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Routine immunization coverage declined in first year of COVID

Jacob Scott

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People’s mobility, livelihoods, access to health services, and public health infrastructure have been adversely affected by the ongoing coronavirus disease 2019 (COVID-19) pandemic.


Additionally, routine immunization (RI) coverage–which is estimated to prevent four to five million deaths worldwide every year–has seen a downward trend.


A new study published on the medRxiv* preprint server investigated changes in RI coverage using two key indicators – diphtheria-tetanus-pertussis first-dose (DTP1) and third-dose (DTP3). DTP3 serves as a general marker for immunization system performance, while DTP1 is used as a proxy for inequity – quantifying Zero Dose (ZD) children–those that receive no childhood vaccinations.


Study: Worldwide routine immunization coverage regressed during the first year of the COVID-19 pandemic. Image Credit: SamaraHeisz5 / Shutterstock


The Study


In this study, vaccination coverage data of the past 20 years were extracted from the World Health Organization (WHO) and United Nations Children’s Fund (UNICEF) Estimates of National Immunization Coverage (WUENIC).


The Results


The findings revealed a global decline in DTP3 coverage of 2.9% from an expected 89.2% to a reported 86.3% across 167 reporting countries. Similar low coverage was last recorded in these countries in 2005 and demarcated a 15-year setback in RI progress.



Expected and reported 2020 vaccine coverage for DTP1 and DTP3: example of five countries with most additional missed DTP3 immunizations in 2020. These graphs show WUENIC-reported coverage data (black dots) and the corresponding ARIMA predictions and the associated 95% confidence intervals (red bars).

For DTP1, the average global coverage decline was 2.2% – from an expected 92.9% to a reported 90.7% across the 167 countries. This signified increases in the quantity of ZD children in some countries – this suggested that the most vulnerable populations have been strongly impacted by the reductions in RI observed in the first year of the pandemic. Hence, the current pandemic has widened the gap between people with limited healthcare access.


Patterns of RI coverage depicted marked variations across United Nations regions, with the most substantial decline observed in the Americas, Asia, and Africa compared to Europe and Oceania. Meanwhile, stronger declines in RI coverage were observed in lower-middle-income countries and upper-middle-income countries than in low-income countries. However, high-income countries did not show notable changes in their RI coverage.



Comparison between 2020 WUENIC-reported DTP3 coverage and expectations derived from historical trends. This scatterplot shows country coverage (WUENIC-reported actuals and ARIMA-predicted expectations) as dots. Lines around individual points illustrate the 95% confidence intervals (CI) of ARIMA predictions. Countries showing significant departure from expected values, i.e., for which actual coverage is outside the 95% CI of predictions, are indicated in red.

Furthermore, regional differences remained after accounting for differences in income groups; however, the converse wasn’t true. India estimated 3.5 million unvaccinated children for DTP3 in 2020, of which 52% were associated with the pandemic disruption. There were 1.1 million missed DTP3 vaccinations in Indonesia, of which 35% were associated with RI coverage declines in 2020. Besides, similar trends were observed for ZD children using DTP1 results.


Nonetheless, this study’s estimated changes in RI coverage suggest a smaller global decline than previously found. Moreover, these findings may be more robust owing to a more comprehensive dataset including data from more countries.


The findings indicate a greater risk of vaccine-preventable disease outbreaks in the near future, especially in the absence of Supplementary Immunization Activities (SIAs) to reach missed children. In addition, ZD populations in key ZD “hotspots” – India, Pakistan, and Indonesia, are estimated to have increased significantly in 2020, posing a genuine public health threat.



Differences between expected and reported DTP3 vaccine coverage in 2020 across (A) UN regions and (B) income groups Points represent individual countries, grouped, and colored according to (A) UN region classification and (B) World Bank income groups. Country coordinates on the X-axis were jittered for visibility. Values on the y-axis are indicated as absolute differences between reported and expected vaccine coverage, in percentages. Boxes show the median (50%), upper (75%) and lower (25%) quartile changes in coverage for each group, with whiskers extending to either the minimum/ maximum changes or the quartile value plus 1.5 times the interquartile range, and crosses indicating the average. The black dashed horizontal lines indicate no change in coverage. LIC: Low-income Country. LMIC: Lower-middle-income Country. UMIC: Upper-middle-income Country. HIC: High-income Country

It was suggested that to alleviate such risks and reduce immunization inequities, SIAs should be targeted towards populations who have limited access to healthcare and encounter vaccine deprivation. In addition, future research should investigate heterogeneities in RI decline at finer scales and identify subpopulations that may have experienced even greater losses to RI coverage.


It was also stated that RI disruption might be worsened by the acceleration of COVID-19 vaccination campaigns, particularly in low- and middle-income countries, potentially competing with RI services. Therefore, careful monitoring is essential. Further studies are needed to understand which factors linked to the COVID-19 crisis impacted vaccination coverage to successfully and efficiently address pandemic-associated losses to coverage.


The findings of this study render a transparent and replicable rationale for estimating lapses in RI coverage across countries, producing an objective measure for missed immunizations and coverage disruptions. The results may serve as a basis for identifying countries most affected by declines in RI coverage and prioritizing efforts to modulate the indirect impact of COVID-19.


*Important Notice


medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Evans, B., & Jombart, T. (2021), “Worldwide routine immunisation coverage regressed during the first year of the COVID-19 pandemic”, medRxiv* preprint, doi: 10.1101/2021.12.03.21267195, https://www.medrxiv.org/content/10.1101/2021.12.03.21267258v1

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Unraveling How Strigoractone Hormone Regulates Massive Gene Networks Controlling Plant Growth

Jacob Scott

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As sessile organisms, plants have to continually adapt their growth and architecture to the ever-changing environment. To do so, plants have evolved distinct molecular mechanisms to sense and respond to the environment and integrate the signals from outside with endogenous developmental programs.

New research from Nitzan Shabek’s laboratory at the UC Davis College of Biological Sciences, published in Nature Plants, unravels the underlying mechanism of protein targeting and destruction in a specific plant hormone signaling pathway.

Our lab aims at deciphering sensing mechanisms in plants and understanding how specific enzymes function can be regulated at the molecular levels. We have been studying a new plant hormone signal, strigolactone, that governs numerous processes of growth and development including branching and root architecture.”

Nitzan Shabek, assistant professor of biochemistry and structural biology, Department of Plant Biology

The work stems from a study by Shabek, published in Nature in 2018, unravelling molecular and structural changes in an enzyme, MAX2 (or D3) ubiquitin ligase. MAX2 was found in locked or unlocked forms that can recruit a strigolactone sensor, D14, and target for destruction a DNA transcriptional repressor complex, D53. Ubiquitins are small proteins, found in all eukaryotes, that “tag” other proteins for destruction within a cell.

To find the key to unlock MAX2 and to better understand its molecular dynamics in plants, postdoctoral fellows Lior Tal and Malathy Palayam, with junior specialist Aleczander Young, used an approach that integrated advanced structural biology, biochemistry, and plant genetics.

“We leveraged structure-guided approaches to systemically mutate MAX2 enzyme in Arabidopsis and created a MAX2 stuck in an unlocked form”, said Shabek, “some of these mutations were made by guiding CRISPR/Cas9 genome editing thus providing us a discovery platform to study and analyze the different signaling outputs and illuminate the role of MAX2 dynamics.”


They found that in the unlocked conformation, MAX2 can target the repressor proteins and biochemically decorate them with small ubiquitin proteins, tagging them for destruction. Removing these repressors allows other genes to be expressed – activating a massive gene network that governs shoot branching, root architecture, leaf senescence, and symbiosis with fungi, Shabek said.

Sending these repressors to the proteasome disposal complexes requires the enzyme to relock again. The team also showed that MAX2 not only target the repressors proteins, but once it is locked the strigolactone sensor itself gets destroyed, returning the system to its original state.

Finally, the study uncovered the key to the lock, an organic acid metabolite that can directly trigger the conformational switch.

“Beyond the implication in plants signaling, this is the first work that placed a primary metabolite as a direct new regulator of this type of ubiquitin ligase enzymes and will open new avenues of study in this direction,” Shabek said.

Additional coauthors on the paper are specialist Mily Ron and Professor Anne Britt, Department of Plant Biology. The study was supported by NSF CAREER and EAGER grants to Shabek. X-ray crystallography data was obtained at the Advanced Light Source, Lawrence Berkeley National Laboratory, a U.S. Department of Energy user facility.

Source:
Journal reference:

Tal, L., et al. (2022) A conformational switch in the SCF-D3/MAX2 ubiquitin ligase facilitates strigolactone signalling. Nature Plants. doi.org/10.1038/s41477-022-01145-7.

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UrFU Sociologists Identify Digital Fears Among Young People

Jacob Scott

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Sociologists at the Ural Federal University (UrFU) have identified digital fears among young people. According to experts, these are additional fears that do not replace, but complement and reinforce traditional ones. They emerged against the background of uncertainty, the growth of forces beyond human control. Developed emotional intelligence, creativity, and the ability to collaborate help to overcome them.

In the study, sociologists interviewed 1,050 people aged 18-30. Respondents were asked to assess which digital risks concern them most. The study was launched in 2020 and the results were published in April 2022 in the Changing Societies & Personalities journal.

The first group of fears is influence and control. It touches on the problem of interference with privacy by technical means. This category is the most significant for young people: 55.8% are afraid of total control by means of video-surveillance and monitoring software on their mobile devices. 48.5% of respondents believe they are at risk of wiretapping, tracking content in social networks, and inability to keep correspondence secret.”

Natalia Antonova, Professor, Department of Applied Sociology, UrFU

45.8% of young people fear the manipulative influence of the media and an increase in fake news. At the same time, only 27.8% and 18.1% of respondents are concerned about microchipping and genetic manipulation, respectively. It is likely that these threats seem more controllable, both from the individual (through control of food choices, medical procedures, etc.) and from government programs, the researchers believe.

The second group of concerns is crime and security. Here young people are wary of illegal actions using digital technology.

“One of the main fears of 56% of young people is the security of personal data. This is related both to the growth of personal information in social networks and messengers, and to the growth of hacker attacks and viruses. 42.9% of young citizens are afraid of Internet fraudsters, and 25.8% are afraid of losing important information, including smashing their phones, not saving data, forgetting their passwords, or being without an Internet connection,” explains Sofia Abramova, Associate Professor at the Department of Applied Sociology at UrFU.

The third group of fears is based on changes in the way and pace of life, ways of interaction. Thus, 28.4% of respondents indicate a constant lack of time, the acceleration of communications, and worries about not being able to complete all tasks in time. Respondents are also concerned about the growth of online communications and communications with electronic systems (bots, autoresponders, product systems, etc.).

“As a result, 15.3% of young people raise problems related to increasing social distrust against the background of increasing dependence of human life and health on other people and electronic systems: in public transport, planes, elevators, medical intervention,” explains Sofia Abramova.

Respondents also fear the negative consequences of technological development. For example, 22.2% of young citizens fear the robotization of labor processes and the displacement of humans by robots. 14.6% speak directly about negative emotions in relation to the expansion of artificial intelligence.

The fifth type of fear is social inequality. Young people negatively assess the growth of inequality in access to information resources and technology, the exclusion of citizens from the economy depending on the level of digital competence and education, and age. As a result, they fear that benefits will be distributed more and more unequally, both among the inhabitants of the country and between countries.

“It is noteworthy that young people are simultaneously afraid of total surveillance via phone and afraid of being left without mobile devices. Fears shape the irrational behavior of the digital generation, entailing serious transformations in everyday life,” says Natalia Antonova.

Source:
Journal reference:

Abramova, S.B., et al. (2022) Digital Fears Experienced by Young People in the Age of Technoscience. Changing Societies & Personalities. doi.org/10.15826/csp.2022.6.1.163.

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Study demonstrates increased incidence of SARS-CoV-2 Omicron breakthrough infection in cancer patients

Jacob Scott

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In a recently published article in the journal Cancer Cell, scientists have demonstrated the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in cancer patients residing in Austria and Italy. The study reveals an induction in Omicron breakthrough infections in patients with hematologic and solid cancers.

Study: Enhanced SARS-CoV-2 breakthrough infections in patients with hematologic and solid cancers due to Omicron. Image Credit: Lightspring/Shutterstock

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of the coronavirus disease 2019 (COVID-19) pandemic, has been found to cause severe infections in immunocompromised patients, including cancer patients. Moreover, a relatively lower level of neutralizing antibodies in response to COVID-19 vaccines has also been observed in cancer patients, especially those receiving B cell-targeting therapies.

The emergence of SARS-CoV-2 variants with improved immune fitness, such as delta and Omicron variants, has caused a sharp increase in breakthrough infections even in fully vaccinated individuals. However, the vaccines still show high protective efficacy against severe and fatal infections. COVID-19 vaccines have shown acceptable efficacy against severe disease, even in Omicron-infected cancer patients. However, the isolation and quarantine measures associated with SARS-CoV-2 infection may impair the routine administration of anticancer therapy, which can reduce the survival prognosis in cancer patients.

In the current study, the scientists have assessed the incidence of SARS-CoV-2 infection in cancer patients throughout the pandemic.

Study design

The study included 3,959 cancer patients, of whom 77% had solid cancer, and 23% had hematologic cancer. About 69% of the patients did not receive any anticancer treatment at the time of COVID-19 vaccination. Regarding vaccine coverage, about 85% of the patients had received at least one vaccine dose, and 15% remained unvaccinated. The incidence of SARS-CoV-2 infection in these patients was assessed between February 2020 and 2022.

Important observations

SARS-CoV-2 infection was detected in about 24% of the patients during the study period. During the delta-dominated wave, vaccine breakthrough infection was observed in 43% of the patients. In contrast, a significantly higher percentage of breakthrough infection (70%) was observed among the patients during the Omicron-dominated wave. During both delta and Omicron waves, cancer patients receiving systemic anticancer treatment showed a significantly higher percentage of breakthrough infection than those not receiving treatment (83% vs. 56%).

Regarding disease severity irrespective of vaccination status, a higher frequency of COVID-19-related hospitalization was observed during the delta wave compared to that during the Omicron wave. However, a relatively shorter duration of hospital stay was observed in vaccinated patients compared to that in unvaccinated patients. In addition, only 9% of patients with breakthrough infections were admitted to the intensive care unit (ICU). This highlights the protective efficacy of COVID-19 vaccines against severe disease.

Humoral immune response to vaccination

To determine vaccine-induced antibody response against delta and Omicron variants, the scientists measured blood levels of anti-delta and anti-Omicron spike receptor-binding domain (RBD) antibodies in a total of 78 cancer patients. In the analysis, they also included 25 healthcare workers as controls.

In response to vaccination, healthcare workers showed higher levels of total anti-spike antibodies compared to cancer patients. The lowest level of wildtype RBD-specific antibodies was observed in hematologic cancer patients receiving B cell-targeted treatment, followed by hematologic cancer patients not receiving B cell-targeted treatment and patients with solid tumors. A similar trend was observed for delta- and Omicron-specific spike RBD antibodies.

The serum samples collected from hematologic cancer patients without B cell-targeted treatment and solid tumor patients significantly inhibited the interaction between wildtype/delta RBD and angiotensin-converting enzyme 2 (ACE2; host cell receptor for viral entry). However, a significantly lower level of inhibition was observed for patients receiving B cell-targeted treatment. Importantly, a marked reduction in inhibition of Omicron RBD – ACE2 interaction was observed for all patients with solid tumors and hematologic cancer.

Study significance

The study demonstrates an increased incidence of vaccine breakthrough infections but a reduced disease severity among patients with solid tumors and hematologic cancer during the Omicron wave compared to the delta wave.

The study also highlights that COVID-19 vaccine-induced antibody response is lower in cancer patients than in healthy individuals. The reduction in antibody response is highest among hematologic patients receiving B cell-targeted treatment. Overall, a significant impairment in vaccine-induced Omicron neutralization has been observed in cancer patients.

Journal reference:
Mair, M. et al. (2022) “Enhanced SARS-CoV-2 breakthrough infections in patients with hematologic and solid cancers due to Omicron”, Cancer Cell. doi: 10.1016/j.ccell.2022.04.003. https://www.cell.com/cancer-cell/fulltext/S1535-6108(22)00165-9

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