Scientific assessment of origins of coronaviruses

[LeGenD]

LEGEND

SARS-CoV-2 = COVID-19 outbreak

In view of following revelations:-

Most NYC Covid-19 Cases Came From Europe, Genome Researchers Say

Read more: https://www.bloomberg.com/news/arti...cases-came-from-europe-genome-researchers-say

The hunt for patient zero: Where did the coronavirus outbreak start?

Read more: https://www.newscientist.com/articl...the-coronavirus-outbreak-start/#ixzz6J7vZ8Df9

- I decided to review ongoing scientific work, and I have some observations to share.

Scientific research have narrowed down to horseshoe bats as being chief carriers and transmitters of coronaviruses worldwide, and coronaviruses have recombinogenic properties which are not apparent in other types of viruses:

Evolutionary origins of the SARS‐CoV‐2 sarbecovirus lineage responsible for the COVID-19 pandemic

Abstract

There are outstanding evolutionary questions on the recent emergence of coronavirus SARS-CoV-2/hCoV-19 in Hubei province that caused the COVID-19 pandemic, including (1) the relationship of the new virus to the SARS-related coronaviruses, (2) the role of bats as a reservoir species, (3) the potential role of other mammals in the emergence event, and (4) the role of recombination in viral emergence. Here, we address these questions and find that the sarbecoviruses – the viral subgenus responsible for the emergence of SARS-CoV and SARS-CoV-2 – exhibit frequent recombination, but the SARS-CoV-2 lineage itself is not a recombinant of any viruses detected to date. In order to employ phylogenetic methods to date the divergence events between SARS-CoV-2 and the bat sarbecovirus reservoir, recombinant regions of a 68-genome sarbecovirus alignment were removed with three independent methods. Bayesian evolutionary rate and divergence date estimates were consistent for all three recombination-free alignments and robust to two different prior specifications based on HCoV-OC43 and MERS-CoV evolutionary rates. Divergence dates between SARS-CoV-2 and the bat sarbecovirus reservoir were estimated as 1948 (95% HPD: 1879-1999), 1969 (95% HPD: 1930-2000), and 1982 (95% HPD: 1948-2009). Despite intensified characterization of sarbecoviruses since SARS, the lineage giving rise to SARS-CoV-2 has been circulating unnoticed for decades in bats and been transmitted to other hosts such as pangolins. The occurrence of a third significant coronavirus emergence in 17 years together with the high prevalence and virus diversity in bats implies that these viruses are likely to cross species boundaries again.

In Brief

The Betacoronavirus SARS-CoV-2 is a member of the sarbecovirus subgenus which shows frequent recombination in its evolutionary history. We characterize the extent of this genetic exchange and identify non-recombining regions of the sarbecovirus genome using three independent methods to remove the effects of recombination. Using these non-recombining genome regions and prior information on coronavirus evolutionary rates, we obtain estimates from three approaches that the most likely divergence date of SARS-CoV-2 from its most closely related available bat sequences ranges from 1948 to 1982.

Key Points

• RaTG13 is the closest available bat virus to SARS-CoV-2; a sub-lineage of these bat viruses is able to infect humans. Two sister lineages of the RaTG13/SARS-CoV-2 lineage infect Malayan pangolins.
  
  
• The sarbecoviruses show a pattern of deep recombination events, indicating that there are high levels of co-infection in horseshoe bats and that the viral pool can generate novel allele combinations and substantial genetic diversity; the sarbecoviruses are efficient ‘explorers’ of phenotype space.
  
  
• The SARS-CoV-2 lineage is not a recent recombinant, at least not involving any of the bat or pangolin viruses sampled to date.
  
  
• Non-recombinant regions of the sarbecoviruses can be identified, allowing for phylogenetic inference and dating to be performed. We constructed three such regions using different methods.
  
  
• We estimate that RaTG13 and SARS-CoV-2 diverged 40 to 70 years ago. There is a diverse unsampled reservoir of generalist viruses established in horseshoe bats.
  
  
• While an intermediate host responsible for the zoonotic event cannot be ruled out, the relevant evolution for spillover to humans very likely occurred in horseshoe bats.

Full read in the following link: https://www.biorxiv.org/content/biorxiv/early/2020/03/31/2020.03.30.015008.full.pdf (PDF format)

The aforementioned findings motivate a look at the global distribution of horseshoe bats and genome sequences:

(1)

Figure 1. Maximum-likelihood phylogeny based on the complete genome sequences of 17 bat CoV species released by ICTV in 2018. A general time-reversible model of nucleotide substitution with estimated base frequencies, the proportion of invariant sites, and the γ distribution of rates across sites were used in the maximum-likelihood analysis. Bootstrap values are shown next to the branches. The scale bar indicates the number of nucleotide substitutions per site. Different colors represent different genera. Red, Alphacoronavirus; blue, Betacoronavirus. Updated subgenera clusters are labelled Setracovirus, Myotacovirus, Rhinacovirus, Colacovirus, Pedacovirus, Decacovirus, Minunacovirus, Nyctacovirus for the Alphacoronavirus and Nobecovirus, Hibecovirus, Sarbecovirus, Merbecovirus for the Betacoronavirus.

(2)

Figure 2. Geographical distribution of bat CoVs from the genera Alphacoronavirus and Betacoronavirus. Each colored region represents the country which reported the discovery of bat CoV. Red regions represent the countries which discovered bat Alphacoornavirus. Green regions represent the countries which discovered bat Betacoronavirus. Red-green striped regions represent the countries which discovered both bat Alphacoronavirus and Betacoronavirus.

(3)

Figure 3. Pie chart showing the relative detection rate of different bat CoVs from different subgenera of Alphacoronavirus and Betacoronavirus in Hong Kong from 2008 to 2017. The potential zoonotic transmission routes of each sub-genus of bat CoV detected are shown. Unclassified Alphacoronavirus represents those without complete genome sequences or genome characterization. Red color represents the sub-genera from Alphacoronavirus; Blue color represents the sub-genera from Betacoronavirus.

(4)

Figure 4. Geographical distribution of different horseshoe bats which were discovered to carry SARS-like BatCoV [114,115,116,117,118,119,120,121,122,123,124,125]. Each colored rectangular box represents the geographical distribution of a specific horseshoe bat species respectively: red box, Rhinolophus affinis; orange box, Rhinolophus blasii; yellow box, Rhinolophus euryale; green box, Rhinolophus ferrumequinum; turquoise box, Rhinolophus hildebrantii; indigo box, Rhinolophus hipposideros; purple box, Rhinolophus macrotis; brown box, Rhinolophus mehelyi; pink box, Rhinolophus pearsonii; gold box, Rhinolophus pusillus; blue-gray box, Rhinolophus rex; black box, Rhinolophus sinicus; lime box, Rhinolophus thomasi. Orange circle represents Yunnan Province; Red circle represents the origin of SARS & SADS outbreaks.

(5)

Figure 5. Geographical distribution of bat CoVs from the genus Betacoronavirus. Each colored region represents the country which reported the discovery of bat CoV from different sub-genera. Navy-blue regions represent the countries which discovered bat CoVs from Sarbecovirus. Yellow regions represent the countries which discovered bat CoVs from Merbecovirus. Purple regions represent the countries which discovered bat CoVs from Nobecovirus.

Aforementioned images (1)(2)(3)(4)(5) taken from the following study:

Global Epidemiology of Bat Coronaviruses

Abstract

Bats are a unique group of mammals of the order Chiroptera. They are highly diversified and are the group of mammals with the second largest number of species. Such highly diversified cell types and receptors facilitate them to be potential hosts of a large variety of viruses. Bats are the only group of mammals capable of sustained flight, which enables them to disseminate the viruses they harbor and enhance the chance of interspecies transmission. This article aims at reviewing the various aspects of the global epidemiology of bat coronaviruses (CoVs). Before the SARS epidemic, bats were not known to be hosts for CoVs. In the last 15 years, bats have been found to be hosts of >30 CoVs with complete genomes sequenced, and many more if those without genome sequences are included. Among the four CoV genera, only alphaCoVs and betaCoVs have been found in bats. As a whole, both alphaCoVs and betaCoVs have been detected from bats in Asia, Europe, Africa, North and South America and Australasia; but alphaCoVs seem to be more widespread than betaCoVs, and their detection rate is also higher. For betaCoVs, only those from subgenera Sarbecovirus, Merbecovirus, Nobecovirus and Hibecovirus have been detected in bats. Most notably, horseshoe bats are the reservoir of SARS-CoV, and several betaCoVs from subgenus Merbecovirus are closely related to MERS-CoV. In addition to the interactions among various bat species themselves, bat–animal and bat–human interactions, such as the presence of live bats in wildlife wet markets and restaurants in Southern China, are important for interspecies transmission of CoVs and may lead to devastating global outbreaks.

Full read in the following link: https://www.mdpi.com/1999-4915/11/2/174

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In light of the above, it make sense to retrace PATIENT ZERO in every country: https://www.weforum.org/agenda/2020/03/coronavirus-covid-19-patient-zero/

This information is useful to those who are looking forward to help combating COVID-19 outbreak and/or already involved in any capacity, and will also help quell affiliated conspiracy theories floating around in this forum and elsewhere. At minimum, this information will contribute to knowledge of people.

Regards and take care.

 

[Grandy]

Covid-19 was modifield DNA/RNA from natural virus.
Globalist mindset (deep-state) who make it happen want something else.

 

[LeGenD]

Covid-19 was modifield DNA/RNA from natural virus.
Globalist mindset (deep-state) who make it happen want something else.

That is a YouTube Masala hypothesis.

Scientific assessment (extensive genome analysis of SARS-CoV-2) refuted that hypothesis.

The proximal origin of SARS-CoV-2

Abstract

Since the first reports of novel pneumonia (COVID-19) in Wuhan, Hubei province, China^1,2, there has been considerable discussion on the origin of the causative virus, SARS-CoV-23 (also referred to as HCoV-19)^4. Infections with SARS-CoV-2 are now widespread, and as of 11 March 2020, 121,564 cases have been confirmed in more than 110 countries, with 4,373 deaths^5.

SARS-CoV-2 is the seventh coronavirus known to infect humans; SARS-CoV, MERS-CoV and SARS-CoV-2 can cause severe disease, whereas HKU1, NL63, OC43 and 229E are associated with mild symptoms^6. Here we review what can be deduced about the origin of SARS-CoV-2 from comparative analysis of genomic data. We offer a perspective on the notable features of the SARS-CoV-2 genome and discuss scenarios by which they could have arisen. Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus.

Notable features of the SARS-CoV-2 genome
Our comparison of alpha- and betacoronaviruses identifies two notable genomic features of SARS-CoV-2: (i) on the basis of structural studies^7,8,9 and biochemical experiments^1,9,10, SARS-CoV-2 appears to be optimized for binding to the human receptor ACE2; and (ii) the spike protein of SARS-CoV-2 has a functional polybasic (furin) cleavage site at the S1–S2 boundary through the insertion of 12 nucleotides^8, which additionally led to the predicted acquisition of three O-linked glycans around the site.

1. Mutations in the receptor-binding domain of SARS-CoV-2
The receptor-binding domain (RBD) in the spike protein is the most variable part of the coronavirus genome^1,2. Six RBD amino acids have been shown to be critical for binding to ACE2 receptors and for determining the host range of SARS-CoV-like viruses^7. With coordinates based on SARS-CoV, they are Y442, L472, N479, D480, T487 and Y4911, which correspond to L455, F486, Q493, S494, N501 and Y505 in SARS-CoV-27. Five of these six residues differ between SARS-CoV-2 and SARS-CoV (Fig. 1a). On the basis of structural studies^7,8,9 and biochemical experiments^1,9,10, SARS-CoV-2 seems to have an RBD that binds with high affinity to ACE2 from humans, ferrets, cats and other species with high receptor homology^7.

Fig. 1: Features of the spike protein in human SARS-CoV-2 and related coronaviruses.

a, Mutations in contact residues of the SARS-CoV-2 spike protein. The spike protein of SARS-CoV-2 (red bar at top) was aligned against the most closely related SARS-CoV-like coronaviruses and SARS-CoV itself. Key residues in the spike protein that make contact to the ACE2 receptor are marked with blue boxes in both SARS-CoV-2 and related viruses, including SARS-CoV (Urbani strain). b, Acquisition of polybasic cleavage site and O-linked glycans. Both the polybasic cleavage site and the three adjacent predicted O-linked glycans are unique to SARS-CoV-2 and were not previously seen in lineage B betacoronaviruses. Sequences shown are from NCBI GenBank, accession codes MN908947, MN996532, AY278741, KY417146 and MK211376. The pangolin coronavirus sequences are a consensus generated from SRR10168377 and SRR10168378 (NCBI BioProject PRJNA573298)^29,30.

While the analyses above suggest that SARS-CoV-2 may bind human ACE2 with high affinity, computational analyses predict that the interaction is not ideal7 and that the RBD sequence is different from those shown in SARS-CoV to be optimal for receptor binding^7,11. Thus, the high-affinity binding of the SARS-CoV-2 spike protein to human ACE2 is most likely the result of natural selection on a human or human-like ACE2 that permits another optimal binding solution to arise. This is strong evidence that SARS-CoV-2 is not the product of purposeful manipulation.

2. Polybasic furin cleavage site and O-linked glycans
The second notable feature of SARS-CoV-2 is a polybasic cleavage site (RRAR) at the junction of S1 and S2, the two subunits of the spike8 (Fig. 1b). This allows effective cleavage by furin and other proteases and has a role in determining viral infectivity and host range^12. In addition, a leading proline is also inserted at this site in SARS-CoV-2; thus, the inserted sequence is PRRA (Fig. 1b). The turn created by the proline is predicted to result in the addition of O-linked glycans to S673, T678 and S686, which flank the cleavage site and are unique to SARS-CoV-2 (Fig. 1b). Polybasic cleavage sites have not been observed in related ‘lineage B’ betacoronaviruses, although other human betacoronaviruses, including HKU1 (lineage A), have those sites and predicted O-linked glycans^13. Given the level of genetic variation in the spike, it is likely that SARS-CoV-2-like viruses with partial or full polybasic cleavage sites will be discovered in other species.

The functional consequence of the polybasic cleavage site in SARS-CoV-2 is unknown, and it will be important to determine its impact on transmissibility and pathogenesis in animal models. Experiments with SARS-CoV have shown that insertion of a furin cleavage site at the S1–S2 junction enhances cell–cell fusion without affecting viral entry^14. In addition, efficient cleavage of the MERS-CoV spike enables MERS-like coronaviruses from bats to infect human cells15. In avian influenza viruses, rapid replication and transmission in highly dense chicken populations selects for the acquisition of polybasic cleavage sites in the hemagglutinin (HA) protein^16, which serves a function similar to that of the coronavirus spike protein. Acquisition of polybasic cleavage sites in HA, by insertion or recombination, converts low-pathogenicity avian influenza viruses into highly pathogenic forms^16. The acquisition of polybasic cleavage sites by HA has also been observed after repeated passage in cell culture or through animals^17.

The function of the predicted O-linked glycans is unclear, but they could create a ‘mucin-like domain’ that shields epitopes or key residues on the SARS-CoV-2 spike protein^18. Several viruses utilize mucin-like domains as glycan shields involved immunoevasion^18. Although prediction of O-linked glycosylation is robust, experimental studies are needed to determine if these sites are used in SARS-CoV-2.

Theories of SARS-CoV-2 origins
It is improbable that SARS-CoV-2 emerged through laboratory manipulation of a related SARS-CoV-like coronavirus. As noted above, the RBD of SARS-CoV-2 is optimized for binding to human ACE2 with an efficient solution different from those previously predicted^7,11. Furthermore, if genetic manipulation had been performed, one of the several reverse-genetic systems available for betacoronaviruses would probably have been used^19. However, the genetic data irrefutably show that SARS-CoV-2 is not derived from any previously used virus backbone^20. Instead, we propose two scenarios that can plausibly explain the origin of SARS-CoV-2: (i) natural selection in an animal host before zoonotic transfer; and (ii) natural selection in humans following zoonotic transfer. We also discuss whether selection during passage could have given rise to SARS-CoV-2.

1. Natural selection in an animal host before zoonotic transfer
As many early cases of COVID-19 were linked to the Huanan market in Wuhan^1,2, it is possible that an animal source was present at this location. Given the similarity of SARS-CoV-2 to bat SARS-CoV-like coronaviruses^2, it is likely that bats serve as reservoir hosts for its progenitor. Although RaTG13, sampled from a Rhinolophus affinis bat1, is ~96% identical overall to SARS-CoV-2, its spike diverges in the RBD, which suggests that it may not bind efficiently to human ACE27 (Fig. 1a).

Malayan pangolins (Manis javanica) illegally imported into Guangdong province contain coronaviruses similar to SARS-CoV-221. Although the RaTG13 bat virus remains the closest to SARS-CoV-2 across the genome1, some pangolin coronaviruses exhibit strong similarity to SARS-CoV-2 in the RBD, including all six key RBD residues21 (Fig. 1). This clearly shows that the SARS-CoV-2 spike protein optimized for binding to human-like ACE2 is the result of natural selection.

Neither the bat betacoronaviruses nor the pangolin betacoronaviruses sampled thus far have polybasic cleavage sites. Although no animal coronavirus has been identified that is sufficiently similar to have served as the direct progenitor of SARS-CoV-2, the diversity of coronaviruses in bats and other species is massively undersampled. Mutations, insertions and deletions can occur near the S1–S2 junction of coronaviruses^22, which shows that the polybasic cleavage site can arise by a natural evolutionary process. For a precursor virus to acquire both the polybasic cleavage site and mutations in the spike protein suitable for binding to human ACE2, an animal host would probably have to have a high population density (to allow natural selection to proceed efficiently) and an ACE2-encoding gene that is similar to the human ortholog.

2. Natural selection in humans following zoonotic transfer
It is possible that a progenitor of SARS-CoV-2 jumped into humans, acquiring the genomic features described above through adaptation during undetected human-to-human transmission. Once acquired, these adaptations would enable the pandemic to take off and produce a sufficiently large cluster of cases to trigger the surveillance system that detected it^1,2.

All SARS-CoV-2 genomes sequenced so far have the genomic features described above and are thus derived from a common ancestor that had them too. The presence in pangolins of an RBD very similar to that of SARS-CoV-2 means that we can infer this was also probably in the virus that jumped to humans. This leaves the insertion of polybasic cleavage site to occur during human-to-human transmission.

Estimates of the timing of the most recent common ancestor of SARS-CoV-2 made with current sequence data point to emergence of the virus in late November 2019 to early December 201923, compatible with the earliest retrospectively confirmed cases24. Hence, this scenario presumes a period of unrecognized transmission in humans between the initial zoonotic event and the acquisition of the polybasic cleavage site. Sufficient opportunity could have arisen if there had been many prior zoonotic events that produced short chains of human-to-human transmission over an extended period. This is essentially the situation for MERS-CoV, for which all human cases are the result of repeated jumps of the virus from dromedary camels, producing single infections or short transmission chains that eventually resolve, with no adaptation to sustained transmission^25.

Studies of banked human samples could provide information on whether such cryptic spread has occurred. Retrospective serological studies could also be informative, and a few such studies have been conducted showing low-level exposures to SARS-CoV-like coronaviruses in certain areas of China^26. Critically, however, these studies could not have distinguished whether exposures were due to prior infections with SARS-CoV, SARS-CoV-2 or other SARS-CoV-like coronaviruses. Further serological studies should be conducted to determine the extent of prior human exposure to SARS-CoV-2.

3. Selection during passage
Basic research involving passage of bat SARS-CoV-like coronaviruses in cell culture and/or animal models has been ongoing for many years in biosafety level 2 laboratories across the world^27, and there are documented instances of laboratory escapes of SARS-CoV^28. We must therefore examine the possibility of an inadvertent laboratory release of SARS-CoV-2.

In theory, it is possible that SARS-CoV-2 acquired RBD mutations (Fig. 1a) during adaptation to passage in cell culture, as has been observed in studies of SARS-CoV^11. The finding of SARS-CoV-like coronaviruses from pangolins with nearly identical RBDs, however, provides a much stronger and more parsimonious explanation of how SARS-CoV-2 acquired these via recombination or mutation^19.

The acquisition of both the polybasic cleavage site and predicted O-linked glycans also argues against culture-based scenarios. New polybasic cleavage sites have been observed only after prolonged passage of low-pathogenicity avian influenza virus in vitro or in vivo^17. Furthermore, a hypothetical generation of SARS-CoV-2 by cell culture or animal passage would have required prior isolation of a progenitor virus with very high genetic similarity, which has not been described. Subsequent generation of a polybasic cleavage site would have then required repeated passage in cell culture or animals with ACE2 receptors similar to those of humans, but such work has also not previously been described. Finally, the generation of the predicted O-linked glycans is also unlikely to have occurred due to cell-culture passage, as such features suggest the involvement of an immune system^18.

Conclusions
In the midst of the global COVID-19 public-health emergency, it is reasonable to wonder why the origins of the pandemic matter. Detailed understanding of how an animal virus jumped species boundaries to infect humans so productively will help in the prevention of future zoonotic events. For example, if SARS-CoV-2 pre-adapted in another animal species, then there is the risk of future re-emergence events. In contrast, if the adaptive process occurred in humans, then even if repeated zoonotic transfers occur, they are unlikely to take off without the same series of mutations. In addition, identifying the closest viral relatives of SARS-CoV-2 circulating in animals will greatly assist studies of viral function. Indeed, the availability of the RaTG13 bat sequence helped reveal key RBD mutations and the polybasic cleavage site.

The genomic features described here may explain in part the infectiousness and transmissibility of SARS-CoV-2 in humans. Although the evidence shows that SARS-CoV-2 is not a purposefully manipulated virus, it is currently impossible to prove or disprove the other theories of its origin described here. However, since we observed all notable SARS-CoV-2 features, including the optimized RBD and polybasic cleavage site, in related coronaviruses in nature, we do not believe that any type of laboratory-based scenario is plausible.

More scientific data could swing the balance of evidence to favor one hypothesis over another. Obtaining related viral sequences from animal sources would be the most definitive way of revealing viral origins. For example, a future observation of an intermediate or fully formed polybasic cleavage site in a SARS-CoV-2-like virus from animals would lend even further support to the natural-selection hypotheses. It would also be helpful to obtain more genetic and functional data about SARS-CoV-2, including animal studies. The identification of a potential intermediate host of SARS-CoV-2, as well as sequencing of the virus from very early cases, would similarly be highly informative. Irrespective of the exact mechanisms by which SARS-CoV-2 originated via natural selection, the ongoing surveillance of pneumonia in humans and other animals is clearly of utmost importance.

LINK: https://www.nature.com/articles/s41591-020-0820-9#Fig1

NATURAL factors in the works...

 

[Ahmet Pasha]

Thought u were done with PDF??

LEGEND

SARS-CoV-2 = COVID-19 outbreak

In view of following revelations:-

Most NYC Covid-19 Cases Came From Europe, Genome Researchers Say

Read more: https://www.bloomberg.com/news/arti...cases-came-from-europe-genome-researchers-say

The hunt for patient zero: Where did the coronavirus outbreak start?

Read more: https://www.newscientist.com/articl...the-coronavirus-outbreak-start/#ixzz6J7vZ8Df9

- I decided to review ongoing scientific work, and I have some observations to share.

Scientific research have narrowed down to horseshoe bats as being chief carriers and transmitters of coronaviruses worldwide, and coronaviruses have recombinogenic properties which are not apparent in other types of viruses:

Evolutionary origins of the SARS‐CoV‐2 sarbecovirus lineage responsible for the COVID-19 pandemic

Abstract

There are outstanding evolutionary questions on the recent emergence of coronavirus SARS-CoV-2/hCoV-19 in Hubei province that caused the COVID-19 pandemic, including (1) the relationship of the new virus to the SARS-related coronaviruses, (2) the role of bats as a reservoir species, (3) the potential role of other mammals in the emergence event, and (4) the role of recombination in viral emergence. Here, we address these questions and find that the sarbecoviruses – the viral subgenus responsible for the emergence of SARS-CoV and SARS-CoV-2 – exhibit frequent recombination, but the SARS-CoV-2 lineage itself is not a recombinant of any viruses detected to date. In order to employ phylogenetic methods to date the divergence events between SARS-CoV-2 and the bat sarbecovirus reservoir, recombinant regions of a 68-genome sarbecovirus alignment were removed with three independent methods. Bayesian evolutionary rate and divergence date estimates were consistent for all three recombination-free alignments and robust to two different prior specifications based on HCoV-OC43 and MERS-CoV evolutionary rates. Divergence dates between SARS-CoV-2 and the bat sarbecovirus reservoir were estimated as 1948 (95% HPD: 1879-1999), 1969 (95% HPD: 1930-2000), and 1982 (95% HPD: 1948-2009). Despite intensified characterization of sarbecoviruses since SARS, the lineage giving rise to SARS-CoV-2 has been circulating unnoticed for decades in bats and been transmitted to other hosts such as pangolins. The occurrence of a third significant coronavirus emergence in 17 years together with the high prevalence and virus diversity in bats implies that these viruses are likely to cross species boundaries again.

In Brief

The Betacoronavirus SARS-CoV-2 is a member of the sarbecovirus subgenus which shows frequent recombination in its evolutionary history. We characterize the extent of this genetic exchange and identify non-recombining regions of the sarbecovirus genome using three independent methods to remove the effects of recombination. Using these non-recombining genome regions and prior information on coronavirus evolutionary rates, we obtain estimates from three approaches that the most likely divergence date of SARS-CoV-2 from its most closely related available bat sequences ranges from 1948 to 1982.

Key Points

• RaTG13 is the closest available bat virus to SARS-CoV-2; a sub-lineage of these bat viruses is able to infect humans. Two sister lineages of the RaTG13/SARS-CoV-2 lineage infect Malayan pangolins.
  
  
• The sarbecoviruses show a pattern of deep recombination events, indicating that there are high levels of co-infection in horseshoe bats and that the viral pool can generate novel allele combinations and substantial genetic diversity; the sarbecoviruses are efficient ‘explorers’ of phenotype space.
  
  
• The SARS-CoV-2 lineage is not a recent recombinant, at least not involving any of the bat or pangolin viruses sampled to date.
  
  
• Non-recombinant regions of the sarbecoviruses can be identified, allowing for phylogenetic inference and dating to be performed. We constructed three such regions using different methods.
  
  
• We estimate that RaTG13 and SARS-CoV-2 diverged 40 to 70 years ago. There is a diverse unsampled reservoir of generalist viruses established in horseshoe bats.
  
  
• While an intermediate host responsible for the zoonotic event cannot be ruled out, the relevant evolution for spillover to humans very likely occurred in horseshoe bats.

Full read in the following link: https://www.biorxiv.org/content/biorxiv/early/2020/03/31/2020.03.30.015008.full.pdf (PDF format)

The aforementioned findings motivate a look at the global distribution of horseshoe bats and genome sequences:

(1)

Figure 1. Maximum-likelihood phylogeny based on the complete genome sequences of 17 bat CoV species released by ICTV in 2018. A general time-reversible model of nucleotide substitution with estimated base frequencies, the proportion of invariant sites, and the γ distribution of rates across sites were used in the maximum-likelihood analysis. Bootstrap values are shown next to the branches. The scale bar indicates the number of nucleotide substitutions per site. Different colors represent different genera. Red, Alphacoronavirus; blue, Betacoronavirus. Updated subgenera clusters are labelled Setracovirus, Myotacovirus, Rhinacovirus, Colacovirus, Pedacovirus, Decacovirus, Minunacovirus, Nyctacovirus for the Alphacoronavirus and Nobecovirus, Hibecovirus, Sarbecovirus, Merbecovirus for the Betacoronavirus.

(2)

Figure 2. Geographical distribution of bat CoVs from the genera Alphacoronavirus and Betacoronavirus. Each colored region represents the country which reported the discovery of bat CoV. Red regions represent the countries which discovered bat Alphacoornavirus. Green regions represent the countries which discovered bat Betacoronavirus. Red-green striped regions represent the countries which discovered both bat Alphacoronavirus and Betacoronavirus.

(3)

Figure 3. Pie chart showing the relative detection rate of different bat CoVs from different subgenera of Alphacoronavirus and Betacoronavirus in Hong Kong from 2008 to 2017. The potential zoonotic transmission routes of each sub-genus of bat CoV detected are shown. Unclassified Alphacoronavirus represents those without complete genome sequences or genome characterization. Red color represents the sub-genera from Alphacoronavirus; Blue color represents the sub-genera from Betacoronavirus.

(4)

Figure 4. Geographical distribution of different horseshoe bats which were discovered to carry SARS-like BatCoV [114,115,116,117,118,119,120,121,122,123,124,125]. Each colored rectangular box represents the geographical distribution of a specific horseshoe bat species respectively: red box, Rhinolophus affinis; orange box, Rhinolophus blasii; yellow box, Rhinolophus euryale; green box, Rhinolophus ferrumequinum; turquoise box, Rhinolophus hildebrantii; indigo box, Rhinolophus hipposideros; purple box, Rhinolophus macrotis; brown box, Rhinolophus mehelyi; pink box, Rhinolophus pearsonii; gold box, Rhinolophus pusillus; blue-gray box, Rhinolophus rex; black box, Rhinolophus sinicus; lime box, Rhinolophus thomasi. Orange circle represents Yunnan Province; Red circle represents the origin of SARS & SADS outbreaks.

(5)

Figure 5. Geographical distribution of bat CoVs from the genus Betacoronavirus. Each colored region represents the country which reported the discovery of bat CoV from different sub-genera. Navy-blue regions represent the countries which discovered bat CoVs from Sarbecovirus. Yellow regions represent the countries which discovered bat CoVs from Merbecovirus. Purple regions represent the countries which discovered bat CoVs from Nobecovirus.

Aforementioned images (1)(2)(3)(4)(5) taken from the following study:

Global Epidemiology of Bat Coronaviruses

Abstract

Bats are a unique group of mammals of the order Chiroptera. They are highly diversified and are the group of mammals with the second largest number of species. Such highly diversified cell types and receptors facilitate them to be potential hosts of a large variety of viruses. Bats are the only group of mammals capable of sustained flight, which enables them to disseminate the viruses they harbor and enhance the chance of interspecies transmission. This article aims at reviewing the various aspects of the global epidemiology of bat coronaviruses (CoVs). Before the SARS epidemic, bats were not known to be hosts for CoVs. In the last 15 years, bats have been found to be hosts of >30 CoVs with complete genomes sequenced, and many more if those without genome sequences are included. Among the four CoV genera, only alphaCoVs and betaCoVs have been found in bats. As a whole, both alphaCoVs and betaCoVs have been detected from bats in Asia, Europe, Africa, North and South America and Australasia; but alphaCoVs seem to be more widespread than betaCoVs, and their detection rate is also higher. For betaCoVs, only those from subgenera Sarbecovirus, Merbecovirus, Nobecovirus and Hibecovirus have been detected in bats. Most notably, horseshoe bats are the reservoir of SARS-CoV, and several betaCoVs from subgenus Merbecovirus are closely related to MERS-CoV. In addition to the interactions among various bat species themselves, bat–animal and bat–human interactions, such as the presence of live bats in wildlife wet markets and restaurants in Southern China, are important for interspecies transmission of CoVs and may lead to devastating global outbreaks.

Full read in the following link: https://www.mdpi.com/1999-4915/11/2/174

---

In light of the above, it make sense to retrace PATIENT ZERO in every country: https://www.weforum.org/agenda/2020/03/coronavirus-covid-19-patient-zero/

This information is useful to those who are looking forward to help combating COVID-19 outbreak and/or already involved in any capacity, and will also help quell affiliated conspiracy theories floating around in this forum and elsewhere. At minimum, this information will contribute to knowledge of people.

Regards and take care.

 

[LeGenD]

Thought u were done with PDF??

Contributing for COVID-19 only.

People should be made aware of authentic information in relation to this pandemic.

 

[Yaseen1]

I think there is a risk that this pandemic may be human influenced as u.s president knew about it in 2005 which creates doubts on their integrity

 

[LeGenD]

I think there is a risk that this pandemic may be human influenced as u.s president knew about it in 2005 which creates doubts on their integrity

Bio-engineering is a reality but COVID-19 pandemic is not man-made.

See study shared in post # 3; genome of the coronavirus strain (SARS-CoV-2) responsible for COVID-19 outbreak shared here and it very closely align with genome of other coronavirus strains. Therefore, this is natural mutation to breach human body.

 

[zectech]

Scientific research have narrowed down to horseshoe bats as being chief carriers and transmitters of coronaviruses worldwide,

Jump to 3:50:

https://www.bitchute.com/video/nI0qv4Bv3hTo/

And then the 'Obama Administration' (Obama was a CIA asset) set up the Chinese several years ago to frame China.

 

[LeGenD]

Jump to 3:50:

https://www.bitchute.com/video/nI0qv4Bv3hTo/

And then the 'Obama Administration' (Obama was a CIA asset) set up the Chinese several years ago to frame China.

Thanks for your input.

Few people are able to understand scientific information in person. Few people understand the value of scientific publication portals and databases - absolute treasuretrove of information out there.

You can imagine how easy it is to fool others who do not understand how things work in reality. This is why scientific education is important to build a better world.

 

[Fracker]

Frankly I don't understand much about gnome or DNA or RNA. But what amaze me the simplicity of COVID-19 that even a normal person like me understand.

1) Attach to lungs cell (epithelial cells), (Strange why Lungs only, and how convenient, looks they just waiting to be infected or otherway around?
2) Penetrate into cell, and insert its genetical meterial into the cell.
3) cell simply replicate the RNA received
4) once it's reaches to maximum level a cell can hold, it's melt the cell and spread in sourounding cells..

Now the problem with this is, its way too simple. And what I understand through evolution or mutations it is anything but simple. So it's very hard to believe it all happened within the bats one of the hostile environment for virus, they need to continuously fight with immune cells of bat, unless these were acient virus just suddenly came out without any trace (which is highly unlikely).

Now the worst thing in humans their immune system detect it very late since humans immune system has no previous record of any of such virus or their family members. Which makes it hard to detect and people keep spreading it without even knowing they are the carriers.

That's the reason I don't think it happened naturally. However we will never know. It's the media to decide what get written into the history..

Anyways, #StayHome#StaySafe

 

[-blitzkrieg-]

LEGEND

SARS-CoV-2 = COVID-19 outbreak

In view of following revelations:-

Most NYC Covid-19 Cases Came From Europe, Genome Researchers Say

Read more: https://www.bloomberg.com/news/arti...cases-came-from-europe-genome-researchers-say

The hunt for patient zero: Where did the coronavirus outbreak start?

Read more: https://www.newscientist.com/articl...the-coronavirus-outbreak-start/#ixzz6J7vZ8Df9

- I decided to review ongoing scientific work, and I have some observations to share.

Scientific research have narrowed down to horseshoe bats as being chief carriers and transmitters of coronaviruses worldwide, and coronaviruses have recombinogenic properties which are not apparent in other types of viruses:

Evolutionary origins of the SARS‐CoV‐2 sarbecovirus lineage responsible for the COVID-19 pandemic

Abstract

There are outstanding evolutionary questions on the recent emergence of coronavirus SARS-CoV-2/hCoV-19 in Hubei province that caused the COVID-19 pandemic, including (1) the relationship of the new virus to the SARS-related coronaviruses, (2) the role of bats as a reservoir species, (3) the potential role of other mammals in the emergence event, and (4) the role of recombination in viral emergence. Here, we address these questions and find that the sarbecoviruses – the viral subgenus responsible for the emergence of SARS-CoV and SARS-CoV-2 – exhibit frequent recombination, but the SARS-CoV-2 lineage itself is not a recombinant of any viruses detected to date. In order to employ phylogenetic methods to date the divergence events between SARS-CoV-2 and the bat sarbecovirus reservoir, recombinant regions of a 68-genome sarbecovirus alignment were removed with three independent methods. Bayesian evolutionary rate and divergence date estimates were consistent for all three recombination-free alignments and robust to two different prior specifications based on HCoV-OC43 and MERS-CoV evolutionary rates. Divergence dates between SARS-CoV-2 and the bat sarbecovirus reservoir were estimated as 1948 (95% HPD: 1879-1999), 1969 (95% HPD: 1930-2000), and 1982 (95% HPD: 1948-2009). Despite intensified characterization of sarbecoviruses since SARS, the lineage giving rise to SARS-CoV-2 has been circulating unnoticed for decades in bats and been transmitted to other hosts such as pangolins. The occurrence of a third significant coronavirus emergence in 17 years together with the high prevalence and virus diversity in bats implies that these viruses are likely to cross species boundaries again.

In Brief

The Betacoronavirus SARS-CoV-2 is a member of the sarbecovirus subgenus which shows frequent recombination in its evolutionary history. We characterize the extent of this genetic exchange and identify non-recombining regions of the sarbecovirus genome using three independent methods to remove the effects of recombination. Using these non-recombining genome regions and prior information on coronavirus evolutionary rates, we obtain estimates from three approaches that the most likely divergence date of SARS-CoV-2 from its most closely related available bat sequences ranges from 1948 to 1982.

Key Points

• RaTG13 is the closest available bat virus to SARS-CoV-2; a sub-lineage of these bat viruses is able to infect humans. Two sister lineages of the RaTG13/SARS-CoV-2 lineage infect Malayan pangolins.
  
  
• The sarbecoviruses show a pattern of deep recombination events, indicating that there are high levels of co-infection in horseshoe bats and that the viral pool can generate novel allele combinations and substantial genetic diversity; the sarbecoviruses are efficient ‘explorers’ of phenotype space.
  
  
• The SARS-CoV-2 lineage is not a recent recombinant, at least not involving any of the bat or pangolin viruses sampled to date.
  
  
• Non-recombinant regions of the sarbecoviruses can be identified, allowing for phylogenetic inference and dating to be performed. We constructed three such regions using different methods.
  
  
• We estimate that RaTG13 and SARS-CoV-2 diverged 40 to 70 years ago. There is a diverse unsampled reservoir of generalist viruses established in horseshoe bats.
  
  
• While an intermediate host responsible for the zoonotic event cannot be ruled out, the relevant evolution for spillover to humans very likely occurred in horseshoe bats.

Full read in the following link: https://www.biorxiv.org/content/biorxiv/early/2020/03/31/2020.03.30.015008.full.pdf (PDF format)

The aforementioned findings motivate a look at the global distribution of horseshoe bats and genome sequences:

(1)

Figure 1. Maximum-likelihood phylogeny based on the complete genome sequences of 17 bat CoV species released by ICTV in 2018. A general time-reversible model of nucleotide substitution with estimated base frequencies, the proportion of invariant sites, and the γ distribution of rates across sites were used in the maximum-likelihood analysis. Bootstrap values are shown next to the branches. The scale bar indicates the number of nucleotide substitutions per site. Different colors represent different genera. Red, Alphacoronavirus; blue, Betacoronavirus. Updated subgenera clusters are labelled Setracovirus, Myotacovirus, Rhinacovirus, Colacovirus, Pedacovirus, Decacovirus, Minunacovirus, Nyctacovirus for the Alphacoronavirus and Nobecovirus, Hibecovirus, Sarbecovirus, Merbecovirus for the Betacoronavirus.

(2)

Figure 2. Geographical distribution of bat CoVs from the genera Alphacoronavirus and Betacoronavirus. Each colored region represents the country which reported the discovery of bat CoV. Red regions represent the countries which discovered bat Alphacoornavirus. Green regions represent the countries which discovered bat Betacoronavirus. Red-green striped regions represent the countries which discovered both bat Alphacoronavirus and Betacoronavirus.

(3)

Figure 3. Pie chart showing the relative detection rate of different bat CoVs from different subgenera of Alphacoronavirus and Betacoronavirus in Hong Kong from 2008 to 2017. The potential zoonotic transmission routes of each sub-genus of bat CoV detected are shown. Unclassified Alphacoronavirus represents those without complete genome sequences or genome characterization. Red color represents the sub-genera from Alphacoronavirus; Blue color represents the sub-genera from Betacoronavirus.

(4)

Figure 4. Geographical distribution of different horseshoe bats which were discovered to carry SARS-like BatCoV [114,115,116,117,118,119,120,121,122,123,124,125]. Each colored rectangular box represents the geographical distribution of a specific horseshoe bat species respectively: red box, Rhinolophus affinis; orange box, Rhinolophus blasii; yellow box, Rhinolophus euryale; green box, Rhinolophus ferrumequinum; turquoise box, Rhinolophus hildebrantii; indigo box, Rhinolophus hipposideros; purple box, Rhinolophus macrotis; brown box, Rhinolophus mehelyi; pink box, Rhinolophus pearsonii; gold box, Rhinolophus pusillus; blue-gray box, Rhinolophus rex; black box, Rhinolophus sinicus; lime box, Rhinolophus thomasi. Orange circle represents Yunnan Province; Red circle represents the origin of SARS & SADS outbreaks.

(5)

Figure 5. Geographical distribution of bat CoVs from the genus Betacoronavirus. Each colored region represents the country which reported the discovery of bat CoV from different sub-genera. Navy-blue regions represent the countries which discovered bat CoVs from Sarbecovirus. Yellow regions represent the countries which discovered bat CoVs from Merbecovirus. Purple regions represent the countries which discovered bat CoVs from Nobecovirus.

Aforementioned images (1)(2)(3)(4)(5) taken from the following study:

Global Epidemiology of Bat Coronaviruses

Abstract

Bats are a unique group of mammals of the order Chiroptera. They are highly diversified and are the group of mammals with the second largest number of species. Such highly diversified cell types and receptors facilitate them to be potential hosts of a large variety of viruses. Bats are the only group of mammals capable of sustained flight, which enables them to disseminate the viruses they harbor and enhance the chance of interspecies transmission. This article aims at reviewing the various aspects of the global epidemiology of bat coronaviruses (CoVs). Before the SARS epidemic, bats were not known to be hosts for CoVs. In the last 15 years, bats have been found to be hosts of >30 CoVs with complete genomes sequenced, and many more if those without genome sequences are included. Among the four CoV genera, only alphaCoVs and betaCoVs have been found in bats. As a whole, both alphaCoVs and betaCoVs have been detected from bats in Asia, Europe, Africa, North and South America and Australasia; but alphaCoVs seem to be more widespread than betaCoVs, and their detection rate is also higher. For betaCoVs, only those from subgenera Sarbecovirus, Merbecovirus, Nobecovirus and Hibecovirus have been detected in bats. Most notably, horseshoe bats are the reservoir of SARS-CoV, and several betaCoVs from subgenus Merbecovirus are closely related to MERS-CoV. In addition to the interactions among various bat species themselves, bat–animal and bat–human interactions, such as the presence of live bats in wildlife wet markets and restaurants in Southern China, are important for interspecies transmission of CoVs and may lead to devastating global outbreaks.

Full read in the following link: https://www.mdpi.com/1999-4915/11/2/174

---

In light of the above, it make sense to retrace PATIENT ZERO in every country: https://www.weforum.org/agenda/2020/03/coronavirus-covid-19-patient-zero/

This information is useful to those who are looking forward to help combating COVID-19 outbreak and/or already involved in any capacity, and will also help quell affiliated conspiracy theories floating around in this forum and elsewhere. At minimum, this information will contribute to knowledge of people.

Regards and take care.

pandemic.

The game is more around stats and fear-mongering than the science itself..

How is this been declared a pandemic when not even 0.02% of the world population is affected yet?apart from the fact that testing methodologies have upto 30% false +ive result, also only 95000 deaths in 4-5 months considering many people die due to seasonal flu in a year, so what was the rush to declare it a pandemic? Trump first called it a hoax than seems he got pushed into accepting it as a pandemic.
Insurance companies in developed world worldwide can only support affected people if WHO declares pandemic so is it just for a benefit for some privileged nations that the whole world has to carry the pandemic burden?


Why NATO countries /pro-democrat US states have most cases and also hiking up their death-toll by even including 'suspected corona deaths' , while pro Trump ones like India,Russia, Saudia are low on deaths or 'hiding' them? Has that got something to do with the US election year?

https://nypost.com/2020/04/07/feds-classify-all-coronavirus-patient-deaths-as-covid-19-deaths/

And how suddenly every tom dick harry has started asking for a new world order.
https://www.theguardian.com/politic...s-for-global-government-to-tackle-coronavirus
https://www.dw.com/en/coronavirus-g...einmeier-calls-for-global-alliance/a-52977214
https://cnsnews.com/commentary/patrick-j-buchanan/kissingers-call-new-world-order
- https://www.washingtontimes.com/news/2020/mar/28/coronavirus-crisis-fit-new-world-order/
https://www.washingtontimes.com/news/2020/mar/28/coronavirus-crisis-fit-new-world-order/

 

[LeGenD]

The game is more around stats and fear-mongering than the science itself..

How is this been declared a pandemic when not even 0.02% of the world population is affected yet?apart from the fact that testing methodologies have upto 30% false +ive result, also only 95000 deaths in 4-5 months considering many people die due to seasonal flu in a year, so what was the rush to declare it a pandemic? Trump first called it a hoax than seems he got pushed into accepting it as a pandemic.
Insurance companies in developed world worldwide can only support affected people if WHO declares pandemic so is it just for a benefit for some privileged nations that the whole world has to carry the pandemic burden?


Why NATO countries /pro-democrat US states have most cases and also hiking up their death-toll by even including 'suspected corona deaths' , while pro Trump ones like India,Russia, Saudia are low on deaths or 'hiding' them? Has that got something to do with the US election year?

https://nypost.com/2020/04/07/feds-classify-all-coronavirus-patient-deaths-as-covid-19-deaths/

And how suddenly every tom dick harry has started asking for a new world order.
https://www.theguardian.com/politic...s-for-global-government-to-tackle-coronavirus
https://www.dw.com/en/coronavirus-g...einmeier-calls-for-global-alliance/a-52977214
https://cnsnews.com/commentary/patrick-j-buchanan/kissingers-call-new-world-order
- https://www.washingtontimes.com/news/2020/mar/28/coronavirus-crisis-fit-new-world-order/
https://www.washingtontimes.com/news/2020/mar/28/coronavirus-crisis-fit-new-world-order/

The recent outbreak (COVID-19) have reached pandemic proportions as of late: https://www.worldometers.info/coronavirus/

However, this is also the first time in history that every government is adopting measures to minimize spread of this outbreak. Therefore, statistics do not matter.

The recent outbreak is caused by 7th coronavirus strain identified as (SARS-CoV-2).

There is a 17 years-long history of earlier outbreaks starting with the original SARS outbreak and followed by the SABS outbreak, then MERS outbreak, and now the most recent COVID-19 outbreak respectively. This reality is increasingly acknowledged in maintream sources now: https://www.healthline.com/health-news/has-anything-changed-since-the-2003-sars-outbreak

Unfortunately, many of these cases were being mistaken for being cases of influenza and even pneumonia in hospitals around the world because some strains cause mild symptoms and other strains cause severe symptoms, and these symptoms match those of influenza to large extent. Only Allah Almighty knows how many are carriers by now.

Now that the world is coming to terms with the fact that they are dealing with a GROUP of viruses (coronaviruses) and a series of outbreaks in humans in succession (a phenomenon), there are calls for global centralization for addressing this phenomenon because this looks beyond the capacity of individual governments to cope with in the long-term.

 

[Yaseen1]

this is due to internet and social media that panic of this pandemic is spread more severely as compared to earlier pandemic of 1918 when there was no such media so even all govts are taking measures it is mostly driven by fear created by media who can be easily manipulated to show fake news

The recent outbreak (COVID-19) have reached pandemic proportions as of late: https://www.worldometers.info/coronavirus/

However, this is also the first time in history that every government is adopting measures to minimize spread of this outbreak. Therefore, statistics do not matter.

The recent outbreak is caused by 7th coronavirus strain identified as (SARS-CoV-2).

There is a 17 years-long history of earlier outbreaks starting with SARS and followed by SABS, MARS and the most recent COVID-19 respectively. This reality is increasingly acknowledged in maintream sources now: https://www.healthline.com/health-news/has-anything-changed-since-the-2003-sars-outbreak

Many of these cases were being mistaken for influenza all along in medical circles around the world because some strains cause mild symptoms and others cause severe symptoms.

Now that the world is coming to terms with the fact that they are dealing with a GROUP of viruses and a series of outbreaks, there are calls for global centralization in addressing this phenomenon.

 

[LeGenD]

Following Chinese study is very telling.

Co-infection with SARS-CoV-2 and Influenza A Virus in Patient with Pneumonia, China

Abstract

We report co-infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus in a patient with pneumonia in China. The case highlights possible co-detection of known respiratory viruses. We noted low sensitivity of upper respiratory specimens for SARS-CoV-2, which could further complicate recognition of the full extent of disease.

Expanded

In December 2019, a series of cases of pneumonia of unknown cause was reported in Wuhan, Hubei Province, China. On January 7, 2020, the causative pathogen was identified as a virus subsequently named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (1–3). We report a case of co-infection with SARS-CoV-2 and influenza A virus in China.

Figure. Radiographs of patient co-infected with 2019 novel coronavirus and influenza A virus, China, 2020. A) Chest computed tomography demonstrating a mass, ground-glass consolidation in the right inferior lobe. B) Chest radiograph...

A 69-year-old man was seen in the clinic of China-Japan Friendship Hospital on January 23, 2020, for fever and dry cough. The patient visited Wuhan from December 18, 2019–January 22, 2020, and began having symptoms January 23. He reported no underlying medical conditions. Routine blood tests revealed a leukocyte count of 5.70 × 109 cells/L (reference range 3.5–9.5 × 109 cells/L) and lymphocyte count of 2.18 × 109 cells/L (reference range 1.1–3.2 × 109 cells/L). Chest computed tomography revealed a mass, ground-glass consolidation in the right inferior lobe of the lungs (Figure, panel A). Because of the patient’s travel history, he was isolated for suspected 2019 novel coronavirus disease (COVID-19).

We obtained a nasopharyngeal swab specimen and conducted real-time reverse transcription-PCR (rRT-PCR) for SARS-CoV-2 by using reagents provided by Shanghai BioGerm Medical Technology Co., Ltd. (http://www.bio-germ.comExternal Link), and Da An Gene Co., Ltd. (Sun Yat-Sen University, http://en.daangene.comExternal Link), on a LightCycler 480 (Roche, https://lifescience.roche.comExternal Link). However, both tests returned negative results 8 hours later. We obtained another nasopharyngeal swab specimen for detection of SARS-CoV-2 and for differentiation of influenza A and B and respiratory syncytial viruses by using Xpert Flu/RSV Xpress assay (Cepheid, https://www.cepheid.comExternal Link). The sample was negative for SARS-CoV-2 but positive for influenza A. The patient was discharged with oral oseltamivir and instructed to stay home for isolation.

On January 30, the patient returned to the hospital reporting persistent fever and aggravated dyspnea. Routine blood tests showed a leukocyte count of 8.23 × 109 cells/L and lymphocyte count of 0.77 × 109 cells/L. A chest radiograph showed diffuse exudative shadows in bilateral lungs, indicating acute respiratory distress syndrome (Figure, panel B). Physical examination revealed respiratory rate of 30 breaths/min and oxygen saturation of 83% on ambient air. We administered oxygen and screened another nasopharyngeal swab specimen, which was negative for SARS-CoV-2. Considering his clinical features, we performed a fourth test for SARS-CoV-2 by using a sputum sample, which also was negative. The patient’s dyspnea and respiratory distress increased, and his oxygenation index was <200. We admitted the patient to the single negative-pressure ward of the medical intensive care unit for severe influenza A pneumonia and administered endotracheal intubation because of severe hypoxemia.

Four days later, the patient’s oxygenation and chest radiographs improved (Figure, panel C). We performed a bronchoscopy and obtained bronchoalveolar lavage fluid (BALF) for metagenomic next-generation sequencing (mNGS) to identify potential pathogens. On February 5, mNGS reported 3,460 sequences that showed 99.8% identity and covered 98.69% of the SARS-CoV-2 genome NC_045512.2|SARS-CoV-2|Wuhan-Hu-1 (GenBank accession no. NC_045512.2). We then performed rRT-PCR by using newly collected sputum and stored BALF, which also tested positive. Cycle threshold values were 34 for sputum and 30 for BALF. However, a fourth nasopharyngeal swab collected concurrently with the second sputum sample remained negative. The next day, the patient was transferred to a designated hospital for further critical care.

This case highlights 2 challenges in the diagnosis of COVID-19. First, the sensitivity of tests to detect SARS-CoV-2 from upper respiratory specimens might be insufficient. Repeated rRT-PCR testing of nasopharyngeal swabs was negative for SARS-CoV-2 before the patient was admitted to the intensive care unit. To date, diagnosis of COVID-19 is made mainly on the basis of nucleic acid detection from nasopharyngeal swabs. For suspected cases, 2 negative findings from nasopharyngeal swabs performed >24 hours apart would exclude a COVID-19 diagnosis (4). In this case, without the clinicians’ persistence because of the patient’s travel history, a COVID-19 diagnosis might never have been established. SARS-CoV-2 finally was identified by using mNGS and rRT-PCR of a BALF sample. Therefore, suitable sputum or BALF specimens are necessary to maximize detection in cases of high clinical suspicion; mNGS also might be a helpful tool for identifying SARS-CoV-2 (1,5).

Second, differentiating other causes of respiratory illness from COVID-19 is difficult, especially during influenza season, because common clinical manifestations of COVID-19, including fever, cough, and dyspnea, mimic those of influenza (6–8). In patients with COVID-19, blood tests typically show leucopenia and lymphopenia and most chest computed tomography scans show ground-glass opacity and consolidation with bilateral lung involvement (7–9). Unfortunately, influenza A and other respiratory viruses share these characteristics (10). Co-detection of SARS-CoV-2 and influenza A virus in this case demonstrates that additional challenges to detection remain, especially when patients test negative for SARS-CoV-2 but positive for another virus.

In summary, our case suggests that COVID-19 might be underdiagnosed because of false-negative tests for upper respiratory specimens or co-infection with other respiratory viruses. Broader viral testing might be needed when an apparent etiology is identified, particularly if it would affect clinical management decisions.

---

Dr. Wu is a pulmonary and critical care physician specializing in respiratory infection at China-Japan Friendship Hospital, Beijing, China. Her research interests include severe lower respiratory infection and new respiratory infectious diseases.

---

Link: https://wwwnc.cdc.gov/eid/article/26/6/20-0299_article

 

[LeGenD]

Following study was published in 2015:

Human Coronavirus-Associated Influenza-Like Illness in the Community Setting in Peru

Abstract

We present findings describing the epidemiology of non-severe acute respiratory syndrome human coronavirus-associated influenza-like illness from a population-based active follow-up study in four different regions of Peru. In 2010, the prevalence of infections by human coronaviruses 229E, OC43, NL63, or HKU1 was 6.4% in participants with influenza-like illness who tested negative for influenza viruses. Ten of 11 human coronavirus infections were identified in the fall–winter season. Human coronaviruses are present in different regions of Peru and are relatively frequently associated with influenza-like illness in Peru.

Full read: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703274/

Refer back to the study shared in post # 3 of this thread:

"SARS-CoV-2 is the seventh coronavirus known to infect humans; SARS-CoV, MERS-CoV and SARS-CoV-2 can cause severe disease, whereas HKU1, NL63, OC43 and 229E are associated with mild symptoms^6. Here we review what can be deduced about the origin of SARS-CoV-2 from comparative analysis of genomic data. We offer a perspective on the notable features of the SARS-CoV-2 genome and discuss scenarios by which they could have arisen. Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus."

DOTS continue to connect.

Humanity is dealing with a GROUP of coronaviruses and a series of outbreaks from different strains since the first SARS episode - 17 years have passed.

---

Looks like Allah Almighty have issued a warning to mankind to correct its ways. The Hour is approaching.