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: 16 - 06 - 2022 (568924 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
1COVID UPDATE: What is the truth?  

Surg Neurol Int2022       LitCov and CORD-19
2Accelerated biological aging in COVID-19 patients  

Chronological age is a risk factor for SARS-CoV-2 infection and severe COVID-19. Previous findings indicate that epigenetic age could be altered in viral infection. However, the epigenetic aging in COVID-19 has not been well studied. In this study, DNA methylation of the blood samples from 232 healthy individuals and 413 COVID-19 patients is profiled using EPIC methylation array. Epigenetic ages of each individual are determined by applying epigenetic clocks and telomere length estimator to the methylation profile of the individual. Epigenetic age acceleration is calculated and compared between groups. We observe strong correlations between the epigenetic clocks and individual’s chronological age (r > 0.8, p < 0.0001). We also find the increasing acceleration of epigenetic aging and telomere attrition in the sequential blood samples from healthy individuals and infected patients developing non-severe and severe COVID-19. In addition, the longitudinal DNA methylation profiling analysis find that the accumulation of epigenetic aging from COVID-19 syndrome could be partly reversed at late clinic phases in some patients. In conclusion, accelerated epigenetic aging is associated with the risk of SARS-CoV-2 infection and developing severe COVID-19. In addition, the accumulation of epigenetic aging from COVID-19 may contribute to the post-COVID-19 syndrome among survivors.

Nat Commun2022       LitCov and CORD-19
3BNT162b2 induced memory T cells respond to the Omicron variant with preserved polyfunctionality  

N/A

Nat Microbiol2022       LitCov and CORD-19
4Trajectory of long covid symptoms after covid-19 vaccination: community based cohort study  

OBJECTIVE: To estimate associations between covid-19 vaccination and long covid symptoms in adults with SARS-CoV-2 infection before vaccination. DESIGN: Observational cohort study. SETTING: Community dwelling population, UK. PARTICIPANTS: 28 356 participants in the Office for National Statistics COVID-19 Infection Survey aged 18-69 years who received at least one dose of an adenovirus vector or mRNA covid-19 vaccine after testing positive for SARS-CoV-2 infection. MAIN OUTCOME MEASURE: Presence of long covid symptoms at least 12 weeks after infection over the follow-up period 3 February to 5 September 2021. RESULTS: Mean age of participants was 46 years, 55.6% (n=15 760) were women, and 88.7% (n=25 141) were of white ethnicity. Median follow-up was 141 days from first vaccination (among all participants) and 67 days from second vaccination (83.8% of participants). 6729 participants (23.7%) reported long covid symptoms of any severity at least once during follow-up. A first vaccine dose was associated with an initial 12.8% decrease (95% confidence interval −18.6% to −6.6%, P<0.001) in the odds of long covid, with subsequent data compatible with both increases and decreases in the trajectory (0.3% per week, 95% confidence interval −0.6% to 1.2% per week, P=0.51). A second dose was associated with an initial 8.8% decrease (95% confidence interval −14.1% to −3.1%, P=0.003) in the odds of long covid, with a subsequent decrease by 0.8% per week (−1.2% to −0.4% per week, P<0.001). Heterogeneity was not found in associations between vaccination and long covid by sociodemographic characteristics, health status, hospital admission with acute covid-19, vaccine type (adenovirus vector or mRNA), or duration from SARS-CoV-2 infection to vaccination. CONCLUSIONS: The likelihood of long covid symptoms was observed to decrease after covid-19 vaccination and evidence suggested sustained improvement after a second dose, at least over the median follow-up of 67 days. Vaccination may contribute to a reduction in the population health burden of long covid, although longer follow-up is needed.

BMJ2022       LitCov and CORD-19
5Limited cross-variant immunity from SARS-CoV-2 Omicron without vaccination  

N/A

Nature2022       LitCov and CORD-19
6Covid-19: Sweden, Norway and Finland suspend use of Moderna vaccine in young people "as a precaution"  

N/A

BMJ2021       LitCov
7Increased emergency cardiovascular events among under-40 population in Israel during vaccine rollout and third COVID-19 wave  

Cardiovascular adverse conditions are caused by coronavirus disease 2019 (COVID-19) infections and reported as side-effects of the COVID-19 vaccines. Enriching current vaccine safety surveillance systems with additional data sources may improve the understanding of COVID-19 vaccine safety. Using a unique dataset from Israel National Emergency Medical Services (EMS) from 2019 to 2021, the study aims to evaluate the association between the volume of cardiac arrest and acute coronary syndrome EMS calls in the 16–39-year-old population with potential factors including COVID-19 infection and vaccination rates. An increase of over 25% was detected in both call types during January–May 2021, compared with the years 2019–2020. Using Negative Binomial regression models, the weekly emergency call counts were significantly associated with the rates of 1st and 2nd vaccine doses administered to this age group but were not with COVID-19 infection rates. While not establishing causal relationships, the findings raise concerns regarding vaccine-induced undetected severe cardiovascular side-effects and underscore the already established causal relationship between vaccines and myocarditis, a frequent cause of unexpected cardiac arrest in young individuals. Surveillance of potential vaccine side-effects and COVID-19 outcomes should incorporate EMS and other health data to identify public health trends (e.g., increased in EMS calls), and promptly investigate potential underlying causes.

Sci Rep2022       LitCov and CORD-19
8Bullous pemphigoid and COVID-19 vaccine  

Med Clin (Engl Ed)2021       LitCov and CORD-19
9Blood DNA methylation and COVID-19 outcomes  

BACKGROUND: There are no prior reports that compare differentially methylated regions of DNA in blood samples from COVID-19 patients to samples collected before the SARS-CoV-2 pandemic using a shared epigenotyping platform. We performed a genome-wide analysis of circulating blood DNA CpG methylation using the Infinium Human MethylationEPIC BeadChip on 124 blood samples from hospitalized COVID-19-positive and COVID-19-negative patients and compared these data with previously reported data from 39 healthy individuals collected before the pandemic. Prospective outcome measures such as COVID-19-GRAM risk-score and mortality were combined with methylation data. RESULTS: Global mean methylation levels did not differ between COVID-19 patients and healthy pre-pandemic controls. About 75% of acute illness-associated differentially methylated regions were located near gene promoter regions and were hypo-methylated in comparison with healthy pre-pandemic controls. Gene ontology analyses revealed terms associated with the immune response to viral infections and leukocyte activation; and disease ontology analyses revealed a predominance of autoimmune disorders. Among COVID-19-positive patients, worse outcomes were associated with a prevailing hyper-methylated status. Recursive feature elimination identified 77 differentially methylated positions predictive of COVID-19 severity measured by the GRAM-risk score. CONCLUSION: Our data contribute to the awareness that DNA methylation may influence the expression of genes that regulate COVID-19 progression and represent a targetable process in that setting. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13148-021-01102-9.

Clin Epigenetics2021       LitCov and CORD-19
10Suppressing Scientific Discourse on Vaccines? Self-perceptions of researchers and practitioners  

The controversy over vaccines has recently intensified in the wake of the global COVID-19 pandemic, with calls from politicians, health professionals, journalists, and citizens to take harsh measures against so-called “anti-vaxxers,” while accusing them of spreading “fake news” and as such, of endangering public health. However, the issue of suppression of vaccine dissenters has rarely been studied from the point of view of those who raise concerns about vaccine safety. The purpose of the present study was to examine the subjective perceptions of professionals (physicians, nurses, researchers) involved with vaccines through practice and/or research and who take a critical view on vaccines, about what they perceive as the suppression of dissent in the field of vaccines, their response to it, and its potential implications on science and medicine. Respondents reported being subjected to a variety of censorship and suppression tactics, including the retraction of papers pointing to vaccine safety problems, negative publicity, difficulty in obtaining research funding, calls for dismissal, summonses to official hearings, suspension of medical licenses, and self-censorship. Respondents also reported on what has been termed a “backfire effect” – a counter-reaction that draws more attention to the opponents’ position. Suppression of dissent impairs scientific discourse and research practice while creating the false impression of scientific consensus.

HEC Forum2022       LitCov and CORD-19
11Are vaccines a potential treatment for long covid?  

N/A

BMJ2022       LitCov and CORD-19
12Examining the impact of sharing COVID-19 misinformation online on mental health  

Misinformation about the COVID-19 pandemic proliferated widely on social media platforms during the course of the health crisis. Experts have speculated that consuming misinformation online can potentially worsen the mental health of individuals, by causing heightened anxiety, stress, and even suicidal ideation. The present study aims to quantify the causal relationship between sharing misinformation, a strong indicator of consuming misinformation, and experiencing exacerbated anxiety. We conduct a large-scale observational study spanning over 80 million Twitter posts made by 76,985 Twitter users during an 18.5 month period. The results from this study demonstrate that users who shared COVID-19 misinformation experienced approximately two times additional increase in anxiety when compared to similar users who did not share misinformation. Socio-demographic analysis reveals that women, racial minorities, and individuals with lower levels of education in the United States experienced a disproportionately higher increase in anxiety when compared to the other users. These findings shed light on the mental health costs of consuming online misinformation. The work bears practical implications for social media platforms in curbing the adverse psychological impacts of misinformation, while also upholding the ethos of an online public sphere.

Sci Rep2022       LitCov and CORD-19
13Immunity from smallpox vaccine persists for decades: a longitudinal study  

N/A

Am J Med2008       CORD-19
14Nonpharmaceutical Measures for Pandemic Influenza in Nonhealthcare Settings-Personal Protective and Environmental Measures  

N/A

Emerg Infect Dis2020       CORD-19
15Covid-19: Government failed to protect doctors during pandemic, BMA inquiry finds  

N/A

BMJ2022       LitCov
16Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection  

N/A

Nat Immunol2022       LitCov and CORD-19
17SARS-CoV-2 is associated with changes in brain structure in UK Biobank  

There is strong evidence of brain-related abnormalities in COVID-19(1–13). However, it remains unknown whether the impact of SARS-CoV-2 infection can be detected in milder cases, and whether this can reveal possible mechanisms contributing to brain pathology. Here we investigated brain changes in 785 participants of UK Biobank (aged 51–81 years) who were imaged twice using magnetic resonance imaging, including 401 cases who tested positive for infection with SARS-CoV-2 between their two scans—with 141 days on average separating their diagnosis and the second scan—as well as 384 controls. The availability of pre-infection imaging data reduces the likelihood of pre-existing risk factors being misinterpreted as disease effects. We identified significant longitudinal effects when comparing the two groups, including (1) a greater reduction in grey matter thickness and tissue contrast in the orbitofrontal cortex and parahippocampal gyrus; (2) greater changes in markers of tissue damage in regions that are functionally connected to the primary olfactory cortex; and (3) a greater reduction in global brain size in the SARS-CoV-2 cases. The participants who were infected with SARS-CoV-2 also showed on average a greater cognitive decline between the two time points. Importantly, these imaging and cognitive longitudinal effects were still observed after excluding the 15 patients who had been hospitalised. These mainly limbic brain imaging results may be the in vivo hallmarks of a degenerative spread of the disease through olfactory pathways, of neuroinflammatory events, or of the loss of sensory input due to anosmia. Whether this deleterious effect can be partially reversed, or whether these effects will persist in the long term, remains to be investigated with additional follow-up.

Nature2022       LitCov and CORD-19
18Characterization and antiviral susceptibility of SARS-CoV-2 Omicron/BA.2  

N/A

Nature2022       LitCov and CORD-19
19Evidence for a connection between coronavirus disease-19 and exposure to radiofrequency radiation from wireless communications including 5G  

BACKGROUND AND AIM: Coronavirus disease (COVID-19) public health policy has focused on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and its effects on human health while environmental factors have been largely ignored. In considering the epidemiological triad (agent-host-environment) applicable to all disease, we investigated a possible environmental factor in the COVID-19 pandemic: ambient radiofrequency radiation from wireless communication systems including microwaves and millimeter waves. SARS-CoV-2, the virus that caused the COVID-19 pandemic, surfaced in Wuhan, China shortly after the implementation of city-wide (fifth generation [5G] of wireless communications radiation [WCR]), and rapidly spread globally, initially demonstrating a statistical correlation to international communities with recently established 5G networks. In this study, we examined the peer-reviewed scientific literature on the detrimental bioeffects of WCR and identified several mechanisms by which WCR may have contributed to the COVID-19 pandemic as a toxic environmental cofactor. By crossing boundaries between the disciplines of biophysics and pathophysiology, we present evidence that WCR may: (1) cause morphologic changes in erythrocytes including echinocyte and rouleaux formation that can contribute to hypercoagulation; (2) impair microcirculation and reduce erythrocyte and hemoglobin levels exacerbating hypoxia; (3) amplify immune system dysfunction, including immunosuppression, autoimmunity, and hyperinflammation; (4) increase cellular oxidative stress and the production of free radicals resulting in vascular injury and organ damage; (5) increase intracellular Ca(2+) essential for viral entry, replication, and release, in addition to promoting pro-inflammatory pathways; and (6) worsen heart arrhythmias and cardiac disorders. RELEVANCE FOR PATIENTS: In short, WCR has become a ubiquitous environmental stressor that we propose may have contributed to adverse health outcomes of patients infected with SARS-CoV-2 and increased the severity of the COVID-19 pandemic. Therefore, we recommend that all people, particularly those suffering from SARS-CoV-2 infection, reduce their exposure to WCR as much as reasonably achievable until further research better clarifies the systemic health effects associated with chronic WCR exposure.

J Clin Transl Res2021       LitCov and CORD-19
20Vaccine-associated enhanced disease: Case definition and guidelines for data collection, analysis and presentation of immunization safety data  

This is a Brighton Collaboration Case Definition of the term “Vaccine Associated Enhanced Disease” to be utilized in the evaluation of adverse events following immunization. The Case Definition was developed by a group of experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of vaccines for SARS-CoV-2 vaccines and other emerging pathogens. The case definition format of the Brighton Collaboration was followed to develop a consensus definition and defined levels of certainty, after an exhaustive review of the literature and expert consultation. The document underwent peer review by the Brighton Collaboration Network and by selected Expert Reviewers prior to submission.

Vaccine2021       LitCov and CORD-19
21coinfection with SARS-CoV-2 Omicron and Delta variants revealed by genomic surveillance  

Co-infections with different variants of SARS-CoV-2 are a key precursor to recombination events that are likely to drive SARS-CoV-2 evolution. Rapid identification of such co-infections is required to determine their frequency in the community, particularly in populations at-risk of severe COVID-19, which have already been identified as incubators for punctuated evolutionary events. However, limited data and tools are currently available to detect and characterise the SARS-CoV-2 co-infections associated with recognised variants of concern. Here we describe co-infection with the SARS-CoV-2 variants of concern Omicron and Delta in two epidemiologically unrelated adult patients with chronic kidney disease requiring maintenance haemodialysis. Both variants were co-circulating in the community at the time of detection. Genomic surveillance based on amplicon- and probe-based sequencing using short- and long-read technologies identified and quantified subpopulations of Delta and Omicron viruses in respiratory samples. These findings highlight the importance of integrated genomic surveillance in vulnerable populations and provide diagnostic pathways to recognise SARS-CoV-2 co-infection using genomic data.

Nat Commun2022       LitCov and CORD-19
22Covid-19: Researcher blows the whistle on data integrity issues in Pfizer's vaccine trial  

N/A

BMJ2021       LitCov and CORD-19
23Immune-mediated hepatitis with the Moderna vaccine, no longer a coincidence but confirmed  

J Hepatol2021       LitCov and CORD-19
24Reemergence of Human Monkeypox and Declining Population Immunity in the Context of Urbanization, Nigeria, 2017-2020  

A monkeypox outbreak in Nigeria during 2017–2020 provides an illustrative case study for emerging zoonoses. We built a statistical model to simulate declining immunity from monkeypox at 2 levels: At the individual level, we used a constant rate of decline in immunity of 1.29% per year as smallpox vaccination rates fell. At the population level, the cohort of vaccinated residents decreased over time because of deaths and births. By 2016, only 10.1% of the total population in Nigeria was vaccinated against smallpox; the serologic immunity level was 25.7% among vaccinated persons and 2.6% in the overall population. The substantial resurgence of monkeypox in Nigeria in 2017 appears to have been driven by a combination of population growth, accumulation of unvaccinated cohorts, and decline in smallpox vaccine immunity. The expanding unvaccinated population means that entire households, not just children, are now more susceptible to monkeypox, increasing risk of human-to-human transmission.

Emerg Infect Dis2021       CORD-19
25On the whereabouts of SARS-CoV-2 in the human body: A systematic review  

Since SARS-CoV-2 appeared in the human population, the scientific community has scrambled to gather as much information as possible to find good strategies for the containment and treatment of this pandemic virus. Here, we performed a systematic review of the current (pre)published SARS-CoV-2 literature with a focus on the evidence concerning SARS-CoV-2 distribution in human tissues and viral shedding in body fluids. In addition, this evidence is aligned with published ACE2 entry-receptor (single cell) expression data across the human body to construct a viral distribution and ACE2 receptor body map. We highlight the broad organotropism of SARS-CoV-2, as many studies identified viral components (RNA, proteins) in multiple organs, including the pharynx, trachea, lungs, blood, heart, vessels, intestines, brain, male genitals and kidneys. This also implicates the presence of viral components in various body fluids such as mucus, saliva, urine, cerebrospinal fluid, semen and breast milk. The main SARS-CoV-2 entry receptor, ACE2, is expressed at different levels in multiple tissues throughout the human body, but its expression levels do not always correspond with SARS-CoV-2 detection, indicating that there is a complex interplay between virus and host. Together, these data shed new light on the current view of SARS-CoV-2 pathogenesis and lay the foundation for better diagnosis and treatment of COVID-19 patients.

PLoS Pathog2020       LitCov and CORD-19
26Systemic and mucosal IgA responses are variably induced in response to SARS-CoV-2 mRNA vaccination and are associated with protection against subsequent infection  

Although SARS-CoV-2 infects the upper respiratory tract, we know little about the amount, type, and kinetics of antibodies (Ab) generated in the oral cavity in response to COVID-19 vaccination. We collected serum and saliva samples from participants receiving two doses of mRNA COVID-19 vaccines and measured the level of anti-SARS-CoV-2 Ab. We detected anti-Spike and anti-Receptor Binding Domain (RBD) IgG and IgA, as well as anti-Spike/RBD associated secretory component in the saliva of most participants after dose 1. Administration of a second dose of mRNA boosted the IgG but not the IgA response, with only 30% of participants remaining positive for IgA at this timepoint. At 6 months post-dose 2, these participants exhibited diminished anti-Spike/RBD IgG levels, although secretory component-associated anti-Spike Ab were more stable. Examining two prospective cohorts we found that participants who experienced breakthrough infections with SARS-CoV-2 variants had lower levels of vaccine-induced serum anti-Spike/RBD IgA at 2–4 weeks post-dose 2 compared to participants who did not experience an infection, whereas IgG levels were comparable between groups. These data suggest that COVID-19 vaccines that elicit a durable IgA response may have utility in preventing infection.

Mucosal Immunol2022       LitCov and CORD-19
27Scent dogs in detection of COVID-19: triple-blinded randomised trial and operational real-life screening in airport setting  

OBJECTIVE: To estimate scent dogs’ diagnostic accuracy in identification of people infected with SARS-CoV-2 in comparison with reverse transcriptase polymerase chain reaction (RT-PCR). We conducted a randomised triple-blinded validation trial, and a real-life study at the Helsinki-Vantaa International Airport, Finland. METHODS: Four dogs were trained to detect COVID-19 using skin swabs from individuals tested for SARS-CoV-2 by RT-PCR. Our controlled triple-blinded validation study comprised four identical sets of 420 parallel samples (from 114 individuals tested positive and 306 negative by RT-PCR), randomly presented to each dog over seven trial sessions. In a real-life setting the dogs screened skin swabs from 303 incoming passengers all concomitantly examined by nasal swab SARS-CoV-2 RT-PCR. Our main outcomes were variables of diagnostic accuracy (sensitivity, specificity, positive predictive value, negative predictive value) for scent dog identification in comparison with RT-PCR. RESULTS: Our validation experiments had an overall accuracy of 92% (95% CI 90% to 93%), a sensitivity of 92% (95% CI 89% to 94%) and a specificity of 91% (95% CI 89% to 93%) compared with RT-PCR. For our dogs, trained using the wild-type virus, performance was less accurate for the alpha variant (89% for confirmed wild-type vs 36% for alpha variant, OR 14.0, 95% CI 4.5 to 43.4). In the real-life setting, scent detection and RT-PCR matched 98.7% of the negative swabs. Scant airport prevalence (0.47%) did not allow sensitivity testing; our only SARS-CoV-2 positive swab was not identified (alpha variant). However, ad hoc analysis including predefined positive spike samples showed a total accuracy of 98% (95% CI 97% to 99%). CONCLUSIONS: This large randomised controlled triple-blinded validation study with a precalculated sample size conducted at an international airport showed that trained scent dogs screen airport passenger samples with high accuracy. One of our findings highlights the importance of continuous retraining as new variants emerge. Using scent dogs may present a valuable approach for high-throughput, rapid screening of large numbers of people.

BMJ Glob Health2022       LitCov and CORD-19
28Systematic review and meta-analysis of the effectiveness and perinatal outcomes of COVID-19 vaccination in pregnancy  

Safety and effectiveness of COVID-19 vaccines during pregnancy is a particular concern affecting vaccination uptake by this vulnerable group. Here we evaluated evidence from 23 studies including 117,552 COVID-19 vaccinated pregnant people, almost exclusively with mRNA vaccines. We show that the effectiveness of mRNA vaccination against RT-PCR confirmed SARS-CoV-2 infection 7 days after second dose was 89·5% (95% CI 69·0-96·4%, 18,828 vaccinated pregnant people, I(2) = 73·9%). The risk of stillbirth was significantly lower in the vaccinated cohort by 15% (pooled OR 0·85; 95% CI 0·73–0·99, 66,067 vaccinated vs. 424,624 unvaccinated, I(2) = 93·9%). There was no evidence of a higher risk of adverse outcomes including miscarriage, earlier gestation at birth, placental abruption, pulmonary embolism, postpartum haemorrhage, maternal death, intensive care unit admission, lower birthweight Z-score, or neonatal intensive care unit admission (p > 0.05 for all). COVID-19 mRNA vaccination in pregnancy appears to be safe and is associated with a reduction in stillbirth.

Nat Commun2022       LitCov and CORD-19
29Impact of School Closures due to COVID-19 on Children with Neurodevelopmental Disorders in Japan  

In March 2020, many schools were closed to prevent the spread of COVID-19 in Japan, and it is predicted that many children, especially those with neurodevelopmental disorders (NDDs), will be affected emotionally and behaviorally. Here, we examined the impact of school closures due to COVID-19 on school-aged children with NDDs using the Child Behavior Checklist. Totally, data on 121 children diagnosed with autism spectrum disorder, attention-deficit hyperactivity disorder, and/or intellectual disorder were analyzed and it was found that externalizing and aggressive behavior increased in all NDDs, regardless of the type of diagnosis. A clear prospect is important for children with NDDs children to lead a stable life, and more generous supports for children with NDDs and their families are needed. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10803-021-05119-0.

J Autism Dev Disord2021       LitCov and CORD-19
30Long-term cardiovascular outcomes of COVID-19  

The cardiovascular complications of acute coronavirus disease 2019 (COVID-19) are well described, but the post-acute cardiovascular manifestations of COVID-19 have not yet been comprehensively characterized. Here we used national healthcare databases from the US Department of Veterans Affairs to build a cohort of 153,760 individuals with COVID-19, as well as two sets of control cohorts with 5,637,647 (contemporary controls) and 5,859,411 (historical controls) individuals, to estimate risks and 1-year burdens of a set of pre-specified incident cardiovascular outcomes. We show that, beyond the first 30 d after infection, individuals with COVID-19 are at increased risk of incident cardiovascular disease spanning several categories, including cerebrovascular disorders, dysrhythmias, ischemic and non-ischemic heart disease, pericarditis, myocarditis, heart failure and thromboembolic disease. These risks and burdens were evident even among individuals who were not hospitalized during the acute phase of the infection and increased in a graded fashion according to the care setting during the acute phase (non-hospitalized, hospitalized and admitted to intensive care). Our results provide evidence that the risk and 1-year burden of cardiovascular disease in survivors of acute COVID-19 are substantial. Care pathways of those surviving the acute episode of COVID-19 should include attention to cardiovascular health and disease.

Nat Med2022       LitCov and CORD-19
31Strong correlation between prevalence of severe vitamin D deficiency and population mortality rate from COVID-19 in Europe  

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a very wide range of disease severity: from completely asymptomatic to fatal, and the reasons for that are not well understood; however, there are some data that show vitamin D may have a protective effect. METHODS: To retrieve the vitamin D levels data, the authors analyzed the vitamin D European population data compiled by 2019 European Calcified Tissue Society (ECTS) statement on vitamin D status published in the European Journal of Endocrinology. For the data set to be used for analysis, only recently published data that included general adult population of both genders aged 40–65 years or wider and must have included the prevalence of vitamin D deficiency. RESULTS: There were data sets from 10 countries that fitted the criteria and were analyzed. Severe vitamin D deficiency was defined as 25(OH)D less than 25 nmol/L (10 ng/dL). Pearson correlation analysis between death rate per million of population from coronavirus disease 2019 (COVID-19) and prevalence of severe vitamin D deficiency showed a strong correlation with r = 0.79, p = 0.007. Over time, correlation strengthened, and r coefficient asymptotically increased. After adjusting for countries’ age structure and per capita health expenditures, multiple linear regression analysis showed that higher prevalence of severe vitamin D deficiency is associated with increased mortality. Each 1% increase in prevalence increased deaths by 55 per million (95% confidence interval, CI 8–102), p = 0.03. CONCLUSION: The authors recommend universal screening for vitamin D deficiency, and further investigation of Vitamin D supplementation in randomized control studies, which may lead to possible treatment or prevention of COVID-19.

Wien Klin Wochenschr2021       LitCov and CORD-19
32DIC-Like Syndrome Following Administration of ChAdOx1 nCov-19 Vaccination  

In recent weeks, adverse reactions have been reported after administration of Oxford–AstraZeneca chimpanzee adenovirus vectored vaccine ChAdOx1 nCoV-19 (AZD1222), in particular thrombus formation, which has led several European Countries to discontinue administration of this vaccine. On March 8, 2021, the European Medicines Agency Safety Committee did not confirm this probable association. We report the case of a patient who developed disseminated intravascular coagulation after the first dose of Oxford-Astra Zeneca vaccine, which resolved in a few days with the administration of dexamethasone and enoxaparin. This work demonstrates the safety of the Oxford-Astra Zeneca vaccine and that any development of side effects can be easily managed with a prompt diagnosis and in a short time with a few commonly used drugs.

Viruses2021       LitCov and CORD-19
33Pediatric Acute Liver Failure Due to Type 2 Autoimmune Hepatitis Associated With SARS-CoV-2 Infection: A Case Report  

Although elevated liver enzymes are common in hospitalized children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, pediatric acute liver failure is an uncommon manifestation of COVID-19 disease. We describe the case of a 3-year-old previously healthy female who developed acute liver failure secondary to type 2 autoimmune hepatitis preceded by mild infection with SARS-CoV-2. Testing for viral hepatitis was negative, and the patient did not meet diagnostic criteria for multisystem inflammatory disease in children (MIS-C). A liver biopsy showed acute submassive hepatocyte necrosis with brisk CD3+ T lymphocyte infiltration and no evidence of fibrosis or chronic liver disease. Treatment with high-dose methylprednisolone resulted in rapid normalization of alanine aminotransferase (ALT), aspartate aminotransferase (AST), international normalized ratio (INR), and ammonia levels, and liver transplantation was avoided. This case highlights a possible association between SARS-CoV-2 infection and subsequent development of autoimmune liver disease presenting with acute liver failure.

JPGN Rep2022       LitCov and CORD-19
34SARS-CoV-2 vaccination can elicit a CD8 T-cell dominant hepatitis  

BACKGROUND & AIMS: Autoimmune hepatitis episodes have been described following SARS-CoV-2 infection and vaccination but their pathophysiology remains unclear. Here, we report the case of a 52-year-old male, presenting with bimodal episodes of acute hepatitis, each occurring 2-3 weeks after BNT162b2 mRNA vaccination and sought to identify the underlying immune correlates. The patient received first oral budesonide, relapsed, but achieved remission under systemic steroids. METHODS: Imaging mass cytometry for spatial immune profiling was performed on liver biopsy tissue. Flow cytometry was performed to dissect CD8 T cell phenotypes and identify SARS-CoV-2-specific and EBV-specific T cells longitudinally. Vaccine-induced antibodies were determined by ELISA. Data was correlated with clinical labs. RESULTS: Analysis of the hepatic tissue revealed an immune infiltrate quantitatively dominated by activated cytotoxic CD8 T cells with panlobular distribution. An enrichment of CD4 T cells, B cells, plasma cells and myeloid cells was also observed compared to controls. The intrahepatic infiltrate showed enrichment for CD8 T cells with SARS-CoV-2-specificity compared to the peripheral blood. Notably, hepatitis severity correlated longitudinally with an activated cytotoxic phenotype of peripheral SARS-CoV-2-specific, but not EBV-specific CD8+ T cells or vaccine-induced immunoglobulins. CONCLUSIONS: COVID19 vaccination can elicit a distinct T cell-dominant immune-mediated hepatitis with a unique pathomechanism associated with vaccination induced antigen-specific tissue-resident immunity requiring systemic immunosuppression. LAY SUMMARY: Liver inflammation is observed during SARS-CoV-2 infection but can also occur in some individuals after vaccination and shares some typical features with autoimmune liver disease. In this report, we show that highly activated T cells accumulate and are evenly distributed in the different areas of the liver in a patient with liver inflammation following SARS-CoV-2 vaccination. Moreover, within these liver infiltrating T cells, we observed an enrichment of T cells that are reactive to SARS-CoV-2, suggesting that these vaccine-induced cells can contribute to the liver inflammation in this context.

J Hepatol2022       LitCov and CORD-19
35Hepatitis C Virus Reactivation Following COVID-19 Vaccination-A Case Report  

PURPOSE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection impacted morbidity and mortality during the pandemic of 2020–2021. A number of anti-COVID-19 vaccines have been developed with an unprecedented speed. While these vaccines have good efficacy and are safe, the experience with their use is limited and hence the knowledge of rare side effects. Identifying rare complications is important for future safe use of these vaccines. MATERIALS AND METHODS: Here, we report a case of a 82-year old patient with dementia who was admitted to a nursing home in the Netherlands. After vaccination with COVID-19 vaccination, physical examinations and lab tests were performed. RESULTS: She had a reactivation of hepatitis C infection after vaccination with the mRNA-based Pfizer–BioNTech COVID-19 vaccine. This reactivation manifested with jaundice, loss of consciousness, hepatic coma and death. CONCLUSION: This reactivation of hepatitis C virus after vaccination with the Pfizer–BioNTech COVID‑19 vaccine suggests a need for critical consideration of individuals with prior HCV infection and considered for COVID-19 vaccination.

Int Med Case Rep J2021       LitCov and CORD-19
36ACE2-independent infection of T lymphocytes by SARS-CoV-2  

SARS-CoV-2 induced marked lymphopenia in severe patients with COVID-19. However, whether lymphocytes are targets of viral infection is yet to be determined, although SARS-CoV-2 RNA or antigen has been identified in T cells from patients. Here, we confirmed that SARS-CoV-2 viral antigen could be detected in patient peripheral blood cells (PBCs) or postmortem lung T cells, and the infectious virus could also be detected from viral antigen-positive PBCs. We next prove that SARS-CoV-2 infects T lymphocytes, preferably activated CD4 + T cells in vitro. Upon infection, viral RNA, subgenomic RNA, viral protein or viral particle can be detected in the T cells. Furthermore, we show that the infection is spike-ACE2/TMPRSS2-independent through using ACE2 knockdown or receptor blocking experiments. Next, we demonstrate that viral antigen-positive T cells from patient undergone pronounced apoptosis. In vitro infection of T cells induced cell death that is likely in mitochondria ROS-HIF-1a-dependent pathways. Finally, we demonstrated that LFA-1, the protein exclusively expresses in multiple leukocytes, is more likely the entry molecule that mediated SARS-CoV-2 infection in T cells, compared to a list of other known receptors. Collectively, this work confirmed a SARS-CoV-2 infection of T cells, in a spike-ACE2-independent manner, which shed novel insights into the underlying mechanisms of SARS-CoV-2-induced lymphopenia in COVID-19 patients.

Signal Transduct Target Ther2022       LitCov and CORD-19
37Antibody responses against SARS-CoV-2 variants induced by four different SARS-CoV-2 vaccines in Healthcare workers in the Netherlands: A prospective cohort study  

BACKGROUND: Emerging and future SARS-CoV-2 variants may jeopardize the effectiveness of vaccination campaigns. Therefore, it is important to know how the different vaccines perform against diverse SARS-CoV-2 variants. METHODS AND FINDINGS: In a prospective cohort of 165 SARS-CoV-2 naive health care workers in the Netherlands, vaccinated with either one of four vaccines (BNT162b2, mRNA-1273, AZD1222 or Ad26.COV2.S), we performed a head-to-head comparison of the ability of sera to recognize and neutralize SARS-CoV-2 variants of concern (VOCs; Alpha, Beta, Gamma, Delta and Omicron). Repeated serum sampling was performed 5 times during a year (from January 2021 till January 2022), including before and after booster vaccination with BNT162b2. Four weeks after completing the initial vaccination series, SARS-CoV-2 wild-type neutralizing antibody titers were highest in recipients of mRNA-1273, followed by recipients of BNT162b2 (geometric mean titers (GMT) of 358 [95% CI 231–556] and 214 [95% CI 153–299], respectively; p<0.05), and substantially lower in those vaccinated with the adenovirus vector-based vaccines AZD1222 and Ad26.COV2.S (GMT of 18 [95% CI 11–30] and 14 [95% CI 8–25] IU/ml, respectively; p<0.001). VOCs neutralization was reduced in all vaccine groups, with the greatest reduction in neutralization GMT observed against the Omicron variant (fold change 0.03 [95% CI 0.02–0.04], p<0.001). The booster BNT162b2 vaccination increased neutralizing antibody titers for all groups with substantial improvement against the VOCs including the Omicron variant. We used linear regression and linear mixed model analysis. All results were adjusted for possible confounding of age and sex. Study limitations include the lack of cellular immunity data. CONCLUSIONS: Overall, this study shows that the mRNA vaccines appear superior to adenovirus vector-based vaccines in inducing neutralizing antibodies against VOCs four weeks after initial vaccination and after booster vaccination, which implies the use of mRNA vaccines for both initial and booster vaccination.

PLoS Med2022       LitCov and CORD-19
38Covid-19: US hospitals continued to perform unnecessary surgeries during pandemic  

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BMJ2022       LitCov
39Immune response in COVID-19: what is next?  

The coronavirus disease 2019 (COVID-19) has been a global pandemic for more than 2 years and it still impacts our daily lifestyle and quality in unprecedented ways. A better understanding of immunity and its regulation in response to SARS-CoV-2 infection is urgently needed. Based on the current literature, we review here the various virus mutations and the evolving disease manifestations along with the alterations of immune responses with specific focuses on the innate immune response, neutrophil extracellular traps, humoral immunity, and cellular immunity. Different types of vaccines were compared and analyzed based on their unique properties to elicit specific immunity. Various therapeutic strategies such as antibody, anti-viral medications and inflammation control were discussed. We predict that with the available and continuously emerging new technologies, more powerful vaccines and administration schedules, more effective medications and better public health measures, the COVID-19 pandemic will be under control in the near future. [Image: see text]

Cell Death Differ2022       LitCov and CORD-19
40More than 50 long-term effects of COVID-19: a systematic review and meta-analysis  

COVID-19 can involve persistence, sequelae, and other medical complications that last weeks to months after initial recovery. This systematic review and meta-analysis aims to identify studies assessing the long-term effects of COVID-19. LitCOVID and Embase were searched to identify articles with original data published before the 1st of January 2021, with a minimum of 100 patients. For effects reported in two or more studies, meta-analyses using a random-effects model were performed using the MetaXL software to estimate the pooled prevalence with 95% CI. PRISMA guidelines were followed. A total of 18,251 publications were identified, of which 15 met the inclusion criteria. The prevalence of 55 long-term effects was estimated, 21 meta-analyses were performed, and 47,910 patients were included (age 17–87 years). The included studies defined long-COVID as ranging from 14 to 110 days post-viral infection. It was estimated that 80% of the infected patients with SARS-CoV-2 developed one or more long-term symptoms. The five most common symptoms were fatigue (58%), headache (44%), attention disorder (27%), hair loss (25%), and dyspnea (24%). Multi-disciplinary teams are crucial to developing preventive measures, rehabilitation techniques, and clinical management strategies with whole-patient perspectives designed to address long COVID-19 care.

Sci Rep2021       LitCov and CORD-19
41A case series of cutaneous phosphorylated alpha-synuclein in Long-COVID POTS  

Clin Auton Res2022       LitCov and CORD-19
42New-onset giant cell arteritis following COVID-19 mRNA (BioNTech/Pfizer) vaccine: a double-edged sword?  

Clin Rheumatol2022       LitCov and CORD-19
43Covid-19: Second boosters may benefit at-risk groups but have "minimal" impact for others, says WHO  

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BMJ2022       LitCov
44Genomic Evidence of In-Flight Transmission of SARS-CoV-2 Despite Predeparture Testing  

Since the first wave of coronavirus disease in March 2020, citizens and permanent residents returning to New Zealand have been required to undergo managed isolation and quarantine (MIQ) for 14 days and mandatory testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of October 20, 2020, of 62,698 arrivals, testing of persons in MIQ had identified 215 cases of SARS-CoV-2 infection. Among 86 passengers on a flight from Dubai, United Arab Emirates, that arrived in New Zealand on September 29, test results were positive for 7 persons in MIQ. These passengers originated from 5 different countries before a layover in Dubai; 5 had negative predeparture SARS-CoV-2 test results. To assess possible points of infection, we analyzed information about their journeys, disease progression, and virus genomic data. All 7 SARS-CoV-2 genomes were genetically identical, except for a single mutation in 1 sample. Despite predeparture testing, multiple instances of in-flight SARS-CoV-2 transmission are likely.

Emerg Infect Dis2021       LitCov and CORD-19
45Post-acute sequelae of COVID-19 in a non-hospitalized cohort: Results from the Arizona CoVHORT  

Clinical presentation, outcomes, and duration of COVID-19 has ranged dramatically. While some individuals recover quickly, others suffer from persistent symptoms, collectively known as long COVID, or post-acute sequelae of SARS-CoV-2 (PASC). Most PASC research has focused on hospitalized COVID-19 patients with moderate to severe disease. We used data from a diverse population-based cohort of Arizonans to estimate prevalence of PASC, defined as experiencing at least one symptom 30 days or longer, and prevalence of individual symptoms. There were 303 non-hospitalized individuals with a positive lab-confirmed COVID-19 test who were followed for a median of 61 days (range 30–250). COVID-19 positive participants were mostly female (70%), non-Hispanic white (68%), and on average 44 years old. Prevalence of PASC at 30 days post-infection was 68.7% (95% confidence interval: 63.4, 73.9). The most common symptoms were fatigue (37.5%), shortness-of-breath (37.5%), brain fog (30.8%), and stress/anxiety (30.8%). The median number of symptoms was 3 (range 1–20). Amongst 157 participants with longer follow-up (≥60 days), PASC prevalence was 77.1%.

PLoS One2021       LitCov and CORD-19
46A review of adverse effects of COVID-19 vaccines  

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Infez Med2022       LitCov and CORD-19
47High viral loads: what drives fatal cases of COVID-19 in vaccinees?-an autopsy study  

The rate of SARS-CoV-2 infections in vaccinees has become a relevant serious issue. This study aimed to determine the causes of death, histological organ alteration, and viral spread in relation to demographic, clinical-pathological, viral variants, and vaccine types for deceased individuals with proven SARS-CoV-2 infection after vaccination who died between January and November 2021. Twenty-nine consecutively collected cases were analyzed and compared to 141 nonvaccinated control cases. Autopsies were performed on 16 partially and 13 fully vaccinated individuals. Most patients were elderly and suffered from several relevant comorbidities. Real-time RT-PCR (RT-qPCR) identified a significantly increased rate of generalized viral dissemination within organ systems in vaccinated cases versus nonvaccinated cases (45% vs. 16%, respectively; P = 0.008) mainly with Ct-values of higher than 25 in non-respiratory samples. However, vaccinated cases also showed high viral loads, reaching Ct-values below 10, especially in the upper airways and lungs. This was accompanied by high rates of pulmonal bacterial or mycotic superinfections and the occurrence of immunocompromising factors, such as malignancies, immunosuppressive drug intake, or decreased immunoglobulin levels. All these findings were particularly accentuated in partially vaccinated patients compared to fully vaccinated individuals. The virus dissemination observed in our case study may indicate that patients with an impaired immune system have a decreased ability to eliminate the virus. However, the potential role of antibody-dependent enhancement must also be ruled out in future studies. Fatal cases of COVID-19 in vaccinees were rare and often associated with severe comorbidities or other immunosuppressive conditions.

Mod Pathol2022       LitCov and CORD-19
48Acute kidney rejection after anti-SARS-CoV-2 virus-vectored vaccine-case report  

COVID-19 infection remains a threat to the health systems of many countries. Potential success in the fight against the COVID-19 pandemic is the vaccination of high-risk groups, including patients with end-stage kidney disease (ESKD) and after solid organ transplantation (SOT). Immunosuppression in kidney transplant recipients can also reduce the immunogenicity of SARS-CoV-2 vaccines (varied by vaccine platform), available data suggest that they are efficacious in approximately 50–70%, compared to non-transplant situations. In this paper, we present a newly developed acute humoral and cellular rejection with acute allograft failure and need of hemodialysis 14 days after administration of the adenovirus vectored SARS-CoV-2 vaccine (AstraZeneca; CHADOx1, AZD1222). This occurred in a patient who previously had an asymptomatic COVID-19 infection. Case reports of acute allograft rejection after vaccination against SARS-CoV-2 can help stratify risk groups of patients who develop hyperimmune reactions. However, it is also possible that those with a previous mild primary COVID-19 infection may also develop acute allograft rejections upon COVID-19 re-infection.

NPJ Vaccines2022       LitCov and CORD-19
49Six-month sequelae of post-vaccination SARS-CoV-2 infection: A retrospective cohort study of 10,024 breakthrough infections  

Vaccination has proven effective against infection with SARS-CoV-2, as well as death and hospitalisation following COVID-19 illness. However, little is known about the effect of vaccination on other acute and post-acute outcomes of COVID-19. Data were obtained from the TriNetX electronic health records network (over 81 million patients mostly in the USA). Using a retrospective cohort study and time-to-event analysis, we compared the incidences of COVID-19 outcomes between individuals who received a COVID-19 vaccine (approved for use in the USA) at least 2 weeks before SARS-CoV-2 infection and propensity score-matched individuals unvaccinated for COVID-19 but who had received an influenza vaccine. Outcomes were ICD-10 codes representing documented COVID-19 sequelae in the 6 months after a confirmed SARS-CoV-2 infection (recorded between January 1 and August 31, 2021, i.e. before the emergence of the Omicron variant). Associations with the number of vaccine doses (1 vs. 2) and age (< 60 vs. ≥ 60 years-old) were assessed. Among 10,024 vaccinated individuals with SARS-CoV-2 infection, 9479 were matched to unvaccinated controls. Receiving at least one COVID-19 vaccine dose was associated with a significantly lower risk of respiratory failure, ICU admission, intubation/ventilation, hypoxaemia, oxygen requirement, hypercoagulopathy/venous thromboembolism, seizures, psychotic disorder, and hair loss (each as composite endpoints with death to account for competing risks; HR 0.70-0.83, Bonferroni-corrected p<.05), but not other outcomes, including long-COVID features, renal disease, mood, anxiety, and sleep disorders. Receiving 2 vaccine doses was associated with lower risks for most outcomes. Associations between prior vaccination and outcomes of SARS-CoV-2 infection were marked in those < 60 years-old, whereas no robust associations were observed in those ≥ 60 years-old. In summary, COVID-19 vaccination is associated with lower risk of several, but not all, COVID-19 sequelae in those with breakthrough SARS-CoV-2 infection. The findings may inform service planning, contribute to forecasting public health impacts of vaccination programmes, and highlight the need to identify additional interventions for COVID-19 sequelae.

Brain Behav Immun2022       LitCov and CORD-19
50Accelerometer-measured physical activity and sedentary time among children and their parents in the UK before and after COVID-19 lockdowns: a natural experiment  

BACKGROUND: Restrictions due to the coronavirus disease 2019 (COVID-19) pandemic reduced physical activity provision for both children and their parents. Recent studies have reported decreases in physical activity levels during lockdown restrictions, but these were largely reliant on self-report methods, with data collected via unrepresentative self-report surveys. The post-pandemic impacts on children’s activity levels remain unknown. A key question is how active children become once lockdown restrictions are lifted. METHODS: Active-6 is a repeated cross-sectional natural experiment. Accelerometer data from 1296 children aged 10–11 and their parents were collected in 50 schools in the Greater Bristol area, UK in March 2017-May 2018 (pre-COVID-19 comparator group), and compared to 393 children aged 10–11 and parents in 23 of the same schools, collected in May-December 2021. Mean minutes of accelerometer-measured moderate-to-vigorous physical activity (MVPA) were derived for weekdays and weekend and compared pre- and post-lockdown via linear multilevel models. RESULTS: After adjusting for seasonality, accelerometer wear time and child/parent demographics, children’s mean weekday and weekend MVPA were 7.7 min (95% CI: 3.5 to 11.9) and 6.9 min (95% CI: 0.9 to 12.9) lower in 2021 than in 2018, respectively, while sedentary time was higher by 25.4 min (95% CI: 15.8 to 35.0) and 14.0 min (95% CI: 1.5 to 26.5). There was no evidence that differences varied by child gender or household education. There was no significant difference in parents’ MVPA or sedentary time, either on weekdays or weekends. CONCLUSIONS: Children’s MVPA was lower by 7–8 min/day in 2021 once restrictions were lifted than before the pandemic for all groups, on both weekdays and weekends. Previous research has shown that there is an undesirable age-related decline in children’s physical activity. The 8-min difference reported here would be broadly comparable to the decline that would have previously been expected to occur over a three-year period. Parents’ physical activity was similar to pre-pandemic levels. Our results suggest that despite easing of restrictions, children’s activity levels have not returned to pre-pandemic levels. There is an urgent need to understand why these changes have occurred and how long they are maintained. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12966-022-01290-4.

Int J Behav Nutr Phys Act2022       LitCov and CORD-19

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