Antibody responses to known and unknown SARS-CoV-2 infections after mRNA vaccine booster

We followed a fully-vaccinated (two mRNA vaccine doses) community cohort (n=41) without prior COVID-19 diagnosis from September 2021 through March 2022 through the Omicron wave following a booster mRNA vaccination. 19.5% of participants reported a known SARS-CoV-2 infection during the Omicron wave, which was confirmed by anti-nucleocapsid IgG. An additional 36.5% also developed anti-nucleocapsid IgG after the boost, consistent with unknown, asymptomatic SARS-CoV-2 infection during this period. Infection defined by anti-nucleocapsid IgG, whether known to participant or not, increased anti-spike IgG levels, relative to those lacking anti-nucleocapsid IgG, at 120 days post-booster.

Low levels of protective humoral immunity following mild or asymptomatic infection with SARS-CoV-2 in a community-based serological study

The degree of protective humoral immunity after mild or asymptomatic SARS-CoV-2 infection is not known. We measured antibody-mediated neutralization of spike protein-ACE2 receptor binding--a surrogate measure of protection against SARS-CoV-2 infection--in a large and diverse community-based seroprevalence study. Comparisons were made across three groups of seropositive participants that differed in the severity of infection and engagement with clinical care (N=790). The clinical group was seropositive for prior infection, symptomatic, and diagnosed with COVID-19 by a healthcare provider. The symptomatic group was seropositive and reported one or more symptoms of infection but received no clinical care. The asymptomatic group was seropositive but reported no symptoms. 86.2% of all infections were mild or asymptomatic; 13.8% received clinical care. Of the clinical cases, 96.3% were outpatient; only 3.7% required hospitalization. Moderate or high levels of neutralizing activity were detected following 27.5% of clinical infections, in comparison with 5.4% of symptomatic and 1.5% of asymptomatic infections. The majority of infections in the general population are mild or asymptomatic and likely result in low levels of antibody-mediated protective immunity.

Comparison of IgG and neutralizing antibody responses after one or two doses of COVID-19 mRNA vaccine in previously infected and uninfected persons

ObjectiveTo compare anti-SARS-CoV-2 spike receptor binding domain (RBD) IgG antibody concentrations and antibody-mediated neutralization of spike-ACE2 receptor binding in vitro following vaccination of non-hospitalized participants by sero-status and acute virus diagnosis history. MethodsParticipants were studied before and after mRNA vaccination in a community-based, home-collected, longitudinal serosurvey; none reported hospitalization for COVID-19. Prior to vaccination, some reported prior positive acute viral diagnostic testing and were seropositive (COVID-19+). Participants who did not report acute viral diagnostic testing were categorized as seropositive or seronegative based on anti-spike RBD IgG test results. Primary measures were anti-spike RBD IgG concentration and percent antibody-mediated neutralization of spike protein-ACE2 interaction prior to vaccination, and after one or two doses of vaccine. ResultsOf 290 unique vaccine recipients, 42 reported a prior COVID-19 diagnosis and were seropositive (COVID-19+). Of the 248 with no history of acute viral diagnostic testing, 105 were seropositive and 143 seronegative before vaccination. The median age was 38yrs (range 21-83) with 65% female and 35% male; 40% were non-white. Responses were evaluated after one (n=140) or two (n=170) doses of BNT162b2/Pfizer or mRNA-1273/Moderna vaccine. After one dose, median post-vaccine IgG concentration and percent neutralization were each significantly higher among the COVID-19+ group (median 47.7 {micro}g/ml, IgG; >99.9% neutralization) compared to the seropositives (3.4 {micro}g /ml IgG; 62.8% neutralization) and seronegatives (2.2 {micro}g /ml IgG; 39.5% neutralization). The latter two groups reached >95% neutralization after the second vaccine dose. ConclusionsA prior outpatient COVID-19 diagnosis was associated with strong anti-spike RBD IgG and in vitro neutralizing responses after one vaccine dose. Persons seropositive for anti-spike RBD IgG in the absence of acute viral diagnostic testing, and those who were seronegative, required two doses to achieve equivalently high levels of IgG and neutralization activity. One mRNA vaccine dose is not sufficient to generate in vitro evidence of strong protection against COVID-19 among most persons previously infected with SARS-CoV-2, nor among seronegative persons.

Patterns and persistence of SARS-CoV-2 IgG antibodies in a US metropolitan site

BackgroundEstimates of seroprevalence to SARS-CoV-2 vary widely and may influence vaccination response. We ascertained IgG levels across a single US metropolitan site, Chicago, from June 2020 through December 2020. MethodsParticipants (n=7935) were recruited through electronic advertising and received materials for a self-sampled dried blood spot assay through the mail or a minimal contact in person method. IgG to the receptor binding domain of SARS-CoV-2 was measured using an established highly sensitive and highly specific assay. ResultsOverall seroprevalence was 17.9%, with no significant difference between method of contact. Only 2.5% of participants reported having had a diagnosis of COVID-19 based on virus detection, consistent with a 7-fold greater exposure to SARS-CoV-2 measured by serology than detected by viral testing. The range of IgG level observed in seropositive participants from this community survey overlapped with the range of IgG levels associated with COVID-19 cases having a documented positive PCR positive test. From a subset of those who participated in repeat testing, half of seropositive individuals retained detectable antibodies for 3-4 months. ConclusionsQuantitative IgG measurements with a highly specific and sensitive assay indicate more widespread exposure to SARS-CoV-2 than observed by viral testing. The range of IgG concentration produced from these asymptomatic exposures is similar to IgG levels occurring after documented non-hospitalized COVID-19, which is considerably lower than that produced from hospitalized COVID-19 cases. The differing ranges of IgG response, coupled with the rate of decay of antibodies, may influence response to subsequent viral exposure and vaccine. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=180 SRC="FIGDIR/small/20233452v3_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@f5986dorg.highwire.dtl.DTLVardef@1ea428dorg.highwire.dtl.DTLVardef@b758c9org.highwire.dtl.DTLVardef@1263310_HPS_FORMAT_FIGEXP M_FIG C_FIG

Differences in Variation of Human Immunodeficiency Virus Type 1 Sequences from Henan and Shanghai Regions of China / 中国病毒学

Illegally paid blood donation was a risk factor for HIV acquisition exclusively in Henan and Hubei Provinces of China, and not in Shanghai. Nucleotide sequences in the gag and env genes of HIV-1 were compared between isolates from Henan and Shanghai regions of China to test whether an expected higher degree of a common source of infections from this unique blood donation transmission risk would be evident as decreased variation among Henan isolates in an exploratory cross-sectional analysis. Among 38 isolates studied, 23 of 23 (100%) from Henan and 8 of 15 (54%) from Shanghai were subtype B. In addition, fewer sequence differences were found in gp41 of subtype B isolates from Henan than from Shanghai isolates. Further studies with additional controls are therefore warranted to confirm the role of the degree of a common source of infections in differences in HIV variation across populations.