14 Nov 2020 Episode 84 Humoral Immunity

Sat, 11/14/2020 - 21:38

Episode 84: News on the role of neutralizing antibodies:

  • Lack of protection against reinfection
  • Nevertheless, evidence of long-term B cell memory and maturation, due intestinal persistence of SARS-CoV-2.
  • Therapeutic value of convalescent plasma, (normal) human Ig and SARS-COV-2 specific monoclonal antibodies remains uncertain.  



Symptomatic SARS-CoV-2 re-infection of a health care worker in a Belgian nosocomial outbreak despite primary neutralizing antibody response.  (Episode 84 Ref 1 Selhorst medRxiv 9 Nov 2020


The symptomatic re-infection (in a young immune competent HCW) occurred after an interval of 185 days, despite the development of an effective humoral immune response following symptomatic primary infection.

The second episode, however, was milder and characterized by a fast rise in serum IgG and neutralizing antibodies.

…., the HCW formed a transmission cluster with 3 patients and showed evidence of virus replication but not of neutralizing antibodies in her nasopharyngeal swabs.


Evolution of Antibody Immunity to SARS-CoV-2 ( Episode 84 Ref 2Gaebler medRxiv 5 Nov 2020)


Humoral memory response in a cohort of 87 individuals assessed at 1.3 and 6.2 months after infection.

  1. Decrease of antibodies:
    • IgM, and IgG anti-SARS-CoV-2 spike protein receptor binding domain (RBD) antibody titers decrease significantly with IgA being less affected.
    • Neutralizing activity in plasma decreases by five-fold in pseudotype virus assays.


  1. In contrast, the number of RBD-specific memory B cells is unchanged. Memory B cells display clonal turnover after 6.2 months, and the antibodies they express have greater somatic hypermutation, increased potency and resistance to RBD mutations, indicative of continued evolution of the humoral response.


  1. Analysis of intestinal biopsies obtained from asymptomatic individuals 3 months after COVID-19 onset, revealed persistence of SARS-CoV-2 in the small bowel of 7 out of 14 volunteers.


We conclude that the memory B cell response to SARS-CoV-2 evolves between 1.3 and 6.2 months after infection in a manner that is consistent with antigen persistence.


Why will it never be known if convalescent plasma (CP) is effective for COVID-19 (Episode 84 Ref 3 Rojas J Transl Autoimmunity 2 Nov 2020)


Herein we report that RCTs of CP disclose a high methodological variability in inclusion criteria, outcomes, appropriate selection of donors, dosage, concentration of neutralizing antibodies and times of transfusion.


Therefore, at this time there is insufficient evidence to recommend for or against the use of CP as a treatment for COVID-19.



Intravenous Immunoglobulin (IVIG) Significantly Reduces Respiratory Morbidity in COVID-­19 Pneumonia: A Prospective Randomized Trial (Episode 84 Ref 4a Soulakas medRxiv 25 July): clearly this product contains purified Ig from healthy donors (Octagram 10% see Episode 84 Ref 4b).  Nevertheless in this small open RCT it seemed to have a clear beneficial effect on several clinical paramters and FDA approved the conduction of a phase 3 multicenter trial  (see Episode 84 Ref 4c)


SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19 (Episode 84 Ref 5 Chen NEJM 28 Oct 2020)  

In this interim analysis of a phase 2 trial BALZE-1, one of three doses of neutralizing antibody LY-CoV555 (Bamlanivimab)  appeared to accelerate the natural decline in viral load over time, whereas

the other doses had not by day 11.

On days 2 to 6, the patients who received LY-CoV555 had a slightly lower severity of symptoms than those who received placebo.

The percentage of patients who had a Covid-19–related hospitalization or visit to an emergency department was 1.6% in the LY-CoV555 group and 6.3% in the placebo group.



Bamlanivimab (Elly) FDA authorized for emergency use (Episode 84 Ref 6 see Press release 9 Nov https://investor.lilly.com/node/43931/pdf  and http://pi.lilly.com/eua/bamlanivimab-eua-factsheet-hcp.pdf)


Bamlanivimab is a recombinant, neutralizing human IgG1 monoclonal antibody (mAb) directed against the spike protein of SARS-CoV-2.

The BLAZE-1 data show bamlanivimab, when given early in the disease course, may help patients clear the virus and reduce COVID-related hospitalizations

To be administered as soon as possible after positive COVID test in patients at high risk for progressing to severe COVID-19 and/or hospitalization

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