The Relationship Between COVID and Cancer (Part 2 of 3)

Part 2 of a 3-Part Interview With Dr. Arijit Chakravarty, "5 Years of the COVID Pandemic"

AC: Cancers were rising before SAR-CoV-2 showed up. In the 2010s, cancer rates were rising among young people. This can distort the signal caused by SARS-CoV-2 infections. If SARS-CoV-2 causes cancers to increase, if it is carcinogenic, it’ll take a big increase in that rate of cancer before people acknowledge that SARS-CoV-2 is now a contributing factor. Similarly, heart disease rates were rising anyway and now we have a virus that is causing increased heart attack risk.

And because it will be harder to see the signal for cancer, it means we are kicking the can down the road with all these delayed consequences. And then at the same time, it’s quite easy to hide the delayed consequences. And what that means is on the day that they acknowledge that this is what’s happening, we’ve locked in this huge burden of delayed disease that will take years to play out because people have already been infected many times over.

So, this is exactly how not to do it. When I said we are taking a primitive approach to disease, we are managing disease through allowing infections, which had never been done before.

The second thing is you’re basically throwing the precautionary principle out the window. That’s gone. And on top of that, to make matters worse, the very same people who have taken us down this path are out there taking a victory lap.

There’s all this talk about how there was overreaction during the “lockdowns.” Go look at Google mobility data. If you can spot the lockdown in that Google mobility data for 2020, your eyes are sharper than mine. Literally the lockdowns they called overreaction looked like a 30 percent decrease in people using public transit for three months. You must squint your eyes to see the drop in the number of people going into restaurants, number of people going into retail stores. You have to squint to see it. And it was literally for only a few months. And now, these legendary lockdowns which somehow happened without any of us noticing them are being blamed for all the deaths and illnesses the virus has caused.

Given this revisionist history, the narrative that’s being put on the table is that somehow these people were right all along; that it was absolutely the right thing to allow everybody to get infected repeatedly. When the bill comes due on all this, there will be no accountability because this will take a while to play out and all these people will be gone by then.

This is a difficult virus from a public health perspective, but public health couldn’t have handled it worse. Although it remains a solvable problem, the way it was addressed has undermined the ability of public health to do anything useful at this point, given the current leadership and controls over public health as they stand. They are doing nothing except reminding us to wash our hands and not eat raw eggs.

BM: On the topic of carcinogenesis of SARS-CoV-2, can you comment on some highlights you’d like to share from your manuscript before it’s published?

AC: The short version is that it’s very well documented that SARS-CoV-2 causes DNA double-strand breaks. [The reader can read this report in the journal Nature on the mechanisms SARS-CoV-2 employs in deregulating cellular machinery and causing DNA damage and the cell’s ability to repair these.] There have been multiple papers that show that it causes unrepaired DNA double-strand breaks. It also inhibits elements of the DNA repair machinery, some of which are oncogenes and some of which are tumor suppressors.

In the old conception of carcinogenesis, there was always emphasis on the role of oncogenes driving cancers. If you will, oncogenes can be viewed as the “accelerator” and tumor suppressor genes as “brakes.” There were billions of dollars spent on hundreds of drug discovery and development programs (“precision medicine”) across the pharma industry pursuing the oncogene addiction hypothesis. [See work by I Bernard Weinstein]. It hasn’t really panned out.

. . .you can make an obvious inference that if . . . cells keep getting infected and they keep dying and new cells come in, there’s going to be some subset of those cells that accumulate DNA double-strand breaks, and that are capable of cycling. That would be both necessary and sufficient to cause, for example, colorectal cancer.

There’s an alternative paradigm for thinking about what drives cancer, and that is the evolutionary paradigm (which I explained in a recent thread on social media). In this paradigm, the initiating event for cancer is the initiation of genomic instability, due to DNA double-strand breaks. Now ordinarily, if there are DNA double-strand breaks, the cell will arrest replication and either repair that damage, or if irreparable, initiate cell suicide to prevent propagating the errors to the daughter cells. But sometimes, the checkpoints that would have prevented cycling of cells with those breaks continuing to replicate are suppressed.

So now, these errors are not caught and repaired, and if a cell has accumulated enough DNA double-strand breaks, the cell can no longer maintain its complement of chromosomes. So, it becomes what’s called chromosomally unstable or genomically unstable. There are other ways to get to genomic instability, but for now, let’s just focus on chromosomal instability.

When you have chromosomal instability, when cancer cells divide, they reassort their chromosomes every time. That generates a tremendous amount of diversity. This evolution is what fuels the growth of cancer. There are multiple lines of evidence that show that cancer evolution is somatic clonal evolution. You have these different subclones within a patient that evolve differently. When people have done high-throughput sequencing of these, the genetic status of even different pieces within the same tumor is different. And when you go look at metastatic tumors, these are very different genetically from the primary tumor. To describe all this, it’s as if a bomb hit the genome, basically. That’s not consistent with just one dysregulated oncogene that is driving the cancer. Genes don’t drive evolution. Genes are acted upon by evolution.

BM: And how does SARS-CoV-2 impact that?

AC: It causes DNA double-strand breaks and suppresses DNA damage checkpoints.

The DNA double-strand break is the initiating event. Downstream of that you have the suppression of checkpoint signaling. In the process you get micronuclei, which are little fragments of DNA hanging out in nuclei of cells in interphase [of the cell cycle: a cell spends most of its time in what is called interphase, and during this time it grows, replicates its chromosomes, and prepares for cell division]. Guess what happens with SARS-CoV-2? We see micronuclei formation.

You might think, “Okay, this is happening, but it can’t be oncogenic because it’s not transforming any cells. So, if this happens in a quiescent cell [a cellular state in which a cell remains out of the cell cycle but retains the capacity to divide], who cares?”

Here’s the thing. SARS-CoV-2 doesn’t just infect cells that are not actively cycling [differentiated cells in mature tissues]. It’s very well documented to infect many different cell types, including cell types that are proliferating.

If you look in the liver or the gut where cells are constantly dividing and reproducing, there are also SARS-CoV-2 infections. In the crypts of the gut, you have cells dividing repeatedly. People have directly documented that SARS-CoV-2 infects those cells. And they’ve directly documented that it causes cell death.

Putting all this together, you can make an obvious inference that if those cells keep getting infected and they keep dying and new cells come in, there’s going to be some subset of those cells that accumulate DNA double-strand breaks, and that are capable of cycling. That would be both necessary and sufficient to cause, for example, colorectal cancer. Now you’re seeing an increase in colorectal cancer among the young already. The problem is that we saw that increase before COVID showed up. So, it’s very difficult to ascribe that increase specifically to SARS-CoV-2 infections. It’s like the worst of both worlds, frankly.

You can make the case inferentially from first principles logic that this is what would happen, and, indeed, it does happen. But if you try to show it epidemiologically, it’s very difficult because you’re dealing with the obscuring factor of a prior increase, which makes the point that when you have something that you can build a plausible case for—SARS-CoV-2 has the potential of driving carcinogenesis—waiting for enough epidemiological data to make that decision could be a huge mistake.

But that’s the route we’re on because every article indicating that SARS-CoV-2 can cause cancer also adds, “But it’s too early to tell.” But by the time we determine it’s not too early to tell, everybody will have been infected 20 times. SARS-CoV-2 causes the same genetic changes as every other virus known to cause cancer. [The idea that viruses can cause or lead to cancers is not new. Viruses like the Epstein-Barr virus, hepatitis B and hepatitis C viruses, HIV and human papillomavirus are well-known pathogens associated with malignancies.]

Continue reading with Part 3, "The Problem and A Solution: How Governments Have Failed at Addressing High-Pandemic-Risk Diseases Like COVID & What Can Be Done" in the Related Posts Below.

"Five years of the COVID-19 pandemic: An interview with Dr. Arijit Chakravarty" by Benjamin Mateus is republished with permission from WSWS.Org.