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

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)

 

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?