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1.
Cell Host Microbe ; 2022 Oct 21.
Article in English | MEDLINE | ID: covidwho-2118002

ABSTRACT

The rapid emergence of SARS-CoV-2 variants challenges vaccination strategies. Here, we collected 201 serum samples from persons with a single infection or multiple vaccine exposures, or both. We measured their neutralization titers against 15 natural variants and 7 variants with engineered spike mutations and analyzed antigenic diversity. Antigenic maps of primary infection sera showed that Omicron sublineages BA.2, BA.4/BA.5, and BA.2.12.1 are distinct from BA.1 and more similar to Beta/Gamma/Mu variants. Three mRNA COVID-19 vaccinations increased neutralization of BA.1 more than BA.4/BA.5 or BA.2.12.1. BA.1 post-vaccination infection elicited higher neutralization titers to all variants than three vaccinations alone, although with less neutralization to BA.2.12.1 and BA.4/BA.5. Those with BA.1 infection after two or three vaccinations had similar neutralization titer magnitude and antigenic recognition. Accounting for antigenic differences among variants when interpreting neutralization titers can aid the understanding of complex patterns in humoral immunity that informs the selection of future COVID-19 vaccine strains.

2.
Int J Environ Res Public Health ; 19(22)2022 Nov 08.
Article in English | MEDLINE | ID: covidwho-2110064

ABSTRACT

This study aimed to evaluate the effect of hand hygiene interventions on the overall hand hygiene (HH) status of teaching instruction of hand hygiene in kindergartens, given the vulnerability of kindergarten children and their high risk due to infectious diseases and the current COVID-19 epidemic. We investigated the HH status of teachers from two kindergartens in the same community. The participants were recruited from 28 classes in both kindergartens. After completing the baseline survey, the intervention program consisted of three components: lectures on infectious diseases, lectures on HH, and seven-step hand washing techniques conducted in two kindergartens. The intervention program effectively increased teachers' perceived disease susceptibility (p < 0.05), reduced the total bacterial colonization of children's hands (p < 0.001), and improved the HH environment (p < 0.01). We recommend that health authorities or kindergartens adopt this HH intervention program to effectively improve the HH status in kindergartens and allow for preventive responses to the COVID-19 epidemic or other emerging infectious diseases.


Subject(s)
COVID-19 , Hand Hygiene , Child , Humans , COVID-19/epidemiology , COVID-19/prevention & control , Guideline Adherence , Hand Disinfection , Schools
3.
J Virol ; 96(17): e0114022, 2022 09 14.
Article in English | MEDLINE | ID: covidwho-2001778

ABSTRACT

The SARS-CoV-2 Omicron variants were first detected in November 2021, and several Omicron lineages (BA.1, BA.2, BA.3, BA.4, and BA.5) have since rapidly emerged. Studies characterizing the mechanisms of Omicron variant infection and sensitivity to neutralizing antibodies induced upon vaccination are ongoing by several groups. In the present study, we used pseudoviruses to show that the transmembrane serine protease 2 (TMPRSS2) enhances infection of BA.1, BA.1.1, BA.2, and BA.3 Omicron variants to a lesser extent than ancestral D614G. We further show that Omicron variants have higher sensitivity to inhibition by soluble angiotensin-converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G. The Omicron variants also more efficiently used ACE2 receptors from 9 out of 10 animal species tested, and unlike the D614G variant, used mouse ACE2 due to the Q493R and Q498R spike substitutions. Finally, neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7- to 8-fold less potent than the D614G. These results provide insights into the transmissibility and immune evasion capacity of the emerging Omicron variants to curb their ongoing spread. IMPORTANCE The ongoing emergence of SARS-CoV-2 Omicron variants with an extensive number of spike mutations poses a significant public health and zoonotic concern due to enhanced transmission fitness and escape from neutralizing antibodies. We studied three Omicron lineage variants (BA.1, BA.2, and BA.3) and found that transmembrane serine protease 2 has less influence on Omicron entry into cells than on D614G, and Omicron exhibits greater sensitivity to endosomal entry inhibition compared to D614G. In addition, Omicron displays more efficient usage of diverse animal species ACE2 receptors than D614G. Furthermore, due to Q493R/Q498R substitutions in spike, Omicron, but not D614G, can use the mouse ACE2 receptor. Finally, three doses of Pfizer/BNT162b2 mRNA vaccination elicit high neutralization titers against Omicron variants, although the neutralization titers are still 7- to 8-fold lower those that against D614G. These results may give insights into the transmissibility and immune evasion capacity of the emerging Omicron variants to curb their ongoing spread.


Subject(s)
Angiotensin-Converting Enzyme 2 , Antibodies, Neutralizing , COVID-19 , Immune Evasion , SARS-CoV-2 , Virus Internalization , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/immunology , Angiotensin-Converting Enzyme 2/metabolism , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , BNT162 Vaccine/administration & dosage , BNT162 Vaccine/immunology , COVID-19/immunology , COVID-19/virology , Humans , Immune Evasion/immunology , Mice , SARS-CoV-2/chemistry , SARS-CoV-2/genetics , SARS-CoV-2/immunology , SARS-CoV-2/metabolism , Species Specificity , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism
4.
J Formos Med Assoc ; 121(8): 1425-1430, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1983427

ABSTRACT

BACKGROUND: As a result of the COVID-19 global pandemic, many intellectual property (IP) owners have signed on to the "Open COVID Pledge", an agreement that makes corporate and university IP available free of charge for the purpose of facilitating the development of technologies that will end the pandemic and minimize the impact of disease. Joining this pledge is relatively straightforward for already-disclosed IPs. However, few, if any, has considered how to encourage owners of "non-disclosed patent applications" and "trade secrets" to sign on to this meaningful pledge. In other words, so far there is no proposal to extend the Open COVID Pledge for confidential pending patents and trade secrets. METHODS: We propose an innovative and flexible framework to cover both non-disclosed patent applications and trade secrets to mobilize inventors to participate in the Open COVID Pledge. RESULTS: By focusing on immediate publication of the patent-applying technology and extending provisional right to such applications which is subject to the Open Pledge during this pandemic, our recommendations are workable for inventors who would like to pledge their non-disclosed technologies for the detection, prevention and treatment of the COVID-19, in the meantime preserving their IP rights for the post-pledge period. CONCLUSION: This paper offers a way forward to guide pledgers and implementers who are interested in supporting the effort by addressing some of the issues associated with the free sharing of non-disclosed patent applications and trade secrets in the fight against COVID-19.


Subject(s)
COVID-19 , COVID-19/prevention & control , Humans , Intellectual Property , Technology , Universities
5.
Sci Transl Med ; 14(645): eabn8543, 2022 05 18.
Article in English | MEDLINE | ID: covidwho-1774930

ABSTRACT

The rapid spread of the highly contagious Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) along with its high number of mutations in the spike gene has raised alarms about the effectiveness of current medical countermeasures. To address this concern, we measured the neutralization of the Omicron BA.1 variant pseudovirus by postvaccination serum samples after two and three immunizations with the Pfizer/BioNTech162b2 SARS-CoV-2 mRNA (Pfizer/BNT162b2) vaccine, convalescent serum samples from unvaccinated individuals infected by different variants, and clinical-stage therapeutic antibodies. We found that titers against the Omicron variant were low or undetectable after two immunizations and in many convalescent serum samples, regardless of the infecting variant. A booster vaccination increased titers more than 30-fold against Omicron to values comparable to those seen against the D614G variant after two immunizations. Neither age nor sex was associated with the differences in postvaccination antibody responses. We also evaluated 18 clinical-stage therapeutic antibody products and an antibody mimetic protein product obtained directly from the manufacturers. Five monoclonal antibodies, the antibody mimetic protein, three antibody cocktails, and two polyclonal antibody preparations retained measurable neutralization activity against Omicron with a varying degree of potency. Of these, only three retained potencies comparable to the D614G variant. Two therapeutic antibody cocktails in the tested panel that are authorized for emergency use in the United States did not neutralize Omicron. These findings underscore the potential benefit of mRNA vaccine boosters for protection against Omicron and the need for rapid development of antibody therapeutics that maintain potency against emerging variants.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , BNT162 Vaccine , COVID-19/therapy , COVID-19 Vaccines , Humans , Immunization, Passive , Vaccination , Vaccines, Synthetic , mRNA Vaccines
6.
Energy Sustain Dev ; 68: 182-191, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1773303

ABSTRACT

The COVID-19 pandemic has introduced opportunities for more research in resilience as globally cities experienced lock-down, causing change to conventional energy consumption pattern especially in the residential sector. This study aims to quantify the increased energy demand during work-from-home arrangement, using high-rise public residential buildings in Hong Kong, where its government announced work-from-home arrangement four times in 2020. Building energy modellings were conducted to compare the total energy demand of residential units during normal and work-from-home arrangements, followed by validation against peer models and empirical data. A 9% residential energy demand increase was demonstrated, hence additional energy supply became desirable for the sake of resilience. This study assesses the possibility to leverage photovoltaic rooftop to supplement the increased energy demand. The photovoltaics' potential contribution was estimated by solar energy simulation and evaluated in terms of the capability to utilize its generation output to supplement the additional energy demand. During the four work-from-home periods, it was shown that a photovoltaic system could have supplemented 6.8% - 11% of the increased energy demand, mainly subject to the air-conditioning operation and solar generation. These findings are valuable to safeguard energy resilience in upcoming grid planning and operation.

7.
Emerg Infect Dis ; 28(4): 828-832, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1771000

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies decay but persist 6 months postvaccination; lower levels of neutralizing titers persist against Delta than wild-type virus. Of 227 vaccinated healthcare workers tested, only 2 experienced outpatient symptomatic breakthrough infections, despite 59/227 exhibiting serologic evidence of SARS-CoV-2 infection, defined as presence of nucleocapsid protein antibodies.


Subject(s)
COVID-19 , Antibodies, Viral , Antibody Formation , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Health Personnel , Humans , SARS-CoV-2 , Vaccination
8.
J Clin Microbiol ; 60(3): e0239021, 2022 03 16.
Article in English | MEDLINE | ID: covidwho-1765077

ABSTRACT

Emergency departments (EDs) can serve as surveillance sites for infectious diseases. The objective of this study was to determine the burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and to monitor the prevalence of vaccination against coronavirus disease 2019 (COVID-19) among patients attending an urban ED in Baltimore City. Using 1,914 samples of known exposure status, we developed an algorithm to differentiate previously infected, vaccinated, and unexposed individuals using a combination of antibody assays. We applied this testing algorithm to 4,360 samples from ED patients obtained in the spring of 2020 and 2021. Using multinomial logistic regression, we determined factors associated with infection and vaccination. For the algorithm, sensitivity and specificity for identifying vaccinated individuals were 100% and 99%, respectively, and 84% and 100% for previously infected individuals. Among the ED subjects, seroprevalence to SARS-CoV-2 increased from 2% to 24% between April 2020 and March 2021. Vaccination prevalence rose to 11% by mid-March 2021. Marked differences in burden of disease and vaccination coverage were seen by sex, race, and ethnicity. Hispanic patients, though accounting for 7% of the study population, had the highest relative burden of disease (17% of total infections) but with similar vaccination rates. Women and white individuals were more likely to be vaccinated than men or Black individuals. Individuals previously infected with SARS-CoV-2 can often be differentiated from vaccinated individuals using a serologic testing algorithm. The utility of this algorithm can aid in monitoring SARS-CoV-2 exposure and vaccination uptake frequencies and can potentially reflect gender, race, and ethnic health disparities.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , COVID-19/prevention & control , Emergency Service, Hospital , Female , Humans , Male , Seroepidemiologic Studies
9.
Viruses ; 13(12)2021 12 11.
Article in English | MEDLINE | ID: covidwho-1572661

ABSTRACT

The SARS-CoV-2 B.1.617 lineage variants, Kappa (B.1.617.1) and Delta (B.1.617.2, AY) emerged during the second wave of infections in India, but the Delta variants have become dominant worldwide and continue to evolve. Here, we compared B.1.617 variants for neutralization resistance by convalescent sera, mRNA vaccine-elicited sera, and therapeutic neutralizing antibodies using a pseudovirus neutralization assay. B.1.617.1, B.1.617.2, and AY.1 pseudoviruses showed a modest 1.5- to 4.4-fold reduction in neutralization by convalescent sera and vaccine-elicited sera. In comparison, similar modest reductions were also observed for C.37, P.1, R.1, and B.1.526 pseudoviruses, but 7- and 16-fold reductions for vaccine-elicited and convalescent sera, respectively, were seen for B.1.351 pseudoviruses. Among twenty-three therapeutic antibodies tested, four antibodies showed either complete or partial loss of neutralization against B.1.617.2 pseudoviruses and six antibodies showed either complete or partial loss of neutralization against B.1.617.1 and AY.1 pseudoviruses. Our results indicate that the current mRNA-based vaccines will likely remain effective in protecting against B.1.617 variants. Finally, the P681R substitution confers efficient cleavage of B.1.617 variants' spike proteins and the spike of Delta variants exhibited greater sensitivity to soluble ACE2 neutralization, as well as fusogenic activity, which may contribute to enhanced spread of Delta variants.


Subject(s)
Antibodies, Neutralizing/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/metabolism , Angiotensin-Converting Enzyme 2/metabolism , Antibodies, Viral/immunology , Antigenic Variation , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/immunology , Cell Fusion , Furin/metabolism , Humans , Protein Binding , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology
11.
Open forum infectious diseases ; 8(Suppl 1):S254-S255, 2021.
Article in English | EuropePMC | ID: covidwho-1564385

ABSTRACT

Background As the COVID-19 pandemic continues, growing attention has been placed on whether patients previously infected with SARS-CoV-2 have an increased risk of developing and/or exacerbating medical complications. Our study aimed to determine whether individuals with previous evidence of SARS-CoV-2 infection prior to their current emergency department (ED) visit were more likely to present with specific clinical sign/symptoms, laboratory markers, and/or clinical complications. Methods A COVID-19 seroprevalence study was conducted at Johns Hopkins Hospital ED (JHH ED) from March 16 to May 31, 2020. Evidence of ever having SARS-CoV-2 infection (PCR positive or IgG Ab positive) was found in 268 ED patients at this time (i.e. infected and/or previously infected). These patients were matched 1:2 to controls, by date, to other patients who attended the JHHED. Clinical signs/symptoms, laboratory markers, and/or clinical complications associated with ED visits and/or hospitalizations at JHH within 6 months after their initial ED visit was ed through chart review for these 804 patients. Cox proportional hazards regression analyses were performed. Results Among 804 ED patients analyzed, 50% were female, 56% Black race, and 15% Hispanic with a mean age of 47 years. 323 (40%) patients had at least 1 subsequent ED visit and additional 70 (9%) had been admitted to JHH. After controlling for race and ethnicity, patients with evidence of current or prior COVID-19 infection were more likely to require supplemental oxygen [hazards ratio (HR) =2.53;p=0.005] and have a cardiovascular complication [HR =2.13;p=0.008] during the subsequent ED visit than the non-infected patients. Conclusion Our findings demonstrate that those previously infected with SARS-CoV-2 have an increased frequency of cardiovascular complications and need for supplemental oxygen in ED visits in the months after their initial SARS-CoV-2 infection was detected. EDs could serve as a critical surveillance site for monitoring post-acute COVID-19 syndrome complications. Disclosures Richard E. Rothman, PhD, MD, Chem bio (Grant/Research Support)

12.
Pediatr Nephrol ; 36(1): 143-151, 2021 01.
Article in English | MEDLINE | ID: covidwho-800908

ABSTRACT

BACKGROUND: In March 2020, COVID-19 infections began to rise exponentially in the USA, placing substantial burden on the healthcare system. As a result, there was a rapid change in transplant practices and policies, with cessation of most procedures. Our goal was to understand changes to pediatric kidney transplantation (KT) at the national level during the COVID-19 epidemic. METHODS: Using SRTR data, we examined changes in pediatric waitlist registration, waitlist removal or inactivation, and deceased donor and living donor (DDKT/LDKT) events during the start of the disease transmission in the USA compared with the same time the previous year. RESULTS: We saw an initial decrease in DDKT and LDKT by 47% and 82% compared with expected events and then a continual increase, with numbers reaching expected prepandemic levels by May 2020. In the early phase of the pandemic, waitlist inactivation and removals due to death or deteriorating condition rose above expected values by 152% and 189%, respectively. There was a statistically significant decrease in new waitlist additions (IRR 0.49 0.65 0.85) and LDKT (IRR 0.17 0.38 0.84) in states with high vs. low COVID activity. Transplant recipients during the pandemic were more likely to have received a DDKT, but had similar calculated panel-reactive antibody (cPRA) values, waitlist time, and cause of kidney failure as before the pandemic. CONCLUSIONS: The COVID-19 pandemic initially reduced access to kidney transplantation among pediatric patients in the USA but has not had a sustained effect.


Subject(s)
Kidney Transplantation/statistics & numerical data , Living Donors/statistics & numerical data , Waiting Lists/mortality , Adolescent , Adult , COVID-19/epidemiology , Child , Child, Preschool , Female , Health Services Accessibility/statistics & numerical data , Humans , Infant , Infant, Newborn , Male , Middle Aged , Pandemics , Registries , SARS-CoV-2 , United States/epidemiology , Young Adult
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