Incredible Coronavirus News! As much as 50% of the population might be immune from Coronavirus

JavyBaez9 · Aug 5, 2020

https://science.sciencemag.org/content/early/2020/08/04/science.abd3871

Many unknowns exist about human immune responses to the SARS-CoV-2 virus. SARS-CoV-2 reactive CD4+ T cells have been reported in unexposed individuals, suggesting pre-existing cross-reactive T cell memory in 20-50% of people.

JavyBaez9 · Aug 5, 2020

The emergence of SARS-CoV-2 in late 2019 and its subsequent global spread has led to millions of infections and substantial morbidity and mortality (1). Coronavirus disease 2019 (COVID-19), the clinical disease caused by SARS-CoV-2 infection, can range from mild self-limiting disease to acute respiratory distress syndrome and death (2). The mechanisms underlying the spectrum of COVID-19 disease severity states, and the nature of protective immunity against COVID-19 currently remains unclear.
Studies dissecting the human immune response against SARS-CoV-2 have begun to characterize SARS-CoV-2 antigen-specific T cell responses (3–8), and multiple studies have described marked activation of T cell subsets in acute COVID-19 patients (9–13). Surprisingly, antigen-specific T cell studies performed with five different cohorts reported that 20-50% of people who had not been exposed to SARS-CoV-2 had significant T cell reactivity directed against peptides corresponding to SARS-CoV-2 sequences (3–7). The studies were from geographically diverse cohorts (USA, Netherlands, Germany, Singapore, and UK), and the general pattern observed was that the T cell reactivity found in unexposed individuals was predominantly mediated by CD4+ T cells. It was speculated that this phenomenon might be due to preexisting memory responses against human “common cold” coronaviruses (HCoVs), such as HCoV-OC43, HCoV-HKU1, HCoV-NL63, or HCoV-229E. These HCoVs share partial sequence homology with SARS-CoV-2, are widely circulating in the general population, and are typically responsible for mild respiratory symptoms (14–16). However, the hypothesis of crossreactive immunity between SARS-CoV-2 and common cold HCoVs still awaits experimental trials. This potential preexisting cross-reactive T cell immunity to SARS-CoV-2 has broad implications, as it could explain aspects of differential COVID-19 clinical outcomes, influence epidemiological models of herd immunity (17, 18), or affect the performance of COVID-19 candidate vaccines.
[h=2]Epitope repertoire in SARS-CoV-2 unexposed individuals[/h]To define the repertoire of CD4+ T cells recognizing SARS-CoV-2 epitopes in previously unexposed individuals, we used in vitro stimulation of PBMCs for 2-weeks with pools of 15-mer peptides. This method is known to be robust for detecting low frequency T cell responses to allergens, bacterial, or viral antigens (19, 20), including naive T cells (21). For screening SARS-CoV-2 epitopes, we utilized PBMC samples from unexposed subjects collected between March 2015 and March 2018, well before the global circulation of SARS-CoV-2 occurred. The unexposed subjects were confirmed seronegative for SARS-CoV-2 (fig. S1A).
SARS-CoV-2 reactive T cells were expanded with one pool of peptides spanning the entire sequence of the spike protein (CD4-S), or a non-spike “megapool” (CD4-R) of predicted epitopes from the non-spike regions (i.e., “remainder”) of the viral genome (4). In total, 474 15-mer SARS-CoV-2 peptides were screened. After 14 days of stimulation, T cell reactivity against intermediate “mesopools,” each encompassing approximately 10 peptides, were assayed using a FluoroSPOT assay (e.g., 22 CD4-R mesopools; fig. S2A). Positive mesopools were further deconvoluted to identify specific individual SARS-CoV-2 epitopes. Representative results from one donor show the deconvolution of mesopools P6 and P18 to identify seven different SARS-CoV-2 epitopes (fig. S2B). Intracellular cytokine staining assays (ICS) specific for IFN-γ determined whether antigen specific T cells responding to the SARS-CoV-2 mesopools were CD4+ or CD8+ T cells (fig. S2C). Results from the 44 donors/CD4-R mesopool and 40 donors/CD4-S mesopool combinations yielding a positive response are shown in fig. S2, D and E, respectively. In 82/88 cases (93.2%) the cells responding to SARS-CoV-2 mesopool stimulation were clearly CD4+ T cells, as judged by the ratio of CD4/CD8 responding cells. In four cases (4.5%), the responding cells were CD8+ T cells, and in two cases (2.3%) the responses were mediated by both CD4+ and CD8+ T cells. The fact that CD8+ T cells were rarely detected was not surprising, since the peptides used in CD4-R encompassed predicted class II epitopes, and the CD4-S is constituted of 15-mer peptides (9-10-mer peptides are optimal for CD8+ T cells). Furthermore, the 2-week restimulation protocol was originally designed to expand CD4+ T cells (20). Overall, these results indicated that the peptide screening strategy utilized mapped SARS-CoV-2 epitopes recognized by CD4+ T cells in unexposed individuals.
A total of 142 SARS-CoV-2 epitopes were identified, 66 from the spike protein (CD4-S) and 76 from the remainder of the genome (CD4-R) (table S1). For each combination of epitope and responding donor, potential HLA restrictions were inferred based on the predicted HLA binding capacity of the particular epitope for the specific HLA alleles present in the responding donor (22). Each donor recognized an average of 11.4 epitopes (range 1 to 33, median 6.5; fig. S3A). Forty of the 142 epitopes were recognized by 2 or more donors (fig. S3B), accounting for 55% of the total response (fig. S3C). These 142 mapped SARS-CoV-2 epitopes may prove useful in future studies as reagents for tracking CD4+ T cells in SARS-CoV-2 infected individuals, and in COVID-19 vaccine trials.

[h=2]Epitope distribution by ORF of origin[/h]While a broad range of different SARS-CoV-2 antigens were recognized, it was striking that several of the epitopes yielding the most frequent (i.e., recognized in multiple donors) or most vigorous (i.e., most SFC/106 cells) responses were derived from the SARS-CoV-2 spike antigen (table S1). We therefore assessed the overall distribution of the 142 T cell epitopes mapped among all SARS-CoV-2 proteins, compared to the relative size of each SARS-CoV-2 antigen (Fig. 1, A and B). Notably, 54% of the total positive response was associated with spike-derived epitopes (Fig. 1A; 11% for RBD, and 44% for the non-RBD portion of spike). Of relevance for COVID-19 vaccine development, only 20% of the spike responses were derived from the receptor-binding domain (RBD) region (Fig. 1A; comparing 11% vs 44%, as described above), and the RBD region accounted for only 11% of the overall CD4+ T cell reactivity (Fig. 1A). Mapped epitopes were fairly evenly distributed across the SARS-CoV-2 genome in proportion to the size of each protein (Fig. 1B; p=0.038, r=0.42). In addition to the strong responses directed to spike, responses were also seen for ORF6, ORF3a, N, ORF8 and within Orf1a/b, where nsp3, nsp12, nsp4, nsp6, nsp2 and nsp14 were more prominently recognized. These mapped epitope results at the ORFeome level partially overlap with the ORFs targeted by CD4+ T cells in COVID-19 cases (4). Notably, no epitopes derived from the membrane protein (M) were identified in unexposed individuals (Fig. 1B), but M is robustly recognized by SARS-CoV-2-specific CD4+ T cell responses in COVID-19 cases (4). The lack of quality class II epitopes in M was unsurprising, based on M molecular biology; M is a small protein with three transmembrane domains. Combined, the data indicate that class II epitopes are relatively broadly available across the SARS-CoV-2 genome, but that SARS-CoV-2 memory CD4+ T cells preferentially target proteins highly expressed during infection, exemplified by M and S (spike) epitope mapping results.

MrBetitall · Aug 5, 2020

lmfao, "immune", ha ha ha

in other news Elvis lives and Trump is a genius

JavyBaez9 · Aug 5, 2020

Mr Bet it all said:
lmfao, "immune", ha ha ha

in other news Elvis lives and Trump is a genius

Note the deranged retard that hates good news.

For those who can't quite understand the article, what this study did is take blood samples from BEFORE Covid19, and then traced their ability to combat Covid19 with memorized t cell formations, and up to 50% of the samples they tested showed a pre-existing ability to combat Covid19, which they developed when they contracted other coronaviruses previously.

StevieRay · Aug 5, 2020

The apocalypse crew is clueless

JavyBaez9 · Aug 5, 2020

StevieRay said:
The apocalypse crew is clueless

I've certainly been exposed to Covid19 and I haven't gotten it.

Some people are immune. 20-50%.

X-Files · Aug 5, 2020

Yes, that is good news, or at least hopeful news. As are reports re many vaccines & treatments being worked on.

Maybe by the end of the year people will be able to book flights to and enter places like Thailand as they did before C-19.

Fingers crossed. Time will tell.

MrBetitall · Aug 5, 2020

JavyBaez9 said:
I've certainly been exposed to Covid19 and I haven't gotten it.

Some people are immune. 20-50%.

yeah, you're immune. Congratulations

X-Files · Aug 5, 2020

How many sickos & child abductions occur in little America the not so great?

X-Files · Aug 5, 2020

Now getting back to our regular scheduled programming & the OP topic:

"Does the Common Cold Protect You from COVID-19?

There are emerging signs that some people might have heightened protection against SARS-CoV-2, perhaps thanks to recent infection by other coronaviruses."

In labs all over the world lately, scientists working on COVID-19 have stumbled on an intriguing sort of finding again and again. They’ve found that blood samples from healthy people who were never exposed to the SARS-CoV-2 coronavirus contain reactive immune cells and targeted antibodies that could, perhaps, help stave off COVID-19.

These people may—it is still just a hypothesis—possess some degree of pre-existing immunity. If correct, it’s even possible that this immunity has saved thousands from the worst manifestations of this terrible disease.

Some of the first hints of pre-existing immunity came via T cells, the white blood cells that destroy infected cells in the body or help other parts of the immune system target an invading pathogen. In one study originally published as a preprint on medRxiv April 22, a group of scientists in Germany reported an intriguing result.

Out of 68 healthy donors who had been tested for prior exposure to SARS-CoV-2 and who were found to be negative, 24 of them had a small number of T cells in their blood that reacted when exposed to the SARS-CoV-2 spike (S) protein—a complex structure protruding from the virus’s exterior surface. The study, which was later published in Nature July 29, explains that the cells in question produced proteins on their surfaces, an indication of an immune response.

If that is indeed what’s going on here, one possible explanation would be that the healthy donors had been infected by another coronavirus relatively recently, perhaps one that causes a common cold, says coauthor Andreas Thiel, an immunologist at the Charité hospital, part of Universitätsmedizin Berlin. Besides more serious diseases such as COVID-19 and SARS, human coronaviruses have been known for decades to cause what are usually much milder infections. The specific viruses that cause these illnesses are found all around the world.

“Although these viruses are not very similar [to SARS-CoV-2], the low degree of similarity is of course sufficient that the immune system, at least partly, is cross-reacting, which is a very normal thing,” he says.

An earlier study in Natureon July 15 from Singapore reported that 23 patients who had caught the original SARS virus 17 years ago and a further 37 individuals who had never been found to have had SARS or COVID-19 possessed CD4+ helper T cells and CD8+ killer T cells that reacted to the SARS-CoV-2 nucleocapsid (N) protein.

Lead author Nina Le Bert, an immunologist at Duke-NUS Medical School in Singapore, says that her paper chimes with Thiel’s work and a few other studies that have also found SARS-CoV-2 reactive T cells in blood from people who never had COVID-19, or who were sampled before the pandemic.

A study in Science today (August 4) also found SARS-CoV-2 reactive T cells in pre-pandemic blood samples from 25 healthy individuals. In this case, the authors also mapped 142 specific points on the SARS-CoV-2 virus called epitopes associated with this activity.

This allowed them to show, in subsequent experiments, that the T cells also reacted when exposed to epitopes on common cold coronaviruses that were similar to SARS-CoV-2 epitopes, supporting the idea that previous exposure to these common viruses might leave our immune systems primed to respond to the novel coronavirus.

Determining whether the T cell activity really is protective against COVID-19 is tricky, Le Bert says. “You would need to study people before and after getting infected.”

See “SARS-CoV-2-Reactive T Cells Found in Patients with Severe COVID-19”

Le Bert adds that having some degree of immunity also does not mean that people definitely won’t get infected in the first place. They may still experience mild symptoms, for example, as their immune system fends off the virus.

Thiel points out that reactive T cells could even produce the opposite result—a detrimental immune response that ultimately harms the patient, for example, when someone experiences excessive inflammation or an inability to clear the virus. “Maybe particularly in the old people, having such cross-reactive T cells could be bad,” he suggests.

Pre-existing immunity might not be limited to T cells. A preprint published on medRxiv July 23 reports that SARS-CoV-2–reactive antibodies were found in blood samples taken from people in the UK between 2018 and early 2020, before COVID-19 became widespread in the country.

Not only did the authors find that 15 out of 262 people who never had COVID-19 have IgG antibodies reactive with certain SARS-CoV-2 proteins, but further tests showed that these antibodies had a neutralizing effect on the SARS-CoV-2 spike protein, which suggests that they might be able to restrict infection by the virus.

One of the most striking findings was that these antibodies were far more prevalent in children between the ages of 1 and 16 years old. In fact, 60 percent of children had neutralizing IgG antibodies—an order of magnitude greater than the proportion of adults who were found to have the same antibodies. Coauthor Rupert Beale, an immunologist at the Francis Crick Institute in London, remarked on Twitter that this particular result was completely unexpected—“a kind of bombshell,” as he put it.

In their preprint, the authors write that kids are generally more frequently exposed to other coronaviruses, such as those that cause common colds. This could explain the prevalence of those IgG antibodies in their blood.

It is notable that, while Beale’s team detected IgG neutralizing antibodies in some of their subjects, none of the healthy donors in the study by Thiel and his colleagues were found to have reactive IgG antibodies, though they did have reactive T cells.

The presence of neutralizing antibodies does not guarantee that these children are immune to COVID-19 but it does offer one possible explanation as to why children, generally speaking, experience milder symptoms when they catch the disease.

The findings are “really interesting,” says Sheena Cruickshank, an immunologist at the University of Manchester in the UK, via email. She notes that, in the study, a different type of antibody that is protective against SARS-CoV-2, IgA, was not detected in the healthy individuals unexposed to the new coronavirus. That might mean any pre-existing immunity is limited. The other big caveat is that immunity to common cold viruses is not thought to be very long-lasting for people, regardless of age, so it is debatable how durable a protective effect would be, she adds.

In Le Bert’s study, patients appeared to have retained reactive T cells for nearly two decades. She and her colleagues write in their report that this has potentially significant implications: that immunity acquired through, say, a vaccine could last for many months or years.

https://www.the-scientist.com/news-opinion/does-the-common-cold-protect-you-from-covid-19--67792