibody responses elicited by the Pfizer and Moderna vaccines after the first dose (Fig. S1). The current analysis represents a convenience sample in which not all participants were able to provide biospecimens for antibody analysis at all the additional time intervals. Ongoing follow-up studies will show whether these early differences in immune responses are maintained over a prolonged time period.

The antibody titers of vaccinees with preexisting immunity were 10 to 45 times as high as those of vaccinees without preexisting immunity at the same time points after the first vaccine dose (e.g., 25 times as high at 13 to 16 days) and also exceeded the median antibody titers measured in participants without preexisting immunity after the second vaccine dose by more than a factor of 6. Although the antibody titers of the vaccinees without preexisting immunity increased by a factor of 3 after the second vaccine dose, no increase in antibody titers was observed in the Covid-19 survivors who received the second vaccine dose. No substantial difference was noted in the dynamics of antibody responses elicited by the Pfizer and Moderna vaccines after the first dose (Fig. S1). The current analysis represents a convenience sample in which not all participants were able to provide biospecimens for antibody analysis at all the additional time intervals. Ongoing follow-up studies will show whether these early differences in immune responses are maintained over a prolonged time period.

In addition, we compared the frequency of local, injection-site–related as well as systemic reactions after the first dose of vaccine in 230 participants (mean age, 39.2 years [range, 22 to 70; ≥60 years, 8%]; 148 seronegative participants [70% female] and 82 seropositive participants [64% female]) (Figure 1B). Overall, both vaccines (156 participants received the Pfizer vaccine and 74 the Moderna vaccine) had no side effects that resulted in hospitalization. A total of 159 of the 230 participants (69%) who completed the PARIS study survey reported having some side effects after the first vaccine dose (46% of the seronegative survey respondents and 89% of the seropositive survey respondents). Most common were localized injection-site symptoms (pain, swelling, and erythema), which occurred with equal frequency independently of the serostatus at the time of vaccination and resolved spontaneously within days after vaccination. Vaccine recipients with preexisting immunity had systemic side effects at higher frequencies than those without preexisting immunity (fatigue, headache, chills, muscle pain, fever, and joint pain, in order of decreasing frequency) (Figure 1B). Because a convenience sample was used and only participants with available data were studied, caution is needed until the full data set, including side effects occurring after the first as well as the second vaccine dose, can be assessed.

We found that a single dose of mRNA vaccine elicited rapid immune responses in seropositive participants, with postvaccination antibody titers that were similar to or exceeded titers found in seronegative participants who received two vaccinations. Whether a single dose of mRNA vaccine provides effective protection in seropositive persons requires investigation.

Long-CoVIDがワクチン接種によって改善するという報告が出ています。

まだ症例数が少なく、medRxivへの報告レベルですが、少なくとも害はありません。

（2021/08/22 管理者記載）

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＜方法＞

最初にCOVID-19で入院した患者に対して、入院後3か月（2020年6月から7月）および8か月（2020年12月から2021年1月）に臨床追跡調査を行う前向き観察研究行いました。 2021年1月から2月の間にPfizer-BioNTech（BNT162b2）またはOxford-AstraZeneca（ChAdOx1 nCoV-19）ワクチンを接種した参加者を特定し、同じコホートの参加者のうちワクチン接種者：ワクチン未接種者=2：1（8か月の症状）の比率で比較しました。ワクチン接種後1か月（またはワクチン接種されていないコホートの一致した時点）に全員を再評価しました。検証された生活の質（SF-36）、精神的健康（WEMWBS）、および進行中の症状がすべての時点で評価されました。正式な統計分析では、線形回帰でベースラインの症状、年齢、性別を使用して、最近の生活の質に対するワクチン接種の効果を比較しました。

＜結果＞

44人のワクチン接種を受けた参加者がワクチン接種後の中央値32日（IQR 20-41）で評価され、22人のワクチン未接種者コホートと比較しました。

殆どが8ヶ月時点でもLong-Covidの症状が強く（両方のグループの82％に少なくとも1つの持続的な症状がありました）、倦怠感（61％）、息切れ（50％）、不眠症（38％）が優勢でした。ワクチン接種前とワクチン接種後の生活の質または精神的健康の測定基準に有意な悪化はありませんでした。ほぼ3分の2（n = 27）が、一過性（72時間未満の持続時間）の全身的影響（発熱、筋肉痛、頭痛を含む）を報告しました。

同じコホートのワクチン未接種者と比較した場合、ワクチン接種者は、Long Covid症状の全体的な改善はわずかでしたが、症状の悪化が減少しました。（ワクチン接種者5.6％ vs ワクチン未接種者14.2％）

ワクチン接種によって症状が解消する人が有意に増加しました。ワクチン接種者で23.2％ vs 非ワクチン接種者 15.4％（p = 0.035）。

Pfizer-BioNTechワクチンとOxford-AstraZenecaワクチンの間に反応の違いは確認されませんでした。

＜結論＞

mRNAまたはアデノウイルスベクターワクチンのいずれかによるワクチン接種は、Long-CoVIDの症状、生活の質、または精神的健康の悪化とは関連していませんでした。 COVID-19の症状が長引く個人は、国のガイダンスで示唆されているように予防接種を受ける必要があります。

Are vaccines safe in patients with Long COVID? A prospective observational study

DT Arnold, A Milne, E Samms, L Stadon, NA Maskell, FW Hamilton

doi: https://doi.org/10.1101/2021.03.11.21253225

https://www.medrxiv.org/content/10.1101/2021.03.11.21253225v3

Abstract

Introduction

Although the efficacy of SARS-CoV-2 vaccination to prevent symptomatic COVID-19 is well established, there are no published studies on the impact on symptoms in patients with Long Covid. Anecdotal reports have suggested both a potential benefit and worsening of symptoms post vaccination with the uncertainty leading to some vaccine hesitancy amongst affected individuals.

Methods

Patients initially hospitalised with COVID-19 were prospectively recruited to an observational study with clinical follow-up at 3 months (June-July 2020) and 8 months (Dec 2020-Jan 2021) post-admission. Participants who received the Pfizer-BioNTech (BNT162b2) or Oxford-AstraZeneca (ChAdOx1 nCoV-19) vaccine between January to February 2021 were identified and matched 2:1 (in terms of 8-month symptoms) with participants from the same cohort who were unvaccinated. All were re-assessed at 1 month post vaccination (or matched timepoint for unvaccinated cohort). Validated quality of life (SF-36), mental wellbeing (WEMWBS) and ongoing symptoms were assessed at all timepoints. Formal statistical analysis compared the effect of vaccination on recent quality of life using baseline symptoms, age, and gender in linear regression.

Results

Forty-four vaccinated participants were assessed at a median of 32 days (IQR 20-41) post vaccination with 22 matched unvaccinated participants. Most were highly symptomatic of Long Covid at 8 months (82% in both groups had at least 1 persistent symptom), with fatigue (61%), breathlessness (50%) and insomnia (38%) predominating. There was no significant worsening in quality-of-life or mental wellbeing metrics pre versus post vaccination. Nearly two-thirds (n=27) reported transient (<72hr duration) systemic effects (including fever, myalgia and headache).

When compared to matched unvaccinated participants from the same cohort, those who had receive a vaccine had a small overall improvement in Long Covid symptoms, with a decrease in worsening symptoms (5.6% vaccinated vs 14.2% unvaccinated) and increase in symptom resolution (23.2% vaccinated vs 15.4% unvaccinated) (p=0.035). No difference in response was identified between Pfizer-BioNTech or Oxford-AstraZeneca vaccines.

Conclusions

Receipt of vaccination with either an mRNA or adenoviral vector vaccine was not associated with a worsening of Long Covid symptoms, quality of life, or mental wellbeing. Individuals with prolonged COVID-19 symptoms should receive vaccinations as suggested by national guidance.