SARS-CoV-2-specific humoral immunity is supported by CD4+ T-cells and negatively correlated with Alphacoronavirus-specific antibody titers

[SNT Gatchaman]

SARS-CoV-2-specicific [sic] humoral immunity in convalescent patients with mild COVID-19 is supported by CD4+ T-cell help and negatively correlated with Alphacoronavirus-specific antibody titer
Marcus Odendahl, Iris Endler, Beate Haubold, Roman N. Rodionov, Stefan R. Bornstein, Torsten Tonn

(Accepted paper - but pre-proofed, with typographical errors)

Highlights

The majority of the examined mild COVID-19 patients and HIs recruited before 2019 show an immune response directed to various SARS-CoV-2 structural proteins.

The existence of an anti-SARS-CoV-2-reactive cellular immune response in HI suggests a pre-existing immunity to common cold HCoVs which share homology with SARS-CoV-2.

The humoral immunity to the S protein of SARS-CoV-2 in convalescent COVID-19 patients positively correlates with the SARS-CoV-2-reactive CD4+ T cells expressing Th1 cytokines indicating the generation of a robust cellular and humoral SARS-CoV-2-directed immunity.

Pre-existing humoral immunity to common cold HCoVs, particularly Alphacoronaviruses, may have an inhibitory imprint on the humoral immune response to SARS-CoV-2 infection in COVID-19 patients.​

Abstract
This study aimed at investigating the nature of SARS-CoV-2-specific immunity in patients with mild COVID-19 and sought to identify parameters most relevant for the generation of neutralizing antibody responses in convalescent COVID-19 patients.

In the majority of the examined patients a cellular as well as humoral immune response directed to SARS-CoV-2 was detected. The finding of an anti-SARS-CoV-2-reactive cellular immune response in healthy individuals suggests a pre-existing immunity to various common cold HCoVs which share close homology with SARS-CoV-2.

The humoral immunity to the S protein of SARS-CoV-2 detected in convalescent COVID-19 patients correlates with the presence of SARS-CoV-2-reactive CD4+ T cells expressing Th1 cytokines. Remarkably, an inverse correlation of SARS-CoV-2 S protein-specific IgGs with HCoV-NL63 and HCoV-229E S1 protein-specific IgGs suggests that pre-existing immunity to Alphacoronaviruses might have had an inhibitory imprint on the immune response to SARS-CoV-2-infection in the examined patients with mild COVID-19.

Link (Pre-proof)

 

[SNT Gatchaman]

Pre-existing immunity to certain other coronaviruses may lead to a cross-reactivity that fails to mount a response to SARS-CoV-2. This may explain the high rates of negative serology, especially in long haulers. Remember the French JAMA paper on patients merely believing they had had COVID?

The inhibitory effect of existing anti-HCoV-NL63 and anti-HCoV-229E S1 protein-specific IgGs may result from the suppression of activation of naive B cells and their subsequent proliferation and differentiation to plasma cells when a simultaneous binding of the antigen in the immune complex to the B cell receptor and to the inhibitory Fc-gammaR IIB occurs. A well-known example is the failure of seroconversion of babies when vaccinated against measles within 6 months after birth as a result of the acquisition of MV-specific antibodies via transplacental transfer of maternal IgGs. Since maternal IgGs have limited half-live MV vaccinations later are much more efficient.

Whether cross-reactive HCoVs-specific immunity is beneficial or detrimental with regard to the susceptibility to SARS-CoV-2 infection or severity of COVID-19 still remains somehow elusive. Recent findings indicate that pre-existing immunity to seasonal coronaviruses may increase the susceptibility to SARS-CoV-2.

In the majority of the examined mild COVID-19 patients and HIs recruited before 2019 an immune response directed to various SARS-CoV-2 structural proteins was detected. The finding of an anti-SARS-CoV-2-reactive cellular immune response in HI suggests a pre-existing immunity to common cold HCoVs which share homology with SARS-CoV-2. The humoral immunity to the S protein of SARS-CoV-2 detected in convalescent COVID-19 patients positively correlates with the presence of SARS-CoV-2-reactive CD4+ T cells expressing Th1 cytokines indicating the generation of a robust cellular and humoral SARS-CoV-2-directed immunity. The inverse correlation of SARS-CoV-2 S protein-specific IgGs with HCoV-NL63 and HCoV-229E S1 protein-specific IgGs suggest that pre-existing humoral immunity to common cold HCoVs, particularly Alphacoronaviruses, may have had an inhibitory imprint on the humoral immune response to SARS-CoV-2 infection detected in patients with mild COVID-19.