\ 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
51Covid-19: Social murder, they wrote-elected, unaccountable and unrepentant  

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BMJ2021       LitCov and CORD-19
52European Respiratory Society statement on long COVID follow-up  

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Eur Respir J2022       LitCov and CORD-19
53Innate immune suppression by SARS-CoV-2 mRNA vaccinations: The role of G-quadruplexes, exosomes and MicroRNAs  

The mRNA SARS-CoV-2 vaccines were brought to market in response to the public health crises of Covid-19. The utilization of mRNA vaccines in the context of infectious disease has no precedent. The many alterations in the vaccine mRNA hide the mRNA from cellular defenses and promote a longer biological half-life and high production of spike protein. However, the immune response to the vaccine is very different from that to a SARS-CoV-2 infection. In this paper, we present evidence that vaccination induces a profound impairment in type I interferon signaling, which has diverse adverse consequences to human health. Immune cells that have taken up the vaccine nanoparticles release into circulation large numbers of exosomes containing spike protein along with critical microRNAs that induce a signaling response in recipient cells at distant sites. We also identify potential profound disturbances in regulatory control of protein synthesis and cancer surveillance. These disturbances potentially have a causal link to neurodegenerative disease, myocarditis, immune thrombocytopenia, Bell's palsy, liver disease, impaired adaptive immunity, impaired DNA damage response and tumorigenesis. We show evidence from the VAERS database supporting our hypothesis. We believe a comprehensive risk/benefit assessment of the mRNA vaccines questions them as positive contributors to public health.

Food Chem Toxicol2022       LitCov and CORD-19
54Increased memory B cell potency and breadth after a SARS-CoV-2 mRNA boost  

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Nature2022       LitCov and CORD-19
55Infectious viral load in unvaccinated and vaccinated individuals infected with ancestral, Delta or Omicron SARS-CoV-2  

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Nat Med2022       LitCov and CORD-19
56An equitable roadmap for ending the COVID-19 pandemic  

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Nat Med2022       LitCov and CORD-19
57Nucleocapsid mutations in SARS-CoV-2 augment replication and pathogenesis  

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PLoS Pathog2022       LitCov
58Clinical outcomes associated with SARS-CoV-2 Omicron (B.1.1.529) variant and BA.1/BA.1.1 or BA.2 subvariant infection in Southern California  

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Nat Med2022       LitCov
59Acute Pancreatitis: A Possible Side Effect of COVID-19 Vaccine  

For the first time, the mRNA technology was utilized to produce a vaccine against COVID-19 after the unprecedented pandemic equally affected every part of the world. Pfizer-BioNTech (BNT162b2) mRNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was granted emergency use authorization (EUA) by Food and Drug Administration (FDA) in December 2020. EUA has been widely discussed in the medical literature and the general public. The safety of the BNT162b2 vaccine has been investigated in short-term trials with data available for three months. We present a case of a 96-year-old female with a past surgical history of cholecystectomy who presented with acute onset severe abdominal pain a few days after getting the first dose of Pfizer-BioNTech COVID-19 vaccine. She was diagnosed with acute pancreatitis with a lipase level of 4036 U/L. Extensive history and investigations were unable to find any etiology. The patient was conservatively managed and discharged home without any complications. There has been some data available in medical literature showing an association between acute pancreatitis and COVID-19 infection. Trial data of Pfizer COVID-19 also shows one case of acute pancreatitis in the treatment group. There have also been individual cases of unexplained acute pancreatitis shared by medical professionals on online forums. Our main goal to write this case is to make medical literature aware of possible emerging side effects of the COVID-19 vaccine, one of such side effects being self-resolving uncomplicated acute pancreatitis.

Cureus2021       LitCov and CORD-19
60The use of masks and respirators to prevent transmission of influenza: a systematic review of the scientific evidence  

Please cite this paper as: bin‐Reza et al. (2012) The use of masks and respirators to prevent transmission of influenza: a systematic review of the scientific evidence. Influenza and Other Respiratory Viruses 6(4), 257–267. There are limited data on the use of masks and respirators to reduce transmission of influenza. A systematic review was undertaken to help inform pandemic influenza guidance in the United Kingdom. The initial review was performed in November 2009 and updated in June 2010 and January 2011. Inclusion criteria included randomised controlled trials and quasi‐experimental and observational studies of humans published in English with an outcome of laboratory‐confirmed or clinically‐diagnosed influenza and other viral respiratory infections. There were 17 eligible studies. Six of eight randomised controlled trials found no significant differences between control and intervention groups (masks with or without hand hygiene; N95/P2 respirators). One household trial found that mask wearing coupled with hand sanitiser use reduced secondary transmission of upper respiratory infection/influenza‐like illness/laboratory‐confirmed influenza compared with education; hand sanitiser alone resulted in no reduction. One hospital‐based trial found a lower rate of clinical respiratory illness associated with non‐fit‐tested N95 respirator use compared with medical masks. Eight of nine retrospective observational studies found that mask and/or respirator use was independently associated with a reduced risk of severe acute respiratory syndrome (SARS). Findings, however, may not be applicable to influenza and many studies were suboptimal. None of the studies established a conclusive relationship between mask/respirator use and protection against influenza infection. Some evidence suggests that mask use is best undertaken as part of a package of personal protection especially hand hygiene. The effectiveness of masks and respirators is likely linked to early, consistent and correct usage.

Influenza Other Respir Viruses2011       CORD-19
61Anti-infection mechanism of phosphodiesterase-5 inhibitors and their roles in COVID-19 (Review)  

Coronavirus disease 2019 (COVID-19) has a variety of impacts on the human body. Severe acute respiratory syndrome coronavirus 2 is the pathogen that causes COVID-19. It invades human tissues through the receptor angiotensin-converting enzyme 2, resulting in an imbalance in the angiotensin II (AngII) level and upregulation of renin-angiotensin system/AngII pathway activity. Furthermore, the binding of AngII to its receptor leads to vasoconstriction, endothelial injury and intravascular thrombosis. In addition, COVID-19 may have adverse effects on male reproductive organs and a marked impact on male reproductive health. Phosphodiesterase-5 inhibitors (PDE5Is) may improve vascular endothelial function, promote testicular and systemic blood circulation and testosterone secretion and enhance epididymal function, as well as sperm maturation and capacitation. PDE5Is may also be of use in the treatment of infectious diseases by enhancing immunity and anti-inflammatory responses and improving vascular endothelial function. Based on the pharmacological mechanism of PDE5Is, they are of unique value in the fight against infectious diseases and may be effective in combination with direct antiviral drugs. The anti-infection mechanisms of PDE5Is and their roles in COVID-19 were reviewed in the present study.

Exp Ther Med2021       LitCov and CORD-19
62Diagnosis and management of postural orthostatic tachycardia syndrome  

CMAJ2022       CORD-19
63Neuropathic symptoms with SARS-CoV-2 vaccination  

BACKGROUND AND OBJECTIVES: Various peripheral neuropathies, particularly those with sensory and autonomic dysfunction may occur during or shortly after acute COVID-19 illnesses. These appear most likely to reflect immune dysregulation. If similar manifestations can occur with the vaccination remains unknown. RESULTS: In an observational study, we studied 23 patients (92% female; median age 40years) reporting new neuropathic symptoms beginning within 1 month after SARS-CoV-2 vaccination. 100% reported sensory symptoms comprising severe face and/or limb paresthesias, and 61% had orthostasis, heat intolerance and palpitations. Autonomic testing in 12 identified seven with reduced distal sweat production and six with positional orthostatic tachycardia syndrome. Among 16 with lower-leg skin biopsies, 31% had diagnostic/subthreshold epidermal neurite densities (≤5%), 13% were borderline (5.01–10%) and 19% showed abnormal axonal swelling. Biopsies from randomly selected five patients that were evaluated for immune complexes showed deposition of complement C4d in endothelial cells. Electrodiagnostic test results were normal in 94% (16/17). Together, 52% (12/23) of patients had objective evidence of small-fiber peripheral neuropathy. 58% patients (7/12) treated with oral corticosteroids had complete or near-complete improvement after two weeks as compared to 9% (1/11) of patients who did not receive immunotherapy having full recovery at 12 weeks. At 5–9 months post-symptom onset, 3 non-recovering patients received intravenous immunoglobulin with symptom resolution within two weeks. CONCLUSIONS: This observational study suggests that a variety of neuropathic symptoms may manifest after SARS-CoV-2 vaccinations and in some patients might be an immune-mediated process.

medRxiv2022       CORD-19
64Covid-19 pandemic: What is the truth?  

The ongoing “pandemic” involving the severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2) has several characteristics that make it unique in the history of pandemics. This entails not only the draconian measures that some countries and individual states within the United States and initiated and made policy, most of which are without precedent or scientific support, but also the completely unscientific way the infection has been handled. For the 1(st) time in medical history, major experts in virology, epidemiology, infectious diseases, and vaccinology have not only been ignored, but are also demonized, marginalized and in some instances, become the victim of legal measures that can only be characterized as totalitarian. Discussions involving various scientific opinions have been eliminated, top scientists have been frightened into silence by threats to their careers, physicians have lost their licenses, and the concept of early treatment has been virtually eliminated. Hundreds of thousands of people have died needlessly as a result of, in my opinion and the opinion of others, poorly designed treatment protocols, mostly stemming from the Center for Disease Control and Prevention, which have been rigidly enforced among all hospitals. The economic, psychological, and institutional damage caused by these unscientific policies is virtually unmeasurable. Whole generations of young people will suffer irreparable damage, both physical and psychological, possibly forever. The truth must be told.

Surg Neurol Int2021       LitCov and CORD-19
65mRNA vaccine induced antibodies more effective than natural immunity in neutralizing SARS-CoV-2 and its high affinity variants  

Several variants of SARS-CoV-2 have emerged. Those with mutations in the angiotensin-converting enzyme (ACE2) receptor binding domain (RBD) are associated with increased transmission and severity. In this study, we developed both antibody quantification and functional neutralization assays. Analyses of both COVID-19 convalescent and diagnostic cohorts strongly support the use of RBD antibody levels as an excellent surrogate to biochemical neutralization activities. Data further revealed that the samples from mRNA vaccinated individuals had a median of 17 times higher RBD antibody levels and a similar degree of increased neutralization activities against RBD-ACE2 binding than those from natural infections. Our data showed that N501Y RBD had fivefold higher ACE2 binding than the original variant. While some antisera from naturally infected subjects had substantially reduced neutralization ability against N501Y RBD, all blood samples from vaccinated individuals were highly effective in neutralizing it. Thus, our data indicates that mRNA vaccination may generate more neutralizing RBD antibodies than natural immunity. It further suggests a potential need to maintain high RBD antibody levels to control the more infectious SARS-CoV-2 variants.

Sci Rep2022       LitCov and CORD-19
66"Anosmia" the mysterious collateral damage of COVID-19  

COVID-19 pandemic spreads worldwide, with more than 100 million positive cases and more than 2 million deaths. From the beginning of the COVID-19 pandemic, several otolaryngologists described many cases of a sudden loss of smell (anosmia) associated with the disease with or without additional symptoms. Anosmia is often the first and sometimes the only sign in the asymptomatic carriers of COVID-19. Still, this disorder is underestimated, and it is not life-threatening. However, it significantly decreases the quality of life. This olfactory dysfunction continues in several cases even after the nasopharyngeal swab was negative. The occurrence of anosmia can be used as a screening tool for COVID-19 patients and can be used to identify these patients to accomplish the isolation and tracking procedures. In this review, we highlighted the possible mechanisms of anosmia in COVID-19 patients, major pathologies and features of anosmia, implications of anosmia in early diagnosis of COVID-19, evaluation of the smell function during COVID-19, and management and treatment options of COVID-19 anosmia.

J Neurovirol2022       LitCov and CORD-19
67Mucosal Immunity in COVID-19: A Neglected but Critical Aspect of SARS-CoV-2 Infection  

The mucosal immune system is the largest component of the entire immune system, having evolved to provide protection at the main sites of infectious threat: the mucosae. As SARS-CoV-2 initially infects the upper respiratory tract, its first interactions with the immune system must occur predominantly at the respiratory mucosal surfaces, during both inductive and effector phases of the response. However, almost all studies of the immune response in COVID-19 have focused exclusively on serum antibodies and systemic cell-mediated immunity including innate responses. This article proposes that there is a significant role for mucosal immunity and for secretory as well as circulating IgA antibodies in COVID-19, and that it is important to elucidate this in order to comprehend especially the asymptomatic and mild states of the infection, which appear to account for the majority of cases. Moreover, it is possible that mucosal immunity can be exploited for beneficial diagnostic, therapeutic, or prophylactic purposes.

Front Immunol2020       LitCov and CORD-19
68Perceived changes of specific attitudes, perceptions and behaviors during the Corona pandemic and their relation to wellbeing  

BACKGROUND: During the COVID-19 pandemic, most people had to cope with the restrictions of the lockdown, leaving them to their fears, insecurity and isolation. On the other hand, due to the unexpected ‘extra time’ there was room for new experiences and for personal reflections on what is essential in life, to perceive nature and relations more consciously etc. We, therefore, intended to analyze perceived changes of attitudes and behaviors during the time of lockdown, and whether these perceptions would contribute to personal wellbeing during the pandemic. METHODS: An anonym cross-sectional online survey was performed for data collection, using standardized questionnaires, i.e., the WHO-Five Well-being Index (WHO-5), Brief Multidimensional Life Satisfaction Scale (BMLSS), Awe/Gratitude scale (GrAw-7), and the newly developed Perceived Changes Questionnaire (PCQ). RESULTS: Within the number of respondents (n = 1277), women were predominating (67.5%). Participants’ mean age was 50.9 ± 14.9 years. Exploratory factor analyses showed that the 24-item Perceived Changes Questionnaire differentiated five factors that would account for 61% of variance: (1) Nature/Silence/Contemplation (Cronbach’s alpha = .87), (2) Spirituality (Cronbach’s alpha = .83), (3) Relationships (Cronbach’s alpha = .80), (4) Reflection on life (Cronbach’s alpha = .74), (5) Digital media usage (Cronbach’s alpha = .74). Strongest changes were observed for Relationships and Nature/Silence/Contemplation. Perceived changes were stronger among older persons, among persons with higher wellbeing, and among those who relied on their faith as a resource. These changes were predicted best by a person’s perception of wondering awe in distinct situations with subsequent feelings of gratitude. Stepwise regression analyzes revealed that participants’ wellbeing was explained best by low perceived burden and high life satisfaction (R(2) = .46). Awe/gratitude, perceived changes in terms of Nature/Silence/Contemplation and low Reflections of live are further variables that would predict a person’s wellbeing among the COVID-19 pandemic. CONCLUSIONS: During the Corona pandemic, people tried to find ways to adapt to the outcomes of the restrictions. The perceived changes of attitudes and behaviors can be interpreted in terms of a reappraisal strategy. These can be measured with the extended version of the PCQ which was found to have good quality indices and a plausible factor structure. The reported changes contribute to persons’ wellbeing only to some extend, indicating that they represent an independent quality of relevance in peoples’ life.

Health Qual Life Outcomes2020       LitCov and CORD-19
69Update June 2022: management of hospitalised adults with COVID-19: a European Respiratory Society living guideline  

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Eur Respir J2022       LitCov
70Clinical and organizational factors associated with mortality during the peak of first COVID-19 wave: the global UNITE-COVID study  

PURPOSE: To accommodate the unprecedented number of critically ill patients with pneumonia caused by coronavirus disease 2019 (COVID-19) expansion of the capacity of intensive care unit (ICU) to clinical areas not previously used for critical care was necessary. We describe the global burden of COVID-19 admissions and the clinical and organizational characteristics associated with outcomes in critically ill COVID-19 patients. METHODS: Multicenter, international, point prevalence study, including adult patients with SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) and a diagnosis of COVID-19 admitted to ICU between February 15th and May 15th, 2020. RESULTS: 4994 patients from 280 ICUs in 46 countries were included. Included ICUs increased their total capacity from 4931 to 7630 beds, deploying personnel from other areas. Overall, 1986 (39.8%) patients were admitted to surge capacity beds. Invasive ventilation at admission was present in 2325 (46.5%) patients and was required during ICU stay in 85.8% of patients. 60-day mortality was 33.9% (IQR across units: 20%–50%) and ICU mortality 32.7%. Older age, invasive mechanical ventilation, and acute kidney injury (AKI) were associated with increased mortality. These associations were also confirmed specifically in mechanically ventilated patients. Admission to surge capacity beds was not associated with mortality, even after controlling for other factors. CONCLUSIONS: ICUs responded to the increase in COVID-19 patients by increasing bed availability and staff, admitting up to 40% of patients in surge capacity beds. Although mortality in this population was high, admission to a surge capacity bed was not associated with increased mortality. Older age, invasive mechanical ventilation, and AKI were identified as the strongest predictors of mortality. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00134-022-06705-1.

Intensive Care Med2022       LitCov and CORD-19
71Effectiveness of face masks in blocking the transmission of SARS-CoV-2: A preliminary evaluation of masks used by SARS-CoV-2-infected individuals  

In 2019, a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is transmitted via the airborne route, caused a new pandemic namely, “coronavirus disease 2019” (COVID-19). Although the effectiveness of face masks to prevent the transmission of SARS-CoV-2 is debated, no study has evaluated the virus-blocking efficacy of masks used by patients. We aimed to evaluate this efficacy of masks used by SARS-CoV-2-infected individuals. Data, masks used, and nasopharyngeal swab samples were obtained from these patients. Forty-five paired samples of nasopharyngeal swabs and masks were obtained and processed; the majority of masks were woven. Viral RNAs were amplified using quantitative reverse‐transcription polymerase chain reaction and detected only on the inner parts of masks. Median viral load (VL) values of swabs and masks were 1.954x10(6) and 2,51x10(3), respectively. Statistically, there was a difference of approximately 1000 RNA copies/mL between swabs and masks and no significant difference in VL values among different types of masks. There were statistically significant differences in VL values between men and women and between symptomatic and asymptomatic patients. Our findings suggest the blocking of virus transmission by different types of masks and reinforce the use of masks by both infected and non-infected individuals.

PLoS One2022       LitCov and CORD-19
72Covid-19: An urgent call for global "vaccines-plus" action  

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BMJ2022       LitCov and CORD-19
73Human lungs show limited permissiveness for SARS-CoV-2 due to scarce ACE2 levels but virus induced expansion of inflammatory macrophages  

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Eur Respir J2022       LitCov
74Evidence 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
75Experimental evidence on learning using low-tech when school is out  

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Nat Hum Behav2022       LitCov
76Menstrual Symptoms After COVID-19 Vaccine: A Cross-Sectional Investigation in the MENA Region  

BACKGROUND: Since the emergence of COVID-19 vaccinations, many women around the world are reporting abnormalities in their menstrual periods post-vaccination. The aim of this study is to investigate the prevalence and impact of menstrual abnormalities after the COVID-19 vaccine among females residing within the Middle East and North Africa (MENA). METHODS: The study utilized a cross-sectional online self-administered survey from July 2021 to August 2021 targeting females living in the MENA region above the age of menarche who had received vaccine and were not pregnant or lactating, and do not have a history of primary ovarian insufficiency, hypothalamic menopause, or have undergone a hysterectomy. The survey was distributed regionally via social media. RESULTS: A total of 2269 females were included in our study, with a mean age of 34.3 ± 8.5 years. About 66.3% of participants reported menstrual symptoms post-vaccination, of which 46.7% experienced them after their first dose. However, in 93.6% of participants, the symptoms resolved within 2 months. Vaccine type did not significantly influence the incidence of abnormalities (p > 0.05). Participants who had confirmed previous COVID-19 infection had a very similar percentage of menstrual abnormalities compared to people who did not have COVID-19 infection or symptoms suspected of COVID-19 infection and did not test (67.5%, 66.8%, respectively); nevertheless, those who had experienced the COVID-19 vaccine general side effects had significantly more abnormalities (p < 0.001). Compared to their pandemic status, females reported significantly more abnormalities post-vaccination. CONCLUSION: The study showed a possible link between the COVID-19 vaccine and menstrual abnormalities that have impacted their quality of life.

Int J Womens Health2022       LitCov and CORD-19
77Covid-19: Long covid risk is lower with omicron than delta, researchers find  

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BMJ2022       LitCov
78Comprehensive investigations revealed consistent pathophysiological alterations after vaccination with COVID-19 vaccines  

Large-scale COVID-19 vaccinations are currently underway in many countries in response to the COVID-19 pandemic. Here, we report, besides generation of neutralizing antibodies, consistent alterations in hemoglobin A1c, serum sodium and potassium levels, coagulation profiles, and renal functions in healthy volunteers after vaccination with an inactivated SARS-CoV-2 vaccine. Similar changes had also been reported in COVID-19 patients, suggesting that vaccination mimicked an infection. Single-cell mRNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) before and 28 days after the first inoculation also revealed consistent alterations in gene expression of many different immune cell types. Reduction of CD8(+) T cells and increase in classic monocyte contents were exemplary. Moreover, scRNA-seq revealed increased NF-κB signaling and reduced type I interferon responses, which were confirmed by biological assays and also had been reported to occur after SARS-CoV-2 infection with aggravating symptoms. Altogether, our study recommends additional caution when vaccinating people with pre-existing clinical conditions, including diabetes, electrolyte imbalances, renal dysfunction, and coagulation disorders.

Cell Discov2021       LitCov and CORD-19
79Postacute COVID-19 is Characterized by Gut Viral Antigen Persistence in Inflammatory Bowel Diseases  

Background and aims The coronavirus disease 2019 (COVID-19) pandemic affects populations, societies and lives for more than two years. Long-term sequelae of COVID-19, collectively termed the post-acute COVID-19 syndrome, are rapidly emerging across the globe. Here, we investigated whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen persistence underlies the post-acute COVID-19 syndrome. Methods We performed an endoscopy study with 46 inflammatory bowel disease (IBD) patients 219 days (range: 94-257) after a confirmed COVID-19 infection. SARS-CoV-2 antigen persistence was assessed in the small and large intestine by qPCR of four viral transcripts, immunofluorescence of viral nucleocapsid and virus cultivation from biopsy tissue. Post-acute COVID-19 was assessed by a standardized questionnaire, and a systemic SARS-CoV-2 immune response was evaluated by flow-cytometry and ELISA at endoscopy. IBD activity was evaluated by clinical, biochemical and endoscopic means. Results We report expression of SARS-CoV-2 RNA in the gut mucosa ∼7 months after mild acute COVID-19 in 32 of 46 patients with IBD. Viral nucleocapsid protein persisted in 24 of 46 patients in gut epithelium and CD8+ T cells. Expression of SARS-CoV-2 antigens was not detectable in stool and viral antigen persistence was unrelated to severity of acute COVID-19, immunosuppressive therapy and gut inflammation. We were unable to culture SARS-CoV-2 from gut tissue of patients with viral antigen persistence. Post-acute sequelae of COVID-19 were reported from the majority of patients with viral antigen persistence, but not from patients without viral antigen persistence. Conclusion Our results indicate that SARS-CoV-2 antigen persistence in infected tissues serves as a basis for post-acute COVID-19. The concept that viral antigen persistence instigates immune perturbation and post-acute COVID-19 requires validation in controlled clinical trials.

Gastroenterology2022       LitCov and CORD-19
80Immune Response and Safety of SARS-CoV-2 mRNA-1273 Vaccine in Patients With Myasthenia Gravis  

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Neurol Neuroimmunol Neuroinfla2022       LitCov
81Trajectory 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
82Exploring the psychological impact of working during COVID-19 on medical and nursing students: a qualitative study  

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BMJ Open2022       LitCov
83A monoclonal antibody against staphylococcal enterotoxin B superantigen inhibits SARS-CoV-2 entry in vitro  

We recently discovered a superantigen-like motif, similar to Staphylococcal enterotoxin B (SEB), near the S1/S2 cleavage site of SARS-CoV-2 Spike protein, which might explain the multisystem-inflammatory syndrome (MIS-C) observed in children and cytokine storm in severe COVID-19 patients. We show here that an anti-SEB monoclonal antibody (mAb), 6D3, can bind this viral motif, and in particular its PRRA insert, to inhibit infection by blocking the access of host cell proteases, TMPRSS2 or furin, to the cleavage site. The high affinity of 6D3 for the furin-cleavage site originates from a poly-acidic segment at its heavy chain CDR2, a feature shared with SARS-CoV-2-neutralizing mAb 4A8. The affinity of 6D3 and 4A8 for this site points to their potential utility as therapeutics for treating COVID-19, MIS-C, or common cold caused by human coronaviruses (HCoVs) that possess a furin-like cleavage site.

bioRxiv2020       CORD-19
84SARS-CoV-2 vaccine effectiveness against infection, symptomatic and severe COVID-19: a systematic review and meta-analysis  

BACKGROUND: The temporal evolution of SARS-CoV-2 vaccine efficacy and effectiveness (VE) against infection, symptomatic, and severe COVID-19 is incompletely defined. The temporal evolution of VE could be dependent on age, vaccine types, variants of the virus, and geographic region. We aimed to conduct a systematic review and meta-analysis of the duration of VE against SARS-CoV-2 infection, symptomatic COVID-19 and severe COVID-19. METHODS: MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, the World Health Organization Global Literature on Coronavirus Disease, and CoronaCentral databases were searched and studies were selected. Independent reviewers selected randomized controlled trials and cohort studies with the outcome of interest. Independent reviewers extracted data, and assessed the risk of bias. Meta-analysis was performed with the DerSimonian-Laird random-effects model with Hartung-Knapp-Sidik-Jonkman variance correction. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used to assess certainty (quality) of the evidence. Primary outcomes included VE as a function of time against SARS-CoV-2 infection, symptomatic and severe COVID-19. RESULTS: Eighteen studies were included representing nearly 7 million individuals. VE against all SARS-CoV-2 infections declined from 83% in the first month after completion of the original vaccination series to 22% at 5 months or longer. Similarly, VE against symptomatic COVID-19 declined from 94% in the first month after vaccination to 64% by the fourth month. VE against severe COVID-19 for all ages was high overall, with the level being 90% (95% CI, 87–92%) at five months or longer after being fully vaccinated. VE against severe COVID-19 was lower in individuals ≥ 65 years and those who received Ad26.COV2.S. CONCLUSIONS: VE against SARS-CoV-2 infection and symptomatic COVID-19 waned over time but protection remained high against severe COVID-19. These data can be used to inform public health decisions around the need for booster vaccination. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-022-07418-y.

BMC Infect Dis2022       LitCov and CORD-19
85SARS-CoV-2 infection and COVID-19 vaccination rates in pregnant women in Scotland  

Population-level data on COVID-19 vaccine uptake in pregnancy and SARS-CoV-2 infection outcomes are lacking. We describe COVID-19 vaccine uptake and SARS-CoV-2 infection in pregnant women in Scotland, using whole-population data from a national, prospective cohort. Between the start of a COVID-19 vaccine program in Scotland, on 8 December 2020 and 31 October 2021, 25,917 COVID-19 vaccinations were given to 18,457 pregnant women. Vaccine coverage was substantially lower in pregnant women than in the general female population of 18−44 years; 32.3% of women giving birth in October 2021 had two doses of vaccine compared to 77.4% in all women. The extended perinatal mortality rate for women who gave birth within 28 d of a COVID-19 diagnosis was 22.6 per 1,000 births (95% CI 12.9−38.5; pandemic background rate 5.6 per 1,000 births; 452 out of 80,456; 95% CI 5.1−6.2). Overall, 77.4% (3,833 out of 4,950; 95% CI 76.2−78.6) of SARS-CoV-2 infections, 90.9% (748 out of 823; 95% CI 88.7−92.7) of SARS-CoV-2 associated with hospital admission and 98% (102 out of 104; 95% CI 92.5−99.7) of SARS-CoV-2 associated with critical care admission, as well as all baby deaths, occurred in pregnant women who were unvaccinated at the time of COVID-19 diagnosis. Addressing low vaccine uptake rates in pregnant women is imperative to protect the health of women and babies in the ongoing pandemic.

Nat Med2022       LitCov and CORD-19
86Myocarditis after COVID-19 mRNA vaccination: clinical observations and potential mechanisms  

The risk of acute myocarditis associated with COVID-19 mRNA vaccination has garnered intense (social) media attention. However, myocarditis after COVID-19 mRNA vaccination is rare and usually resolves within days or weeks. Moreover, the risks of hospitalization and death associated with COVID-19 are greater than the risk associated with COVID-19 vaccination. Therefore, COVID-19 vaccination should be recommended in adolescents and adults.

Nat Rev Cardiol2021       LitCov and CORD-19
87Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials  

Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I² = 0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I² = 0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.

Nat Commun2021       LitCov and CORD-19
88Asymptomatic Shedding of Respiratory Virus among an Ambulatory Population across Seasons  

Most observation of human respiratory virus carriage is derived from medical surveillance; however, the infections documented by this surveillance represent only a symptomatic fraction of the total infected population. As the role of asymptomatic infection in respiratory virus transmission is still largely unknown and rates of asymptomatic shedding are not well constrained, it is important to obtain more-precise estimates through alternative sampling methods. We actively recruited participants from among visitors to a New York City tourist attraction. Nasopharyngeal swabs, demographics, and survey information on symptoms, medical history, and recent travel were obtained from 2,685 adults over two seasonal arms. We used multiplex PCR to test swab specimens for a selection of common respiratory viruses. A total of 6.2% of samples (168 individuals) tested positive for at least one virus, with 5.6% testing positive in the summer arm and 7.0% testing positive in the winter arm. Of these, 85 (50.6%) were positive for human rhinovirus (HRV), 65 (38.7%) for coronavirus (CoV), and 18 (10.2%) for other viruses (including adenovirus, human metapneumovirus, influenza virus, and parainfluenza virus). Depending on the definition of symptomatic infection, 65% to 97% of infections were classified as asymptomatic. The best-fit model for prediction of positivity across all viruses included a symptom severity score, Hispanic ethnicity data, and age category, though there were slight differences across the seasonal arms. Though having symptoms is predictive of virus positivity, there are high levels of asymptomatic respiratory virus shedding among the members of an ambulatory population in New York City. IMPORTANCE Respiratory viruses are common in human populations, causing significant levels of morbidity. Understanding the distribution of these viruses is critical for designing control methods. However, most data available are from medical records and thus predominantly represent symptomatic infections. Estimates for asymptomatic prevalence are sparse and span a broad range. In this study, we aimed to measure more precisely the proportion of infections that are asymptomatic in a general, ambulatory adult population. We recruited participants from a New York City tourist attraction and administered nasal swabs, testing them for adenovirus, coronavirus, human metapneumovirus, rhinovirus, influenza virus, respiratory syncytial virus, and parainfluenza virus. At recruitment, participants completed surveys on demographics and symptomology. Analysis of these data indicated that over 6% of participants tested positive for shedding of respiratory virus. While participants who tested positive were more likely to report symptoms than those who did not, over half of participants who tested positive were asymptomatic.

mSphere2018       CORD-19
89Omicron variant (B.1.1.529) of SARS-CoV-2: Mutation, infectivity, transmission and vaccine resistance  

The appearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant Omicron (B.1.1.529) has caused panic responses around the world because of its high transmission rate and number of mutations. This review summarizes the highly mutated regions, the essential infectivity, transmission, vaccine breakthrough and antibody resistance of the Omicron variant of SARS-CoV-2. The Omicron is highly transmissible and is spreading faster than any previous variant, but may cause less severe symptoms than previous variants. The Omicron is able to escape the immune system’s defenses and coronavirus disease 2019 vaccines are less effective against the Omicron variant. Early careful preventive steps including vaccination will always be key for the suppression of the Omicron variant.

World J Clin Cases2022       LitCov and CORD-19
90Nicotine and SARS-CoV-2: COVID-19 may be a disease of the nicotinic cholinergic system  

Toxicol Rep2020       LitCov and CORD-19
91Incidence, co-occurrence and evolution of long-COVID features: A 6-month retrospective cohort study of 273,618 survivors of COVID-19  

BACKGROUND: Long-COVID refers to a variety of symptoms affecting different organs reported by people following Coronavirus Disease 2019 (COVID-19) infection. To date, there have been no robust estimates of the incidence and co-occurrence of long-COVID features, their relationship to age, sex, or severity of infection, and the extent to which they are specific to COVID-19. The aim of this study is to address these issues. METHODS AND FINDINGS: We conducted a retrospective cohort study based on linked electronic health records (EHRs) data from 81 million patients including 273,618 COVID-19 survivors. The incidence and co-occurrence within 6 months and in the 3 to 6 months after COVID-19 diagnosis were calculated for 9 core features of long-COVID (breathing difficulties/breathlessness, fatigue/malaise, chest/throat pain, headache, abdominal symptoms, myalgia, other pain, cognitive symptoms, and anxiety/depression). Their co-occurrence network was also analyzed. Comparison with a propensity score–matched cohort of patients diagnosed with influenza during the same time period was achieved using Kaplan–Meier analysis and the Cox proportional hazard model. The incidence of atopic dermatitis was used as a negative control. Among COVID-19 survivors (mean [SD] age: 46.3 [19.8], 55.6% female), 57.00% had one or more long-COVID feature recorded during the whole 6-month period (i.e., including the acute phase), and 36.55% between 3 and 6 months. The incidence of each feature was: abnormal breathing (18.71% in the 1- to 180-day period; 7.94% in the 90- to180-day period), fatigue/malaise (12.82%; 5.87%), chest/throat pain (12.60%; 5.71%), headache (8.67%; 4.63%), other pain (11.60%; 7.19%), abdominal symptoms (15.58%; 8.29%), myalgia (3.24%; 1.54%), cognitive symptoms (7.88%; 3.95%), and anxiety/depression (22.82%; 15.49%). All 9 features were more frequently reported after COVID-19 than after influenza (with an overall excess incidence of 16.60% and hazard ratios between 1.44 and 2.04, all p < 0.001), co-occurred more commonly, and formed a more interconnected network. Significant differences in incidence and co-occurrence were associated with sex, age, and illness severity. Besides the limitations inherent to EHR data, limitations of this study include that (i) the findings do not generalize to patients who have had COVID-19 but were not diagnosed, nor to patients who do not seek or receive medical attention when experiencing symptoms of long-COVID; (ii) the findings say nothing about the persistence of the clinical features; and (iii) the difference between cohorts might be affected by one cohort seeking or receiving more medical attention for their symptoms. CONCLUSIONS: Long-COVID clinical features occurred and co-occurred frequently and showed some specificity to COVID-19, though they were also observed after influenza. Different long-COVID clinical profiles were observed based on demographics and illness severity.

PLoS Med2021       LitCov and CORD-19
92More 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
93A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence  

The emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome (MERS)-CoV underscores the threat of cross-species transmission events leading to outbreaks in humans. In this study, we examine the disease potential for SARS-like CoVs currently circulating in Chinese horseshoe bat populations. Utilizing the SARS-CoV infectious clone, we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse adapted SARS-CoV backbone. The results indicate that group 2b viruses encoding the SHC014 spike in a wild type backbone can efficiently utilize multiple ACE2 receptor orthologs, replicate efficiently in primary human airway cells, and achieve in vitro titers equivalent to epidemic strains of SARS-CoV. Additionally, in vivo experiments demonstrate replication of the chimeric virus in mouse lung with notable pathogenesis. Evaluation of available SARS-based immune-therapeutic and prophylactic modalities revealed poor efficacy; both monoclonal antibody and vaccine approaches failed to neutralize and protect from CoVs utilizing the novel spike protein. Importantly, based on these findings, we synthetically rederived an infectious full length SHC014 recombinant virus and demonstrate robust viral replication both in vitro and in vivo. Together, the work highlights a continued risk of SARS-CoV reemergence from viruses currently circulating in bat populations.

Nat Med2015       CORD-19
94COVID-Related Athletic Deaths: Another Perfect Storm?  

Front Sports Act Living2022       LitCov and CORD-19
95A systematic review and meta-analysis of long-term physical and mental sequelae of COVID-19 pandemic: call for research priority and action  

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Mol Psychiatry2023       LitCov
96Outcomes of 2111 COVID-19 Hospitalized Patients Treated with Hydroxychloroquine/Azithromycin and Other Regimens in Marseille, France, 2020: A Monocentric Retrospective Analysis  

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Ther Clin Risk Manag2022       LitCov
9710-Year Weight Gain in 13,802 US Adults: The Role of Age, Sex and Race  

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J Obes2022       CORD-19
98Long term implications of covid-19 in pregnancy  

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BMJ2022       LitCov
99Clinical Characteristics and Mechanisms of Musculoskeletal Pain in Long COVID  

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J Pain Res2022       LitCov
100Recommendation for standardized medical care for children and adolescents with long COVID  

This current consensus paper for long COVID complements the existing AWMF S1 guidelines for long COVID with a detailed overview on the various clinical aspects of long COVID in children and adolescents. Members of 19 different pediatric societies of the DGKJ convent and collaborating societies together provide expert-based recommendations for the clinical management of long COVID based on the currently available but limited academic evidence for long COVID in children and adolescents. It contains screening questions for long COVID and suggestions for a structured, standardized pediatric medical history and diagnostic evaluation for patients with suspected long COVID. A time and resource-saving questionnaire, which takes the clinical complexity of long COVID into account, is offered via the DGKJ and DGPI websites as well as additional questionnaires suggested for an advanced screening of specific neurocognitive and/or psychiatric symptoms including post-exertional malaise (PEM) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). According to the individual medical history as well as clinical signs and symptoms a step by step diagnostic procedure and a multidisciplinary therapeutic approach are recommended.

Monatsschr Kinderheilkd2022       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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