d**********u
发帖数: 1 | | d**********u
发帖数: 1 | 2 居然说2019年9月12日就有新冠病毒了，
难道意大利不应该被美国开除出地球球籍吗？ | d**********u
发帖数: 1 | 3 Evidence of earliest SARS-CoV-2 infections
Although considerable uncertainty around the early phases of the epidemic in
Wuhan remains, the earliest patient with laboratory-confirmed COVID-19
reported in literature developed symptoms on 1 December 2019.8 However,
several literature reports provide clues for virus circulation during that
time and earlier in other parts of the world9 (table 1). In the USA, SARS-
CoV-2 reactive antibodies were detected in over 100 blood samples collected
in several different states in early December 2019.10 In Brazil,
environmental surveillance monitoring demonstrated early SARS-CoV-2
community spread at the end of November 2019 by detecting viral RNA in
wastewater.11 A study performed in the UK identified a few blood donors in
May 2019 whose sera presented SARS-CoV-2 S-reactive antibodies associated
with a presumed current immune response.12 In France, antibodies against
SARS-CoV-2 were found in serum samples collected in November 2019, and viral
RNA was detected in December 2019 in a respiratory sample from a patient
hospitalised for haemoptysis.13 14 However, most of the studies that
investigated and found evidence for early SARS-CoV-2 circulation were
performed in Italy, the first European country reporting sustained community
transmission.
VIEW INLINE VIEW POPUP
Table 1
Considered retrospective studies that found evidence for an early SARS-CoV-2
circulation
The first official and confirmed non-travel-related Italian COVID-19 case
was identified on 20 February 2020, in Codogno, a small town located in
Lombardy, the most populous region of Italy. Italy quickly became the
epicentre of the COVID-19 European epidemic and by March 2020, it surpassed
China in the number of officially reported cases. Within Italy, Lombardy was
the most affected region during the first pandemic wave.1 15–18 During
March–May 2020, Italy registered a 31.7% increase in all-cause deaths
compared with the same period in the quinquennia 2015–2019 (excess deaths
due to all causes), an increase to which the heaviest contributors were the
regions from the north (+61.1%) and especially Lombardy, which experienced
111.8% increase.18 Lombardy was the first area of the Western World to be
severely affected by the pandemic and one of the regions that suffered its
heaviest consequences. These reasons are likely why many research groups
were induced to retrospectively investigate the initial phases of the COVID-
19 outbreak in Italy.
From the very beginning, it was clear that sustained viral spread started in
Lombardy weeks before the first detection of the virus in the Codogno case.
Indeed, the estimated net reproduction number had been above the epidemic
threshold since late January 2020 and contact tracing demonstrated ongoing
transmission throughout January 2020.19 20 A study performed later by the
Italian National Institute of Health demonstrated that the virus was
circulating in Milan (Lombardy) and Turin (Piedmont) by the end of 2019 in
sufficient numbers to allow the detection of viral RNA in sewage water
samples collected on 18 December 2019.21 Finally, several studies performed
independently by different groups demonstrated the presence of antibodies
against SARS-CoV-2 in blood samples since September 201922–24 and of viral
RNA in clinical samples collected from patients with cutaneous
manifestations (dermatosis and measles-like rash) as early as 12 September
2019.24–26
Criticisms and supporting facts
The spread of SARS-CoV-2 outside of China prior to December 2019 directly
contradicts the currently hypothesised timeline of the original viral
emergence in China’s Hubei province around November 20193 27 28 and its
subsequent introduction in Europe and North America in January 2020.29 30
However, sequence-based relaxed molecular clock methods used to date
ancestral nodes in phylogenetic trees are influenced by sequence
availability and temporal signal present in the data. The addition of even a
few early strains, which may have gone undetected at the beginning, can
significantly shift the relative likelihoods of these predictions.24 31 More
recent computational analyses including a very large number of complete
genomes have moved the time of viral emergence to well before the major
Wuhan outbreak, up to the summer of 2019.32–34
Because of these disagreements, laboratory evidence for early circulation is
often dismissed and labelled as a result of false-positive testing.
Antibody detection results can indeed be affected by the presence in sera of
antibodies which, although able to recognise SARS-CoV-2 antigens, were
induced by other agents.12 However, the presence of SARS-CoV-2 neutralising
activity in these sera and the fact that several patients presented more
than one class of antibodies recognising SARS-CoV-2 suggest that, although
some cross-reactivity should be taken into account, at least some of the
sera could contain antibodies induced by a prior SARS-CoV-2 infection.10 12
22–24
Direct evidence for early viral circulation can be obtained by detecting
SARS-CoV-2 RNA. Techniques used for this purpose, especially if accompanied
by sequencing, are more specific and less influenced by previous infections
due to other pathogens. However, PCR-based methods are highly sensitive and,
therefore, more prone to false-positive results. Various methods have been
used to detect SARS-CoV-2 RNA in 2019 samples collected outside of China,
including RNA fluorescence in-situ hybridisation,26 RT-qPCR11 14 21 and
nested-PCR,21 24 25 and most of the results obtained were confirmed by
sequencing.11 21 24 25 Unfortunately, none of these studies could recover
complete genomic sequences needed for phylogenetic and coalescence analyses.
This is likely a problem tracing back to the unsuitability of the available
samples, which did not contain high enough concentrations of high-quality
RNA. Even in clinical samples found to be RNA positive, viral load was low,
implying that only a few viral templates would be available for
amplification. For instance, the positive oropharyngeal and urine samples
were collected within the framework of measles surveillance from patients
who developed a skin rash,24 25 which may appear late during infection, when
respiratory symptoms have been resolved, or even before the onset of other
COVID-19 symptoms,35 36 resulting in low viral loads in swabs collected at
the moment of the rash onset. Interestingly, one study detected multiple
positive patients, some of whom also presented SARS-CoV-2-recognising
antibodies, and observed polymorphisms in viral sequences, a factor that
excludes laboratory contamination by a single positive control sequence.24
Implications of available early circulation evidence
Some studies that retrospectively screened respiratory samples collected
from patients with influenza-like and respiratory symptoms, including those
collected within the framework of influenza surveillance, found no evidence
for SARS-CoV-2 (table 2),37–41 including during times when community SARS-
CoV-2 transmission in respective populations was already occurring.20
Nonetheless, the combination of all knowledge acquired so far from
retrospective studies strongly suggests that SARS-CoV-2 was circulating
outside of China considerably earlier than the currently postulated time
frame of late December 2019/early January 2020, at least in some parts of
the world.
VIEW INLINE VIEW POPUP
Table 2
Considered retrospective studies that found no evidence for an early SARS-
CoV-2 circulation
Good epidemiological insight comes from sewage water testing. For the virus
to be detectable in wastewater, a somewhat sustained virus circulation must
be happening, as demonstrated in a recent publication performing
environmental surveillance in Lombardy.42 Fongaro et al showed that SARS-CoV
-2 load remained temporally constant in the wastewater of Santa Catarina,
Brazil, but increased in March 2020 in concomitance with the surge in COVID-
19 cases.11 Results from La Rosa et al, who detected the virus in the
wastewater of Milan and Turin in December 2019,21 are supported by the
detection of SARS-CoV-2 in clinical samples since September 201924 and by
the subsequent steady increase in COVID-19 cases observed at the beginning
of 2020,20 before the exponential growth in cases became evident. However,
it remains puzzling why the virus was detected in samples collected within
the framework of measles surveillance and not in those available to the
influenza surveillance network. This incongruence could be explained by the
fact that skin manifestations draw more attention than respiratory signs and
are almost always reported, making measles surveillance more sensitive and
comprehensive, while also monitoring a lower and more manageable number of
cases. In fact, mild COVID-19 cases may have been masked by the ongoing
influenza season43 and the high number of respiratory infections common to
this time of the year.
Although the notion of a somewhat sustained but unnoticed viral circulation
may be difficult to accept after so many deaths and so many months of
pandemic viral circulation, this possibility is ‘not astonishing’, as
recently noted by Petti.9 Certainly, the virus had been circulating for some
time before such dramatic excess mortality could have become noticeable and
a low number of COVID-19-related deaths could have gone unnoticed among the
high number of deaths associated with pneumonia of unknown origin that
occur every year. Although currently difficult to establish without
extensive sequencing of early strains, a virus with reduced transmissibility
and/or virulence could explain a slow, undetected diffusion during the
early months of its spread, causing only sporadic cases and/or limited
outbreaks.44 The emergence of more infectious strains occurred several times
during this pandemic,45 and differences in replication dynamics have been
demonstrated in vitro for some early strains.46 However, preliminary
sequencing results suggest that the strain circulating in pre-pandemic
Europe in late 2019 may have been already capable of efficient human-to-
human transmission24 and it has been recently hypothesised that SARS-CoV-2
strains may have acquired adaptive mutations in Europe, while spreading in
parallel with Asian strains.47 Scattered circulation combined with the lack
of awareness may have contributed to a slow and undetected early spread.44
48 49 These are aspects that future studies should investigate by
retrospectively identifying, sequencing and studying in vitro early
circulating strains.
To determine whether SARS-CoV-2 was already spreading outside of China in
2019, it is crucial to broaden our efforts and consider a wider geographical
area and a larger timespan when investigating viral emergence. In
particular, future research should focus on samples where a higher viral
load can be expected and thus that are more suitable for virus detection and
sequencing, that is, on severe cases of patients with pneumonia admitted to
intensive care units.
Scepticism and reluctance to consider the early origin hypothesis
An analysis of the information transmission chain regarding the hypothesis
of early circulation outside China reveals not only a dismissive attitude
towards this hypothesis,50 but also that this hypothesis is linked to other
hypotheses regarding SARS-CoV-2. In other words, accepting the idea that
SARS-CoV-2 or its progenitor(s) might have circulated in many regions of the
world for months before it was discovered in Wuhan challenges several
widely accepted assumptions about this virus. However, it is important to
note that the early origin of SARS-CoV-2 has no bearing on the debate about
the laboratory leak versus natural origin, and it does not exclude the
possibility of its origin in Hubei or somewhere else in China. The
acceptance of the early origin is inconvenient in that we may no longer be
able to use the circumstantial evidence of time and location of the first
detection of SARS-CoV-2 as our final answer.
Despite the increasing documentation available in support of its early
circulation, current scientific literature discussing the origin of SARS-CoV
-2 is almost exclusively focused on the November/December 2019 hypothesis,
completely ignoring this growing body of contradictory evidence. In fact,
the possibility of early circulation is only seldom mentioned or discussed
in such papers. Furthermore, as this alternative hypothesis clearly
contradicts the timeline that is today held as the most likely, when these
studies are cited, it is done dismissively, minimising the results obtained
by numerous independent research groups. This attitude, pervasive among high
-ranking journals, clearly demonstrates scepticism and has the consequence
of avoiding a more critical interpretation of scientific data and of
discouraging a constructive scientific debate that should consider all
available facts when advancing a hypothesis and re-evaluate assumptions in
light of new evidence. Additionally, this bias often results in rejection of
manuscripts in support of an early SARS-CoV-2 circulation, reinforcing the
‘echo chamber’ effect. Science is a quest for ultimate truth, which shall
not be discouraged by such mindset.
Conclusions
Research into the origins of SARS-CoV-2 is a challenging and fraught
undertaking and there is still much that needs to be elucidated. Each study
providing evidence for early circulation of SARS-CoV-2 might look
inconclusive, but combining all data together reveals an emerging pattern.
As all it would take to establish early circulation is a single confirmed
positive case, attributing all results to false positives quickly becomes
probabilistically untenable. Nonetheless, given the critical implications of
these findings, it is important to obtain confirmatory proof for an early
viral spread or lack thereof by independent investigations performed in WHO-
accredited laboratories, as already occurred in one instance.23 Rescreening
with more standardised and sensitive methods will provide confirmation for
studies that found evidence for an early circulation and for those that did
not. This aspect is crucial especially in those geographical areas affected
during the first wave and where the lack of early viral detection is in
obvious conflict with overwhelming epidemiological evidence. Additional
approaches—such as metagenomic sequencing—could also be used to obtain
more sequence information, which is essential for dating the beginning of
viral spread more accurately. Finally, a more systematic approach to
retrospectively test for anti-SARS-CoV-2 antibodies in numerous serum
samples collected from a broad area could allow the identification of
seroprevalence peaks that would help filter out potential background noise
caused by cross-reactivity. International public health authorities should
ideally coordinate such studies.
SARS-CoV-2 has cost the world the lives of millions of people, and the next
(inevitable) pandemic might have more devastating outcomes. To be better
prepared in the future and timely identify the emergence of novel pathogens,
it is crucial to fully understand this pandemic and learn from our
successes and our failures. Despite the technical limitations of available
early origin studies, even a remote possibility that positive tests indicate
an early SARS-CoV-2 circulation should be considered sufficient to warrant
the scaling up of research to more samples from more regions and through a
wider timespan. Time is running out: valuable samples that may contain the
key to the understanding of SARS-CoV-2 origin might already have been
destroyed as their regulatory storage time requirements lapse. Many more
will meet the same fate in the coming months and years. What is there to
lose in accepting this hypothesis as tenable and exploring it urgently
before the chances of finding the answers to explain how this pandemic
emerged are gone forever? | p*a
发帖数: 7676 | 4 中国人花钱买的。全世界都知道。根本不符合事实和逻辑的宣传品而已。除了中国人，
没人把它当真。 | d**********u
发帖数: 1 | 5 你帮中国人出的钱吗？
丢不起那人。
WHO重复检测过了，难道也是中国买通了WHO的检测专家？
【在 p*a 的大作中提到】
: 中国人花钱买的。全世界都知道。根本不符合事实和逻辑的宣传品而已。除了中国人，
: 没人把它当真。
| d**********u
发帖数: 1 | 6 Waiting for the truth，这是人意大利科学家的呼吁！ | r*******j
发帖数: 2445 | 7 预印本啥意思，你搞明白了吗？
【在 d**********u 的大作中提到】
: https://gh.bmj.com/content/7/3/e008386
| d**********u
发帖数: 1 | 8 你读过phD吗？
我只是说预印本还注明杂志名，就是正式出版。
只有预印本没杂志名，那就是单纯的预印本。
【在 r*******j 的大作中提到】
: 预印本啥意思，你搞明白了吗？
| p********2
发帖数: 1 | | d**********u
发帖数: 1 | 10 丘成桐的弟弟写了篇Springer的文章，说数学模型推出来新冠是印度或者美国起源。
我一直都下不到正式的文献的免费预印本，因为那个正式pdf下载要$29.95,
我可没钱下载那个文章。 | d**********u
发帖数: 1 | 11
赶快去扰骚这帮不要脸的帮中国脱罪的大力科研人员。他们有留Email，赶快去电邮轰
炸。
https://orcid.org/0000-0002-9959-128XMarta Canuti1, https://orcid.org/0000-
0002-1365-9408Silvia Bianchi1,2, Otto Kolbl3, https://orcid.org/0000-0003-
4817-4029Sergei L Kosakovsky Pond4,5, https://orcid.org/0000-0002-9918-
8212Sudhir Kumar4,5,6, https://orcid.org/0000-0001-6478-2791Maria Gori1,2,
https://orcid.org/0000-0002-1573-5531Clara Fappani1,2, https://orcid.org/
0000-0002-4079-1957Daniela Colzani1,2, https://orcid.org/0000-0002-1893-
0455Elisa Borghi1,2, https://orcid.org/0000-0002-2795-9874Gianvincenzo
Zuccotti7,8, https://orcid.org/0000-0002-9331-2067Mario C Raviglione9, https
0002-0499-8977Antonella Amendola1,2
Correspondence to Dr Marta Canuti; [email protected]; Dr Silvia Bianchi
; [email protected]; Professor Antonella Amendola; [email protected]
unimi.it
【在 p********2 的大作中提到】
: 瑞士爱德华写的？
| S*******l
发帖数: 4637 | | r*******j
发帖数: 2445 | 13 预印本（Preprint）也称未定稿本。在学术出版领域，预印本是指尚未在需要同行评审
的科学期刊上出版的科学文献的草稿。
作者在写作完成后，可能在出版之前将草稿预先公开让大家阅读并提出更改建议，并在
稍后提交学术期刊进行出版。学术期刊一般会让选定的业内人士对投稿的文章做同行评
审后才发表，但是某些杂志机构也会将未经专家评审的未定稿本发表在该杂志／机构的
网站上。
【在 d**********u 的大作中提到】
: 你读过phD吗？
: 我只是说预印本还注明杂志名，就是正式出版。
: 只有预印本没杂志名，那就是单纯的预印本。
| r*******j
发帖数: 2445 | 14 https://www.nature.com/articles/d41586-022-00584-8
Wuhan market was epicentre of pandemic’s start, studies suggest
Report authors say that the coronavirus SARS-CoV-2 jumped to people from
animals sold at the market on two occasions in late 2019 — but some
scientists want more definitive evidence.
The Wuhan Hygiene Emergency Response Team leave the closed Huanan Seafood
Wholesale Market in Wuhan, China, on January 11, 2020.
Scientists have released three studies that reveal intriguing new clues
about how the COVID-19 pandemic started. Two of the reports trace the
outbreak back to a massive market that sold live animals, among other goods,
in Wuhan, China1,2, and a third suggests that the coronavirus SARS-CoV-2
spilled over from animals — possibly those sold at the market — to humans
at least twice in November or December 20193. Posted on 25 and 26 February,
all three are preprints, and so have not been published in a peer-reviewed
journal. | d**********u
发帖数: 1 | 15 在美国，2019 年 12 月上旬在几个不同州采集的 100 多份血液样本中检测到 SARS-
CoV-2 反应性抗体。
在巴西，环境监测监测显示，2019 年 11 月末，通过检测废水中的病毒 RNA。
在英国进行的一项研究在 2019 年 5 月确定了一些献血者，他们的血清呈现出与假定
的当前免疫反应相关的 SARS-CoV-2 S 反应性抗体。
在法国，针对 SARS-CoV- 2 在 2019 年 11 月采集的血清样本中发现，2019 年 12 月
在一名因咯血住院的患者的呼吸道样本中检测到病毒 RNA。
然而，大多数调查并发现早期 SARS-CoV-2 传播的证据 研究是在意大利进行，这是第
一个报告持续社区传播的欧洲国家。
英国2019 年 5 月血清样本，呵呵，看起来美国的2019年5月“麻疹”邮轮跑不掉了。
http://www.nytimes.com/2019/05/02/world/americas/measles-scientology-cruise-ship.html
扭腰时报 | r*******j
发帖数: 2445 | 16 然而世卫要求继续调查武汉
【在 d**********u 的大作中提到】
: 在美国，2019 年 12 月上旬在几个不同州采集的 100 多份血液样本中检测到 SARS-
: CoV-2 反应性抗体。
: 在巴西，环境监测监测显示，2019 年 11 月末，通过检测废水中的病毒 RNA。
: 在英国进行的一项研究在 2019 年 5 月确定了一些献血者，他们的血清呈现出与假定
: 的当前免疫反应相关的 SARS-CoV-2 S 反应性抗体。
: 在法国，针对 SARS-CoV- 2 在 2019 年 11 月采集的血清样本中发现，2019 年 12 月
: 在一名因咯血住院的患者的呼吸道样本中检测到病毒 RNA。
: 然而，大多数调查并发现早期 SARS-CoV-2 传播的证据 研究是在意大利进行，这是第
: 一个报告持续社区传播的欧洲国家。
: 英国2019 年 5 月血清样本，呵呵，看起来美国的2019年5月“麻疹”邮轮跑不掉了。
| d**********u
发帖数: 1 | 17 派兵来啊，你们国军不反攻大陆了吗？
你们中华民国在WHO没代表权吗？
【在 r*******j 的大作中提到】
: 然而世卫要求继续调查武汉
| r*******j
发帖数: 2445 | 18 然而武汉已经配合过世卫调查了
【在 d**********u 的大作中提到】
: 派兵来啊，你们国军不反攻大陆了吗？
: 你们中华民国在WHO没代表权吗？
| d**********u
发帖数: 1 | 19 哦，原来武汉P4已经接受调查并证明清白了呀。
那你还唧唧歪歪个啥？
拿蔡英文的钱，发贴，只是讨个生活对不对？理解，明白！
所以，我也没断你的财路。
【在 r*******j 的大作中提到】
: 然而武汉已经配合过世卫调查了
| r*******j
发帖数: 2445 | 20 然而世卫要求继续调查武汉
【在 d**********u 的大作中提到】
: 哦，原来武汉P4已经接受调查并证明清白了呀。
: 那你还唧唧歪歪个啥？
: 拿蔡英文的钱，发贴，只是讨个生活对不对？理解，明白！
: 所以，我也没断你的财路。
| d**********u
发帖数: 1 | 21 这是支持自然起源的。
自然起源能给“美国实验室制造并泄露”解套。
goods,
【在 r*******j 的大作中提到】
: https://www.nature.com/articles/d41586-022-00584-8
: Wuhan market was epicentre of pandemic’s start, studies suggest
: Report authors say that the coronavirus SARS-CoV-2 jumped to people from
: animals sold at the market on two occasions in late 2019 — but some
: scientists want more definitive evidence.
: The Wuhan Hygiene Emergency Response Team leave the closed Huanan Seafood
: Wholesale Market in Wuhan, China, on January 11, 2020.
: Scientists have released three studies that reveal intriguing new clues
: about how the COVID-19 pandemic started. Two of the reports trace the
: outbreak back to a massive market that sold live animals, among other goods,
| r*******j
发帖数: 2445 | 22 即使自然起源，也得从武汉查起。中国拒绝世卫调查武汉，就是做贼心虚。
：这是支持自然起源的。
：自然起源能给“美国实验室制造并泄露”解套。 | d**********u
发帖数: 1 | 23
强词夺理。
美国从全球抓蝙蝠，提取了10万毒株。
没准新冠就是10万里面的其中一个。
所以，即便是自然起源，也得从美国查起。美国拒绝调查，还特么WHO退群，就是做贼
心虚。
【在 r*******j 的大作中提到】
: 即使自然起源，也得从武汉查起。中国拒绝世卫调查武汉，就是做贼心虚。
:
: ：这是支持自然起源的。
: ：自然起源能给“美国实验室制造并泄露”解套。
| r*******j
发帖数: 2445 | 24 武汉是全世界有目共睹首先单点爆发。
世卫是唯一有调查权的。世卫提出要调查武汉。世卫从没说过要查美国。
世卫27人科学家小组三分之二都是中俄亚非拉，这个科学家小组最新报告也建议调查武
汉，压根没提美国。
五毛再怎么打滚，世界人民心里还是清楚的 还是像苏联老老实实承认切尔诺贝利核泄
漏是人祸那样老实接受世卫调查为好。
：
：【 在 ridgwaymj (ridgwaymj) 的大作中提到: 】 | C*********g
发帖数: 1 | 25 接受调查了没错，因为不配合，世卫要求中国配合并重新调查。证明清白了屁，欲盖弥
彰才是
【在 d**********u 的大作中提到】
: 哦，原来武汉P4已经接受调查并证明清白了呀。
: 那你还唧唧歪歪个啥？
: 拿蔡英文的钱，发贴，只是讨个生活对不对？理解，明白！
: 所以，我也没断你的财路。
|
|
