Neat idea, although immune responses can be tissue specific (to a certain degree).
Nicholas Campbell
Karma: 3
MD here.
Could the coronavirus be interfering with the immune system in a way that is allowing Pneumocystis pneumonia to thrive?
A: Yes. COVID has been linked to CD4+ (T helper) lymphopenia, possible via cytokine storm. The main risk factor for PCP is CD4+ lymphoooenia caused by HIV.
My understanding is that Pneumocystis pneumonia, otherwise known as PJP or PCP, is caused by a fungus. It is highly opportunistic, and is rarely seen in people with healthy immune systems. It is highly associated with AIDS/HIV.
A: Its actually rarely seen with HIV these days (due to ART), useally in transplant or immunosupressed patients.
The fungus that causes it is widespread, and likely exists in the lungs of most healthy people.
I’m not sure about this one, but it seems relatively difficult to test for. Given it’s rarity, it seems it is most are assumed to have it if they present symptoms and are positive for HIV/AIDS. If they are suspected, it seems they test for HIV/AIDS first.
A: It is easy to test for (PCR for the gene or antibody based assays), but a bronchoscopy is needed to get fluid from the lung. As this causes aerosolization, this shouldn’t be done in a COVID patient. You are right to say that a positive test cannot distinguish between colonization or infection, although infectious burden (DNA copy number by PCR) is becoming a useful marker.
Symptoms sound similar, if not the same as coronavirus.
A: Yes, although PCP doesn’t cause a quick and spectacular deterioration like COVID.
CT scans of those suffering from coronavirus and PJP are very similar, and both are very different from more typical pneumonia.
A: Yes, but the image is really not specific and can be caused by any atypical infection, drug reaction or auto-immunity.
I have seen some papers that indicated the coronavirus may lower CD4 T-Cell counts, which is one of the reasons PJP is seen in HIV/AIDS patients. Not sure if this has been well studied and peer reviewed yet.
There exists a very effective treatment for PJP, Bactrim.
I could see how this might be overlooked given its rarity. Also I am not sure how much experience China has with HIV/AIDS and PJP. I also not an expert, and this might look foolish to someone who is more knowledgeable. I hope that person is out there and can weigh in.
A: You make an interesting point. Could the deterioration in COVID patients be caused by a secondary infection (PCP) due to COVID’s effects on the immune system?
I think that it is unlikely. One, the crash seen around day 7-10 in COVID patients is really rapid, happening in the course of a few hours/a day. This is strongly suggestive of an immune cause. Even a typical, aggressive bacterial. pneumonia wouldn’t progress that quickly. PCP is more indolent and symptoms progress over days to weeks.
Secondly, the immune suppression is too short for PCP to take hold. For example, when we do stem cell transplants, we kill off the host immune system. To prevent PCP, we start Bactrim around day 30 after the transplant. Despite the patient having next to no immune system for a month, I have never seen PCP develop in that time frame. In addition, after we treat PCP infection, we would start Bactrim at lower doses to prevent recurrence. Generally we have a couple of weeks before the risk of infection increases to start it.
So, in sum, interesting idea, outside the box and impressive if you are not in the medical field. But no, I really don’t think that this is what is happening.
The current evidence seems to point to immune dysregulation causing the severe cases. Generally, when there is such a wide discrepancy in symptoms (most patients are asymptomatic and a minority die in the ICU), something funky is going on in the immune system. There is clearly a cytokine storm happening in some patients (reflective of an inability to clear the viral infection) and this is probably causing the severe lung disease (ARDS-acute respiratory distress syndrome).
Why this is happening is unclear, personally i think that ADE (antibody dependent enhancement) may play a role. Briefly, an non-neutralizing antibody, possibly from previous coronavirus infection, binds the virus and the binds to the macrophage. The virus then infects the macrophage (which it can’t normally since the macrophage doesn’t express the receptor (ACE-2)) and replicates. Macrophage freaks out and activates, which can then activates CD4+ and CD8+ lymphocytes causing the cytokine storm. Incidentally, this has been well described in other infections that target macrophages, such as leishmania. For some unclear reason, the CD8+ lymphocytes can’t kill the macrophages.
Anyways, hope this helped.
″ At first blush SARS-CoV-2 is not doing anything all that different to the immune system than any other acute virus infection. ″
Not sure about this, it does seem to create a cytokine storm and lypmphopenia in a minority.