Global Analysis of SARS-CoV-2 Serology, Part 2

We sought to assess pre-vaccination and post-vaccination seroprevalences of anti-SARS-CoV-2 antibodies in Kuwait and to compare antibody levels between vaccine types. In phase 1 (pre-vaccination period, n = 19,363), blood samples were collected before the launch of COVID-19 vaccination in Kuwait between 1 September and 31 December 2020. Blood samples for phase 2 (post-vaccination period, n = 4973) were collected between 1 September and 30 November 2021. We tested subjects for anti-SARS-CoV-2 antibodies using the DiaSorin LIAISON^® SARS-CoV-2 IgM and Trimeric S IgG tests. In the pre-vaccination period, the prevalence of SARS-CoV-2 IgM and IgG was 14.50% (95% CI: 14.01–15.00) and 24.89% (95% CI: 24.29–25.50), respectively. The trend of seropositivity increased with age and was higher for females and non-Kuwaiti participants (p < 0.0001). Interestingly, seroprevalence was significantly higher for those who had received one dose of BNT162b2 (95.21%) than those who had received one dose of ChAdOx1-nCov-19 (92.86%). In addition, those who reported receiving two doses had higher seroprevalence, 96.25%, 95.86%, and 94.93% for ChA-dOx1-nCov-19/AstraZeneca, mix-and-match, and BNT162b2 recipients, respectively. After the second dose, median spike-specific responses showed no significant difference between ChAdOx1-nCov-19 and BNT162b2. Furthermore, statistical analysis showed no significant difference between median anti-trimeric S antibody levels of vaccinated individuals according to sex, age, or nationality (p > 0.05). In contrast, a negative correlation between age and anti-trimeric S IgG titers of BNT162b2-vaccinated subjects was observed (r = −0.062, p = 0.0009). Antibody levels decreased with time after vaccination with both vaccines. Our findings indicate that seroprevalence was very low during the pre-vaccination period (25%) in the general population and was greater than 95% in the vaccinated population in Kuwait. Furthermore, ChAdOx1-nCov-19 and BNT162b2 are effective in generating a similar humoral response. Full article

Background: Many serological assays to detect SARS-CoV-2 antibodies were developed during the COVID-19 pandemic. Differences in the detection mechanism of SARS-CoV-2 serological assays limited the comparability of seroprevalence estimates for populations being tested. Methods: We conducted a systematic review and meta-analysis of serological assays used in SARS-CoV-2 population seroprevalence surveys, searching for published articles, preprints, institutional sources, and grey literature between 1 January 2020, and 19 November 2021. We described features of all identified assays and mapped performance metrics by the manufacturers, third-party head-to-head, and independent group evaluations. We compared the reported assay performance by evaluation source with a mixed-effect beta regression model. A simulation was run to quantify how biased assay performance affects population seroprevalence estimates with test adjustment. Results: Among 1807 included serosurveys, 192 distinctive commercial assays and 380 self-developed assays were identified. According to manufacturers, 28.6% of all commercial assays met WHO criteria for emergency use (sensitivity [Sn.] >= 90.0%, specificity [Sp.] >= 97.0%). However, manufacturers overstated the absolute values of Sn. of commercial assays by 1.0% [0.1, 1.4%] and 3.3% [2.7, 3.4%], and Sp. by 0.9% [0.9, 0.9%] and 0.2% [−0.1, 0.4%] compared to third-party and independent evaluations, respectively. Reported performance data was not sufficient to support a similar analysis for self-developed assays. Simulations indicate that inaccurate Sn. and Sp. can bias seroprevalence estimates adjusted for assay performance; the error level changes with the background seroprevalence. Conclusions: The Sn. and Sp. of the serological assay are not fixed properties, but varying features depending on the testing population. To achieve precise population estimates and to ensure the comparability of seroprevalence, serosurveys should select assays with high performance validated not only by their manufacturers and adjust seroprevalence estimates based on assured performance data. More investigation should be directed to consolidating the performance of self-developed assays. Full article

Background: The emergence of the Omicron variant (B.1.1.529), which correlated with dramatic losses in cross-neutralization capacity of post-vaccination sera, raised concerns about the effectiveness of COVID-19 vaccines against infection and disease. Several clinically relevant sub-variants subsequently emerged rapidly. Methods: We evaluated published and pre-print studies reporting sub-variant specific reductions in cross-neutralization compared to the prototype strain of SARS-CoV-2 and between sub-variants. Median fold-reduction across studies was calculated by sub-variant and vaccine platform. Results: Among 178 studies with post-vaccination data, after primary vaccination the sub-variant specific fold-reduction in neutralization capacity compared to the prototype antigen varied widely, from median 4.2-fold for BA.3 to 40.1-fold for BA.2.75; in boosted participants fold-reduction was similar for most sub-variants (5.3-fold to 7.0-fold); however, a more pronounced fold-change was observed for sub-variants related to BA.4 and BA.5 (10.4-fold to 14.2-fold). Relative to BA.1, the other Omicron sub-variants had similar neutralization capacity post-primary vaccination (range median 0.8-fold to 1.1-fold) and post-booster (0.9-fold to 1.4-fold) except for BA.4/5-related sub-variants which was higher (2.1-fold to 2.7-fold). Omicron sub-variant-specific responder rates were low post-primary vaccination (range median 28.0% to 65.9%) compared to the prototype (median 100%) but improved post-booster (range median 73.3% to 100%). Conclusions: Fold-reductions in neutralization titers were comparable post-booster except for sub-variants related to BA.4 and BA.5, which had higher fold-reduction. Assessment after primary vaccination was not possible because of overall poor neutralization responses causing extreme heterogeneity. Considering large fold-decreases in neutralization titers relative to the parental strain for all Omicron sub-variants, vaccine effectiveness is very likely to be reduced against all Omicron sub-variants, and probably more so against variants related to BA.4 or BA.5. Full article

Primary series vaccination with BNT162b2 followed by a booster 5 months later has been recommended for healthy adolescents. We aimed to describe the immunogenicity in a fractional dose of BNT162b2. Adolescents aged 12–18 years were randomized into six arms for primary series administration: 3wPZ30/30 (reference group), 3wPZ30/20, 3wPZ20/20, 6wPZ30/30, 6wPZ30/20, and 6wPZ20/20 μg. A booster was given at 5 months after the second dose using either 10 or 15 μg of BNT162b2. Immunogenicity following vaccination was determined by IgG against receptor-binding domain (anti-S-RBD IgG; BAU/mL), surrogate virus neutralization test (sVNT; %inhibition) and pseudovirus neutralization (pVNT;ID₅₀) against Omicron. Non-inferiority criteria were defined as a lower boundary of the geometric mean ratio (GMR) being greater than 0.67. From September to October 2021, 118 adolescents with a median age (IQR) of 14.9 years (13.9–16.7) were enrolled. Fourteen days after the primary series, the geometric means (GMs) of anti-S-RBD IgG (BAU/mL) were 3090 (95% CI 2761–3460) in 3wPZ30/30. The GMRs of anti-S-RBD were: 0.80 (95% CI 0.67–0.97) in 3wPZ30/20; 1.00 (95% CI 0.83–1.20) in 3wPZ20/20; 1.37 (95% CI 1.13–1.65) in 6wPZ30/30; 1.24 (95% CI 1.02–1.50) in 6wPZ30/20; and 1.36 (1.13–1.64) in 6wPZ20/20. After a booster dose with 15 μg (n = 24) of BNT162b2, sVNT and pVNT against Omicron variant were 91.6 (95% CI 88.4–94.9) and 331 (95% CI 221–495), respectively. In the group that received 10 μg of BNT162b2 (n = 25), sVNT was 85.6 (95% CI 80.0–91.6) and pVNT was 397 (95% CI 267–590). Healthy adolescents had good immune responses to the fractional dose regimen of BNT162b2 and this may be considered as an alternative option. Full article

Despite the intense research work since the beginning of the pandemic, the pathogenesis of COVID-19 is not yet clearly understood. The previous mechanism of COVID-19, based on ACE2 tropism and explained through a single receptor, is insufficient to explain the pathogenesis due to the absence of angiotensin-converting enzyme 2 (ACE2) receptors in most of the affected organs. In the current study, we used the PatchDock server to run a molecular docking study of both the gonadotropin-releasing hormone receptor (GnRHR) and G-protein-coupled-receptor (GPCR) with the SARS-CoV-2 spike protein. Molecular Dynamics (MD) simulations were run to analyze the stability of the complexes using the GROMACS package. The docking results showed a high affinity between the spike protein with the GnRHR (−1424.9 kcal/mol) and GPCR (−1451.8 kcal/mol). The results of the MD simulations revealed the significant stability of the spike protein with the GnRHR and GPCR up to 100 ns. The SARS-CoV-2 spike protein had strong binding interactions with the GPCRs and GnRHRs, which are highly expressed in the brain, endocrine organs, and olfactory neurons. This study paves the way towards understanding the complex mechanism of neuroendocrine involvement and peripheral organ involvement, may explain the changing symptoms in patients due to new variants, and may lead to the discovery of new drug targets for COVID-19. In vitro studies involving genetic engineering or gene knockdown of the GPCRs and GnRHRs are needed to further investigate the role of these receptors in COVID-19 pathogenesis. Full article

The heterogeneity of the severity of symptoms of COVID-19 experienced by the young and healthy individuals is poorly understood. The present study was undertaken to mainly examine whether the respective diets and the type of symptoms experienced by patients are predictive of having long COVID-19. Disease severity was assessed with a symptomatology questionnaire and used to group 55 participants in asymptomatic (AS), mild symptoms (S) and long COVID (LC). We found that experiencing a higher number of symptoms as well as fatigue were predictors of developing LC whereas those who experienced rhinorrhea were less likely to develop LC. Blood samples were also taken to measure vitamin D [25(OH)D] concentrations and duration of spike IgG antibodies. In this study, serum 25(OH)D was not significantly different between 3 symptom groups with median (IQR) ng/mL levels of 22.0 (12.3) in the AS, 22.3 (7.5) in S, and 24.9 (9.4) in the LC group (p ≥ 0.05). The duration of IgG antibody response was found to vary greatly, with some individuals showing raised IgG over a year after infection. To examine whether dietary factors can influence the severity of symptoms, diet was analysed using 4–7-day food diaries as well as a Food Frequency Questionnaire (FFQ). Some nutrients such as vitamin E, polyunsaturated fatty acids, fibre, and iron were associated with lower severity of COVID-19. Lower intake of vitamin E was associated with having LC with a median (IQR) intake of 6.2 mg (3.8) seen in LC vs. 8.6 mg (7.2) in the AS group (p = 0.047). This pilot study has highlighted a few differences in the number and type of symptoms experienced by the young non-hospitalised individuals with mild and long COVID-19 and identified a few dietary components for their potential protective role against long COVID-19, however, the findings need to be confirmed with further large scale studies. Full article