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1.
Preprint in English | bioRxiv | ID: ppbiorxiv-486173

ABSTRACT

Large-scale populations in the world have been vaccinated with COVID-19 vaccines, however, breakthrough infections of SARS-CoV-2 are still growing rapidly due to the emergence of immune-evasive variants, especially Omicron. It is urgent to develop effective broad-spectrum vaccines to better control the pandemic of these variants. Here, we present a mosaic-type trimeric form of spike receptor-binding domain (mos-tri-RBD) as a broad-spectrum vaccine candidate, which carries the key mutations from Omicron and other circulating variants. Tests in rats showed that the designed mos-tri-RBD, whether used alone or as a booster shot, elicited potent cross-neutralizing antibodies against not only Omicron but also other immune-evasive variants. Neutralizing antibody titers induced by mos-tri-RBD were substantially higher than those elicited by homo-tri-RBD (containing homologous RBDs from prototype strain) or the inactivated vaccine BBIBP-CorV. Our study indicates that mos-tri-RBD is highly immunogenic, which may serve as a broad-spectrum vaccine candidate in combating SARS-CoV-2 variants including Omicron.

2.
Morbidity and Mortality Weekly Report ; 70(4):109-113, 2021.
Article in English | GIM | ID: covidwho-1395395

ABSTRACT

The study analysed the screening rates for cervical cancer in women before and after the stay-away order was lifted. It found that the rates were lower after the order was lifted. Women with no cervix or a history of precancerous conditions were excluded from the study. Age-specific screening tests were calculated based on the screening rates for cervical cancer. The 2019 KPSC membership cohort included over four million women. The group's enrollment rate was stable over the previous years. In 2020, the screening rates for women aged 21 to 29 years were lower before and after the stay at home order was placed. These decreases were similar to those for women aged 30 to 65 years. The data collected by KPSC allowed us to evaluate the impact of HPV vaccinations caused by the COVID-19 pandemic. The results of the study showed that the prevalence of HPV screening decreased during the pandemic. The decline in cancer screening rates was similar across all ethnic and racial groups during the stay-at-home order. These findings are compatible with findings of a major decline in cancer screening during 2020 in other parts of the country. The COVID-19 pandemic presented various challenges to the healthcare system, including the need to maintain cancer screening. In California, for instance, many hospitals canceled elective procedures because of the pandemic. While providing care, the clinic staff and providers faced challenges in implementing COVID-19 protocols. Some of these included the use of personal protective equipment and establishing physical barriers. Patients were also reluctant to visit the clinic due to their fear of contracting COVID-19 infection. The closure of the facility led to a spike in telehealth visits.

3.
Preprint in English | bioRxiv | ID: ppbiorxiv-448958

ABSTRACT

The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 is an attractive target for COVID-19 vaccine developments, which naturally exists in a trimeric form. Here, guided by structural and computational analyses, we present a mutation-integrated trimeric form of RBD (mutI tri-RBD) as a broadly protective vaccine candidate, in which three RBDs were individually grafted from three different circulating SARS-CoV-2 strains including the prototype, Beta (B.1.351) and Kappa (B.1.617). The three RBDs were then connected end-to-end and co-assembled to possibly mimic the native trimeric arrangements in the natural S protein trimer. The recombinant expression of the mutI tri-RBD, as well as the homo-tri-RBD where the three RBDs were all truncated from the prototype strain, by mammalian cell exhibited correct folding, strong bio-activities, and high stability. The immunization of both the mutI tri-RBD and homo-tri-RBD plus aluminum adjuvant induced high levels of specific IgG and neutralizing antibodies against the SARS-CoV-2 prototype strain in mice. Notably, regarding to the "immune-escape" Beta (B.1.351) variant, mutI tri-RBD elicited significantly higher neutralizing antibody titers than homo-tri-RBD. Furthermore, due to harboring the immune-resistant mutations as well as the evolutionarily convergent hotspots, the designed mutI tri-RBD also induced strong broadly neutralizing activities against various SARS-CoV-2 variants, especially the variants partially resistant to homo-tri-RBD. Homo-tri-RBD has been approved by the China National Medical Products Administration to enter clinical trial (No. NCT04869592), and the superior broad neutralization performances against SARS-CoV-2 support the mutI tri-RBD as a more promising vaccine candidate for further clinical developments.

4.
MMWR Morb Mortal Wkly Rep ; 70(4): 109-113, 2021 Jan 29.
Article in English | MEDLINE | ID: covidwho-1112895

ABSTRACT

On March 19, 2020, the governor of California issued a statewide stay-at-home order to contain the spread of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19).* The order reduced accessibility to and patient attendance at outpatient medical visits,† including preventive services such as cervical cancer screening. In-person clinic visits increased when California reopened essential businesses on June 12, 2020.§ Electronic medical records of approximately 1.5 million women served by Kaiser Permanente Southern California (KPSC), a large integrated health care system, were examined to assess cervical cancer screening rates before, during, and after the stay-at-home order. KPSC policy is to screen women aged 21-29 years every 3 years with cervical cytology alone (Papanicolaou [Pap] test); those aged 30-65 years were screened every 5 years with human papillomavirus (HPV) testing and cytology (cotesting) through July 15, 2020, and after July 15, 2020, with HPV testing alone, consistent with the latest recommendations from U.S. Preventive Services Task Force.¶ Compared with the 2019 baseline, cervical cancer screening rates decreased substantially during the stay-at-home order. Among women aged 21-29 years, cervical cytology screening rates per 100 person-months declined 78%. Among women aged 30-65 years, HPV test screening rates per 100 person-months decreased 82%. After the stay-at-home order was lifted, screening rates returned to near baseline, which might have been aided by aspects of KPSC's integrated, organized screening program (e.g., reminder systems and tracking persons lost to follow-up). As the pandemic continues, groups at higher risk for developing cervical cancers and precancers should be evaluated first. Ensuring that women receive preventive services, including cancer screening and appropriate follow-up in a safe and timely manner, remains important.


Subject(s)
COVID-19/prevention & control , Delivery of Health Care, Integrated , Early Detection of Cancer/statistics & numerical data , Quarantine/legislation & jurisprudence , Uterine Cervical Neoplasms/prevention & control , Adult , Aged , COVID-19/epidemiology , California/epidemiology , Female , Humans , Middle Aged , Young Adult
5.
Preprint in English | bioRxiv | ID: ppbiorxiv-431566

ABSTRACT

The pandemic of the COVID-19 disease caused by SARS-CoV-2 has led to more than 100 million infections and over 2 million deaths worldwide. The progress in the developments of effective vaccines and neutralizing antibody therapeutics brings hopes to eliminate the threat of COVID-19. However, SARS-CoV-2 continues to mutate, and several new variants have been emerged. Among the various naturally-occurring mutations, the E484K mutation shared by both the 501Y.V2 and 501Y.V3 variants attracted serious concerns, which may potentially enhance the receptor binding affinity and reduce the immune response. In the present study, the molecular mechanism behind the impacts of E484K mutation on the binding affinity of the receptor-binding domain (RBD) with the receptor human angiotensin-converting enzyme 2 (hACE2) was investigated by using the molecular dynamics (MD) simulations combined with the molecular mechanics-generalized Born surface area (MMGBSA) method. Our results indicate that the E484K mutation results in more favorable electrostatic interactions compensating the burial of the charged and polar groups upon the binding of RBD with hACE2, which significantly improves the RBD-hACE2 binding affinity. Besides that, the E484K mutation also causes the conformational rearrangements of the loop region containing the mutant residue, which leads to more tight binding interface of RBD with hACE2 and formation of some new hydrogen bonds. The more tight binding interface and the new hydrogen bonds formation also contribute to the improved binding affinity of RBD to the receptor hACE2. In addition, six neutralizing antibodies and nanobodies complexed with RBD were selected to explore the effects of E484K mutation on the recognition of these antibodies to RBD. The simulation results show that the E484K mutation significantly reduces the binding affinities to RBD for most of the studied neutralizing antibodies, and the decrease in the binding affinities is mainly owing to the unfavorable electrostatic interactions caused by the mutation. Our studies revealed that the E484K mutation may improve the binding affinity between RBD and the receptor hACE2, implying more transmissibility of the E484K-containing variants, and weaken the binding affinities between RBD and the studied neutralizing antibodies, indicating reduced effectiveness of these antibodies. Our results provide valuable information for the effective vaccine development and antibody drugs design.

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