Thread by @nanogenomic

We know that the SARS-CoV-2 virus has evolved to bind to the ACE2 receptor approximately 10x stronger than SARS-CoV-1. ACE2 also circulates in the blood. There are several mechanisms whereby ACE2 will displace antibodies.

Let me elaborate.

Here is a great example to start off, from From Ju, B., Zhang, Q., Ge, X., Wang, R., Yu, J., Shan, S., ... & Ge, J. (2020). Potent human neutralizing antibodies elicited by SARS-CoV-2 infection. BioRxiv.

"Here, we report on the isolation and characterization of 206 RBD-specific monoclonal antibodies (mAbs) derived from single B cells of eight SARS-CoV-2 infected individuals."

"In samples from one patient selected for further analyses, we found coexistence of germline and germline divergent clones. Both clone types demonstrated impressive binding and neutralizing activity against pseudovirus and live SARS-CoV-2." (sounds great, right?)

"However, the antibody neutralizing potency is determined by competition with ACE2 receptor for RBD binding. The specificity and neutralizing characteristics of this plasma cross-reactivity requires further investigation."

What are the authors really saying? The authors are saying that recovered COVID patients DO generate strong antibodies against the virus. The antibodies just aren't as strong enough to outcompete ACE2 binding.

biorxiv.org/content/10.110…

Why are so many COVID patients getting chronic disease lasting for months or longer? Why are some people asymptomatic for up to 14 days before exhibiting symptoms? Could immune cloaking and ineffective antibody generation have a role in this?

Why are critically ill #SARSCoV2 patients producing "enormous numbers of antibody secreting cells"?

"COVID-19 has vexed clinicians across the globe with its spectrum of illness severity and seemingly maladaptive immune response."

"Through careful humoral immunophenotyping, the current study offers four important observations in the clinical course in cases of severe illness: 1. while ASCs are robustly expanded in serious infection, their presence cannot be considered a correlate of productive..."

"...or protective immunity. While the present studies do not address the possible production of anti-COVID-19 antibodies by the expanded ASC, their expansion in early infection carries an ominous prognosis."

"Whether this just a reflection of an exuberant inflammatory responses or indicates a direct role of ASC in pathogenic responses through the generation of pathogenic antibodies... remains to be determined."

medrxiv.org/content/medrxi…

Additionally, the "debunking" of patients who had COVID testing negative and then testing positive again, based on RNA testing, assumes that they were in fact not positive again because of false-positives towards "dead virus." THIS IS A BIG ASSUMPTION.
reuters.com/article/us-hea…

Anecdotal reports are surfacing all over social media, with many people complaining of chronic symptoms persisting for more than two months.
reddit.com/r/COVID19posit…

Dr. Anthony Fauci on Good Morning America:
“There’s an assumption — a reasonable assumption — that when you have an antibody that you are protected against reinfection. That has not been proven for this particular virus.”
ihoneida.com/2020/05/04/hea…

"A mild case of Covid-19 might not yield abundant, long-term antibodies. In China, one-third of survivors had very low antibody levels that might not protect them in the future."
discovermagazine.com/health/covid-1…

Repeat infection may be possible, and an antibody response does not guarantee protection against the virus.
Kellam, P., & Barclay, W. (2020). The Dynamics of Humoral Immune Responses Following SARS-CoV-2 Infection and the Potential for Reinfection.

bloomberg.com/news/articles/…

"Her experience adds to a growing number of reports of patients appearing to have a reactivation of symptoms, testing positive again, or even potentially being reinfected. Such incidents don’t align with the generally accepted understanding..."

nytimes.com/2020/04/13/opi…

COVID-19 is more chronic than is currently being reported, with long-term effects both neurological and vascular. Reinfection is likely to affect millions. Currently, more than one million people are infected with active cases in the USA. Very few cases reported as "recovered."

In addition to these severe issues, RNA vaccine approaches such as Moderna's, DNA vaccines, and recombinant spike protein vaccine technologies are likely to generate many of the wrong antibodies, which can lead to antibody-dependent enhancement and worsening of viral symptoms.