scholarly journals SARS-CoV-2 virus masking of RBD epitopes; unmasking and cross-reactivity induced by mRNA vaccines

Author(s):  
Rafael Ramiro de Assis ◽  
Aarti Jain ◽  
Rie Nakajima ◽  
Algis Jasinskas ◽  
Saahir Kahn ◽  
...  

Abstract We analyzed data from two ongoing COVID-19 longitudinal serological surveys in Orange County, CA., between April 2020 and March 2021. A total of 8,476 finger stick blood specimens were collected before and after an aggressive mRNA vaccination campaign. IgG levels were determined using a multiplex antigen microarray containing 10 SARS-CoV-2 antigens, 4 SARS, 3 MERS, 12 Common CoV, and 8 Influenza antigens. Twenty-six percent of 3,347 specimens from unvaccinated Orange County residents in December 2020 were SARS-CoV-2 seropositive. The Ab response was predominantly against nucleocapsid (NP), full length spike and the spike S2 domain. Anti-receptor binding domain (RBD) reactivity was low and there was no cross-reactivity against SARS S1 or SARS RBD. An aggressive mRNA vaccination campaign at the UCI Medical Center started on December 16, 2020 and 6,724 healthcare workers were vaccinated within 3 weeks. Seroprevalence increased from 13% in December to 79% in January, 93% in February and 99% in March. mRNA vaccination induced much higher Ab levels especially against the RBD domain and significant cross-reactivity against SARS RBD and S1 was also observed. Nucleocapsid protein Abs can be used to distinguish individuals in a population of vaccinees to classify those who have been previously infected and those who have not, because nucleocapsid is not in the vaccine. Previously infected individuals developed higher Ab titers to the vaccine than those who have not been previously exposed. These results indicate that mRNA vaccination rapidly induces a much stronger and broader Ab response than SARS-CoV-2 infection.

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Rafael Assis ◽  
Aarti Jain ◽  
Rie Nakajima ◽  
Algis Jasinskas ◽  
Saahir Khan ◽  
...  

AbstractWe analyzed data from two ongoing COVID-19 longitudinal serological surveys in Orange County, CA., between April 2020 and March 2021. A total of 8476 finger stick blood specimens were collected before and after a vaccination campaign. IgG levels were determined using a multiplex antigen microarray containing antigens from SARS-CoV-2, SARS, MERS, Common CoV, and Influenza. Twenty-six percent of specimens from unvaccinated Orange County residents in December 2020 were SARS-CoV-2 seropositive; out of 852 seropositive individuals 77 had symptoms and 9 sought medical care. The antibody response was predominantly against nucleocapsid (NP), full length, and S2 domain of spike. Anti-receptor binding domain (RBD) reactivity was low and not cross-reactive against SARS S1 or SARS RBD. A vaccination campaign at the University of California Irvine Medical Center (UCIMC) started on December, 2020 and 6724 healthcare workers were vaccinated within 3 weeks. Seroprevalence increased from 13% pre-vaccination to 79% post-vaccination in January, 93% in February, and 99% in March. mRNA vaccination induced higher antibody levels than natural exposure, especially against the RBD domain and cross-reactivity against SARS RBD and S1 was observed. Nucleocapsid protein antibodies can be used to distinguish vaccinees to classify pre-exposure to SARS-CoV-2 Previously infected individuals developed higher antibody titers to the vaccine than non pre-exposed individuals. Hospitalized patients in intensive care with severe disease reach significantly higher antibody levels than mild cases, but lower antibody levels compared to the vaccine. These results indicate that mRNA vaccination rapidly induces a much stronger and broader antibody response than SARS-CoV-2 infection.


2021 ◽  
Vol 10 (18) ◽  
pp. 4204
Author(s):  
Marcello Salvaggio ◽  
Federica Fusina ◽  
Filippo Albani ◽  
Maurizio Salvaggio ◽  
Rasula Beschi ◽  
...  

The Pfizer/BioNtech Comirnaty vaccine (BNT162b2 mRNA COVID-19) against SARS-CoV-2 is currently in use in Italy. Antibodies to evaluate SARS-CoV-2 infection prior to administration are not routinely tested; therefore, two doses may be administered to asymptomatic previously exposed subjects. The aim of this study is to assess if any difference in antibody concentration between subjects exposed and not exposed to SARS-CoV-2 prior to BNT162b2 was present after the first dose and after the second dose of vaccine. Data were retrospectively collected from the clinical documentation of 337 healthcare workers who underwent SARS-CoV-2 testing before and after BNT162b2. Total anti RBD (receptor-binding domain) antibodies against SARS-CoV-2′s spike protein were measured before and 21 days after the first dose, and 12 days after the second dose of BNT162b2. Twenty-one days after the first dose, there was a statistically significant difference in antibody concentration between the two groups, which was also maintained twelve days after the second dose. In conclusion, antibody response after receiving BNT162b2 is greater in subjects who have been previously exposed to SARS-CoV-2 than in subjects who have not been previously exposed to the virus, both after 21 days after the first dose and after 12 days from the second dose. Antibody levels, 21 days after the first dose, reached a titer considered positive by the test manufacturer in the majority of subjects who have been previously infected with SARS-CoV-2. Evaluating previous infection prior to vaccination in order to give the least effective number of doses should be considered.


2021 ◽  
Author(s):  
Catherine Jacob-Dolan ◽  
Jared Feldman ◽  
Katherine McMahan ◽  
Jingyou Yu ◽  
Roland Zahn ◽  
...  

Vaccines are being rapidly developed with the goal of ending the SARS-CoV-2 pandemic. However, the extent to which SARS-CoV-2 vaccination induces serum responses that cross-react with other coronaviruses remains poorly studied. Here we define serum profiles in rhesus macaques after vaccination with DNA or Ad26 based vaccines expressing SARS-CoV-2 Spike protein followed by SARS-CoV-2 challenge, or SARS-CoV-2 infection alone. Analysis of serum responses showed robust reactivity to the SARS-CoV-2 full-length Spike protein and receptor binding domain (RBD), both included in the vaccine. However, serum cross-reactivity to the closely related sarbecovirus SARS-CoV-1 Spike and RBD, was reduced. Reactivity was also measured to the distantly related common cold alpha-coronavirus, 229E and NL63, and beta-coronavirus, OC43 and HKU1, Spike proteins. Using SARS-COV-2 and SARS-CoV-1 lentivirus based pseudoviruses, we show that neutralizing antibody responses were predominantly SARS-CoV-2 specific. These data define patterns of cross-reactive binding and neutralizing serum responses induced by SARS-CoV-2 infection and vaccination in rhesus macaques. Our observations have important implications for understanding polyclonal responses to SARS-CoV-2 Spike, which will facilitate future CoV vaccine assessment and development. Importance The rapid development and deployment of SARS-CoV-2 vaccines has been unprecedented. In this study, we explore the cross-reactivity of SARS-CoV-2 specific antibody responses to other coronaviruses. By analyzing responses from NHPs both before and after immunization with DNA or Ad26 vectored vaccines, we find patterns of cross reactivity that mirror those induced by SARS-CoV-2 infection. These data highlight the similarities between infection and vaccine induced humoral immunity for SARS-CoV-2 and cross-reactivity of these responses to other CoVs.


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S384-S385
Author(s):  
Bhagyashri D Navalkele ◽  
Jose Lucar ◽  
James B Brock ◽  
Jason Parham

Abstract Background Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 virus affected healthcare workers (HCWs) adding additional burden on staffing shortages. COVID-19 vaccination (mRNA 1273 and BNT162b2) has been shown to protect against severe disease, death and reduced risk of asymptomatic infection and transmission from fully vaccinated individuals. Here, we present the impact of COVID-19 vaccination (CoVac) on risk of developing COVID-19 based on test results among unvaccinated and vaccinated HCWs. Methods Our academic medical center with 11,785 HCWs on its Jackson campus initiated non-mandatory CoVac among HCWs with BNT162b2 on December 16, 2020. Individuals ≥ 2 weeks after 1st dose of vaccine were defined as partially vaccinated and those ≥2 weeks from 2nd dose of vaccine were defined as fully vaccinated. Per facility policy, all symptomatic HCWs (irrespective of vaccination status) were recommended to undergo SARS-CoV-2 RT-PCR testing. Asymptomatic HCWs were also tested upon household exposure, however, this policy was changed on March 9th 2021 to allow fully vaccinated asymptomatic HCWs to work without need for quarantine or testing. Universal masking policy among HCWs remained effective at our center during study period. Results Between the launch of COVID-19 vaccination on December 16, 2020 and April 30, 2021, 5,855 HCWs received one dose of vaccine, and 5,687 received both doses. A total of 1,329 unique HCWs underwent COVID-19 testing between January 4, 2021 and April 30, 2021. Of those, 217 (16.3%) tested positive for SARS-CoV-2 infection; 204 were unvaccinated, 7 were partially vaccinated, and 6 were fully vaccinated (figure 1). Of the 6 fully vaccinated employees, 1 was asymptomatic (testing for travel purposes), 4 had mild symptoms, and one elderly employee required hospitalization with oxygen supplementation and had a complete recovery. No facility outbreaks were reported related to asymptomatic, work exposed, fully vaccinated HCWs. Unvaccinated healthcare workers were more likely to test positive for SARS-CoV-2 compared to partially and fully vaccinated healthcare workers. Conclusion COVID-19 vaccination protected HCWs by reducing risk for developing COVID-19. Vaccinating healthcare workers is a crucial infection prevention measure to reduce disease burden, avoid staffing shortages and create a safe environment in the healthcare facility to prevent transmission to other staff and at-risk patients. Disclosures All Authors: No reported disclosures


2008 ◽  
Vol 29 (2) ◽  
pp. 111-115 ◽  
Author(s):  
Jennifer L. Kuntz ◽  
Stephanie Holley ◽  
Charles M. Helms ◽  
Joseph E. Cavanaugh ◽  
Jeff Vande Berg ◽  
...  

Objective.To determine the effect of a pandemic influenza preparedness drill on the rate of influenza vaccination among healthcare workers (HCWs).Design.Before-after intervention trial.Setting.The University of Iowa Hospitals and Clinics (UIHC), a large, academic medical center, during 2005.Subjects.Staff members at UIHC.Methods.UIHC conducted a pandemic influenza preparedness drill that included a goal of vaccinating a large number of HCWs in 6 days without disrupting patient care. Peer vaccination and mobile vaccination teams were used to vaccinate HCWs, educational tools were distributed to encourage HCWs to be vaccinated, and resources were allocated on the basis of daily vaccination reports. Logit models were used to compare vaccination rates achieved during the 2005 vaccination drill with the vaccination rates achieved during the 2003 vaccination campaign.Results.UIHC vaccinated 54% of HCWs (2,934 of 5,467) who provided direct patient care in 6 days. In 2 additional weeks, this rate increased to 66% (3,625 of 5,467). Overall, 66% of resident physicians (311 of 470) and 63% of nursing staff (1,429 of 2,255) were vaccinated. Vaccination rates in 2005 were significantly higher than the hospitalwide rate of 41% (5,741 of 14, 086) in 2003.Conclusions.UIHC dramatically increased the influenza vaccination rate among HCWs by conducting a pandemic influenza preparedness drill. Additionally, the drill allowed us to conduct a bioemergency drill in a realistic scenario, use innovative methods for vaccine delivery, and secure administrative support for future influenza vaccination campaigns. Our study demonstrates how a drill can be used to improve vaccination rates significantly.


Author(s):  
Ryan M Pace ◽  
Janet E Williams ◽  
Kirsi M Järvinen ◽  
Mandy B Belfort ◽  
Christina DW Pace ◽  
...  

Background: It is not known whether SARS-CoV-2 can be transmitted from mother to infant during breastfeeding, and if so whether the benefits of breastfeeding outweigh this risk. This study was designed to evaluate 1) if SARS-CoV-2 RNA can be detected in milk and on the breast of infected women, 2) concentrations of milk-borne anti-SARS-CoV-2 antibodies, and 3) the capacity of milk to neutralize SARS-CoV-2 infectivity. Methods: We collected 37 milk samples and 70 breast swabs (before and after breast washing) from 18 women recently diagnosed with COVID-19. Samples were analyzed for SARS-CoV-2 RNA using RT-qPCR. Milk was also analyzed for IgA and IgG specific for the nucleocapsid protein, receptor binding domain (RBD), S2 subunit of the spike protein of SARS-CoV-2, as well as 2 seasonal coronaviruses using ELISA; and for its ability to neutralize SARS-CoV-2. Results: We did not detect SARS-CoV-2 RNA in any milk sample. In contrast, SARS-CoV-2 RNA was detected on several breast swabs, although only one was considered conclusive. All milk contained SARS-CoV-2-specific IgA and IgG, and levels of anti-RBD IgA correlated with SARS-CoV-2 neutralization. Strong correlations between levels of IgA and IgG to SARS-CoV-2 and seasonal coronaviruses were noted. Conclusions: Our data do not support maternal-to-child transmission of SARS-CoV-2 via milk; however, risk of transmission via breast skin should be further evaluated. Importantly, milk produced by infected mothers is a source of anti-SARS-CoV-2 IgA and IgG and neutralizes SARS-CoV-2 activity. These results support recommendations to continue breastfeeding during mild-to-moderate maternal COVID-19 illness.


2021 ◽  
Author(s):  
Rafael Assis ◽  
Aarti Jain ◽  
Rie Nakajima ◽  
Al Jasinskas ◽  
Saahir Kahn ◽  
...  

AbstractWe analyzed data from two ongoing serologic surveys, a longitudinal cohort of health care workers (HCW) from the University of California Irvine Medical Center (Orange County, CA, USA), collected from May and December 2020 through March 2021, and a cross sectional county-wide study in July 2020 (actOC; Orange County, CA) and a more focused community study in the city of Santa Ana (Santa Ana Cares; Orange County, CA, USA), collected in December 2020 - in order to compare the antibody responses to SARS-CoV-2 natural infection and vaccination. In addition, we serially tested 9 volunteers at multiple time points to analyze the time course of vaccine-induced antibody response in more detail. In May 2020, 1060 HCW were enrolled and had finger stick samples collected. Finger stick samples were again collected in December 2020, before vaccination, as well as January, February and March 2021 during vaccination campaign. A total of 8,729 finger stick blood specimens were probed and analyzed for IgG and IgM antibodies using a coronavirus antigen microarray (COVAM).The microarray contained 10 SARS-CoV-2 antigens including nucleocapid protein (NP) and several varying fragments of the spike protein, as well as 4 SARS, 3 MERS, 12 Common CoV, and 8 Influenza antigens.Based on a random forest based prediction algorithm, between May and December, prior to vaccine rollout, we observed that seropositivity in the HCW cohort increased from 4.5% to 13%. An intensive vaccination campaign with mRNA vaccines was initiated on December 16, 2020 and 6,724 healthcare workers were vaccinated within 3 weeks. The observed seropositivity of the HCW specimens taken in the last week of January 2021 jumped to 78%, and by the last week in February it reached 93%, and peaked at 98% seropositive in March. The antibody profile induced by natural exposure differed from the profile induced after mRNA vaccination. Messenger RNA vaccines induced elevated antibody (Ab) reactivity levels against the Receptor Binding Domain (RBD) domain of SARS-CoV-2 spike, and cross-reactive responses against SARS and MERS RBD domains. Nucleocapsid protein (NP), which is an immunodominant antigen induced after natural exposure, is not present in the vaccine and can be used as a biomarker of past exposure. The results show that naturally-exposed individuals mount a stronger anti-spike response upon vaccination than individuals that were not previously exposed. Longitudinal specimens taken at approximately weekly intervals from 9 individuals show variation in the response to the mRNA vaccine, with some showing a vigorous response to the first dose (prime) and others requiring a subsequent dose (boost) to reach high anti-SARS-CoV-2 levels. Antibody titers determined by serial dilution of the specimens were used to accurately compare antibody levels in these samples. mRNA vaccinees after the boost have higher Ab titers (up to 10 times higher) than convalescent plasmas from donors who recovered from natural infection. The results of this study exemplify the time course and outcomes expected from similar mRNA mass vaccination campaigns conducted in other institutions.


Author(s):  
Cam Le ◽  
Erik Lehman ◽  
Thanh Nguyen ◽  
Timothy Craig

Lack of proper hand hygiene among healthcare workers has been identified as a core facilitator of hospital-acquired infections. Although the concept of hand hygiene quality assurance was introduced to Vietnam relatively recently, it has now become a national focus in an effort to improve the quality of care. Nonetheless, barriers such as resources, lack of education, and cultural norms may be limiting factors for this concept to be properly practiced. Our study aimed to assess the knowledge and attitude of healthcare workers toward hand hygiene and to identify barriers to compliance, as per the World Health Organization’s guidelines, through surveys at a large medical center in Vietnam. In addition, we aimed to evaluate the compliance rate across different hospital departments and the roles of healthcare workers through direct observation. Results showed that, in general, healthcare workers had good knowledge of hand hygiene guidelines, but not all believed in receiving reminders from patients. The barriers to compliance were identified as: limited resources, patient overcrowding, shortage of staff, allergic reactions to hand sanitizers, and lack of awareness. The overall compliance was 31%; physicians had the lowest rate of compliance at 15%, while nurses had the highest rate at 39%; internal medicine had the lowest rate at 16%, while the intensive care unit had the highest rate at 40%. In summary, it appears that addressing cultural attitudes in addition to enforcing repetitive quality assurance and assessment programs are needed to ensure adherence to safe hand washing.


Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 835
Author(s):  
Mohammed Noushad ◽  
Mohammad Zakaria Nassani ◽  
Anas B. Alsalhani ◽  
Pradeep Koppolu ◽  
Fayez Hussain Niazi ◽  
...  

The COVID-19 pandemic has caused largescale morbidity and mortality and a tremendous burden on the healthcare system. Healthcare workers (HCWs) require adequate protection to avoid onward transmission and minimize burden on the healthcare system. Moreover, HCWs can also influence the general public into accepting the COVID-19 vaccine. Therefore, determining COVID-19 vaccine intention among HCWs is of paramount importance to plan tailor-made public health strategies to maximize vaccine coverage. A structured questionnaire was administered in February and March 2021 among HCWs in Saudi Arabia using convenience sampling, proceeding the launch of the vaccination campaign. HCWs from all administrative regions of Saudi Arabia were included in the study. In total, 674 out of 1124 HCWs responded and completed the survey (response rate 59.9%). About 65 percent of the HCWs intended to get vaccinated. The intention to vaccinate was significantly higher among HCWs 50 years of age or older, Saudi nationals and those who followed the updates about COVID-19 vaccines (p < 0.05). The high percentage (26 percent) of those who were undecided in getting vaccinated is a positive sign. As the vaccination campaign gathers pace, the attitude is expected to change over time. Emphasis should be on planning healthcare strategies to convince the undecided HCWs into accepting the vaccine in order to achieve the coverage required to achieve herd immunity.


Author(s):  
Ayala Kobo-Greenhut ◽  
Ortal Sharlin ◽  
Yael Adler ◽  
Nitza Peer ◽  
Vered H Eisenberg ◽  
...  

Abstract Background Preventing medical errors is crucial, especially during crises like the COVID-19 pandemic. Failure Modes and Effects Analysis (FMEA) is the most widely used prospective hazard analysis in healthcare. FMEA relies on brainstorming by multi-disciplinary teams to identify hazards. This approach has two major weaknesses: significant time and human resource investments, and lack of complete and error-free results. Objectives To introduce the algorithmic prediction of failure modes in healthcare (APFMH) and to examine whether APFMH is leaner in resource allocation in comparison to the traditional FMEA and whether it ensures the complete identification of hazards. Methods The patient identification during imaging process at the emergency department of Sheba Medical Center was analyzed by FMEA and APFMH, independently and separately. We compared between the hazards predicted by APFMH method and the hazards predicted by FMEA method; the total participants’ working hours invested in each process and the adverse events, categorized as ‘patient identification’, before and after the recommendations resulted from the above processes were implemented. Results APFMH is more effective in identifying hazards (P &lt; 0.0001) and is leaner in resources than the traditional FMEA: the former used 21 h whereas the latter required 63 h. Following the implementation of the recommendations, the adverse events decreased by 44% annually (P = 0.0026). Most adverse events were preventable, had all recommendations been fully implemented. Conclusion In light of our initial and limited-size study, APFMH is more effective in identifying hazards (P &lt; 0.0001) and is leaner in resources than the traditional FMEA. APFMH is suggested as an alternative to FMEA since it is leaner in time and human resources, ensures more complete hazard identification and is especially valuable during crisis time, when new protocols are often adopted, such as in the current days of the COVID-19 pandemic.


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