\ BIP! Finder for COVID-19 - Impact-based ranking

BIP! Finder for COVID-19

This version of BIP! Finder aims to ease the exploration of COVID-19-related literature by enabling ranking articles based on various impact metrics.

Last Update: 18 - 01 - 2023 (628506 entries)

Provided impact measures:
Popularity: Citation-based measure reflecting the current impact.
Influence: Citation-based measure reflecting the total impact.
Reader Attention: The current number of Mendeley readers.
Social Media Attention: The number of recent tweets related to this article.
*More details on these impact measures can be found here.
Score interpretations:
Exceptional score (in top 0.01%).
Substantial score (in top 1%).
Average score (in bottom 99%).
Score not available.
Main data sources:
CORD-19 dataset(1) (list of papers)
LitCovid hub(2) (list of papers)
PMC & PubMed (citations)
Mendeley (number of readers)
COVID-19-TweetIDs(3) (tweets)

Use:  Impact  Relevance & Impact
TitleVenueYearImpactSource
5501Using Administrative Data to Explore Potentially Aberrant Provision of Virtual Care During COVID-19: Retrospective Cohort Study of Ontario Provincial Data  

BACKGROUND: The COVID-19 pandemic has led to a rapid increase in virtual care use across the globe. Many health care systems have responded by creating virtual care billing codes that allow physicians to see their patients over telephone or video. This rapid liberalization of billing requirements, both in Canada and other countries, has led to concerns about potential abuse, but empirical data are limited. OBJECTIVE: The objectives of this study were to examine whether there were substantial changes in physicians’ ambulatory visit volumes coinciding with the liberalization of virtual care billing rules and to describe the characteristics of physicians who significantly increased their ambulatory visit volumes during this period. We also sought to describe the relationship between visit volume changes in 2020 and the volumes of virtual care use among individual physicians and across specialties. METHODS: We conducted a population-based, retrospective cohort study using health administrative data from the Ontario Health Insurance Plan, which was linked to the ICES Physician Database. We identified a unique cohort of providers based on physicians’ billings and calculated the ratio of total in-person and virtual ambulatory visits over the period from January to June 2020 (virtual predominating) relative to that over the period from January to June 2019 (in-person predominating) for each physician. Based on these ratios, we then stratified physicians into four groups: low-, same-, high-, and very high–use physicians. We then calculated various demographic and practice characteristics of physicians in each group. RESULTS: Among 28,383 eligible physicians in 2020, the mean ratio of ambulatory visits in January to June 2020:2019 was 0.99 (SD 2.53; median 0.81, IQR 0.59-1.0). Out of 28,383 physicians, only 2672 (9.4%) fell into the high-use group and only 291 (1.0%) fell into the very high–use group. High-use physicians were younger, more recent graduates, more likely female, and less likely to be international graduates. They also had, on average, lower-volume practices. There was a significant positive correlation between percent virtual care and the 2020:2019 ratio only in the group of physicians who maintained their practice (R=0.35, P<.001). There was also a significant positive correlation between the 2020:2019 ratio and the percent virtual care per specialty (R=0.59, P<.01). CONCLUSIONS: During the early stages of the pandemic, the introduction of virtual care did not lead to significant increases in visit volume. Our results provide reassuring evidence that relaxation of billing requirements early in the COVID-19 pandemic in Ontario were not associated with widespread and aberrant billing behaviors. Furthermore, the strong relationship between the ability to maintain practice volumes and the use of virtual care suggests that the introduction of virtual care allowed for continued access to care for patients.

J Med Internet Res2021       LitCov and CORD-19
5502Cerebral venous sinus thrombosis after ChAdOx1 nCov-19 vaccination with a misleading first cerebral MRI scan  

Vaccine-induced immune thrombotic thrombocytopenia (VITT) and cerebral venous sinus thrombosis (CVST) have been recently described as rare complications following vaccination against SARS-CoV-2 with vector vaccines. We report a case of a young woman who presented with VITT and cerebral CVST 7 days following vaccination with ChAdOx1 nCov-19 (AstraZeneca). While the initial MRI was considered void of pathological findings, MRI 3 days later revealed extensive CVST of the transversal and sigmoidal sinus with intracerebral haemorrhage. Diagnostic tests including a platelet-factor-4-induced platelet activation assay confirmed the diagnosis of VITT. Treatment with intravenous immunoglobulins and argatroban resulted in a normalisation of platelet counts and remission of CVST.

Stroke Vasc Neurol2021       LitCov and CORD-19
5503SARS-CoV-2 seroprevalence trends in healthy blood donors during the COVID-19 outbreak in Milan  

N/A

Blood Transfus2021       LitCov and CORD-19
5504Evaluation of the Online Learning Experience of Dalhousie Dentistry and Dental Hygiene Students during COVID-19 Pandemic Outbreak  

N/A

J Can Dent Assoc2021       LitCov and CORD-19
5505Recall response to COVID-19 antigen is preserved in people with multiple sclerosis on anti-CD20 medications-A pilot study  

BACKGROUND: Antibody responses to SARS-CoV-2 vaccination are impaired in people with multiple sclerosis (MS) under anti-CD20 therapies. It is however unclear, whether patients who received the basic immunization prior to anti-B cell medication start respond to the COVID-19 booster dose, once B cells are depleted. AIM: To investigate the humoral response to recall antigen by COVID-19 booster vaccines in people with MS (pwMS), who recently started an anti-CD20 therapy compared to people with long-term B cell depletion. METHODS: We enrolled 15 pwMS who had received booster vaccination on anti-CD20 therapy. Of these, 11 had established anti-CD20 medications and were therefore vaccinated during a continuous state of B cell depletion (CD20-vaccine cohort). Four pwMS had received the basic immunization prior to anti-CD20 therapy commencement and only the booster dose (vaccine-CD20-vaccine cohort) under conditions of B cell depletion. We assessed SARS-CoV-2 specific antibody responses after booster vaccination among both groups and evaluated accompanying B cell numbers and proportions from the peripheral circulation. RESULTS: The booster dose of SARS-CoV-2 vaccination elicited measurable antibody responses in 18% of individuals from the CD20-vaccine cohort compared to 100% from the vaccine-CD20-vaccine cohort. Antibody-levels were significantly higher among patients from the vaccine-CD20-vaccine cohort compared to the CD20-vaccine cohort (mean 951.25 ± 1137.96 BAU/ml, vs mean 12.36 ± 11.94 BAU/ml; mean difference 938 BAU/ml (95% CI: 249–1629 BAU/ml), p <0.0001). Among the vaccine-CD20-vaccine cohort, the booster immunization led to augmentation of spike antibody levels in 75% despite concomitant B cell depletion, and values increased by 3.8 – 9.4-fold compared to basic immunization. We observed no correlation of B cell kinetics and SARS-CoV-2 antibody levels. CONCLUSION: Our study suggests that antibody production to recall COVID-19 antigens is preserved in pwMS despite concomitant anti-CD20 therapy. If corroborated in bigger cohorts, this could have implications in the management of individuals about to start B cell medications.

Mult Scler Relat Disord2022       LitCov and CORD-19
5506Post-COVID Public Health Surveillance and Privacy Expectations in the United States: Scenario-Based Interview Study  

BACKGROUND: Smartphone-based apps designed and deployed to mitigate the COVID-19 pandemic may become infrastructure for postpandemic public health surveillance in the United States. Through the lenses of privacy concerns and user expectations of digital pandemic mitigation techniques, we identified possible long-term sociotechnical implications of such an infrastructure. OBJECTIVE: We explored how people in the United States perceive the possible routinization of pandemic tracking apps for public health surveillance in general. Our interdisciplinary analysis focused on the interplay between privacy concerns, data practices of surveillance capitalism, and trust in health care providers. We conducted this analysis to achieve a richer understanding of the sociotechnical issues raised by the deployment and use of technology for pandemic mitigation. METHODS: We conducted scenario-based, semistructured interviews (n=19) with adults in the United States. The interviews focused on how people perceive the short- and long-term privacy concerns associated with a fictional smart thermometer app deployed to mitigate the “outbreak of a contagious disease.” In order to elicit future-oriented discussions, the scenario indicated that the app would continue functioning “after the disease outbreak has dissipated.” We analyzed interview transcripts using reflexive thematic analysis. RESULTS: In the context of pandemic mitigation technology, including app-based tracking, people perceive a core trade-off between public health and personal privacy. People tend to rationalize this trade-off by invoking the concept of “the greater good.” The interplay between the trade-off and rationalization forms the core of sociotechnical issues that pandemic mitigation technologies raise. Participants routinely expected that data collected through apps related to public health would be shared with unknown third parties for the financial gain of the app makers. This expectation suggests a perceived alignment between an app-based infrastructure for public health surveillance and the broader economics of surveillance capitalism. Our results highlight unintended and unexpected sociotechnical impacts of routinizing app-based tracking on postpandemic life, which are rationalized by invoking a nebulous concept of the greater good. CONCLUSIONS: While technologies such as app-based tracking could be useful for pandemic mitigation and preparedness, the routinization of such apps as a form of public health surveillance may have broader, unintentional sociotechnical implications for individuals and the societies in which they live. Although technology has the potential to increase the efficacy of pandemic mitigation, it exists within a broader network of sociotechnical concerns. Therefore, it is necessary to consider the long-term implications of pandemic mitigation technologies beyond the immediate needs of addressing the COVID-19 pandemic. Potential negative consequences include the erosion of patient trust in health care systems and providers, grounded in concerns about privacy violations and overly broad surveillance.

JMIR Mhealth Uhealth2021       LitCov and CORD-19
5507Chronic COVID syndrome: Need for an appropriate medical terminology for long-COVID and COVID long-haulers  

N/A

J Med Virol2021       LitCov and CORD-19
5508Prevalence and Predictors of Emotional Eating among Healthy Young Saudi Women during the COVID-19 Pandemic  

Emotional eating (EE) is prevalent among women and is associated with obesity. The coronavirus 2019 (COVID-19) pandemic and mandatory quarantine increased the risk of mental symptoms and, inferentially, emotional eating (EE). We investigated the EE prevalence and predictors during this pandemic. Overall, 638 women, ages 18–39, completed an online survey incorporating the Emotional Eating Scale, Perceived Stress Scale, Generalized Anxiety Disorder-7 Scale, Patient Health Questionnaire-9, Pittsburgh Sleep Quality Index, and Global Physical Activity Questionnaire. We asked about nutrition and collected data on weight, height, and pandemic responses. Most respondents (47.2%) reported low EE; 40.4% were “moderate” and 12.4% “high” emotional eaters; 42.8% reported depression, 27% anxiety, 71% moderate stress, and 12.5% severe stress. The main EE indicators/predictors were fat intake (β = 0.192, p = 0.004), number of meals (β = 0.187, p < 0.001), sugar consumption (β = 0.150, p < 0.001), body mass index (β = 0.149, p < 0.001), stress (β = 0.143, p = 0.004), energy intake (β = 0.134, p = 0.04), and fast food intake frequency (β = 0.111, p < 0.01). EE score correlated negatively with increased family income (β = −0.081, p = 0.049). Higher stress correlated with worse sleep, less sleep, and less physical activity. Emotional eating is common among young Saudi women during the pandemic. We recommend healthy food choices and increased physical activity to improve sleep and mitigate stress.

Nutrients2020       LitCov and CORD-19
5509The inflammatory biomarkers profile of hospitalized patients with COVID-19 and its association with patient's outcome: A single centered study  

Several reports highlighted the central role of inflammation in the pathogenesis of corona virus disease-19 (COVID-19) disease. Also, the hyper-inflammatory response that is triggered by severe acute respiratory syndrom-Covid-2 (SARS-CoV-2) infection was believed to play an essential role in disease severity and adverse clinical course. For that reason, the classical inflammatory markers were proposed as a possible indicator for COVID-19 severity. However, an extensive analysis of the predictive value of inflammatory biomarkers in large patients’ cohorts is still limited and critically needed. In this study we investigated the predictive value of the classical inflammatory biomarkers in a patient cohort consists of 541 COVID-19 patients admitted to Al Kuwait Hospital, Dubai, UAE. A detailed analysis of the association between the essential inflammatory markers and clinical characteristics as well as clinical outcome of the patients were made. In addition, the correlation between those markers and a wide range of laboratory biomarkers and incidence of acute organs injury were investigated. Our results showed a significant elevation of many inflammatory markers including white cell count (WBC) count, neutrophils count, C-reactive protein (CRP), D-Dimer, ferritin, procalcitonin (PCT), and lactate dehydrogenase (LDH) levels in patients with more severe illness. Also, our results highlighted that higher levels of those markers can predict worse patient outcome including the need of ventilation, intensive care unit (ICU) admission, multiple organs dysfunction as well as death. In addition, Our results showed that the presence of lymphopenia and lower absolute lymphocyte count (ALC) at the time of admission were associated with severe to critical COVID-19 illness (P<0.0001), presence of acute respiratory distress syndrome (ARDS) (P<0.0001) and the need for ventilation and ICU admission., Moreover, our results showed a strong association between lower ALC count and multiple organs dysfunction and patient’s death (P<0.0001). In conclusion, our results highlighted the possible use of classical inflammatory biomarkers at time of admission as a potential predictive marker for more severe clinical course in COVID-19 patients that might need more aggressive therapeutic approach including the need of ventilators and ICU admission. The presence of such predictive markers might improve patient’s stratification and help in the direction of the available resources to patients in need, which in turn help in improving our response to the disease pandemic.

PLoS One2021       LitCov and CORD-19
5510Decline of Psychological Health Following the Designation of COVID-19 as a Pandemic: Descriptive Study  

BACKGROUND: COVID-19 was declared a pandemic by the World Health Organization on March 11, 2020, and as of this writing, Texas, United States, has reported >675,000 cases with over 14,000 deaths. Many of the preventive measures implemented during the pandemic can increase sedentary lifestyles, which can lead to the development of chronic diseases, including obesity, among the general population and cause serious threats to people’s physical health and overall quality of life. Individuals with pre-existing comorbidities are at an increased risk of COVID-19 and may hence have higher levels of stress. OBJECTIVE: This study aimed to investigate the relationship between physical activity levels and mental health status on an individual level and to compare them between those with and those without comorbidities in a cohort of Texas residents, before and after COVID-19 was declared a pandemic. METHODS: An electronic survey was disseminated throughout various regions of Texas. In total, 160 individuals were asked questions about their demographic characteristics, time spent on daily physical activities, and daily mental health status before and after COVID-19 was declared a pandemic. Frequency distributions and descriptive statistics were analyzed. RESULTS: Overall, 94 (58%) participants reported having ≥1 medical condition, and 31 (13.1%) had >3 medical conditions. Physical activity levels among participants with ≥1 pre-existing comorbidity drastically—but not significantly—decreased, as evident from a 10% increase in sedentary lifestyles after COVID-19 was declared a pandemic. On the contrary, we observed a 9% increase in the number of individuals without a pre-existing comorbidity who reported 30-60 min of physical activity per week. There was a 2-fold increase in the number of participants reporting more frequent feelings of nervousness, too much worry, trouble relaxing, and the fear of something awful happening after the pandemic. More specifically, individuals with pre-existing medical conditions reported, on average, a 10% higher incidence of feelings of stress, anxiety, and sadness compared to their healthy counterparts after COVID-19 was declared a pandemic. CONCLUSIONS: Stressful life conditions and chronic comorbidities are risk factors that can affect mental health and reduce the ability to perform activities of daily life. Therefore, when implementing pandemic protocols, municipalities should consider providing mental health support to their citizens to protect them from this rather inconspicuous adverse effect.

J Med Internet Res2021       LitCov and CORD-19
5511Performance of anti-SARS-CoV-2 antibody testing in asymptomatic or mild COVID-19 patients: A retrospective study in outbreak on a cruise ship  

OBJECTIVES: A few studies on antibody testing have focused on asymptomatic or mild coronavirus disease 2019 (COVID-19) patients with low initial anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody responses. Anti-SARS-CoV-2 antibody-testing performance was evaluated using blood samples from asymptomatic or mild COVID-19 patients. METHODS: Blood samples were collected from 143 COVID-19 patients during an outbreak on a cruise ship 3 weeks after diagnosis. Simultaneously, a follow-up SARS-CoV-2 genetic test was performed. Samples stored before the COVID-19 pandemic were also used to evaluate the lateral flow immunochromatographic assay (LFA) and electrochemiluminescence immunoassay (ECLIA). Titers of anti-SARS-CoV-2 IgM and IgG antibodies against the nucleocapsid and spike proteins were measured using the enzyme-linked immunosorbent assay to confirm which antibodies were influenced on LFA- and ECLIA- false-negative result in crew-member samples. RESULTS: Sensitivity, specificity, positive-predictive, and negative-predictive values of LFA-detected IgM antibodies were 0.231, 1.000, 1.000, and 0.613, respectively; those of LFA-detected IgG antibodies were 0.483, 0.989, 0.972, and 0.601, respectively; and those of ECLIA-detected total antibodies were 0.783, 1.000, 1.000, and 0.848, respectively. All antibody titers measured using ELISA were significantly lower in blood samples with negative results than in those with positive results in both LFA and ECLIA. In the patients with negative results from the follow-up genetic testing, IgM-, IgG-, and total-antibody positivity rates were 22.9%, 47.6%, and 72.4%, respectively. CONCLUSIONS: These findings suggest that anti-SARS-CoV-2 antibody testing has lower performance in asymptomatic or mild COVID-19 patients than required in the guidelines.

PLoS One2021       LitCov and CORD-19
5512Tracking discussions of complementary, alternative and integrative medicine in the context of the COVID-19 pandemic: a month-by-month sentiment analysis of Twitter data  

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a novel infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite the paucity of evidence, various complementary, alternative and integrative medicines (CAIMs) have been being touted as both preventative and curative. We conducted sentiment and emotion analysis with the intent of understanding CAIM content related to COVID-19 being generated on Twitter across 9 months. METHODS: Tweets relating to CAIM and COVID-19 were extracted from the George Washington University Libraries Dataverse Coronavirus tweets dataset from March 03 to November 30, 2020. We trained and tested a machine learning classifier using a large, pre-labelled Twitter dataset, which was applied to predict the sentiment of each CAIM-related tweet, and we used a natural language processing package to identify the emotions based on the words contained in the tweets. RESULTS: Our dataset included 28 713 English-language Tweets. The number of CAIM-related tweets during the study period peaked in May 2020, then dropped off sharply over the subsequent three months; the fewest CAIM-related tweets were collected during August 2020 and remained low for the remainder of the collection period. Most tweets (n = 15 612, 54%) were classified as positive, 31% were neutral (n = 8803) and 15% were classified as negative (n = 4298). The most frequent emotions expressed across tweets were trust, followed by fear, while surprise and disgust were the least frequent. Though volume of tweets decreased over the 9 months of the study, the expressed sentiments and emotions remained constant. CONCLUSION: The results of this sentiment analysis enabled us to establish key CAIMs being discussed at the intersection of COVID-19 across a 9-month period on Twitter. Overall, the majority of our subset of tweets were positive, as were the emotions associated with the words found within them. This may be interpreted as public support for CAIM, however, further qualitative investigation is warranted. Such future directions may be used to combat misinformation and improve public health strategies surrounding the use of social media information.

BMC Complement Med Ther2022       LitCov and CORD-19
5513SARS-CoV-2 Naturally Acquired Immunity vs Vaccine induced Immunity, Reinfections vs Breakthrough Infections: A Retrospective Cohort Study  

BACKGROUND: Waning of protection against infection with SARS-CoV-2 conferred by 2 doses of the BNT162b2 vaccine begins shortly after inoculation and becomes substantial within four months. With that, the impact of prior infection on incident SARS-CoV-2 reinfection is unclear. Therefore, we examined the long-term protection of naturally acquired immunity (protection conferred by previous infection) compared to vaccine-induced immunity. METHODS: A retrospective observational study of 124,500 persons, compared two groups: (1) SARS-CoV-2-naïve individuals who received a two-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 vaccine, and (2) previously infected individuals who have not been vaccinated. Two multivariate logistic regression models were applied, evaluating four SARS-CoV-2-related outcomes - infection, symptomatic disease (COVID-19), hospitalization and death – between June 1 to August 14, 2021, when the Delta variant was dominant in Israel. RESULTS: SARS-CoV-2-naïve vaccinees had a 13.06-fold (95% CI, 8.08-21.11) increased risk for breakthrough infection with the Delta variant compared to unvaccinated-previously-infected individuals, when the first event (infection or vaccination) occurred during January and February of 2021. The increased risk was significant for symptomatic disease as well. When allowing the infection to occur at any time between March 2020 to February 2021, evidence of waning naturally acquired immunity was demonstrated, though SARS-CoV-2 naïve vaccinees still had a 5.96-fold (95% CI, 4.85-7.33) increased risk for breakthrough infection and a 7.13-fold (95% CI, 5.51-9.21) increased risk for symptomatic disease. CONCLUSIONS: Naturally acquired immunity confers stronger protection against infection and symptomatic disease caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 two-dose vaccine-induced immunity.

Clin Infect Dis2022       LitCov and CORD-19
5514Impact of sex and gender on COVID-19 outcomes in Europe  

BACKGROUND: Emerging evidence from China suggests that coronavirus disease 2019 (COVID-19) is deadlier for infected men than women with a 2.8% fatality rate being reported in Chinese men versus 1.7% in women. Further, sex-disaggregated data for COVID-19 in several European countries show a similar number of cases between the sexes, but more severe outcomes in aged men. Case fatality is highest in men with pre-existing cardiovascular conditions. The mechanisms accounting for the reduced case fatality rate in women are currently unclear but may offer potential to develop novel risk stratification tools and therapeutic options for women and men. CONTENT: The present review summarizes latest clinical and epidemiological evidence for gender and sex differences in COVID-19 from Europe and China. We discuss potential sex-specific mechanisms modulating the course of disease, such as hormone-regulated expression of genes encoding for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) entry receptors angiotensin converting enzyme (ACE) 2 receptor and TMPRSS2 as well as sex hormone-driven innate and adaptive immune responses and immunoaging. Finally, we elucidate the impact of gender-specific lifestyle, health behavior, psychological stress, and socioeconomic conditions on COVID-19 and discuss sex specific aspects of antiviral therapies. CONCLUSION: The sex and gender disparities observed in COVID-19 vulnerability emphasize the need to better understand the impact of sex and gender on incidence and case fatality of the disease and to tailor treatment according to sex and gender. The ongoing and planned prophylactic and therapeutic treatment studies must include prospective sex- and gender-sensitive analyses.

Biol Sex Differ2020       LitCov and CORD-19
5515The K18-Human ACE2 Transgenic Mouse Model Recapitulates Non-severe and Severe COVID-19 in Response to an Infectious Dose of the SARS-CoV-2 Virus  

A comprehensive analysis and characterization of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection model that mimics non-severe and severe coronavirus disease 2019 (COVID-19) in humans is warranted for understating the virus and developing preventive and therapeutic agents. Here, we characterized the K18-hACE2 mouse model expressing human (h)ACE2 in mice, controlled by the human keratin 18 (K18) promoter, in the epithelia, including airway epithelial cells where SARS-CoV-2 infections typically start. We found that intranasal inoculation with higher viral doses (2 × 10(3) and 2 × 10(4) PFU) of SARS-CoV-2 caused lethality of all mice and severe damage of various organs, including lung, liver, and kidney, while lower doses (2 × 10(1) and 2 × 10(2) PFU) led to less severe tissue damage and some mice recovered from the infection. In this hACE2 mouse model, SARS-CoV-2 infection damaged multiple tissues, with a dose-dependent effect in most tissues. Similar damage was observed in postmortem samples from COVID-19 patients. Finally, the mice that recovered from infection with a low dose of virus survived rechallenge with a high dose of virus. Compared to other existing models, the K18-hACE2 model seems to be the most sensitive COVID-19 model reported to date. Our work expands the information available about this model to include analysis of multiple infectious doses and various tissues with comparison to human postmortem samples from COVID-19 patients. In conclusion, the K18-hACE2 mouse model recapitulates both severe and non-severe COVID-19 in humans being dose-dependent and can provide insight into disease progression and the efficacy of therapeutics for preventing or treating COVID-19. IMPORTANCE The pandemic of coronavirus disease 2019 (COVID-19) has reached nearly 240 million cases, caused nearly 5 million deaths worldwide as of October 2021, and has raised an urgent need for the development of novel drugs and therapeutics to prevent the spread and pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To achieve this goal, an animal model that recapitulates the features of human COVID-19 disease progress and pathogenesis is greatly needed. In this study, we have comprehensively characterized a mouse model of SARS-CoV-2 infection using K18-hACE2 transgenic mice. We infected the mice with low and high doses of SARS-CoV-2 to study the pathogenesis and survival in response to different infection patterns. Moreover, we compared the pathogenesis of the K18-hACE2 transgenic mice with that of the COVID-19 patients to show that this model could be a useful tool for the development of antiviral drugs and therapeutics.

J Virol2022       LitCov and CORD-19
5516Age and sex-specific risks of myocarditis and pericarditis following Covid-19 messenger RNA vaccines  

N/A

Nat Commun2022       LitCov
5517The prevalence of SARS-CoV-2 antibodies in triage-negative patients and staff of a fertility setting from lockdown release throughout 2020  

STUDY QUESTION: What is the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in triage-negative patients undergoing ART and fertility care providers after lockdown release and throughout 2020? SUMMARY ANSWER: Out of the triage-negative patients whose blood samples were assessed for SARS-CoV-2 antibodies over 6 months, 5.2% yielded positive results with a significantly higher rate in health care workers (HCWs) and a significant month-by-month increase in those with evidence of antibodies. WHAT IS KNOWN ALREADY: Patients of reproductive age are more prone to asymptomatic or minimal forms of coronavirus disease 2019 (COVID-19) as compared to older age groups, and the identification of those with active infection and those already exposed (and probably immunized) is important for safety and cost-effective use of testing resources in the fertility setting. Data on the prevalence of SARS-CoV-2 in ART patients are limited and encompass short time frames; current rates are unknown. There is also no consensus on the optimal way of screening triage-negative ART patients in moderate/high-risk areas. STUDY DESIGN, SIZE, DURATION: A prospective longitudinal unicentric study on triage negative ART patients (n = 516) and clinical staff (n = 30) was carried out. We analyzed 705 serological tests for SARS-CoV-2 sampled between 17 May 2020 (the first working day after lockdown release) up to 1 December 2020, to assess the positivity rates for SARS-CoV-2 antibodies. PARTICIPANTS/MATERIALS, SETTING, METHODS: We collected data on the serological status for IgM and IgG antibodies against SARS-CoV-2 in 516 triage-negative men (n = 123) and women (n = 393) undergoing ART at a private fertility center and 30 HCWs that were at work during the study period. Antibodies were detected with a capture chemiluminescence assay (CLIA) targeting the highly Immunogenic S1 and S2 domains on the virus spike protein. We also analyzed the molecular test results of the cases exhibiting a positive serology. MAIN RESULTS AND THE ROLE OF CHANCE: The data showed that 5.2% of the triage-negative ART patients had a positive serological result for SARS-CoV-2, with an overall conversion rate of 2.1% for IgG and 4.6% for IgM. There was no significant difference in seroprevalence between sexes. The small cohort (n = 30) of HCWs had a markedly increased seroprevalence (12.9% for Ig M and 22.6% for IgG). The highest seropositivity in our cohort was recorded in November (16.2%). The IgM positivity rates revealed significant monthly increments, paralleling official prevalence rates based on nasopharyngeal swabs. No positive molecular tests were identified in cases exhibiting a solitary positive IgG result. We show that despite a 6-fold increase in the number of ART patients with a positive serology between May and December 2020, most of our patients remain unexposed to the virus. The study was undertaken in a high-risk area for COVID-19, with a 20-times increase in the active cases across the study period. LIMITATIONS, REASONS FOR CAUTION: The geographical restriction, alongside the lack of running a second, differently-targeted immunoassay (orthogonal testing), could limit the generalizability and translation of our results to other fertility settings or other immunoassays. WIDER IMPLICATIONS OF THE FINDINGS: The low positivity rates for IgG against the SARS-CoV-2 spike protein seen at the end of 2020 imply that most of the fertility patients are still at risk for SARS-CoV-2 infection. Until mass vaccination and other measures effectively diminish the pandemic, risk mitigation strategies must be maintained in the fertility units in the foreseeable future. Patients with a solitary IgG+ status are most likely ‘non-infectious’ and can elude further testing without giving up the strict use of universal protective measures. With increasing seroprevalences owing to infection or vaccination, and with the consecutive increase in test performance, it is possible that serological screening of ART patients might be more cost-effective than PCR testing, especially for the many patients with repeat treatments/procedures in a time-frame of months. STUDY FUNDING/COMPETING INTERESTS: This research received no external funding. All authors declare having no conflict of interest with regard to this trial.

Hum Reprod Open2021       LitCov and CORD-19
5518Echocardiographic Findings in Pediatric Multisystem Inflammatory Syndrome Associated With COVID-19 in the United States  

Background Centers from Europe and United States have reported an exceedingly high number of children with a severe inflammatory syndrome in the setting of COVID-19, which has been termed multisystem inflammatory syndrome in children (MIS-C). Objectives This study aimed to analyze echocardiographic manifestations in MIS-C. Methods We retrospectively reviewed 28 MIS-C, 20 healthy controls and 20 classic Kawasaki disease (KD) patients. We reviewed echocardiographic parameters in acute phase of MIS-C and KD groups, and during subacute period in MIS-C group (interval: 5.2 ± 3 days). Results Only 1 case in MIS-C (4%) manifested coronary artery dilatation (z score=3.15) in acute phase, showing resolution during early follow up. Left ventricular (LV) systolic and diastolic function measured by deformation parameters, were worse in MIS-C compared to KD. Moreover, MIS-C patients with myocardial injury (+) were more affected than myocardial injury (-) MIS-C with respect to all functional parameters. The strongest parameters to predict myocardial injury in MIS-C were global longitudinal strain (GLS), global circumferential strain (GCS), peak left atrial strain (LAS) and peak longitudinal strain of right ventricular free wall (RVFWLS) (Odds ratio: 1.45 (1.08-1.95), 1.39 (1.04-1.88), 0.84 (0.73-0.96), 1.59 (1.09-2.34) respectively). The preserved LVEF group in MIS-C showed diastolic dysfunction. During subacute period, LVEF returned to normal (median: from 54% to 64%, p<0.001) but diastolic dysfunction persisted. Conclusions Unlike classic KD, coronary arteries may be spared in early MIS-C, however, myocardial injury is common. Even preserved EF patients showed subtle changes in myocardial deformation, suggesting subclinical myocardial injury. During an abbreviated follow-up, there was good recovery of systolic function but persistence of diastolic dysfunction and no coronary aneurysms. Condensed abstract Multisystem inflammatory syndrome in children (MIS-C) is an illness that resembles Kawasaki Disease (KD) or toxic shock, reported in children with a recent history of COVID-19 infection. This study analyzed echocardiographic manifestations of this illness. In our cohort of 28 MIS-C patients, left ventricular systolic and diastolic function were worse than in classic KD. These functional parameters correlated with biomarkers of myocardial injury. However, coronary arteries were typically spared. The strongest predictors of myocardial injury were global longitudinal strain, right ventricular strain, and left atrial strain. During subacute period, there was good recovery of systolic function, but diastolic dysfunction persisted.

J Am Coll Cardiol2020       LitCov and CORD-19
5519Potential harmful effects of discontinuing ACE-inhibitors and ARBs in COVID-19 patients  

The discovery of angiotensin converting enzyme-2 (ACE-2) as the receptor for SARS- CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) has implicated the renin-angiotensin-aldosterone system in acute respiratory distress syndrome (ARDS) and respiratory failure in patients with coronavirus disease-19 (COVID-19). The angiotensin converting enzyme-1–angiotensin II–angiotensin AT(1) receptor pathway contributes to the pathophysiology of ARDS, whereas activation of the ACE-2–angiotensin(1-7)-angiotensin AT(2) receptor and the ACE-2–angiotensin(1-7)–Mas receptor pathways have been shown to be protective. Here we propose and discuss therapeutic considerations how to increase soluble ACE-2 in plasma in order for ACE-2 to capture and thereby inactivate SARS-CoV-2. This could be achieved by administering recombinant soluble ACE-2. We also discuss why and how ACEIs and ARBs provide cardiovascular, renal and also pulmonary protection in SARS-CoV-2- associated ARDS. Discontinuing these medications in COVID-19 patients may therefore potentially be harmful.

Elife2020       LitCov and CORD-19
5520An accelerated shift in the use of remote systems in epilepsy due to the COVID-19 pandemic  

PURPOSE: The purpose of the study was to describe epileptologists' opinion on the increased use of remote systems implemented during the COVID-19 pandemic across clinics, education, and scientific meetings activities. METHODS: Between April and May 2020, we conducted a cross-sectional, electronic survey on remote systems use before and during the COVID-19 pandemic through the European reference center for rare and complex epilepsies (EpiCARE) network, the International and the French Leagues Against Epilepsy, and the International and the French Child Neurology Associations. After descriptive statistical analysis, we compared the results of France, China, and Italy. RESULTS: One hundred and seventy-two respondents from 35 countries completed the survey. Prior to the COVID-19 pandemic, 63.4% had experienced remote systems for clinical care. During the pandemic, the use of remote clinics, either institutional or personal, significantly increased (p < 10(−4)). Eighty-three percent used remote systems with video, either institutional (75%) or personal (25%). During the pandemic, 84.6% of respondents involved in academic activities transformed their courses to online teaching. From February to July 2020, few scientific meetings relevant to epileptologists and routinely attended was adapted to virtual meeting (median: 1 [25th–75th percentile: 0–2]). Responders were quite satisfied with remote systems in all three activity domains. Interestingly, before the COVID-19 pandemic, remote systems were significantly more frequently used in China for clinical activity compared with France or Italy. This difference became less marked during the pandemic. CONCLUSION: The COVID-19 pandemic has dramatically altered how academic epileptologists carry out their core missions of clinical care, medical education, and scientific discovery and dissemination. Close attention to the impact of these changes is merited.

Epilepsy Behav2020       LitCov and CORD-19
5521Monitoring Incidence of COVID-19 Cases, Hospitalizations and Deaths, by Vaccination Status-13 US Jurisdictions, April 4-July 17, 2021  

COVID-19 vaccine breakthrough infection surveillance helps monitor trends in disease incidence and severe outcomes in fully vaccinated persons, including the impact of the highly transmissible B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19. Reported COVID-19 cases, hospitalizations, and deaths occurring among persons aged ≥18 years during April 4-July 17, 2021, were analyzed by vaccination status across 13 U.S. jurisdictions that routinely linked case surveillance and immunization registry data. Averaged weekly, age-standardized incidence rate ratios (IRRs) for cases among persons who were not fully vaccinated compared with those among fully vaccinated persons decreased from 11.1 (95% confidence interval [CI] = 7.8-15.8) to 4.6 (95% CI = 2.5-8.5) between two periods when prevalence of the Delta variant was lower (<50% of sequenced isolates; April 4-June 19) and higher (≥50%; June 20-July 17), and IRRs for hospitalizations and deaths decreased between the same two periods, from 13.3 (95% CI = 11.3-15.6) to 10.4 (95% CI = 8.1-13.3) and from 16.6 (95% CI = 13.5-20.4) to 11.3 (95% CI = 9.1-13.9). Findings were consistent with a potential decline in vaccine protection against confirmed SARS-CoV-2 infection and continued strong protection against COVID-19-associated hospitalization and death. Getting vaccinated protects against severe illness from COVID-19, including the Delta variant, and monitoring COVID-19 incidence by vaccination status might provide early signals of changes in vaccine-related protection that can be confirmed through well-controlled vaccine effectiveness (VE) studies.

MMWR Morb Mortal Wkly Rep2021       LitCov and CORD-19
5522Six-month psychophysical evaluation of olfactory dysfunction in patients with COVID-19  

This study prospectively assessed the six-month prevalence of self-reported and psychophysically measured olfactory dysfunction in subjects with mild-to-moderate COVID-19. Self-reported smell or taste impairment was prospectively evaluated by SNOT-22 at diagnosis, 4-week, 8-week, and 6-month. At 6 months from the diagnosis, psychophysical evaluation of olfactory function was also performed using the 34-item culturally adapted University of Pennsylvania Smell Identification Test (CA-UPSIT). 145 completed both the 6-month subjective and psychophysical olfactory evaluation. According to CA-UPSIT, 87 subjects (60.0%) exhibited some smell dysfunction, with 10 patients being anosmic (6.9%) and 7 being severely microsmic (4.8%). At the time CA-UPSIT was administered, a weak correlation was observed between the self-reported alteration of sense of smell or taste and olfactory test scores (Spearman’s r=-0.26). Among 112 patients who self-reported normal sense of smell at last follow-up, CA-UPSIT revealed normal smell in 46 (41.1%), mild microsmia in 46 (41.1%), moderate microsmia in 11 (9.8%), severe microsmia in 3 (2.3%), and anosmia in 6 (5.4%) patients; however, of those patients self-reporting normal smell but who were found to have hypofunction on testing, 62 out of 66 had self-reported reduction in sense of smell or taste at an earlier time point. Despite most patients report a subjectively normal sense of smell, we observed a high percentage of persistent smell dysfunction at 6 months from the diagnosis of SARS-CoV-2 infection, with 11.7% of patients being anosmic or severely microsmic. These data highlight a significant long-term rate of smell alteration in patients with previous SARS-COV-2 infection.

Chem Senses2021       LitCov and CORD-19
5523Rate and severity of suspected SARS-Cov-2 reinfection in a cohort of PCR-positive COVID-19 patients  

OBJECTIVES: To estimate the burden and severity of suspected reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: A retrospective cohort of members of Kaiser Permanente Southern California with PCR-positive SARS-CoV-2 infection between 1st March 2020 and 31st October 2020 was followed through electronic health records for subsequent positive SARS-CoV-2 tests (suspected reinfection) ≥90 days after initial infection, through 31st January 2021. Incidence of suspected reinfection was estimated using the Kaplan–Meier method. Cox proportional hazards models estimated the association of suspected reinfection with demographic and clinical characteristics, hospitalization, and date of initial infection. RESULTS: The cohort of 75 149 was predominantly Hispanic (49 648/75 149, 66.1%) and included slightly more females than males (39 736, 52.9%), with few immunocompromised patients (953, 1.3%); 315 suspected reinfections were identified, with a cumulative incidence at 270 days of 0.8% (95% confidence interval (CI) 0.7–1.0%). Hospitalization was more common at suspected reinfection (36/315, 11.4%) than initial infection (4094/75 149, 5.4%). Suspected reinfection rates were higher in females (1.0%, CI 0.8–1.2% versus 0.7%, CI 0.5–0.9%, p 0.002) and immunocompromised patients (2.1%, CI 1.0–4.2% versus 0.8%, CI 0.7–1.0%, p 0.004), and lower in children than adults (0.2%, CI 0.1–0.4% versus 0.9%, CI 0.7–1.0%, p 0.023). Patients hospitalized at initial infection were more likely to have suspected reinfection (1.2%, CI 0.6–1.7% versus 0.8%, CI 0.7–1.0%, p 0.030), as were those with initial infections later in 2020 (150-day incidence 0.4%, CI 0.2–0.5% September–October versus 0.2%, CI 0.1–0.3% March–May and 0.3%, CI 0.2–0.3% June–August, p 0.008). In an adjusted Cox proportional hazards model, being female (hazard ratio (HR) 1.44, CI 1.14–1.81), adult (age 18–39, HR 2.71, CI 1.38–5.31, age 40–59 HR 2.22, CI 1.12–4.41, age ≥60 HR 2.52, CI 1.23–5.17 versus <18 years), immunocompromised (HR 2.48, CI 1.31–4.68), hospitalized (HR 1.60, CI 1.07–2.38), and initially infected later in 2020 (HR 2.26, CI 1.38–3.71 September–October versus March–May) were significant independent predictors of suspected reinfection. CONCLUSIONS: Reinfection with SARS-CoV-2 is uncommon, with suspected reinfections more likely in women, adults, immunocompromised subjects, and those previously hospitalized for coronavirus 2019 (COVID-19). This suggests a need for continued precautions and vaccination in patients with COVID-19 to prevent reinfection.

Clin Microbiol Infect2021       LitCov and CORD-19
5524Evaluation of Immune Response and Disease Status in Systemic Lupus Erythematosus Patients Following SARS-CoV-2 Vaccination  

OBJECTIVE: To evaluate seroreactivity and disease flares after COVID‐19 vaccination in a multi‐ethnic/racial cohort of patients with systemic lupus erythematosus (SLE). METHODS: 90 SLE patients and 20 healthy controls receiving a complete COVID‐19 vaccine regimen were included. IgG seroreactivity to the SARS‐CoV‐2 spike receptor‐binding domain (RBD) and SARS‐CoV‐2 microneutralization were used to evaluate B cell responses; IFN‐γ production to assess T cell responses was measured by ELISpot. Disease activity was measured by the hybrid SLE disease activity index (SLEDAI) and flares were assigned by the SELENA/SLEDAI flare index. RESULTS: Overall, fully vaccinated SLE patients produced significantly lower IgG antibodies against SARS‐CoV‐2 spike RBD than controls. Twenty‐six SLE patients (28.8%) generated an IgG response below that of the lowest control (<100 units/ml). In logistic regression analyses, the use of any immunosuppressant or prednisone and a normal anti‐dsDNA level prior to vaccination associated with decreased vaccine responses. IgG seroreactivity to the SARS‐CoV‐2 Spike RBD strongly correlated with the SARS‐CoV‐2 microneutralization titers and antigen‐specific IFN‐γ production determined by ELISpot. In a subset of patients with poor antibody responses, IFN‐γ production was likewise diminished. Pre‐/post‐vaccination SLEDAI scores were similar. Only 11.4% of patients had a post‐vaccination flare; 1.3% were severe. CONCLUSION: In a multi‐ethnic/racial study of SLE patients 29% had a low response to the COVID‐19 vaccine which was associated with being on immunosuppression. Reassuringly, disease flares were rare. While minimal protective levels remain unknown, these data suggest protocol development is needed to assess efficacy of booster vaccination.

Arthritis Rheumatol2021       LitCov and CORD-19
5525SARS-CoV-2, the pandemic coronavirus: Molecular and structural insights  

The outbreak of a novel coronavirus associated with acute respiratory disease, called COVID‐19, marked the introduction of the third spillover of an animal coronavirus (CoV) to humans in the last two decades. The genome analysis with various bioinformatics tools revealed that the causative pathogen (SARS‐CoV‐2) belongs to the subgenus Sarbecovirus of the genus Betacoronavirus, with highly similar genome as bat coronavirus and receptor‐binding domain (RBD) of spike glycoprotein as Malayan pangolin coronavirus. Based on its genetic proximity, SARS‐CoV‐2 is likely to have originated from bat‐derived CoV and transmitted to humans via an unknown intermediate mammalian host, probably Malayan pangolin. Further, spike protein S1/S2 cleavage site of SARS‐CoV‐2 has acquired polybasic furin cleavage site which is absent in bat and pangolin suggesting natural selection either in an animal host before zoonotic transfer or in humans following zoonotic transfer. In the current review, we recapitulate a preliminary opinion about the disease, origin and life cycle of SARS‐CoV‐2, roles of virus proteins in pathogenesis, commonalities, and differences between different corona viruses. Moreover, the crystal structures of SARS‐CoV‐2 proteins with unique characteristics differentiating it from other CoVs are discussed. Our review also provides comprehensive information on the molecular aspects of SARS‐CoV‐2 including secondary structures in the genome and protein–protein interactions which can be useful to understand the aggressive spread of the SARS‐CoV‐2. The mutations and the haplotypes reported in the SARS‐CoV‐2 genome are summarized to understand the virus evolution.

J Basic Microbiol2021       LitCov and CORD-19
5526Association of Social and Demographic Factors With COVID-19 Incidence and Death Rates in the US  

IMPORTANCE: Descriptive data have revealed significant racial/ethnic disparities in coronavirus disease 2019 (COVID-19) cases in the US, but underlying mechanisms of disparities remain unknown. OBJECTIVE: To examine the association between county-level sociodemographic risk factors and US COVID-19 incidence and mortality. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed the association between US county-level sociodemographic risk factors and COVID-19 incidence using mixed-effects negative binomial regression, and COVID-19 mortality using zero-inflated negative binomial regression. Data on COVID-19 incidence and mortality were collected from January 20 to July 29, 2020. The association of social risk factors with weekly cumulative incidence and mortality was also examined by interacting time with the index measures, using a random intercept to account for repeated measures. MAIN OUTCOMES AND MEASURES: Sociodemographic data from publicly available data sets, including the US Centers for Disease Control and Prevention’s Social Vulnerability Index (SVI), which includes subindices of socioeconomic status, household composition and disability, racial/ethnic minority and English language proficiency status, and housing and transportation. RESULTS: As of July 29, 2020, there were a total of 4 289 283 COVID-19 cases and 147 074 COVID-19 deaths in the US. An increase of 0.1 point in SVI score was associated with a 14.3% increase in incidence rate (incidence rate ratio [IRR], 1.14; 95% CI, 1.13-1.16; P < .001) and 13.7% increase in mortality rate (IRR, 1.14; 95% CI, 1.12-1.16; P < .001), or an excess of 87 COVID-19 cases and 3 COVID-19 deaths per 100 000 population for a SVI score change from 0.5 to 0.6 in a midsize metropolitan county; subindices were also associated with both outcomes. A 0.1-point increase in the overall SVI was associated with a 0.9% increase in weekly cumulative increase in incidence rate (IRR, 1.01; 95% CI, 1.01-1.01; P < .001) and 0.5% increase in mortality rate (IRR, 1.01; 95% CI, 1.01-1.01; P < .001). CONCLUSIONS AND RELEVANCE: In this cross-sectional study, a wide range of sociodemographic risk factors, including socioeconomic status, racial/ethnic minority status, household composition, and environmental factors, were significantly associated with COVID-19 incidence and mortality. To address inequities in the burden of the COVID-19 pandemic, these social vulnerabilities and their root causes must be addressed.

JAMA Netw Open2021       LitCov and CORD-19
5527Assessment of Racial/Ethnic Disparities in Hospitalization and Mortality in Patients With COVID-19 in New York City  

IMPORTANCE: Black and Hispanic populations have higher rates of coronavirus disease 2019 (COVID-19) hospitalization and mortality than White populations but lower in-hospital case-fatality rates. The extent to which neighborhood characteristics and comorbidity explain these disparities is unclear. Outcomes in Asian American populations have not been explored. OBJECTIVE: To compare COVID-19 outcomes based on race and ethnicity and assess the association of any disparities with comorbidity and neighborhood characteristics. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted within the New York University Langone Health system, which includes over 260 outpatient practices and 4 acute care hospitals. All patients within the system’s integrated health record who were tested for severe acute respiratory syndrome coronavirus 2 between March 1, 2020, and April 8, 2020, were identified and followed up through May 13, 2020. Data were analyzed in June 2020. Among 11 547 patients tested, outcomes were compared by race and ethnicity and examined against differences by age, sex, body mass index, comorbidity, insurance type, and neighborhood socioeconomic status. EXPOSURES: Race and ethnicity categorized using self-reported electronic health record data (ie, non-Hispanic White, non-Hispanic Black, Hispanic, Asian, and multiracial/other patients). MAIN OUTCOMES AND MEASURES: The likelihood of receiving a positive test, hospitalization, and critical illness (defined as a composite of care in the intensive care unit, use of mechanical ventilation, discharge to hospice, or death). RESULTS: Among 9722 patients (mean [SD] age, 50.7 [17.5] years; 58.8% women), 4843 (49.8%) were positive for COVID-19; 2623 (54.2%) of those were admitted for hospitalization (1047 [39.9%] White, 375 [14.3%] Black, 715 [27.3%] Hispanic, 180 [6.9%] Asian, 207 [7.9%] multiracial/other). In fully adjusted models, Black patients (odds ratio [OR], 1.3; 95% CI, 1.2-1.6) and Hispanic patients (OR, 1.5; 95% CI, 1.3-1.7) were more likely than White patients to test positive. Among those who tested positive, odds of hospitalization were similar among White, Hispanic, and Black patients, but higher among Asian (OR, 1.6, 95% CI, 1.1-2.3) and multiracial patients (OR, 1.4; 95% CI, 1.0-1.9) compared with White patients. Among those hospitalized, Black patients were less likely than White patients to have severe illness (OR, 0.6; 95% CI, 0.4-0.8) and to die or be discharged to hospice (hazard ratio, 0.7; 95% CI, 0.6-0.9). CONCLUSIONS AND RELEVANCE: In this cohort study of patients in a large health system in New York City, Black and Hispanic patients were more likely, and Asian patients less likely, than White patients to test positive; once hospitalized, Black patients were less likely than White patients to have critical illness or die after adjustment for comorbidity and neighborhood characteristics. This supports the assertion that existing structural determinants pervasive in Black and Hispanic communities may explain the disproportionately higher out-of-hospital deaths due to COVID-19 infections in these populations.

JAMA Netw Open2020       LitCov and CORD-19
5528Evaluating the antibody response to SARS-COV-2 vaccination amongst kidney transplant recipients at a single nephrology center  

BACKGROUND AND OBJECTIVES: Kidney transplant recipients are highly vulnerable to the serious complications of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infections and thus stand to benefit from vaccination. Therefore, it is necessary to establish the effectiveness of available vaccines as this group of patients was not represented in the randomized trials. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 707 consecutive adult kidney transplant recipients in a single center in the United Kingdom were evaluated. 373 were confirmed to have received two doses of either the BNT162b2 (Pfizer-BioNTech) or AZD1222 (Oxford-AstraZeneca) and subsequently had SARS-COV-2 antibody testing were included in the final analysis. Participants were excluded from the analysis if they had a previous history of SARS-COV-2 infection or were seropositive for SARS-COV-2 antibody pre-vaccination. Multivariate and propensity score analyses were performed to identify the predictors of antibody response to SARS-COV-2 vaccines. The primary outcome was seroconversion rates following two vaccine doses. RESULTS: Antibody responders were 56.8% (212/373) and non-responders 43.2% (161/373). Antibody response was associated with greater estimated glomerular filtration (eGFR) rate [odds ratio (OR), for every 10 ml/min/1.73m(2) = 1.40 (1.19–1.66), P<0.001] whereas, non-response was associated with mycophenolic acid immunosuppression [OR, 0.02(0.01–0.11), p<0.001] and increasing age [OR per 10year increase, 0.61(0.48–0.78), p<0.001]. In the propensity-score analysis of four treatment variables (vaccine type, mycophenolic acid, corticosteroid, and triple immunosuppression), only mycophenolic acid was significantly associated with vaccine response [adjusted OR by PSA 0.17 (0.07–0.41): p<0.001]. 22 SARS-COV-2 infections were recorded in our cohort following vaccination. 17(77%) infections, with 3 deaths, occurred in the non-responder group. No death occurred in the responder group. CONCLUSION: Vaccine response in allograft recipients after two doses of SARS-COV-2 vaccine is poor compared to the general population. Maintenance with mycophenolic acid appears to have the strongest negative impact on vaccine response.

PLoS One2022       LitCov and CORD-19
5529The impact of the COVID-19 pandemic on physical activity in US children  

BACKGROUND: Daily moderate-to-vigorous physical activity (MVPA) is vital to the physical, mental, and social well-being of children. Early restrictions during the coronavirus disease 2019 (COVID-19) pandemic included the closure of schools and physical activity (PA) amenities across the US. This study aimed to examine the impact of the pandemic on the PA and play behavior of U.S. children and to provide evidence-based recommendations to improve their PA. METHODS: A cross-sectional, online, parent-reported survey was conducted of children aged 3–18 years between April and June 2020 to assess light PA and MVPA using a modified Godin Leisure-Time Exercise Questionnaire. Additional items included family/child socioeconomic demographics, child adaptability to the pandemic, and community access. The survey was shared through social media and snowball sampling distribution. RESULTS: Analysis of 1310 surveys indicated child PA scores declined significantly during the pandemic (from 56.6 to 44.6, max 119, p < 0.001). Specifically, MVPA score decreased (from 46.7 to 34.7, max 98, p < 0.001) while light PA remained the same. Age-based changes were seen in the quantity, variety, and intensity of PA, with the lowest pandemic-related impact seen in preschoolers and the highest in high schoolers (–4.7 vs. –17.2, p < 0.001). Community-based peer PA decreased across all age groups. CONCLUSION: This study shows decreased PA levels in U.S. children, according to parent reporting, during the COVID-19 pandemic. Recommendations for community leaders, educators, and parents to improve PA in children are provided. With continued spread of COVID-19, these results and recommendations may be imperative to the physical well-being of U.S. children.

J Sport Health Sci2021       LitCov and CORD-19
5530The Impacts of the COVID-19 Pandemic on HIV Testing Utilization Among Men Who Have Sex With Men in China: Cross-sectional Online Survey  

BACKGROUND: The COVID-19 pandemic has created disruptions in HIV prevention and sexual health services for men who have sex with men (MSM). OBJECTIVE: This study compared HIV testing utilization in 3 different reference periods (period 1: before the COVID-19 outbreak, November 2019-January 2020; period 2: after the outbreak, February-April 2020; and period 3: after the pandemic was under initial control, May-July 2020). Factors associated with HIV testing utilization after the COVID-19 outbreak (combined periods 2 and 3) were also investigated. METHODS: Participants were MSM aged ≥18 years living in Shenzhen, China. Those self-reporting as HIV positive were excluded. A total of 595 participants recruited through multiple sources completed a self-administered online survey during August-September 2020. HIV testing utilization after the COVID-19 outbreak was the dependent variable, and multivariate logistic regression models were fitted. RESULTS: HIV testing utilization was significantly lower in period 2 than in period 1 (n=262 vs 363, 44.0% vs 61.0%, P<.001). However, HIV testing utilization was not significantly higher in period 3 than in period 2 (n=277 vs 262, 46.6% vs 44.0%, P=.21). The prevalence of HIV testing utilization after the COVID-19 outbreak was seen in 331 (55.6%) participants. After adjusting for significant background characteristics, condomless anal intercourse (CAI) with regular male sex partners (RPs; adjusted odds ratio [AOR] 2.15, 95% CI 1.29-3.57) and sexualized drug use (SDU; AOR 2.94, 95% CI 1.41-6.06) both before and after the COVID-19 outbreak, CAI with RPs (AOR 2.07, 95% CI 1.06-4.07) and nonregular male sex partners (NRPs; AOR 3.57, 95%CI: 1.43-8.89) only after the COVID-19 outbreak was positively associated with the dependent variable. Regarding HIV prevention service utilization, HIV testing utilization before the COVID-19 outbreak (AOR 10.75, 95% CI 7.22-16.02) and the use of sexually transmitted infection (STI) testing (AOR 7.02, 95% CI 4.10-12.02), other HIV/STI prevention (AOR 3.15, 95% CI 2.16-4.60), and preexposure prophylaxis (PrEP; AOR 3.58, 95% CI 1.54-8.34) after the COVID-19 outbreak were associated with higher HIV testing utilization. The current perceived risk of HIV infection was higher than that before the COVID-19 outbreak (AOR 1.15, 95% CI 1.01-1.30), and perceived COVID-19 preventive measures taken by HIV testing service providers to be effective (AOR 1.52, 95% CI 1.29-1.78) and perceived higher behavioral control to undergo HIV testing (AOR 1.18, 95% CI 1.00-1.40) were positively associated with HIV testing utilization. Concerns about COVID-19 infection during HIV testing (AOR 0.78, 95% CI 0.68-0.89), avoiding crowded places (AOR 0.68, 95% CI 0.48-0.98), and HIV testing service providers reducing their working hours (AOR 0.59, 95% CI 0.48-0.98) were negatively associated with the dependent variable. CONCLUSIONS: HIV testing utilization among Chinese MSM declined after the COVID-19 outbreak and did not increase after the pandemic was under initial control. Removing structural barriers to accessing HIV testing caused by COVID-19, modifying perceptions related to HIV testing, and making use of HIV self-testing (HIVST) might be useful strategies to improve HIV testing among MSM during the pandemic.

JMIR Public Health Surveill2022       LitCov and CORD-19
5531Changes in physical activity and sedentary behaviours from before to during the COVID-19 pandemic lockdown: a systematic review  

OBJECTIVE: In March 2020, several countries banned unnecessary outdoor activities during COVID-19, commonly called ‘lockdowns. These lockdowns have the potential to impact associated levels of physical activity and sedentary behaviour. Given the numerous health outcomes associated with physical activity and sedentary behaviour, the aim of this review was to summarise literature that investigated differences in physical activity and sedentary behaviour before vs during the COVID-19 lockdown. DESIGN, DATA SOURCES AND ELIGIBILITY CRITERIA: Electronic databases were searched from November 2019 to October 2020 using terms and synonyms relating to physical activity, sedentary behaviour and COVID-19. The coprimary outcomes were changes in physical activity and/or sedentary behaviour captured via device-based measures or self-report tools. Risk of bias was measured using the Newcastle-Ottawa Scale. RESULTS: Sixty six articles met the inclusion criteria and were included in the review (total n=86 981). Changes in physical activity were reported in 64 studies, with the majority of studies reporting decreases in physical activity and increases in sedentary behaviours during their respective lockdowns across several populations, including children and patients with a variety of medical conditions. CONCLUSION: Given the numerous physical and mental benefits of increased physical activity and decreased sedentary behaviour, public health strategies should include the creation and implementation of interventions that promote safe physical activity and reduce sedentary behaviour should other lockdowns occur.

BMJ Open Sport Exerc Med2021       LitCov and CORD-19
5532Experiences of nurses working with COVID-19 patients: A qualitative study  

BACKGROUND: The global COVID‐19 pandemic has led to massive disruptions in daily life, business, education, lifestyle and economies worldwide. Nurses are a professional group who care directly for COVID‐19 patients and thus face direct exposure to the virus. The nurses who work on the front lines during this period put their own well‐being at risk to care for these patients. PURPOSE/AIM: The aim of this study was to identify the experiences and challenges faced by nurses working in pandemic clinics in Turkey during the COVID‐19 pandemic. METHODS: This qualitative study was based on semi‐structured in‐depth interviews conducted through the mobile application Whatsapp with 19 nurses who were actively working in pandemic clinics. Due to the pandemic, the snowball sampling method was used to reach the sample group. Interviews were continued until data saturation was achieved. All interviews were audio recorded and later transcribed. The study data were interpreted according to themes identified using thematic analysis. Throughout the study, the authors followed the COREQ checklist. RESULTS: The experiences of nurses caring for COVID‐19 patients were summarised into five major themes: psychosocial adaptation, protection, difficulty in care and treatment, access to information and working conditions. CONCLUSION: Nurses caring for COVID‐19 patients in Turkey have been affected psychologically, socially and physiologically. They experienced stigmatisation, exhaustion and burnout. One of the biggest challenges for the nurses was difficulty providing physical care and treatment due to the use of personal protective equipment. Nurses want improved compensation in addition to applause from the public. Interventions to help bolster nurses’ psychological and physiological strength are recommended. RELEVANCE TO CLINICAL PRACTICE: This study emphasised nurses’ psychologically, socially and physiologically affected. Therefore, improvements in financial and moral support would provide psychological reinforcement for nurses during the epidemic. Informing the public is necessary to reduce the stigmatisation of nurses working in pandemic clinics.

J Clin Nurs2021       LitCov and CORD-19
5533Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, 2012  

OBJECTIVE: To provide an update to the “Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock,” last published in 2008. DESIGN: A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS: The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Recommendations were classified into three groups: (1) those directly targeting severe sepsis; (2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and (3) pediatric considerations. RESULTS: Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 h after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 h of the recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 h of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1B); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients (1C); fluid challenge technique continued as long as hemodynamic improvement is based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥65 mmHg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7–9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a Pao (2)/Fio (2) ratio of ≤100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 h) for patients with early ARDS and a Pao (2)/Fi o (2) <150 mm Hg (2C); a protocolized approach to blood glucose management commencing insulin dosing when two consecutive blood glucose levels are >180 mg/dL, targeting an upper blood glucose ≤180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 h after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 h of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5–10 min (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven “absolute”’ adrenal insufficiency (2C). CONCLUSIONS: Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00134-012-2769-8) contains supplementary material, which is available to authorized users.

Intensive Care Med2013       CORD-19
5534Risk of COVID-19-related death among patients with chronic obstructive pulmonary disease or asthma prescribed inhaled corticosteroids: an observational cohort study using the OpenSAFELY platform  

BACKGROUND: Early descriptions of patients admitted to hospital during the COVID-19 pandemic showed a lower prevalence of asthma and chronic obstructive pulmonary disease (COPD) than would be expected for an acute respiratory disease like COVID-19, leading to speculation that inhaled corticosteroids (ICSs) might protect against infection with severe acute respiratory syndrome coronavirus 2 or the development of serious sequelae. We assessed the association between ICS and COVID-19-related death among people with COPD or asthma using linked electronic health records (EHRs) in England, UK. METHODS: In this observational study, we analysed patient-level data for people with COPD or asthma from primary care EHRs linked with death data from the Office of National Statistics using the OpenSAFELY platform. The index date (start of follow-up) for both cohorts was March 1, 2020; follow-up lasted until May 6, 2020. For the COPD cohort, individuals were eligible if they were aged 35 years or older, had COPD, were a current or former smoker, and were prescribed an ICS or long-acting β agonist plus long-acting muscarinic antagonist (LABA–LAMA) as combination therapy within the 4 months before the index date. For the asthma cohort, individuals were eligible if they were aged 18 years or older, had been diagnosed with asthma within 3 years of the index date, and were prescribed an ICS or short-acting β agonist (SABA) only within the 4 months before the index date. We compared the outcome of COVID-19-related death between people prescribed an ICS and those prescribed alternative respiratory medications: ICSs versus LABA–LAMA for the COPD cohort, and low-dose or medium-dose and high-dose ICSs versus SABAs only in the asthma cohort. We used Cox regression models to estimate hazard ratios (HRs) and 95% CIs for the association between exposure categories and the outcome in each population, adjusted for age, sex, and all other prespecified covariates. We calculated e-values to quantify the effect of unmeasured confounding on our results. FINDINGS: We identified 148 557 people with COPD and 818 490 people with asthma who were given relevant respiratory medications in the 4 months before the index date. People with COPD who were prescribed ICSs were at increased risk of COVID-19-related death compared with those prescribed LABA–LAMA combinations (adjusted HR 1·39 [95% CI 1·10–1·76]). Compared with those prescribed SABAs only, people with asthma who were prescribed high-dose ICS were at an increased risk of death (1·55 [1·10–2·18]), whereas those given a low or medium dose were not (1·14 [0·85–1·54]). Sensitivity analyses showed that the apparent harmful association we observed could be explained by relatively small health differences between people prescribed ICS and those not prescribed ICS that were not recorded in the database (e value lower 95% CI 1·43). INTERPRETATION: Our results do not support a major role for regular ICS use in protecting against COVID-19-related death among people with asthma or COPD. Observed increased risks of COVID-19-related death can be plausibly explained by unmeasured confounding due to disease severity. FUNDING: UK Medical Research Council.

Lancet Respir Med2020       LitCov and CORD-19
5535Real-world effectiveness of molnupiravir and nirmatrelvir plus ritonavir against mortality, hospitalisation and in-hospital outcomes among community-dwelling, ambulatory patients with confirmed SARS-CoV-2 infection during the omicron wave in Hong Kong: an observational study  

N/A

Lancet2022       LitCov
5536Confidence and Receptivity for COVID-19 Vaccines: A Rapid Systematic Review  

While COVID-19 continues raging worldwide, effective vaccines are highly anticipated. However, vaccine hesitancy is widespread. Survey results on uptake intentions vary and continue to change. This review compared trends and synthesized findings in vaccination receptivity over time across US and international polls, assessing survey design influences and evaluating context to inform policies and practices. Data sources included academic literature (PubMed, Embase, and PsycINFO following PRISMA guidelines), news and official reports published by 20 October 2020. Two researchers independently screened potential peer-reviewed articles and syndicated polls for eligibility; 126 studies and surveys were selected. Declining vaccine acceptance (from >70% in March to <50% in October) with demographic, socioeconomic, and partisan divides was observed. Perceived risk, concerns over vaccine safety and effectiveness, doctors’ recommendations, and inoculation history were common factors. Impacts of regional infection rates, gender, and personal COVID-19 experience were inconclusive. Unique COVID-19 factors included political party orientation, doubts toward expedited development/approval process, and perceived political interference. Many receptive participants preferred to wait until others have taken the vaccine; mandates could increase resistance. Survey wording and answer options showed influence on responses. To achieve herd immunity, communication campaigns are immediately needed, focusing on transparency and restoring trust in health authorities.

Vaccines (Basel)2020       LitCov and CORD-19
5537Global health research partnerships in the context of the Sustainable Development Goals (SDGs)  

This themed issue on global health research has come at an opportune time in the middle of the ongoing global public health crisis arising from the coronavirus disease (COVID-19) pandemic which has claimed nearly 756,000 lives in 210 countries and territories around the world as of August 15, 2020. The public health crisis underscores the importance of global health research partnerships and collaborations to develop and evaluate the requisite health technologies to assist in containing COVID-19, other diseases, and health-related concerns that defy national borders. The 17 Sustainable Development Goals (SDGs), adopted by the member countries of the United Nations in September 2015, provide a framework for global development efforts including global health research. SDG3, which promotes health and well-being for the world populations across the age spectrum, highlights disease areas for special focus which can be adapted in specific global health research programs to serve local health needs. SDG17 promotes partnerships between high income (HIC) and low and middle-income countries (LMIC) for sustainable and equitable global development. However, given the wide disparities in fiscal and overall capacity for research between researchers in HIC and their counterparts in LMIC as well as the greater vulnerabilities of the LMIC communities when serving as research locations, a spotlight on the nature of such global health research partnerships in the context of the SDGs is desirable. This is to ensure that they are meaningful and mutually-beneficial partnerships which address local health concerns and promote long-term value for the communities involved. The objective of this commentary is, therefore, to provide a brief overview of the SDGs by way of context; explore the power differences at play when researchers from HIC are seeking research opportunities in LMIC; examine the social determinants of health and the disproportionate burden of global diseases carried by populations in LMIC to establish their vulnerability; discuss global research partnerships; and attempt to make a case for why community-based participatory research may be the preferred type of global health research partnership in the context of the SDGs.

Res Social Adm Pharm2020       LitCov and CORD-19
5538Women's views on accepting COVID-19 vaccination during and after pregnancy and for their babies: a multi-methods study in the UK  

BACKGROUND: COVID-19 vaccines are advised for pregnant women in the United Kingdom (UK) however COVID-19 vaccine uptake among pregnant women is inadequate. METHODS: An online survey and semi-structured interviews were used to investigate pregnant women’s views on COVID-19 vaccine acceptability for themselves when pregnant, not pregnant and for their babies. One thousand one hundred eighty-one women, aged over 16 years, who had been pregnant since 23rd March 2020, were surveyed between 3rd August–11th October 2020. Ten women were interviewed. RESULTS: The majority of women surveyed (81.2%) reported that they would ‘definitely’ or were ‘leaning towards’ accepting a COVID-19 vaccine when not pregnant. COVID-19 vaccine acceptance was significantly lower during pregnancy (62.1%, p < 0.005) and for their babies (69.9%, p < 0.005). Ethnic minority women were twice as likely to reject a COVID-19 vaccine for themselves when not pregnant, pregnant and for their babies compared to women from White ethnic groups (p < 0.005). Women from lower-income households, aged under 25-years, and from some geographic regions were more likely to reject a COVID-19 vaccine when not pregnant, pregnant and for their babies. Multivariate analysis revealed that income and ethnicity were the main drivers of the observed age and regional differences. Women unvaccinated against pertussis in pregnancy were over four times more likely to reject COVID-19 vaccines when not pregnant, pregnant and for their babies. Thematic analysis of the survey freetext responses and interviews found safety concerns about COVID-19 vaccines were common though wider mistrust in vaccines was also expressed. Trust in vaccines and the health system were also reasons women gave for accepting COVID-19 vaccines. CONCLUSION: Safety information on COVID-19 vaccines must be clearly communicated to pregnant women to provide reassurance and facilitate informed pregnancy vaccine decisions. Targeted interventions to promote COVID-19 vaccine uptake among ethnic minority and lower-income women may be needed. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12884-021-04321-3.

BMC Pregnancy Childbirth2022       LitCov and CORD-19
5539Determinants of Patients' Intention to Use the Online Inquiry Services Provided by Internet Hospitals: Empirical Evidence From China  

BACKGROUND: Internet hospitals show great potential for adequately fulfilling people’s demands for high-quality outpatient services, and with the normalization of the epidemic prevention and control of COVID-19, internet hospitals play an increasingly important role in delivering health services to the public. However, the factors that influence patients’ intention to use the online inquiry services provided by internet hospitals remain unclear. Understanding the patients’ behavioral intention is necessary to support the development of internet hospitals in China and promote patients’ intention to use online inquiry services provided by internet hospitals during the prevention and control of the COVID-19 epidemic. OBJECTIVE: The purpose of this study is to identify the determinants of patients’ intention to use the online inquiry services provided by internet hospitals based on the theory of planned behavior (TPB). METHODS: The hypotheses of our research model were developed based on the TPB. A questionnaire was developed through patient interviews, verified using a presurvey, and used for data collection for this study. The cluster sampling technique was used to include respondents with chronic diseases. Structural equation modeling was used to test the research hypotheses. RESULTS: A total of 638 valid responses were received from patients with chronic diseases. The goodness-of-fit indexes corroborated that the research model was a good fit for the collected data. The model explained 45.9% of the variance in attitude toward the behavior and 60.5% of the variance in behavioral intention. Perceived behavioral control and perceived severity of disease had the strongest total effects on behavioral intention (β=.624, P=.004 and β=.544, P=.003, respectively). Moreover, perceived convenience, perceived information risk, emotional preference, and health consciousness had indirect effects on behavioral intention, and these effects were mediated by attitude toward the behavior. Among the four constructs, perceived convenience had the highest indirect effect on behavioral intention (β=.207; P=.001). CONCLUSIONS: Perceived behavioral control and perceived severity of disease are the most important determinants of patients’ intention to use the online inquiry services provided by internet hospitals. Therefore, internet hospitals should further optimize the design of online service delivery and ensure a reasonable assembly of high-quality experts, which will benefit the promotion of patients’ adoption intention toward online inquiry services for health purposes. Perceived convenience, emotional preference, and perceived risks also have effects on behavioral intention. Therefore, the relevant quality control standards and regulations for internet hospitals should be further developed and improved, and the measures to protect personal information should be strengthened to ensure the patient safety. Our study supports the use of the TPB in explaining patients’ intention to use online inquiry services provided by internet hospitals.

J Med Internet Res2020       LitCov and CORD-19
5540Changes and Inequities in Adult Mental Health-Related Emergency Department Visits During the COVID-19 Pandemic in the US  

IMPORTANCE: The COVID-19 pandemic has negatively affected adult mental health (MH), with racial and ethnic minoritized groups disproportionately affected. OBJECTIVE: To examine changes in adult MH-related emergency department (ED) visits into the Delta variant pandemic period and identify changes and inequities in these visits before and during COVID-19 case surges. DESIGN, SETTING, AND PARTICIPANTS: This epidemiologic cross-sectional study used National Syndromic Surveillance Program data from US adults aged 18 to 64 years from 1970 to 2352 ED facilities from January 1, 2019, to August 14, 2021. All MH-related ED visits and visits related to 10 disorders (ie, anxiety, depressive, bipolar, schizophrenia spectrum, trauma- and stressor-related, attention-deficit/hyperactivity, disruptive behavioral and impulse, obsessive-compulsive, eating, and tic disorders) were identified. EXPOSURES: The following periods of MH-related ED visits were compared: (1) high Delta variant circulation (July 18-August 14, 2021) with a pre-Delta period (April 18-May 15, 2021), (2) after a COVID-19 case peak (February 14-March 13, 2021) with during a peak (December 27, 2020-January 23, 2021), and (3) the Delta period and the period after a COVID-19 case peak with the respective corresponding weeks during the prepandemic period. MAIN OUTCOMES AND MEASURES: ED visits for 10 mental disorders and all MH-related visits. RESULTS: This cross-sectional study included 107 761 319 ED visits among adults aged 18 to 64 years (59 870 475 [56%] women) from January 1, 2019, to August 14, 2021. There was stability in most MH-related ED visit counts between the Delta and pre-Delta periods (percentage change, −1.4% to −7.5%), except for eating disorders (−11.9%) and tic disorders (−19.8%) and after a COVID-19 case peak compared with during a peak (0.6%-7.4%). Most MH-related ED visit counts declined in the Delta period relative to the prepandemic period (−6.4% to −30.7%); there were fluctuations by disorder when comparing after a COVID-19 case peak with the corresponding prepandemic period (−15.4% to 11.3%). Accounting for ED visit volume, MH-related ED visits were a smaller proportion of visits in the Delta period compared with the pre-Delta period (visit ratio, 0.86; 95% CI, 0.85-0.86) and prepandemic period (visit ratio, 0.80; 95% CI, 0.79-0.80). After a COVID-19 case peak, MH-related ED visits were a larger proportion of ED visits compared with during a peak (visit ratio, 1.04; 95% CI, 1.03-1.04) and the corresponding prepandemic period (visit ratio, 1.11; 95% CI, 1.11-1.12). Of the 2 510 744 ED visits included in the race and ethnicity analysis, 24 592 (1%) were American Indian or Alaska Native persons, 33 697 (1%) were Asian persons, 494 198 (20%) were Black persons, 389 740 (16%) were Hispanic persons, 5000 (0.2%) were Native Hawaiian or Other Pacific Islander persons, and 1 172 683 (47%) were White persons. There was between- and within-group variation in ED visits by race and ethnicity and increases in selected disorders after COVID-19 peaks for adults aged 18 to 24 years. CONCLUSIONS AND RELEVANCE: Results of this cross-sectional study suggest that EDs may have increases in MH-related visits after COVID-19 surges, specifically for young adults and individual racial and ethnic minoritized subpopulations. Public health practitioners should consider subpopulation-specific messaging and programmatic strategies that address differences in MH needs, particularly for those historically marginalized.

JAMA Psychiatry2022       LitCov and CORD-19
5541Immune responses against SARS-CoV-2 variants after heterologous and homologous ChAdOx1 nCoV-19/BNT162b2 vaccination  

Currently approved viral vector-based and mRNA-based vaccine approaches against coronavirus disease 2019 (COVID-19) consider only homologous prime-boost vaccination. After reports of thromboembolic events, several European governments recommended using AstraZeneca’s ChAdOx1-nCov-19 (ChAd) only in individuals older than 60 years, leaving millions of already ChAd-primed individuals with the decision to receive either a second shot of ChAd or a heterologous boost with mRNA-based vaccines. However, such combinations have not been tested so far. We used Hannover Medical School’s COVID-19 Contact Study cohort of healthcare professionals to monitor ChAd-primed immune responses before and 3 weeks after booster with ChAd (n = 32) or BioNTech/Pfizer’s BNT162b2 (n = 55). Although both vaccines boosted prime-induced immunity, BNT162b2 induced significantly higher frequencies of spike-specific CD4(+) and CD8(+) T cells and, in particular, high titers of neutralizing antibodies against the B.1.1.7, B.1.351 and P.1 variants of concern of severe acute respiratory syndrome coronavirus 2.

Nat Med2021       LitCov and CORD-19
5542Waning immune responses against SARS-CoV-2 variants of concern among vaccinees in Hong Kong  

BACKGROUND: Nearly 4 billion doses of the BNT162b2-mRNA and CoronaVac-inactivated vaccines have been administrated globally, yet different vaccine-induced immunity against SARS-CoV-2 variants of concern (VOCs) remain incompletely investigated. METHODS: We compare the immunogenicity and durability of these two vaccines among fully vaccinated Hong Kong people. FINDINGS: Standard BNT162b2 and CoronaVac vaccinations were tolerated and induced neutralizing antibody (NAb) (100% and 85.7%) and spike-specific CD4 T cell responses (96.7% and 82.1%), respectively. The geometric mean NAb IC(50) and median frequencies of reactive CD4 subsets were consistently lower among CoronaVac-vaccinees than BNT162b2-vaccinees. CoronaVac did not induce measurable levels of nucleocapsid protein-specific IFN-γ(+) CD4(+) T or IFN-γ(+) CD8(+) T cells compared with unvaccinated. Against VOCs, NAb response rates and geometric mean IC(50) titers against B.1.617.2 (Delta) and B.1.1.529 (Omicron) were significantly lower for CoronaVac (50%, 23.2 and 7.1%, <20) than BNT162b2 (94.1%, 131 and 58.8%, 35.0), respectively. Three months after vaccinations, NAbs to VOCs dropped near to detection limit, along with waning memory T cell responses, mainly among CoronaVac-vaccinees. INTERPRETATION: Our results indicate that vaccinees especially CoronaVac-vaccinees with significantly reduced NAbs may probably face higher risk to pandemic VOCs breakthrough infection. FUNDING: This study was supported by the Hong Kong Research Grants Council Collaborative Research Fund (C7156-20GF and C1134-20GF); the Wellcome Trust (P86433); the National Program on Key Research Project of China (Grant 2020YFC0860600, 2020YFA0707500 and 2020YFA0707504); Shenzhen Science and Technology Program (JSGG20200225151410198 and JCYJ20210324131610027); HKU Development Fund and LKS Faculty of Medicine Matching Fund to AIDS Institute; Hong Kong Innovation and Technology Fund, Innovation and Technology Commission and generous donation from the Friends of Hope Education Fund. Z.C.’s team was also partly supported by the Theme-Based Research Scheme (T11-706/18-N).

EBioMedicine2022       LitCov and CORD-19
5543Sleep characteristics in health workers exposed to the COVID-19 pandemic  

INTRODUCTION: The development of sleep disorders, and specifically insomnia, has been linked to the exposure to different stressors. In this line, Coronavirus disease 2019 (COVID-19) outbreak caused by the new coronavirus SARS-CoV-2, has caused a huge impact on our environment, and has exposed healthcare workers to an unprecedented threat. In this study, we try to assess sleep quality and the development of sleep disorders in health personnel directly dedicated to the care of COVID-19 patients at the height of the pandemic, compared to the general population. MATERIALS AND METHODS: A cross-sectional, anonymized, self-reported questionnaire survey was carried out at the “12 de Octubre” Hospital, in Madrid, Spain, during the outbreak of COVID-19, from March 1(th) to April 30(th) 2020. We compared two groups, healthcare workers who have treated directly COVID-19 patients versus non-healthcare workers. The questionnaire included demographic data, sleep related aspects, Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index, (PSQI), Insomnia Severity Index (ISI) and 17-items Hamilton Rating Scale (HRS). RESULTS: In total 170 participants completed the questionnaire successfully,100 healthcare workers and 70 non-healthcare workers. Self-reported insomnia, nightmares, sleepwalking, sleep terrors and PSQI>6 were more frequent in the healthcare group (p<0,05). Shift work was associated to greater risk when performing multiple logistic regression analysis. CONCLUSIONS: We observed that, during the outbreak of COVID-19, healthcare workers on the front line developed more sleep disturbances than non-healthcare professionals, and they had worse quality of sleep. Special attention should be paid to shift workers. Concrete protection and prevention measures for particularly exposed population should be considered in pandemic situations.

Sleep Med2020       LitCov and CORD-19
5544SARS-CoV-2 infection among hospitalised pregnant women and impact of different viral strains on COVID-19 severity in Italy: a national prospective population-based cohort study  

OBJECTIVE: The primary aim of this article was to describe SARS‐CoV‐2 infection among pregnant women during the wild‐type and Alpha‐variant periods in Italy. The secondary aim was to compare the impact of the virus variants on the severity of maternal and perinatal outcomes. DESIGN: National population‐based prospective cohort study. SETTING: A total of 315 Italian maternity hospitals. SAMPLE: A cohort of 3306 women with SARS‐CoV‐2 infection confirmed within 7 days of hospital admission. METHODS: Cases were prospectively reported by trained clinicians for each participating maternity unit. Data were described by univariate and multivariate analyses. MAIN OUTCOME MEASURES: COVID‐19 pneumonia, ventilatory support, intensive care unit (ICU) admission, mode of delivery, preterm birth, stillbirth, and maternal and neonatal mortality. RESULTS: We found that 64.3% of the cohort was asymptomatic, 12.8% developed COVID‐19 pneumonia and 3.3% required ventilatory support and/or ICU admission. Maternal age of 30–34 years (OR 1.43, 95% CI 1.09–1.87) and ≥35 years (OR 1.62, 95% CI 1.23–2.13), citizenship of countries with high migration pressure (OR 1.75, 95% CI 1.36–2.25), previous comorbidities (OR 1.49, 95% CI 1.13–1.98) and obesity (OR 1.72, 95% CI 1.29–2.27) were all associated with a higher occurrence of pneumonia. The preterm birth rate was 11.1%. In comparison with the pre‐pandemic period, stillbirths and maternal and neonatal deaths remained stable. The need for ventilatory support and/or ICU admission among women with pneumonia increased during the Alpha‐variant period compared with the wild‐type period (OR 3.24, 95% CI 1.99–5.28). CONCLUSIONS: Our results are consistent with a low risk of severe COVID‐19 disease among pregnant women and with rare adverse perinatal outcomes. During the Alpha‐variant period there was a significant increase of severe COVID‐19 illness. Further research is needed to describe the impact of different SARS‐CoV‐2 viral strains on maternal and perinatal outcomes.

BJOG2021       LitCov and CORD-19
5545Risk prediction of covid-19 related death and hospital admission in adults after covid-19 vaccination: national prospective cohort study  

OBJECTIVES: To derive and validate risk prediction algorithms to estimate the risk of covid-19 related mortality and hospital admission in UK adults after one or two doses of covid-19 vaccination. DESIGN: Prospective, population based cohort study using the QResearch database linked to data on covid-19 vaccination, SARS-CoV-2 results, hospital admissions, systemic anticancer treatment, radiotherapy, and the national death and cancer registries. SETTINGS: Adults aged 19-100 years with one or two doses of covid-19 vaccination between 8 December 2020 and 15 June 2021. MAIN OUTCOME MEASURES: Primary outcome was covid-19 related death. Secondary outcome was covid-19 related hospital admission. Outcomes were assessed from 14 days after each vaccination dose. Models were fitted in the derivation cohort to derive risk equations using a range of predictor variables. Performance was evaluated in a separate validation cohort of general practices. RESULTS: Of 6 952 440 vaccinated patients in the derivation cohort, 5 150 310 (74.1%) had two vaccine doses. Of 2031 covid-19 deaths and 1929 covid-19 hospital admissions, 81 deaths (4.0%) and 71 admissions (3.7%) occurred 14 days or more after the second vaccine dose. The risk algorithms included age, sex, ethnic origin, deprivation, body mass index, a range of comorbidities, and SARS-CoV-2 infection rate. Incidence of covid-19 mortality increased with age and deprivation, male sex, and Indian and Pakistani ethnic origin. Cause specific hazard ratios were highest for patients with Down’s syndrome (12.7-fold increase), kidney transplantation (8.1-fold), sickle cell disease (7.7-fold), care home residency (4.1-fold), chemotherapy (4.3-fold), HIV/AIDS (3.3-fold), liver cirrhosis (3.0-fold), neurological conditions (2.6-fold), recent bone marrow transplantation or a solid organ transplantation ever (2.5-fold), dementia (2.2-fold), and Parkinson’s disease (2.2-fold). Other conditions with increased risk (ranging from 1.2-fold to 2.0-fold increases) included chronic kidney disease, blood cancer, epilepsy, chronic obstructive pulmonary disease, coronary heart disease, stroke, atrial fibrillation, heart failure, thromboembolism, peripheral vascular disease, and type 2 diabetes. A similar pattern of associations was seen for covid-19 related hospital admissions. No evidence indicated that associations differed after the second dose, although absolute risks were reduced. The risk algorithm explained 74.1% (95% confidence interval 71.1% to 77.0%) of the variation in time to covid-19 death in the validation cohort. Discrimination was high, with a D statistic of 3.46 (95% confidence interval 3.19 to 3.73) and C statistic of 92.5. Performance was similar after each vaccine dose. In the top 5% of patients with the highest predicted covid-19 mortality risk, sensitivity for identifying covid-19 deaths within 70 days was 78.7%. CONCLUSION: This population based risk algorithm performed well showing high levels of discrimination for identifying those patients at highest risk of covid-19 related death and hospital admission after vaccination.

BMJ2021       LitCov and CORD-19
5546SARS-CoV-2 Omicron Variant Neutralization in Serum from Vaccinated and Convalescent Persons  

N Engl J Med2022       LitCov and CORD-19
5547Reduced Rate of Hospital Admissions for ACS during Covid-19 Outbreak in Northern Italy  

N Engl J Med2020       LitCov and CORD-19
5548Social Isolation and Loneliness during COVID-19 Lockdown: Associations with Depressive Symptoms in the German Old-Age Population  

Lockdowns during the COVID-19 pandemic increase the risk of social isolation and loneliness, which may affect mental wellbeing. Therefore, we aimed to investigate associations between social isolation and loneliness with depressive symptoms in the German old-age population during the first COVID-19 lockdown. A representative sample of randomly selected individuals at least 65 years old (n = 1005) participated in a computer-assisted standardized telephone interview in April 2020. Sociodemographic data, aspects of the personal life situation, attitudes towards COVID-19 and standardized screening measures on loneliness (UCLA 3-item loneliness scale), depression (Brief Symptom Inventory/BSI-18), and resilience (Brief Resilience Scale/BRS) were assessed. Associations were inspected using multivariate regression models. Being lonely, but not isolated (β = 0.276; p < 0.001) and being both isolated and lonely (β = 0.136; p < 0.001) were associated with higher depressive symptoms. Being isolated, but not lonely was not associated with depressive symptoms. Thus, the subjective emotional evaluation, i.e., feeling lonely, of the social situation during lockdown seems more relevant than the objective state, i.e., being isolated. Normal (β = −0.203; p < 0.001) and high resilience (β = −0.308; p < 0.001) were associated with lower depressive symptoms across groups. Therefore, strengthening coping skills may be a support strategy during lockdowns, especially for lonely older individuals.

Int J Environ Res Public Healt2021       LitCov and CORD-19
5549Poverty and food insecurity may increase as the threat of COVID-19 spreads  

This article discusses the relationship between both poverty and food insecurity (FI) and the COVID-19 pandemic, as well as presenting possible strategies and actions for increasing social protection in the fight against these conditions in the current epidemiological context, especially for low-income countries. This is a narrative review concerning COVID-19, poverty, and food and nutritional insecurity. The COVID-19 pandemic may increase poverty and FI levels, resulting from the absence of or weak political, economic and social interventions to maintain jobs, as well as compromised food production and distribution chains and reduced access to healthy foods in different countries around the world, especially the poorest ones, where social and economic inequality was already historically high; the pandemic heightens and uncovers the vulnerability of poor populations. Public policies focused on guaranteeing the human right to adequate food must be improved and implemented for populations in contexts of poverty with the aim of providing food security.

Public Health Nutr2020       LitCov and CORD-19
5550COVID-19 Re-infection by a Phylogenetically Distinct SARS-CoV-2 Strain Confirmed by Whole Genome Sequencing  

BACKGROUND: Waning immunity occurs in patients who have recovered from COVID-19. However, it remains unclear whether true re-infection occurs. METHODS: Whole genome sequencing was performed directly on respiratory specimens collected during two episodes of COVID-19 in a patient. Comparative genome analysis was conducted to differentiate re-infection from persistent viral shedding. Laboratory results, including RT-PCR Ct values and serum SARS-CoV-2 IgG, were analyzed. RESULTS: The second episode of asymptomatic infection occurred 142 days after the first symptomatic episode in an apparently immunocompetent patient. During the second episode, there was serological evidence of elevated C-reactive protein and SARS-CoV-2 IgG seroconversion. Viral genomes from first and second episodes belong to different clades/lineages. Compared to viral genomes in GISAID, the first virus genome has a stop codon at position 64 of orf8 leading to a truncation of 58 amino acids, and was phylogenetically closely related to strains collected in March/April 2020, while the second virus genome was closely related to strains collected in July/August 2020. Another 23 nucleotide and 13 amino acid differences located in 9 different proteins, including positions of B and T cell epitopes, were found between viruses from the first and second episodes. CONCLUSIONS: Epidemiological, clinical, serological and genomic analyses confirmed that the patient had re-infection instead of persistent viral shedding from first infection. Our results suggest SARS-CoV-2 may continue to circulate among the human populations despite herd immunity due to natural infection or vaccination. Further studies of patients with re-infection will shed light on protective correlates important for vaccine design.

Clin Infect Dis2020       LitCov and CORD-19

(1) COVID-19 Open Research Dataset (CORD-19). 2020. Version 2022-06-02. Retrieved from https://ai2-semanticscholar-cord-19.s3-us-west-2.amazonaws.com/historical_releases.html. Accessed 2022-06-05. doi:10.5281/zenodo.3715506
(2) Chen Q, Allot A, & Lu Z. (2020) Keep up with the latest coronavirus research, Nature 579:193 and Chen Q, Allot A, Lu Z. LitCovid: an open database of COVID-19 literature. Nucleic Acids Research. 2020. (version 2023-01-10)
(3) Currently tweets of June 23rd to June 29th 2022 have been considered.

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