A Tool for Visualization and Analysis of Neighbourhoods, Clusters, and Indicators during the COVID-19 Pandemic

Visual analytics tools for spatiotemporal analysis can be used to manage and monitor the propagation of an epidemic. The problem is that dashboards encountered in the literature do not take into consideration how the geolocation characteristics, such as socioeconomic indicators, influence the infection risk or other epidemic variables. This analysis can support health officials in managing the outbreak to consider information about indicators in compartment models for propagation prediction and intervention simulation. The objective of this work was to bring widgets that offer a more profound exploration and analysis of the impact of the pandemic on socioeconomic indicators. In our approach, the association of epidemic variables and indicators can be explored with commonly adopted visualization plots. Also, we propose a way to gather the specialist's risk perception, and as a result, a risk heatmap is produced, allowing the reduction of time series data cluttering. Finally, it is possible to use the risk heatmap information to compare neighbourhoods and socioeconomic indicators by ranking them according to a severity score. Some use cases were performed to demonstrate the use and capability of the proposed widgets. [ABSTRACT FROM AUTHOR] Copyright of Mathematical Problems in Engineering is the property of Hindawi Limited and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

An analytical tool to support public policies and isolation barriers against SARS-CoV-2 based on mobility patterns and socio-economic aspects

It is crucial to develop spatiotemporal analysis tools to mitigate risks during a pandemic. Many dashboards encountered in the literature do not consider how the geolocation characteristics and travel patterns may influence the spread of the virus. This work brings an interactive tool that is capable of crossing information about mobility patterns, geolocation characteristics and epidemiologic variables. To do so, our system uses a mobility network, generated through anonymized mobile location data, which enables the division of a region into representative clusters. The clusters' aggregated socioeconomic, and epidemiologic indicators can be analyzed through multiple coordinated views. The proposal is to enable users to understand how different locations commute citizens, monitor risk over time, and understand what locations need more assistance, considering different layers of visualization, such as clusters and individual locations. The main novelty is the interactive way to construct the mobility network that defines the social distancing level and the way that risks are managed, since many different geolocation characteristics can be considered and visualized, such as socioeconomic indicators of a location, the economic importance of a set of locations, and the connection of important neighborhoods of a city with other cities. The proposed tool was built and verified by experts assembled to give scientific recommendations to the city administration of Recife, the capital city of Pernambuco. Our analysis shows how a policymaker could use the tool to evaluate different isolation scenarios considering the trade-off between economic activity and contamination risk, where the practical insights can also be used to tighten and relax mitigation measures in other phases of a pandemic.

An analytical tool to support public policies and isolation barriers against SARS-CoV-2 based on mobility patterns and socio-economic aspects.

It is crucial to develop spatiotemporal analysis tools to mitigate risks during a pandemic. Many dashboards encountered in the literature do not consider how the geolocation characteristics and travel patterns may influence the spread of the virus. This work brings an interactive tool that is capable of crossing information about mobility patterns, geolocation characteristics and epidemiologic variables. To do so, our system uses a mobility network, generated through anonymized mobile location data, which enables the division of a region into representative clusters. The clusters' aggregated socioeconomic, and epidemiologic indicators can be analyzed through multiple coordinated views. The proposal is to enable users to understand how different locations commute citizens, monitor risk over time, and understand what locations need more assistance, considering different layers of visualization, such as clusters and individual locations. The main novelty is the interactive way to construct the mobility network that defines the social distancing level and the way that risks are managed, since many different geolocation characteristics can be considered and visualized, such as socioeconomic indicators of a location, the economic importance of a set of locations, and the connection of important neighborhoods of a city with other cities. The proposed tool was built and verified by experts assembled to give scientific recommendations to the city administration of Recife, the capital city of Pernambuco. Our analysis shows how a policymaker could use the tool to evaluate different isolation scenarios considering the trade-off between economic activity and contamination risk, where the practical insights can also be used to tighten and relax mitigation measures in other phases of a pandemic.

Age-dependent impairment in antibody responses elicited by a homologous CoronaVac booster dose.

The emergence of the SARS-CoV-2 Omicron sublineages resulted in increased transmission rates and reduced protection from vaccines. To counteract these effects, multiple booster strategies were used in different countries, although data comparing their efficiency in improving protective immunity remain sparse, especially among vulnerable populations, including older adults. The inactivated CoronaVac vaccine was among the most widely distributed vaccine worldwide and was essential in the early control of SARS-CoV-2-related hospitalizations and deaths. However, it is not well understood whether homologous versus heterologous booster doses in those fully vaccinated with CoronaVac induce distinct humoral responses or whether these responses vary across age groups. We analyzed plasma antibody responses from CoronaVac-vaccinated younger or older individuals who received a homologous CoronaVac or heterologous BNT162b2 or ChAdOx1 booster vaccine. All three evaluated boosters resulted in increased virus-specific IgG titers 28 days after the booster dose. However, we found that both IgG titers against SARS-CoV-2 Spike or RBD and neutralization titers against Omicron sublineages were substantially reduced in participants who received homologous CoronaVac compared with the heterologous BNT162b2 or ChAdOx1 booster. This effect was specifically prominent in recipients >50 years of age. In this group, the CoronaVac booster induced low virus-specific IgG titers and failed to elevate neutralization titers against any Omicron sublineage. Our results point to the notable inefficiency of CoronaVac immunization and boosting in mounting protective antiviral humoral immunity, particularly among older adults, during the Omicron wave. These observations also point to benefits of heterologous regimens in high-risk populations fully vaccinated with CoronaVac.

Association between primary or booster COVID-19 mRNA vaccination and Omicron lineage BA.1 SARS-CoV-2 infection in people with a prior SARS-CoV-2 infection: A test-negative case-control analysis.

BACKGROUND: The benefit of primary and booster vaccination in people who experienced a prior Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection remains unclear. The objective of this study was to estimate the effectiveness of primary (two-dose series) and booster (third dose) mRNA vaccination against Omicron (lineage BA.1) infection among people with a prior documented infection. METHODS AND FINDINGS: We conducted a test-negative case-control study of reverse transcription PCRs (RT-PCRs) analyzed with the TaqPath (Thermo Fisher Scientific) assay and recorded in the Yale New Haven Health system from November 1, 2021, to April 30, 2022. Overall, 11,307 cases (positive TaqPath analyzed RT-PCRs with S-gene target failure [SGTF]) and 130,041 controls (negative TaqPath analyzed RT-PCRs) were included (median age: cases: 35 years, controls: 39 years). Among cases and controls, 5.9% and 8.1% had a documented prior infection (positive SARS-CoV-2 test record ≥90 days prior to the included test), respectively. We estimated the effectiveness of primary and booster vaccination relative to SGTF-defined Omicron (lineage BA.1) variant infection using a logistic regression adjusted for date of test, age, sex, race/ethnicity, insurance, comorbidities, social venerability index, municipality, and healthcare utilization. The effectiveness of primary vaccination 14 to 149 days after the second dose was 41.0% (95% confidence interval (CI): 14.1% to 59.4%, p 0.006) and 27.1% (95% CI: 18.7% to 34.6%, p < 0.001) for people with and without a documented prior infection, respectively. The effectiveness of booster vaccination (≥14 days after booster dose) was 47.1% (95% CI: 22.4% to 63.9%, p 0.001) and 54.1% (95% CI: 49.2% to 58.4%, p < 0.001) in people with and without a documented prior infection, respectively. To test whether booster vaccination reduced the risk of infection beyond that of the primary series, we compared the odds of infection among boosted (≥14 days after booster dose) and booster-eligible people (≥150 days after second dose). The odds ratio (OR) comparing boosted and booster-eligible people with a documented prior infection was 0.79 (95% CI: 0.54 to 1.16, p 0.222), whereas the OR comparing boosted and booster-eligible people without a documented prior infection was 0.54 (95% CI: 0.49 to 0.59, p < 0.001). This study's limitations include the risk of residual confounding, the use of data from a single system, and the reliance on TaqPath analyzed RT-PCR results. CONCLUSIONS: In this study, we observed that primary vaccination provided significant but limited protection against Omicron (lineage BA.1) infection among people with and without a documented prior infection. While booster vaccination was associated with additional protection against Omicron BA.1 infection in people without a documented prior infection, it was not found to be associated with additional protection among people with a documented prior infection. These findings support primary vaccination in people regardless of documented prior infection status but suggest that infection history may impact the relative benefit of booster doses.

Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation.

COVID survivors frequently experience lingering neurological symptoms that resemble cancer-therapy-related cognitive impairment, a syndrome for which white matter microglial reactivity and consequent neural dysregulation is central. Here, we explored the neurobiological effects of respiratory SARS-CoV-2 infection and found white-matter-selective microglial reactivity in mice and humans. Following mild respiratory COVID in mice, persistently impaired hippocampal neurogenesis, decreased oligodendrocytes, and myelin loss were evident together with elevated CSF cytokines/chemokines including CCL11. Systemic CCL11 administration specifically caused hippocampal microglial reactivity and impaired neurogenesis. Concordantly, humans with lasting cognitive symptoms post-COVID exhibit elevated CCL11 levels. Compared with SARS-CoV-2, mild respiratory influenza in mice caused similar patterns of white-matter-selective microglial reactivity, oligodendrocyte loss, impaired neurogenesis, and elevated CCL11 at early time points, but after influenza, only elevated CCL11 and hippocampal pathology persisted. These findings illustrate similar neuropathophysiology after cancer therapy and respiratory SARS-CoV-2 infection which may contribute to cognitive impairment following even mild COVID.

Multiscale PHATE identifies multimodal signatures of COVID-19.

As the biomedical community produces datasets that are increasingly complex and high dimensional, there is a need for more sophisticated computational tools to extract biological insights. We present Multiscale PHATE, a method that sweeps through all levels of data granularity to learn abstracted biological features directly predictive of disease outcome. Built on a coarse-graining process called diffusion condensation, Multiscale PHATE learns a data topology that can be analyzed at coarse resolutions for high-level summarizations of data and at fine resolutions for detailed representations of subsets. We apply Multiscale PHATE to a coronavirus disease 2019 (COVID-19) dataset with 54 million cells from 168 hospitalized patients and find that patients who die show CD16hiCD66blo neutrophil and IFN-γ+ granzyme B+ Th17 cell responses. We also show that population groupings from Multiscale PHATE directly fed into a classifier predict disease outcome more accurately than naive featurizations of the data. Multiscale PHATE is broadly generalizable to different data types, including flow cytometry, single-cell RNA sequencing (scRNA-seq), single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq), and clinical variables.

Longitudinal Immune Profiling of a Severe Acute Respiratory Syndrome Coronavirus 2 Reinfection in a Solid Organ Transplant Recipient.

BACKGROUND: The underlying immunologic deficiencies enabling severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection are currently unknown. We describe deep longitudinal immune profiling of a transplant recipient hospitalized twice for coronavirus disease 2019 (COVID-19). METHODS: A 66-year-old male renal transplant recipient was hospitalized with COVID-19 March 2020 then readmitted to the hospital with COVID-19 233 days after initial diagnosis. Virologic and immunologic investigations were performed on samples from the primary and secondary infections. RESULTS: Whole viral genome sequencing and phylogenetic analysis revealed that viruses causing both infections were caused by distinct genetic lineages without evidence of immune escape mutations. Longitudinal comparison of cellular and humoral responses during primary SARS-CoV-2 infection revealed that this patient responded to the primary infection with low neutralization titer anti-SARS-CoV-2 antibodies that were likely present at the time of reinfection. CONCLUSIONS: The development of neutralizing antibodies and humoral memory responses in this patient failed to confer protection against reinfection, suggesting that they were below a neutralizing titer threshold or that additional factors may be required for efficient prevention of SARS-CoV-2 reinfection. Development of poorly neutralizing antibodies may have been due to profound and relatively specific reduction in naive CD4 T-cell pools. Seropositivity alone may not be a perfect correlate of protection in immunocompromised patients.

Caregivers of Individuals with Cancer in the COVID-19 Pandemic: A Phenomenological Study.

Caregivers of individuals with cancer in the COVID-19 pandemic are faced with the demands of cancer and the health needs produced by it, along with their own health and self-care needs, and the uncertainties of expectations and risks. A qualitative analytical phenomenological study with caregivers of individuals with cancer registered at the state referral hospital supplying medications, who answered the sociodemographic assessment questionnaires and semi-structured questions about their feelings and perceptions in the COVID-19 pandemic. Bardin's content analysis was used, with methodological quality assessed using SRQR Standards for Reporting Qualitative Research and the MAXQDA software. Most of the caregivers are women, married, Catholic, of low income and education, aged between 30 and 60 years, optimistic, comply with health guidelines regarding social distancing, use of masks, and routine hand hygiene, do not practice regular physical activities, mention concern for their own physical and financial survival, and that of their family. The main need identified in the affective sphere was to reframe contact with family members, seeking to strengthen the bonds of affection. The feeling of emotional vulnerability shows the importance of building effective public policies for social support consistent with the improvement of health care for this population.

Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity.

The emergence of SARS-CoV-2 variants with mutations in major neutralizing antibody-binding sites can affect humoral immunity induced by infection or vaccination1-6. Here we analysed the development of anti-SARS-CoV-2 antibody and T cell responses in individuals who were previously infected (recovered) or uninfected (naive) and received mRNA vaccines to SARS-CoV-2. While individuals who were previously infected sustained higher antibody titres than individuals who were uninfected post-vaccination, the latter reached comparable levels of neutralization responses to the ancestral strain after the second vaccine dose. T cell activation markers measured upon spike or nucleocapsid peptide in vitro stimulation showed a progressive increase after vaccination. Comprehensive analysis of plasma neutralization using 16 authentic isolates of distinct locally circulating SARS-CoV-2 variants revealed a range of reduction in the neutralization capacity associated with specific mutations in the spike gene: lineages with E484K and N501Y/T (for example, B.1.351 and P.1) had the greatest reduction, followed by lineages with L452R (for example, B.1.617.2). While both groups retained neutralization capacity against all variants, plasma from individuals who were previously infected and vaccinated displayed overall better neutralization capacity than plasma from individuals who were uninfected and also received two vaccine doses, pointing to vaccine boosters as a relevant future strategy to alleviate the effect of emerging variants on antibody neutralizing activity.

Longitudinal immune profiling of a SARS-CoV-2 reinfection in a solid organ transplant recipient.

The underlying immunologic deficiencies enabling SARS-CoV-2 reinfections are currently unknown. Here we describe a renal-transplant recipient who developed recurrent, symptomatic SARS-CoV-2 infection 7 months after primary infection. To elucidate the immunological mechanisms responsible for reinfection, we performed longitudinal profiling of cellular and humoral responses during both primary and recurrent SARS-CoV-2 infection. We found that the patient responded to the primary infection with transient, poor-quality adaptive immune responses that was further compromised by intervening treatment for acute rejection of the renal allograft prior to reinfection. Importantly, we identified the development of neutralizing antibodies and humoral memory responses prior to SARS-CoV-2 reinfection. However, these neutralizing antibodies failed to confer protection against reinfection, suggesting that additional factors are required for efficient prevention of SARS-CoV-2 reinfection. Further, we found no evidence supporting viral evasion of primary adaptive immune responses, suggesting that susceptibility to reinfection may be determined by host factors rather than pathogen adaptation.

Sex differences in immune responses that underlie COVID-19 disease outcomes.

There is increasing evidence that coronavirus disease 2019 (COVID-19) produces more severe symptoms and higher mortality among men than among women1-5. However, whether immune responses against severe acute respiratory syndrome coronavirus (SARS-CoV-2) differ between sexes, and whether such differences correlate with the sex difference in the disease course of COVID-19, is currently unknown. Here we examined sex differences in viral loads, SARS-CoV-2-specific antibody titres, plasma cytokines and blood-cell phenotyping in patients with moderate COVID-19 who had not received immunomodulatory medications. Male patients had higher plasma levels of innate immune cytokines such as IL-8 and IL-18 along with more robust induction of non-classical monocytes. By contrast, female patients had more robust T cell activation than male patients during SARS-CoV-2 infection. Notably, we found that a poor T cell response negatively correlated with patients' age and was associated with worse disease outcome in male patients, but not in female patients. By contrast, higher levels of innate immune cytokines were associated with worse disease progression in female patients, but not in male patients. These findings provide a possible explanation for the observed sex biases in COVID-19, and provide an important basis for the development of a sex-based approach to the treatment and care of male and female patients with COVID-19.

Kynurenic acid may underlie sex-specific immune responses to COVID-19.

Coronavirus disease 2019 (COVID-19) has poorer clinical outcomes in males than in females, and immune responses underlie these sex-related differences. Because immune responses are, in part, regulated by metabolites, we examined the serum metabolomes of COVID-19 patients. In male patients, kynurenic acid (KA) and a high KA-to-kynurenine (K) ratio (KA:K) positively correlated with age and with inflammatory cytokines and chemokines and negatively correlated with T cell responses. Males that clinically deteriorated had a higher KA:K than those that stabilized. KA inhibits glutamate release, and glutamate abundance was lower in patients that clinically deteriorated and correlated with immune responses. Analysis of data from the Genotype-Tissue Expression (GTEx) project revealed that the expression of the gene encoding the enzyme that produces KA, kynurenine aminotransferase, correlated with cytokine abundance and activation of immune responses in older males. This study reveals that KA has a sex-specific link to immune responses and clinical outcomes in COVID-19, suggesting a positive feedback between metabolites and immune responses in males.

Diverse functional autoantibodies in patients with COVID-19.

COVID-19 manifests with a wide spectrum of clinical phenotypes that are characterized by exaggerated and misdirected host immune responses1-6. Although pathological innate immune activation is well-documented in severe disease1, the effect of autoantibodies on disease progression is less well-defined. Here we use a high-throughput autoantibody discovery technique known as rapid extracellular antigen profiling7 to screen a cohort of 194 individuals infected with SARS-CoV-2, comprising 172 patients with COVID-19 and 22 healthcare workers with mild disease or asymptomatic infection, for autoantibodies against 2,770 extracellular and secreted proteins (members of the exoproteome). We found that patients with COVID-19 exhibit marked increases in autoantibody reactivities as compared to uninfected individuals, and show a high prevalence of autoantibodies against immunomodulatory proteins (including cytokines, chemokines, complement components and cell-surface proteins). We established that these autoantibodies perturb immune function and impair virological control by inhibiting immunoreceptor signalling and by altering peripheral immune cell composition, and found that mouse surrogates of these autoantibodies increase disease severity in a mouse model of SARS-CoV-2 infection. Our analysis of autoantibodies against tissue-associated antigens revealed associations with specific clinical characteristics. Our findings suggest a pathological role for exoproteome-directed autoantibodies in COVID-19, with diverse effects on immune functionality and associations with clinical outcomes.

Delayed production of neutralizing antibodies correlates with fatal COVID-19.

Recent studies have provided insights into innate and adaptive immune dynamics in coronavirus disease 2019 (COVID-19). However, the exact features of antibody responses that govern COVID-19 disease outcomes remain unclear. In this study, we analyzed humoral immune responses in 229 patients with asymptomatic, mild, moderate and severe COVID-19 over time to probe the nature of antibody responses in disease severity and mortality. We observed a correlation between anti-spike (S) immunoglobulin G (IgG) levels, length of hospitalization and clinical parameters associated with worse clinical progression. Although high anti-S IgG levels correlated with worse disease severity, such correlation was time dependent. Deceased patients did not have higher overall humoral response than discharged patients. However, they mounted a robust, yet delayed, response, measured by anti-S, anti-receptor-binding domain IgG and neutralizing antibody (NAb) levels compared to survivors. Delayed seroconversion kinetics correlated with impaired viral control in deceased patients. Finally, although sera from 85% of patients displayed some neutralization capacity during their disease course, NAb generation before 14 d of disease onset emerged as a key factor for recovery. These data indicate that COVID-19 mortality does not correlate with the cross-sectional antiviral antibody levels per se but, rather, with the delayed kinetics of NAb production.

Social inequalities and the pandemic of COVID-19: the case of Rio de Janeiro.

BACKGROUND: The novel coronavirus (SARS-CoV-2) is a global pandemic. The lack of protective vaccine or treatment led most of the countries to follow the flattening of the infection curve with social isolation measures. There is evidence that socioeconomic inequalities have been shaping the COVID-19 burden among low and middle-income countries. This study described what sociodemographic and socioeconomic factors were associated with the greatest risk of COVID-19 infection and mortality and how did the importance of key neighbourhood-level socioeconomic factors change over time during the early stages of the pandemic in the Rio de Janeiro municipality, Brazil. METHODS: We linked socioeconomic attributes to confirmed cases and deaths from COVID-19 and computed age-standardised incidence and mortality rates by domains such as age, gender, crowding, education, income and race/ethnicity. RESULTS: The evidence suggests that although age-standardised incidence rates were higher in wealthy neighbourhoods, age-standardised mortality rates were higher in deprived areas during the first 2 months of the pandemic. The age-standardised mortality rates were also higher in males, and in areas with a predominance of people of colour, which are disproportionately represented in more vulnerable groups. The population also presented COVID-19 'rejuvenation', that is, people became risk group younger than in developed countries. CONCLUSION: We conclude that there is a strong health gradient for COVID-19 death risk during the early stages of the pandemic. COVID-19 cases continued to move towards the urban periphery and to more vulnerable communities, threatening the health system functioning and increasing the health gradient.

Gynecological Surgery and COVID-19: What is the Impact and How Should I Manage it?

It is estimated that around 28 million surgeries will be postponed or canceled worldwide as a result of this pandemic, causing a delay in the diagnosis and treatment of more than 2 million cancer cases. In Brazil, both the National Health Agency (ANS) and National Health Surveillance Agency (ANVISA) advised the postponement of elective and non-essential surgeries, causing a considerable impact on the number of surgical procedures that decreased by 33.4% in this period. However, some women need treatment for various gynecological diseases that cannot be postponed. The purpose of this article is to present recommendations on surgical treatment during the COVID-19 pandemic. Resumo Estima-se que cerca de 28 milhões de cirurgias sejam postergadas ou canceladas nomundo em decorrência desta pandemia, causando atraso no diagnóstico e tratamento de mais de 2 milhões de casos oncológicos. No Brasil, tanto a ANS (Agencia Nacional de Saúde) comoa ANVISA (Agencia Nacional de Vigilância Sanitária) orientaram o adiamento das cirurgias eletivas e não essenciais, tendo um impacto considerável no número de procedimentos cirúrgicos comdiminuição de 33,4% neste período no Brasil.No entanto, algumasmulheres necessitam de tratamento para várias doenças ginecológicas, algumas das quais não podem ser adiadas. O objetivo deste artigo é apresentar recomendações sobre o tratamento cirúrgico durante a pandemia de COVID-19.

A city cluster risk-based approach for Sars-CoV-2 and isolation barriers based on anonymized mobile phone users' location data.

Given the recent outbreak of Sars-CoV-2, several countries started to seek different strategies to control contamination and minimize fatalities, which are usually the primary objectives for all strategies. Secondary objectives are related to economic factors, therefore ensuring that society would be able is to keep its essential activities and avoid supply disruptions. This paper presents an application of anonymized mobile phone users' location data to estimate population flow amongst cities with an origin-destination matrix. The work includes a clustering analysis of cities, which may enable policymakers (and epidemiologists) to develop public policies giving the appropriate consideration for each set of cities within a Province or State. Risk measures are included to analyze the severity of the spread among the clusters, which can be ranked. Then, intelligence can be obtained from the analysis, and some clusters could be isolated to avoid contagion while keeping their economic activities. Therefore, this analysis is reproducible for other states of Brazil and other countries and can be adapted for districts within a city, especially considering the possibility of a second wave COVID-19 pandemic.