OBSERVATION
OC43, NL63, SARS-CoV-2 RBD, coronavirus disease 2019
CORONAVIRUS DISEASE 2019, MAY, CORONAVIRUS, CORONAVIRUS, HEAT
The influence of preexisting antibodies to the four endemic human coronaviruses (ehCoV) (229E, OC43, NL63, and HKU1) on severe (hospitalization) coronavirus disease 2019 (COVID-19) outcomes has not been fully characterized (The prospective association of severe COVID-19 with elevated ehCoV antibody levels at illness onset has not been investigated (This substudy of a larger trial (Antibodies that bind the spike proteins from 229E, NL63, OC43, HKU1, and SARS-CoV-2 were measured using the Meso Scale Diagnostics (MSD; Rockville, MD) V-PLEX COVID-19 coronavirus panel 3 IgG kit at a dilution of 1:5,000. Plates were read on a Meso QuickPlex SQ 120 instrument, and the arbitrary units (AU) were calculated using the MSD Discovery Workbench software according to the manufacturer’s protocol. For the samples in the spike competition experiment, purified recombinant full-length WA-1 SARS-CoV-2 spike protein (150 μg/mL) (The nonhospitalized subset (Characteristics of substudy participants compared to those in the parent study (In CCP donors, the ehCoV spike antibodies were 1.2 to 2 times greater than the control donor unit levels, while the donor CCP SARS-CoV-2 spike antibodies were more than 600 times the levels of the control units (ehCoV antibody levels in donors and nonhospitalized recipients in the early treatment outpatient CCP study. (A) Coronavirus antibody levels (arbitrary units [AU] per milliliter) shown in donor CCP (red circles; Endogenous human coronavirus (ehCoV) antibody levels in hospitalized participants in the early treatment outpatient CCP study. (A) Antibody levels (AU per milliliter) before and 30 min after transfusion of CCP in participants who were eventually hospitalized (red circles; (A) Coronavirus antibody levels (AU/mL) before and 30 min after transfusion of CCP in participants who were seropositive for SARS-CoV-2 RBD prior to transfusion (The increase in convalescent antibody levels against HKU1 and OC43 seen in this study, both of which are also betacoronaviruses, might be from cross-reactivity with elevated SARS-CoV-2 spike antibodies or induction of ehCoV-specific B cells to generate more ehCoV antibodies. We added purified SARS-CoV-2 spike at 150 μg spike/mL plasma (Competition of antibody signal with recombinant SARS-CoV-2 full-length spike protein: 13 donor units (red, no competition) were preincubated with 150 mcg recombinant WA-1 SARS-CoV-2 spike (Heterogeneity heat maps of antibody levels sorted by 229E indicated similar patterns among those hospitalized to those not hospitalized (Heterogeneity of viral antibody levels at the individual level with arbitrary units per milliliter depicted on log scale. (A) Antibody levels at enrollment (screening) for the 50 participants who were hospitalized, including those who received CCP or control plasma, sorted ascending by measured 229E. (B) Screening antibody levels for the 50 antibody-positive, vaccine-negative participants, including those who received CCP or control plasma, sorted ascending by measured 229E. (C) Screening antibody levels for the 100 antibody-negative, vaccine-negative participants who received control plasma, sorted ascending by measured 229E. (D) Screening antibody levels for the 100 antibody-negative, vaccine-negative participants who received CCP, sorted ascending by measured 229E. Download CCP and control plasma donors segregated by region of donation by the 4 ehCoV. CCP are indicated by red circles and control plasma by blue circles. CCP: Washington DC and Maryland (Individual CCP donors, sorted by date of donation during the collection period of the early treatment trial from 1 May to 30 September, for 229E (A), HKU1 (B), NL63 (C), and OC43 (D), with arbitrary units (AU) shown per milliliter. Download The antibody levels of ehCoV in COVID-19 convalescent plasma were only 2-fold different between the control and convalescent plasma. The volume of distribution of the plasma was 3 to 6 L. The measured fold dilution when transfused into healthy individuals was 25-fold with a 200-mL CCP transfusion (Measurement of the available 17 hospitalized participants in the COVID-19 convalescent plasma arm and the 34 in the control plasma arm indicated no absolute ehCoV antibody level differences between these two groups or with 250 other paired participants. Even combining all 51 hospitalized participants to compare them to the 250 participants not hospitalized at screening before transfusion showed no differences.In this study, the EhCoV antibody levels of those hospitalized and those not hospitalized were not distinguishable during the first week of illness, at which time there exists greatest risk for impact on severe COVID-19 outcome. Thus, it is unlikely that preexisting ehCoV antibodies in plasma have any clinically relevant impact on COVID-19 outcomes.