1 It is not all about ACE2 in #Covid-19 and #LongCovid. The SARS-CoV-2 spike also binds with high affinity to a ubiquitous and abundant cell surface protein: the transferrin receptor.

Human transferrin receptor can mediate SARS-CoV-2 infection
pnas.org/doi/10.1073/pn… 2 "SARS-CoV-2 has been detected in almost all organs of COVID-19 patients, although some of the organs express little or no ACE2. Single-cell sequencing indicates that SARS-CoV-2 is present in diverse immune cells, which do not express ACE2 ..."

1 Analysis of gene expression from the cerebrospinal fluid of those with #LongCovid cognitive impairments is consistent with a persistent SARS-CoV-2 viral infection. A very good article based on the complex Rutger's research. @AEscalanteMD psychologytoday.com/intl/blog/shou… 2 The actual research paper: cell.com/cell-reports-m…

Strong evidence for viral persistence in those with #LongCovid for an average of 2+ years. Digital transcriptomics to detect viral RNAs in the blood of long-haulers. Also reduced immunometabolism in many and higher levels of IgE. 2) Q. What does the viral ORF7a protein do? A. It helps the virus hide by decreasing Interferon type I production in infected cells.

"Ubiquitination of SARS-CoV-2 ORF7a promotes antagonism of interferon response"

Another pair of promising biomarkers suitable for a blood-based #LongCovid diagnostic test.

Not only that, direct evidence of SARS-CoV-2 VIRAL PERSISTENCE even in those with Long Covid for more than 2 years.

"We demonstrate SARS-CoV-2 viral RNA persistence in Long COVID patients compared to matched post-pandemic controls, at higher frequencies than recently reported at the protein level ... and for a longer period after acute COVID-19 infection (>24 months vs. 10-14 months)."

1/3 "A 2-gene biomarker, including FYN and SARS-CoV-2 antisense RNA, correctly classifies Long COVID with 93.8% sensitivity and 91.7% specificity."

2/3

1/5 From my informal 2023 Symptom Survey survey of those with #LongCovid,  more than 1/3rd had a gap between their initial #Covid infection and the start of their long-haul symptoms. 
I call this "Delayed Onset Long Covid".
#CovidIsNotOver #COVID19 2/5      Of those with a delay before developing #LongCovid symptoms, 2/3rds reported moderate or strenuous exercise in the week before first developing symptoms.    Note, I put walks or hikes longer than 2 hours in the moderate exercise category.

My summary of the recent Cell paper on Serotonin and #LongCovid. Several important puzzle pieces from U Penn researchers and @MaayanLevy_Lab

-> Viral inflammation drives serotonin deficiency

As in acute COVID-19, serotonin levels were strongly decreased by other viral infections (Figure 2B), suggesting that this might be a more general characteristic of systemic viral infection.
Collectively, these findings suggest that the pathway of viral RNA sensing and type I interferon induction by TLR3 (a cellular pathogen sensor) leads to serotonin depletion (Figure 2Q).

1/4) Almost a year later and still no commercially available #LongCovid tests. Yet we have two good blood plasma biomakers; ANG-1 and P-SEL from the Toronto research of Patel et al, 2022.
molmed.biomedcentral.com/articles/10.11… 2/4) In my opinion, this should be a standard medical lab test available for any patient suspected of possible Long Covid.

Basic research has shown that Amantadine increases autophagy and reduces Hepatitis A viral replication. @AMannanBaig Similarly, a few compounds that induce autophagy have been shown to reduce SARS-CoV-2 replication in cells. nature.com/articles/s4146…

1/5 A new #Covid_19 autopsy study finds viral persistence in the cartilage rings surrounding the bronchi in the lungs. These patients were testing negative by PCR for Covid-19 but had persistent lung inflammation - eventually resulting in their death. doi.org/10.1002/path.6… 2/5 POTENTIALLY, viral persistence in the bronchial cartilage could relate to the chest/rib pains experienced by many with Long Covid #pwLC and Post-Vax symptoms #vaccineinjuries This is one of the top 30 symptoms from my informal patient surveys. recoverfromlongcovid.com/vaccine-injure…

#LongCovid
1/3 Viral persistence and spike shedding may decrease the amount of ACE2 in some cell types and tissues. 2012 research showed that knock-out of the ACE2 gene in mice resulted in greatly increased inflammation in the gut following intestinal damage. 2/3
POTENTIALLY, this is a factor for those with Long Covid.
"genetic inactivation of ... ACE2 results in severe colitis following intestinal injury. "

ncbi.nlm.nih.gov/pmc/articles/P…

Two promising biomarkers for long covid in the blood. Two factors, ANG-1 and P-SEL involved in blood vessel inflammation - at about 90 days post infection. The researchers still need to follow long-haulers over time to see how the levels change. molmed.biomedcentral.com/articles/10.11… "two vascular biomarkers were identified that distinguished Long-COVID patients from acutely ill COVID-19 inpatients and healthy control subjects (accuracy of 96%). Our data suggest that both of the two, ANG-1 and P-SEL, have potential as disease biomarkers"

A logical reason for Tinnitus and Dizziness - viral infection of the Inner Ear. nature.com/articles/s4385… "Here, we describe patients with COVID-19 and new-onset of hearing loss, tinnitus and/or dizziness."

A little known but potentially important clinical trial using a mixed probiotic for mild Covid-19 for 30 days. 3 of the 4 strains were Lactobacillus plantarum strains. ab21probiotic.com The majority of #longhaulers, experience a flare-up of their symptoms after taking just one capsule of L plantarum. Sometimes for 3 or 4 or 5 days. This may be stimulating Type I interferon production via one of our cell's Pathogen Recognition Receptors: cGAS