ABSTRACT
During early 2021, Peru had the highest COVID-19-associated per-capita mortality rate globally. Socioeconomic inequality and insufficiently prepared healthcare and surveillance systems likely contributed to high mortality, potentially coupled with early SARS-CoV-2 introduction. We tested 1,441 individuals with fever sampled during August 2019-May 2021 in Lima, Peru, for SARS-CoV-2-specific antibodies. Serologic testing included a chemiluminescence immunoassay and confirmatory surrogate virus neutralization testing. Early positive samples (n=24) from January-March 2020 were further tested using a plaque-reduction neutralization and avidity tests based on SARS-CoV-2 spike and nucleoprotein antigens. None of the early samples were PRNT-confirmed, in contrast to 81.8% (18/22) of a subsample from April 2020 onwards (Fischer-exact test, p<0.0001). SARS-CoV-2 antibody detection rate was 0.9% in mid-April 2020 (1/104; 95% confidence interval (CI), 0.1-5.8%), suggesting onset of viral circulation in early-mid March 2020, consistent with the first molecular detection of SARS-CoV-2 in Peru on March 6th. Mean avidity increase of 62-77% to 81-94% from all PRNT-confirmed samples during early 2020, were consistent with onset of SARS-CoV-2 circulation during late February/March 2020. Early circulation of SARS-CoV-2 was confirmed in a Susceptible, Exposed, Infected and Recovered mathematical model that projected an effective reproduction number >1, during February-March 2020. Robust serologic testing thus confirmed that early SARS-CoV-2 introduction contributed to high COVID-19 mortality in Peru. Emphasizing the role of diagnostic confirmation, our study highlights the importance of early detection and accurate testing in managing infectious disease outbreaks.
Subject(s)
Fever , Communicable Diseases , COVID-19ABSTRACT
Since SARS-CoV-2 emerged in China, it has spread rapidly around the world. Effective vaccines and therapeutics for SARS-CoV-2−induced disease (coronavirus disease 2019; COVID19) are urgently needed. In order to assess the immune response to immunization with SARS-CoV-2 and the ability of the immune serum to neutralize the virus infection, we immunized a llama ( Lama glama) with the inactivated SARS-CoV-2 virus, and tested serum samples with an ELISA assay specific to the SARS-CoV-2, and viral neutralization by plaque-reduction neutralization test (PRNT). An increase in seroreactivity was observed for the immunized llama from week 4 onward, revealing seroconversion induced by the immunization, with the highest antibody titers on the 8 th boost. On the reactive serum sample, we performed Western Blot analysis that confirmed the positive ELISA findings, and antibodies from immune serum recognized various viral proteins. The gold standard PRNT showed a visible viral neutralization corresponding with ELISA results. Thus, our findings suggest this llama hyperimmune serum as a possible source of therapeutically antibodies against the SARS-CoV-2 virus infections to evaluate in further studies.
Subject(s)
COVID-19 , Severe Acute Respiratory SyndromeABSTRACT
The COVID-19 pandemic has claimed the lives of millions of people worldwide and threatens to become an endemic problem, therefore the need for as many types of vaccines as possible is of high importance. Because of the millions of doses required, it is desirable that vaccines are not only safe and effective, but also easy to administer, store, and inexpensive to produce. Newcastle Disease Virus (NDV) is responsible for a respiratory disease in chickens. It has no pathogenic homologue in humans. NDV is recognized as an oncolytic virus, and its use in humans for oncological treatment is being evaluated. In the present work, we have developed two types of NDV-vectored candidate vaccines, which carry the surface-exposed RBD and S1 antigens of SARS-CoV-2, respectively. These vaccine candidates were produced in specific-pathogen-free embryonating chicken eggs, and purified from allantoic fluid before lyophilization. These vaccines were administered intranasally to three different animal models: mice, rats and hamsters, and evaluated for safety, toxicity, immunogenicity, stability and efficacy. Efficacy was evaluated in a challenge assay against active SARS-CoV-2 virus in the Golden Syrian hamster model. The NDV-vectored vaccine based on the S1 antigen was shown to be safe and highly immunogenic, with the ability to neutralize SARS-CoV-2 in-vitro, even with an extreme dilution of 1/640. Our results reveal that this vaccine candidate protects the lungs of the animals, preventing cellular damage in this tissue. In addition, this vaccine reduces the viral load in the lungs, suggesting that it may significantly reduce the likelihood of transmission. Being lyophilized, this vaccine candidate is very stable and can be stored for several months at 4-8{degrees}C. In conclusion, our NDV-based vaccine candidate has shown a very favorable performance in the pre-clinical study, serving as evidence for a future evaluation in a Phase-I human clinical trial. This candidate represents a promising tool in the fight against COVID-19.