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Source: Medical News - SARS-CoV-2 Origins  Aug 31, 2022  26 days ago
BREAKING! Italian And American Scientist Provide Evidence That SARS-CoV-2 Was Already Circulating in Europe As Early As September 2019!
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BREAKING! Italian And American Scientist Provide Evidence That SARS-CoV-2 Was Already Circulating in Europe As Early As September 2019!
Source: Medical News - SARS-CoV-2 Origins  Aug 31, 2022  26 days ago
SARS-CoV-2 Origins: A new study led by researchers from the University of Milan-Italy and the Institute for Genomics and Evolutionary Medicine at Temple University-Philadelphia-USA has found evidence of SARS-CoV-2 in clinical samples in Italy dated as early as September 2019!


 
The study team was evaluating the association between SARS-CoV-2 infection and measles-like syndromes in Lombardy and came across evidence that showed the undetected early circulation of SARS-CoV-2.
 
As a Laboratory for measles and rubella surveillance in Lombardy, the study team received every year oropharyngeal swabs and/or urine from patients who present with morbilliform rash and the team would perform molecular and serological diagnostics to monitor the metropolitan Milan area and its surroundings including other Lombardy provinces, i.e., Brescia, Varese, Como, and Monza-Brianza.
 
In all, 435 clinical samples from 156 patients were investigated. RNA from oropharyngeal swabs (N = 148) and urine (N = 141) was screened with four hemi-nested PCRs.
 
Interestingly, molecular evidence for SARS-CoV-2 infection was found in 13 subjects. Two of the positive patients were from the pandemic period (2/12, 16.7%, March 2020–March 2021) but 11 were from the pre-pandemic period (11/44, 25%, August 2019–February 2020).
 
Sera (N = 146) were tested for anti-SARS-CoV-2 IgG, IgM, and IgA antibodies. Five of the RNA-positive individuals also had detectable anti-SARS-CoV-2 antibodies.
 
No strong evidence of infection was found in samples collected between August 2018 and July 2019 from 100 patients.
 
However, the earliest sample with evidence of SARS-CoV-2 RNA was from September 12, 2019, and the positive patient was also positive for anti-SARS-CoV-2 antibodies (IgG and IgM). Mutations typical of B.1 strains previously reported to have emerged in January 2020 (C3037T, C14408T, and A23403G), were identified in samples collected as early as October 2019 in Lombardy. One of these mutations (C14408T) was also identified among sequences downloaded from public databases that were obtained by others from samples collected in Brazil in November 2019.
 
The SARS-CoV-2 Origins study team concluded that a SARS-CoV-2 progenitor capable of producing a measles-like syndrome may have emerged in late June-late July 2019 and that viruses with mutations characterizing B.1 strain may have been spreading globally before the first Wuhan outbreak.
 
The study findings should be complemented by high-throughput sequencing to obtain additional sequence information.
 
The study team highlighted the importance of retrospective surveillance studies in understanding the early dynamics of COVID-19 spread and they also encourage other groups to perform retrospective investigations to seek confirmatory proofs of early SARS-CoV-2 circulation.
 
The study findings were published in the peer reviewed journal: Environmental Research. https://www.sciencedirect.com/science/article/pii/S0013935122013068
 
While the study initially focused on the association of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with morbi lliform skin rash, it also provided evidence of the early circulation of SARS-CoV-2 in Northern Italy prior to the start of the coronavirus disease 2019 (COVID-19) pandemic.
 
In mid-December 2019, SARS-CoV-2 was first identified in China following reports of hospitalized patients experiencing atypical pneumonia. Soon after, molecular evolutionary experiments revealed that SARS-CoV-2 likely spilled over to humans from a bat reservoir; however, its original spillover mechanism remains debatable.
 
To date, there is the lack of a definitive timeline on when SARS-CoV-2 initially emerged.
 
Past evolutionary studies indicate that the virus likely circulated in China for several months before the first outbreak was recorded in Wuhan, China. Soon after, an increasing number of cases were reported in several European and North American countries by mid-January 2020.
 
Interestingly, Italy was the first European country to report sustained SARS-CoV-2 community transmission. This country subsequently became the epicenter of the epidemic in Europe, with Lombardy being the most affected.
 
However, it should be noted that the SARS-CoV-2 strain that circulated in Lombardy, as well as much of Europe soon after its initial detection in Italy, differed from the Wuhan-Hu-1 strain, which was the reference genome originally identified in China. I
 
Importantly, some of the different mutations present within this strain included A23403G (Spike D614G), C14408T (RdRp P323L), and C3037T (synonymous). This strain, which has since been named B.1 in Pangolin and 20A in NextStrain, is often referred to as the DG1111 haplotype and comprises an αβ mutational signature.
 
Many other studies have suggested that SARS-CoV-2 was circulating in many nations prior to its official detection. In fact, SARS-CoV-2 ribonucleic acid (RNA) has been detected in wastewater samples obtained in Brazil and Northern Italy in 2019. https://www.sciencedirect.com/science/article/pii/S0048969720352402
 
https://www.sciencedirect.com/science/article/pii/S0048969721012651
 
The SARS-CoV-2 virus was also detected in the respiratory samples of a French patient with hemoptysis, the lungs and blood of a patient in Milan who died of acute circulatory insufficiency, and oropharyngeal swabs of a Lombardy child with suspected measles in December 2019.
https://www.sciencedirect.com/science/article/pii/S0924857920301643
 
https://wwwnc.cdc.gov/eid/article/27/2/20-4632_article
 
https://www.frontiersin.org/articles/10.3389/fmicb.2022.886317/full\
 
https://journals.sagepub.com/doi/10.1177/0300891620974755
 
https://www.mdpi.com/1999-4915/14/1/61
 
Interestingly, viral RNA and antigens have also been detected in paraffin-embedded skin biopsies of women in Milan with dermatosis in November 2019.
https://onlinelibrary.wiley.com/doi/10.1111/bjd.19804

The study team noted that a variety of skin manifestations have been reported in patients diagnosed with COVID-19. These manifestations can occur at any stage of the disease.
 
Importantly, besides the variable duration, prognosis, and severity of these dermatological effects, these symptoms can even occur in the absence of the common respiratory symptoms of COVID-19, thus causing diagnosis to be even more challenging.
 
It was also noted that in 2019, suspected measles and rubella cases were two times higher as compared to the average of the previous two years. Moreover, the percentage of suspected cases that tested negative increased from 30% to 70% during the first wave of the pandemic and 100% by 2021.
 
It was this increased incidence of both measles and rubella, combined with the skin manifestations associated with COVID-19 that led the study team to investigate whether COVID-19 could cause morbilliform skin eruptions.
 
The study was conducted by the Network of Italian Reference Laboratories for Measles and Rubella (MoRoNet) and the World Health Organization (WHO)-accredited Subnational Reference Laboratory for measles and rubella surveillance.
 
In all, a total of 435 urine, serum, and oropharyngeal samples were collected from 156 patients tested for SARS-CoV-2.
 
It should be noted that all samples included in the current analysis were negative for both measles and rubella.
 
The clinical samples from 44 cases were collected between August 2019, which coincided with the unexpected increase in suspected measles/rubella cases, as well as late February 2020, which were considered pre-pandemic cases.
 
Also, twelve samples were also collected between March 2020 and March 2021 and were referred to as pandemic cases.
 
Clinical samples collected from 100 cases between August 2018 and July 2019 were used as controls.
 
In all, 289 urine and oropharyngeal samples were analyzed for the presence of SARS-CoV-2 RNA followed by sequence analysis. Sera from 38 pre-pandemic, 98 control, and 10 pandemic cases were analyzed for anti-SARS-CoV-2 immunoglobulin A (IgA), IgM, and IgG.Plaque reduction neutralization assays were used to determine neutralizing antibody titers.
 
Corresponding author Dr Elisabetta Tanzi from the Department of Health Sciences, University of Milan told Thailand Medical News, “The study findings surprisingly showed that positive SARS-CoV-2 infection was identified in 11 pre-pandemic and two pandemic cases. Of these 13 subjects, viral RNA was detected in urine and respiratory samples for six and seven patients, respectively. Notably, viral RNA was detected in the urine of only pandemic cases.”
 
The study team said that of the 11 pre-pandemic samples that tested positive for SARS-CoV-2, nine were collected in 2019. The earliest SARS-CoV-2-positive urine sample was collected on September 12, 2019, from an eight-month-old child who also had detectable serum levels of SARS-CoV-2 IgG and IgM.
 
Importantly, none of the SARS-CoV-2-positive samples were positive when the Real-Time polymerase chain reaction (PCR) diagnostic protocol was used. This indicates that all samples exhibited low viral loads that were less than the detection threshold level.
 
The study team found that four pre-pandemic samples were positive for anti-SARS-CoV-2 antibodies, with IgM most frequently detected. Only one of these serum samples contained partially neutralizing antibodies.
 
On the other side of the findings, neutralizing antibodies were detected in two pandemic samples. However, both of these samples were SARS-CoV-2 RNA-negative!
 
The study findings also showed that twelve samples collected before the first aforementioned SARS-CoV-2-positive sample was collected on September 12, 2019, were positive for IgA, IgM, and IgG.
 
However only four of these samples exhibited partial neutralization.
 
It was also found that early pre-pandemic samples that tested positive for SARS-CoV-2 were mostly localized Brescia and Milan, with most Milanese cases localized in north-western Milan. All pandemic samples were also localized in the province of Milan.
 
Of the 11 pre-pandemic cases, five were collected between October 12, 2019, and October 23, 2019, whereas all pandemic samples were collected during early 2021.
 
It was also found that most of the viral sequences obtained from pre-pandemic samples exhibited several major mutations including C3037T, A23403G, and C14408T that belonged to the β group of mutations. Pre-pandemic SARS-CoV-2 strains are believed to be approximately six mutations away from the SARS-CoV-2 progenitor strain and belong to the αβ lineage, which has produced all major circulating strains to date.
 
The study findings confirm that SARS-CoV-2 was circulating in Northern Italy by late 2019, as confirmed by the presence of SARS-CoV-2 genetic material in several urine and oropharyngeal swab samples. Importantly, none of the samples that tested positive for SARS-CoV-2 were obtained from patients with a history of international travel.
 
The research data also suggest an association between morbilliform eruptions and SARS-CoV-2 infection.
 
More detailed future studies are warranted to better understand the relationship between this type of skin rash and COVID-19.
 
Also, more retrospective studies in areas with early SARS-CoV-2 circulation that utilize metagenomic methods are needed to accurately determine the evolutionary history and time of SARS-CoV-2 emergence.
 
Thailand Medical News would like to add the hypothesis the SARS-CoV-2 could have actually originated from the African continent and spread to Europe as a result of lax border controls. Further more it should also be noted that there were also a lot of Africans travelling to China along with the fact that a lot of illegal wild-life was being smuggled to China from Africa. Detailed research and investigations are warranted from this perspective and to date, none has been done yet strangely! The WHO has also been very evasive about this perspective!
 
The African continent is a hot bed for numerous emerging diseases ranging from Ebola, Marburg, Crimean Hemorrhagic Fever, a new strain of measles, monkeypox and even some of the SARS-CoV-2 variants of concern. The complete lax of border controls and non-banning of travelers from the African continent who have not been properly screened medically will lead to even more global outbreaks of newer diseases.
 
For the latest on SARS-CoV-2 Origins, keep on logging to Thailand Medical News.
 

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