So a physician, one with expertise in teaching medicine and in treating Covid-19 patients, read my earlier article here: The Longhaulers Hidden Virus Hypothesis (updated). I’m not giving his name because he hasn’t decided whether he’d like to support this hypothesis or not yet. He’s looking into it further. And certainly, since I’m not a doctor or a researcher, I could be wrong. But I am looking into this idea further myself. He mentioned that other cell types are immune privileged, other than the ones I mentioned, which were the anagen hair follicles and the CNS. So let’s take a look at those other cell types.

Important Note: Late in the day on August 18th, I happened across an article on longhauler syndrome proposing the same idea, which I had thought was original to me; it’s not. William Petri, M.D., Ph.D., professor of medicine at the University of Virginia, has proposed the same concept, that longhauler syndrome is caused by the virus hiding in immune privileged cells. (Embarrassed emoji x 100!) Anyway, I will keep working on this hypothesis, even though I was not the first to think of it.

Let’s review all the immune privileged cells (IPCs) and see if Longhaulers have symptoms indicating that the virus has infected those cells. Note well, however, that for the hypothesis to be correct, not every type of IPC has to be infected with the virus in every person. What will support the hypothesis further is if many longhaulers have symptoms in each IPC type.

The Central Nervous System (CNS) is the most important system that contains IPCs. As explained in my previous article here, the most common and most severe symptoms of longhauler syndrome are CNS symptoms. In addition, the same previous article notes that anagen hair follicles are also IPCs, and longhaulers often have the symptom of their hair falling out! — That is the symptom that, to my mind, confirmed this hypothesis as on the right track.

Other IPCs: eyes, testes, ovaries, placenta, and fetus [3]

We have two studies, non-scientific, but they are the most comprehensive data so far available on longhaulers symptoms. Their references are in the Endnotes [1, 2].

1. Survivor Corps’ Long Hauler Symptoms Survey Report, by Dr. Lambert et al.
2. The Patient-Led Research Team Survey by a team of Covid-19 patients from the “Body Politic” Slack Group and other volunteers.

These will be termed the “Survivor Corp Survey” and the “Patient-Led Survey” for short. They both report substantial and unusual symptoms in the eyes, which could be from a viral infection. Let’s review these.

The Eyes

The eyes are immune privileged. So do longhaulers have eye symptoms, what are they, and might those symptoms be explained by the presence of the SARS-CoV-2 virus?

The Survivor Corp Survey: “While the impact of COVID-19 on the lungs and vascular system have received some media and medical attention, the results of this survey suggest that brain, whole body, eye, and skin symptoms are also frequent-occurring health problems for people recovering from COVID-19” [2].

The brain and the eye are immune privileged sites (IPS). The eye symptoms reported in the Survivor Corps Survey included: floaters or flashes of light in vision, blurry vision, dry eyes, and eye stye or infection.

Then the Patient-Led Survey reported eye symptoms including: eye burning, changes to the eye (including eye discharge and redness on the outside of the eye), sensitivity to light, blurry vision, and double vision.

These symptoms could be explained by the infection of cells in the eyes by SARS-CoV-2. And the symptoms were reported to be common, not unusual, among longhaulers.

Testes and Ovaries

No symptoms that could be related to the testes or ovaries were reported in the two surveys.

However, a study published in Andrologia found that Covid-19 does affect the testes [4]:

“This might be the first direct evidence for the influence of COVID-19 on testicles’ ability to produce sex hormones; however, the results of this study should be followed by a more direct analysis of the seminal fluid of COVID-19 patients to evaluate the effect-if any-on sperm count, volume, morphology or motility. It has been reported that SARS-CoV causes orchitis in addition to other complications (Xu et al., 2006), so it is also possible that SARS-CoV-2 may cause the same complication in males.” [4]

Another study [8] reported two important results: First, that out of 34 patients, “Six patients (19%) demonstrated scrotal discomfort suggestive of viral orchitis around the time of COVID-19 confirmation.” [8] Second, that the cells of the testes show “sparse expression of ACE2 and TMPRSS2, with almost no overlapping gene expression,” [8] meaning that almost no cell types of both ACE2 and TMPRSS2, and both are thought to be needed for the typical path of cell infection.

The Placenta and Fetus

A study published in Modern Pathology is titled: “SARS-CoV-2 can infect the placenta and is not associated with specific placental histopathology: a series of 19 placentas from COVID-19-positive mothers.” [5]. That study found virus in placental cells, even though they are immune privileged, as did another study [7]. A third study found that the virus can be transmitted through the placenta to the fetus [6]. However, this was not common; only 2 of 22 pregnant Covid-19 patients transmitted virus to, and caused the infection of, the fetus.

Fortunately, infection of the placenta and transmission to the fetus is uncommon. However, this does prove that SARS-CoV-2 can reach the immune privileged cells: the placenta and the fetus. The fetus is immune privileged in the sense that the unborn child is isolated via the placenta from the mother.

Summary

The SARS-CoV-2 virus can infect every type of immune privileged cell, including in the CNS, the anagen hair follicles, the placenta and fetus, the eyes, and the testes. I could not find any evidence of infection of the ovaries, but it is likely from the aforementioned cases that this is also possible.

Therefore, the hypothesis, first asserted by William Petri, M.D., Ph.D., that longhaulers is cased by the infection of IPCs by the Covid-19 virus is supported by multiple studies and surveys showing that the IPCs do show evidence of infection by the symptomology, or, in the case of the placenta and fetus, by the identification of the virus itself.

The Longhaulers Hidden Virus Hypothesis is worthy of further study. Physicians treating Longhaulers patients should consider that at least some of the medications they use should be able to permeate the blood-brain barrier, in order to reach the virus in the CNS.

Ronald L. Conte Jr.
The author is neither a physician nor a healthcare professional.

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Endnotes:

1. Lambert, N. J. & Survivor Corps., COVID-19 “Long Hauler” Symptoms Survey Report. Indiana University School of Medicine; 2020; Report Link (PDF)

2. “What Does COVID-19 Recovery Actually Look Like?”, Analysis of the Prolonged COVID-19 Symptoms Survey by Patient-Led Research Team; Generated from survey data organized by decentralized team of COVID-19 patients; Report created and written by volunteers from the COVID-19 Body Politic Slack Group including: Gina Assaf, Hannah Davis, Lisa McCorkell, Hannah Wei., O’Neil Brooke, Athena Akrami, Ryan Low, Jared Mercier, and Adetutu A. Survey Authors and Contributors Include: Gina Assaf., Tina L., Annie C., Monica S., Jared Mercier, Lauren N., Noel H., JD Davids, and Susie. Report released on May 11th, 2020 by PatientResearchCovid19.com; Report Link (PDF)

3. Vojnits, K., and Y. Li. “The current knowledge of immune privilege in stem cells.” J Transplant Stem Cel Biol 1.1 (2014): 4.

4. Batiha, Osamah, et al. “Impact of COVID-19 and other viruses on reproductive health.” Andrologia: e13791.

5. Hecht, Jonathon L., et al. “SARS-CoV-2 can infect the placenta and is not associated with specific placental histopathology: a series of 19 placentas from COVID-19-positive mothers.” Modern Pathology (2020): 1-12.

6. Patanè, L., et al. “Vertical transmission of coronavirus disease 2019: severe acute respiratory syndrome coronavirus 2 RNA on the fetal side of the placenta in pregnancies with coronavirus disease 2019-positive mothers and neonates at birth.” Am. J. Obstet. Gynecol. MFM 100145 (2020).

7. Hosier, Hillary, et al., “SARS-CoV-2 infection of the placenta.” August 17, 2020. J Clin Invest. 2020. Study

8. Pan, Feng, et al. “No evidence of SARS-CoV-2 in semen of males recovering from COVID-19.” Fertility and sterility (2020).