And so we usher in the field of viral therapy once again. It seems that from my non medical/biological point of view we’ve spent our recent history trying to eradicate bacteria and viruses from our life only to find out they can be used for good. Modulating the harmful effects of bacteria and viruses to amplify things like this seems to be a away forward in medicine...
Here, it's not really the harmful virus doing good, but some bit of immunological magic that it put into motion. Viruses just as often cause lasting immunological and other harm. It'd be best to figure out what this response is, so we could put it in a drug.
Indeed, another virus -- Epstein-Barr-- caused the lymphoma in the first place.
Not sure if they still do it this way, but some thirty years back we use to treat B-cells with Epstein Barr Virus (EBV) to cause them to immortalize. You basically shredded the red blood cells and hit the white blood cells with a heavy concentration of EBV. From there, you would look for antibody production for what you were after and then isolate those cells as they replicated.
Biontech was actually founded to use mRNA "vaccines" to mark tumor cells for your immune system, so that your immune system starts attacking the tumor cells. It was never the plan to produce actual vaccines against viral diseases, but due to their research, they were perfectly positioned to do so, when the pandemic struck.
AFAIK this is somewhat incorrect. Biotech switched to vaccine focus before SARS2 and the reason for the rapid development was the groundwork done for a SARS(1) vaccine.
It is also worth noting, the mRNA part wasn't the innovative technology, but the nano lipid vehicle allowing immune evasion and cell fusion.
Because of that, the SARS2 pandemic fast tracked the tech for numerous targets and will benefit cancer medicine as well as future vaccine developments.
There are other cases in literature of viruses causing cancer to go into remission. If memory serves there have been cases of herpes viruses (chickenpox / herpex simplex) doing this. It's quite fascinating.
It's a nice story, and hopefully this leads to some useful therapy, but it's a sample size of _one_ person. There is no proof that the covid infection triggered remission, although it's a valid _hypothesis_.
Its called a case study - it usually the first step to multi-person large breadth studies.
Its a “we encountered X anomaly, which is very i interesting and hopeful, and we arent taking money to get lambos. Plz give funding”
Just the scientific method,
Case 0 (we are effed, ppl die. God will be done)
Case 1 (ooooh) - case study
Case E(mperical, study funding yay - larger chunk of department funding allotted)
Case E+1 Peer review, fellow/sister studies adding proof. Sometimes skipped for major which bring experience or reputation, often natural sciences due the existence of logical verification methods.
* For social sciences, we have tests such as ANOVA, Eta^2 and Omega^2 (McDonald’s reliability) - there is an absence of logical verifications here due to systemic constraints, ie: its impossible to do studies with (Inf) participants.
Case E+1 -> N+1 (proof or generialized applicability, or enough confidence to yolo a vaccine or medicine or new tech onto the population)
Edited: actually E comes before N and N+1 by expanding the case study to studies with control groups and more participants.
Thank you for laying this out. I remember in my early years as a aspiring scientific thinker, I fell into the trap of thinking things were gold standard or BS. This is the clearest breakdown I’ve seen of how knowledge actually solidifies in the real world (with Temporel and financial constraints considered). This or a refined version of it should be shared far more broadly!
Steal it please, what do you think about my modification?
I have MS (brain damage, makes me forgetful and erratic/eccentric) and suck at self promotion. I wouldnt know where to start.
In my editing bonanza, i cut an important step:
Case N(umerical hypothesis, doctoral work and more funding for the PhD: hypothesis getting formulated in more rigorous ways, maybe finding roots and improving on older methods, comparing with older methods, or disproving older methods)
I cant seem to edit the comment anymore, i will come back to it later today and see! For now, i posted it as a new submission and hope it finds audience
Sure. Spontaneous remission of cancer-- even later stage cancer-- happens frequently enough to be well documented in literature. And especially so with lymphomas etc.
As I understand it, having had Hodgkins when I was younger: Lymphoma will be called out specifically because lymphoma is potentially a relatively simple mutation. Cancer needs a bunch of unusual major characteristics from cells, and the lymphatic system already has all but one of those characteristics, it makes cells that are intended to wander about the body (whereas say your skin cells or brain cells are designed to always stay in one place), it sometimes makes lots of them (to fight disease, whereas most cells are replaced only slowly over a long period), however the cells aren't supposed to refuse to self-destruct. If a mutation disables the self-destruct in a lymphatic cell line now you've for a recipe for cancer.
So if it's just one or two mutations, on the one hand it becomes more likely that you get it (and we see lots of 20-something men get Hodgkins whereas obviously very few of them get stuff like lung cancer) and on the other hand it is easier to cure, basically just kill the patient slowly, cross fingers the cancer cells die first then you save the patient.
That's a very high level idea of the plan for the chemotherapy + radiotherapy used. In medicine the goal is to find reliable ways to do this that kill the fewest patients while reliably getting rid of the cancer, and then also aiming not to make the side effects suck too badly when you cure people (e.g. my lungs are trashed so that I permanently have a mild cough, which wasn't a huge annoyance for a middle aged guy who frankly doesn't eat well enough or exercise anyway, but I can see it'd ruin your life if you were previously a world class athlete and now you'll never achieve that potential). But obviously Mother Nature could very easily randomly cure some people from a single mutation by luck.
To add to your point, lymphoma is special because stage IV does not _inherently indicate mutagenic burden or tumor diversity.
Metastatic solid tumors _have to had "privilege escalation" mutations. AND those _indicate an overall greater genetic diversity.
As always diversity promotes adaptation and here evolutionary evasion of the disease.
However, staging incidentally still correlates with survival in non-hodgekins lymphoma as it's generally a nasty tissue class misbehaving. Treatment options got much, much better tho, with monoclonal antibodies and immune therapy.
Yes, as other have pointed out. I want to add, you also sometimes see spontaneous remission of distant lesions caused by local treatment, e.g. radiation therapy. There is research into exacerbating the tumor "auto-vaccination" by pretreating the lesion with immuno-stimulants.
Btw. 'full remission' doesn't mean cured, but clinical clearance or stagnation. Immune reactions may be limited to a major branch on the individual tree of lif.. death and other subclinical branches may emerge years later.
There are other cancers which may feature very high tissue differentiation/maturation (early) and are dependent on a certain trigger. E.g. treating heliobacter pylori or chlamydia with antibiotics, may cause full remission in MALT lymphoma.
The title of the paper is strongly misleading. Here is the whole basis of the article:
> Shortly after diagnosis he was admitted with breathlessness and wheeze and was diagnosed with PCR‐positive SARS‐CoV‐2
> Four months later, palpable lymphadenopathy had reduced and an interim PET/CT scan revealed widespread resolution of the lymphadenopathy and reduced metabolic uptake throughout
And the claim:
> We hypothesise that the SARS‐CoV‐2 infection triggered an anti‐tumour immune response
There are spontaneous remissions everywhere without identified causes. It's jumping to conclusions to assume that it was thanks to SARS-CoV-2 in that case.
"We hypothesise that the SARS‐CoV‐2 infection triggered an anti‐tumour immune response, as has been described with other infections in the context of high‐grade non‐Hodgkin lymphoma."
That suggests this has happened before and is not specific to this particular virus. Seems like an odd omission when you're after "the whole basis of the article".
It’d be pretty useless to only research and document phenomena that you already understand. But in case it seems that odd to you, here’s 16 other cases of cancer that went into remission after a viral infection:
My intention was to narrow my quotes around the elements that illustrated my point. I didn't mean to misrepresent what they were saying, thanks for stepping up and providing more context.
In spite of this, I still believe that the title is strongly misleading.
That made me try to find the remission rate of Hodgkins Lymphoma, and according to this 2005 paper [0] it is indeed very rare, the paper says that only 15 cases have been recorded. The interesting part: The patient in that paper had "complete remission during intensified care for interstitial pneumonia".
Fever may be an important factor. IIRC statistically people who had one severe fever in their life, have a lower incidence of cancer.
I think the double edged blade here is not the anti-viral response, but autoimmune reactions, which are excerbrated by tissue destruction and an overall activated immune system.
Cancer needs to gain immune cloaking and a viral infection may present the misbehaving cells by chance.
> We hypothesise that the SARS‐CoV‐2 infection triggered an anti‐tumour immune response
A completely different hypothesis: what if the tumor was sustained by the EBV infection, and SARS-CoV-2 displaced or outcompeted it? There are signs that viruses can compete and suppress each other, e.g. influenza rates have apparently dropped dramatically during the SARS-2 pandemic.
"Triggering an immune response" is probably the mechanism (perhaps tautologically: everything viruses do is done by commandeering the host's cells, and having them kill another virus would be classified as "immune response"), the difference is that viruses may have evolved ways to actively stimulate immunity against rival viruses.
There's no way to say that conclusively. Influenza also spreads via aerosols, and the size of the virion is in the same range as that of the coronavirus. It's unclear why the same physical measures, applied with the same degree of compliance, should fail to stop one but nearly completely stop the other.
