Improving SARS-CoV-2 variants monitoring in the absence of genomic surveillance capabilities: a serological study in Bolivian blood donors in October 2021 and June 2022 (preprint)

Unlike genomic data, serological data have not been previously leveraged to evaluate the SARS-CoV-2 variants circulation. In Bolivia, sustained genomic surveillance capacities were lacking especially at the beginning of the pandemic. In 2021 and 2022 we estimated the prevalence of anti-SARS-CoV-2 antibodies in Bolivian blood donors and explored the feasibility of using virus serum neutralization data for variants thought to have circulated to map their circulation across all departments over a year-long follow-up period. Anti-S1 and anti-NCP SARS-CoV-2 IgGs were studied, along with virus neutralization tests for ancestral-D614G, Gamma, Delta, and Omicron BA.1 lineages of SARS-CoV-2. Between 2021 and 2022, the overall prevalence of anti-S1 and anti-NCP antibodies increased reaching values over 90%, demonstrating that a large proportion of the Bolivian population was no longer naive to the virus. Viral neutralization data, analyzed through multiple approaches, revealed the spread of the Gamma variant up to 2021, particularly impacting northern departments. In 2022, Gamma continued to circulate in southernmost departments of the country and the emergence of Omicron BA.1 was detected. These trends align with publicly available genomic data from neighboring countries. Our serological analyses successfully identified both new antigenic groups, such as Omicron BA.1, and individual variants related to previously circulating groups, such as Delta. The study contributes insights into overall population immunity to SARS-CoV-2 and variant-specific immunity levels across different regions of Bolivia. It also emphasizes the potency of seroprevalence studies in informing public health decisions and underscore their value in capturing the initial phases of emerging epidemics when variant diversity is limited, facilitating timely genomic surveillance setup.

SARS-CoV-2 IgG seroprevalence surveys in blood donors before the vaccination campaign, France 2020-2021 (preprint)

SUMMARY We conducted a cross-sectional study for SARS-CoV-2 anti-S1 IgG prevalence in French blood donors (n=32605), from May-2020 to January-2021. A mathematical model combined seroprevalence with daily number of hospital admissions to estimate the probability of hospitalization upon infection and determine the number of infections while correcting for antibody decay. There was an overall seroprevalence increase over the study period and we estimate that ∼15% of the French population had been infected by SARS-CoV-2 by January-2021. The infection/hospitalization ratio increased with age, from 0.56% (18-30yo) to 6.75% (61-70yo). Half of the IgG-S1 positive individuals had no detectable antibodies 4 to 5 months after infection. The seroprevalence in group O donors (7.43%) was lower (p=0.003) than in A, B and AB donors (8.90%). We conclude, based on seroprevalence data and mathematical modelling, that the overall immunity in the French population before the vaccination campaign started was too low to achieve herd immunity.

Protein scaffold-based multimerization of soluble ACE2 efficiently blocks SARS-CoV-2 infection in vitro (preprint)

Soluble ACE2 (sACE2) decoy receptors are promising agents to inhibit SARS-CoV-2 as they are not affected by common escape mutations in viral proteins. However, their success may be limited by their relatively poor potency. To address these challenges, we developed a highly active multimeric sACE2 decoy receptor via a SunTag system that could neutralize both pseudoviruses bearing SARS-CoV-2 spike protein and SARS-CoV-2 clinical isolates. This fusion protein demonstrated a neutralization efficiency nearly 250-fold greater than monomeric sACE2. SunTag in combination with a more potent version of sACE2 achieved near complete neutralization at a sub-nanomolar range, which is comparable with clinical monoclonal antibodies. We demonstrate that this activity is due to greater occupancy of the multimeric decoy receptors on Spike protein as compared to monomeric sACE2. Overall, these highly potent multimeric sACE2 decoy receptors offer a promising treatment approach against SARS-CoV-2 infections including its novel variants.

Infectivity of Adult and Pediatric COVID-19 Patients (preprint)

We report infectivity of adult and pediatric COVID-19 patients in presence of  viral shedding and anti-SARS-CoV-2  antibody response A total of 408 consequent samples from eleven adult and five pediatric patients with SARS-CoV-2 infection were included. The samples every second day from saliva, nasopharynx, feces, serum, urine, tear were studied by RT-PCR and viral culture. Anti-SARS-CoV-2 antibodies were measured. The median duration of RNA shedding in all specimens was 7(2-15) days in adults and 5(3-19) days in children. The median duration from onset of symptoms to admission was three days.The viral RNA was positive in 44.7 % of the nasopharynx and 37.6% of saliva samples up 16 days in adults and 19 days in chldren. The latest viral culture positivity was detected on day 8 of symptoms in nasopharynx. The viral RNA was found in 6.1% of feces, 4.4% ofserum, 4.3 % of tear, 2.9% of urine. The earliest seroconversion was the 7th day for adults and 8th day for children. Atthe 14th day, total antibody positivity was 78% in adults, and 80% in children. After seroconversion, the viral RNA was still detected in the nasopharynx and saliva of three patients, however, the infectious virus was not present. Earlier hospital admission could be associated with shorter SARS-CoV-2 RNA shedding. The infectivity of patient is very low after 8 days of symptoms. The risk of fecal-oral transmission is very low, and strict hand hygiene measures could be preventive. The positive antibody test result could be used as a discharge criterion.