\ 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
1451Association of COVID-19 Vaccinations With Intensive Care Unit Admissions and Outcome of Critically Ill Patients With COVID-19 Pneumonia in Lombardy, Italy  

N/A

JAMA Netw Open2022       LitCov
1452Physical Activity Behavior Before, During and After COVID-19 Restrictions: Longitudinal Smartphone-Tracking Study of Adults in the UK  

BACKGROUND: The COVID-19 pandemic led to the implementation of worldwide restrictive measures to reduce social contact and viral spread. These measures have been reported to have a negative effect on physical activity (PA). Studies of PA during the pandemic have primarily used self-reported data. The single academic study that used tracked data did not report on demographics. OBJECTIVE: This study aimed to explore patterns of smartphone-tracked activity before, during, and immediately after lockdown in the United Kingdom, and examine differences by sociodemographic characteristics and prior levels of PA. METHODS: Tracked longitudinal weekly minutes of PA were captured using the BetterPoints smartphone app between January and June 2020. Data were plotted by week, demographics, and activity levels at baseline. Nonparametric tests of difference were used to assess mean and median weekly minutes of activity at significant points before and during the lockdown, and as the lockdown was eased. Changes over time by demographics (age, gender, Index of Multiple Deprivation, baseline activity levels) were examined using generalized estimating equations (GEEs). RESULTS: There were 5395 users with a mean age of 41 years (SD 12) and 61% (n=3274) were female. At baseline, 26% (n=1422) of users were inactive, 23% (n=1240) were fairly active, and 51% (n=2733) were active. There was a relatively even spread across deprivation deciles (31% [n=1693] in the least deprived deciles and 23% in the most [n=1261]). We found significant changes in PA from the week before the first case of COVID-19 was announced (baseline) to the week that social distancing restrictions were relaxed (Friedman test: χ(2)(2)=2331, P<.001). By the first full week of lockdown, the median change in PA was 57 minutes less than baseline. This represents a 37% reduction in weekly minutes of PA. Overall, 63% of people decreased their level of activity between baseline and the first week of COVID-19 restrictions. Younger people showed more PA before lockdown but the least PA after lockdown. In contrast, those aged >65 years appeared to remain more active throughout and increased their activity levels as soon as lockdown was eased. Levels of PA among those classed as active at baseline showed a larger drop compared with those considered to be fairly active or inactive. Socioeconomic group and gender did not appear to be associated with changes in PA. CONCLUSIONS: Our tracked PA data suggests a significant drop in PA during the United Kingdom’s COVID-19 lockdown. Significant differences by age group and prior PA levels suggests that the government’s response to COVID-19 needs to be sensitive to these individual differences and the government should react accordingly. Specifically, it should consider the impact on younger age groups, encourage everyone to increase their PA, and not assume that people will recover prior levels of PA on their own.

J Med Internet Res2021       LitCov and CORD-19
1453Impact of the COVID-19 pandemic on teaching and learning in health professional education: a mixed methods study protocol  

BACKGROUND: Due to the complex nature of healthcare professionals’ roles and responsibilities, the education of this workforce is multifaceted and challenging. It relies on various sources of learning from teachers, peers, patients and may focus on Work Integrated Learning (WIL). The COVID-19 pandemic has impacted many of these learning opportunities especially those in large groups or involving in person interaction with peers and patients. Much of the curriculum has been adapted to an online format, the long-term consequence of which is yet to be recognized. The changed format is likely to impact learning pedagogy effecting both students and teachers. This requires a systematic approach to evaluation of online teaching and learning adaptation, in comparison to the previous format, where, in person education may have been the focus. METHODS: The proposed study is a broad based evaluation of health professional education in a major Australian University. The protocol describes a mixed methods convergent design to evaluate the impact of online education on students and teachers in health professional courses including Medicine, Nursing, Allied Health and Biomedical Science. A framework, developed at the university, using Contribution Analysis (CA), will guide the evaluation. Quantitative data relating to student performance, student evaluation of units, quantity of teaching activities and resource utilization will be collected and subjected to relevant statistical analysis. Data will be collected through surveys (500 students and 100 teachers), focus groups (10 groups of students) and interviews of students and teachers (50 students beyond graduation and 25 teachers, for long term follow up to 12 months). Application of CA will be used to answer the key research questions on the short term and long-term impact of online education on teaching and learning approaches. DISCUSSION: The protocol describes the study, which will be widely implemented over the various courses in Health Professional Education and Biomedical Science. It will evaluate how students and teachers engage with the online delivery of the curriculum, student performance, and resources used to implement these changes. It also aims to evaluate longitudinal outcome of student learning attributes and impact on graduate outcomes, which is poorly reported in educational literature.

BMC Med Educ2021       LitCov and CORD-19
1454Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy  

Abstract Background Few data are available on the rate and characteristics of thromboembolic complications in hospitalized patients with COVID-19. Methods We studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02.2020–10.04.2020). The primary outcome was any thromboembolic complication, including venous thromboembolism (VTE), ischemic stroke, and acute coronary syndrome (ACS)/myocardial infarction (MI). Secondary outcome was overt disseminated intravascular coagulation (DIC). Results We included 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]). Thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward. Thromboembolic events occurred in 28 (7.7% of closed cases; 95%CI 5.4%–11.0%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward). Half of the thromboembolic events were diagnosed within 24 h of hospital admission. Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%). Computed tomography pulmonary angiography (CTPA) was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed in 10 (33% of CTPA). The rate of ischemic stroke and ACS/MI was 2.5% and 1.1%, respectively. Overt DIC was present in 8 (2.2%) patients. Conclusions The high number of arterial and, in particular, venous thromboembolic events diagnosed within 24 h of admission and the high rate of positive VTE imaging tests among the few COVID-19 patients tested suggest that there is an urgent need to improve specific VTE diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients.

Thromb Res2020       LitCov and CORD-19
1455The pivotal link between ACE2 deficiency and SARS-CoV-2 infection  

Abstract Angiotensin converting enzyme-2 (ACE2) receptors mediate the entry into the cell of three strains of coronavirus: SARS-CoV, NL63 and SARS-CoV-2. ACE2 receptors are ubiquitous and widely expressed in the heart, vessels, gut, lung (particularly in type 2 pneumocytes and macrophages), kidney, testis and brain. ACE2 is mostly bound to cell membranes and only scarcely present in the circulation in a soluble form. An important salutary function of membrane-bound and soluble ACE2 is the degradation of angiotensin II to angiotensin1-7. Consequently, ACE2 receptors limit several detrimental effects resulting from binding of angiotensin II to AT1 receptors, which include vasoconstriction, enhanced inflammation and thrombosis. The increased generation of angiotensin1-7 also triggers counter-regulatory protective effects through binding to G-protein coupled Mas receptors. Unfortunately, the entry of SARS-CoV2 into the cells through membrane fusion markedly down-regulates ACE2 receptors, with loss of the catalytic effect of these receptors at the external site of the membrane. Increased pulmonary inflammation and coagulation have been reported as unwanted effects of enhanced and unopposed angiotensin II effects via the ACE→Angiotensin II→AT1 receptor axis. Clinical reports of patients infected with SARS-CoV-2 show that several features associated with infection and severity of the disease (i.e., older age, hypertension, diabetes, cardiovascular disease) share a variable degree of ACE2 deficiency. We suggest that ACE2 down-regulation induced by viral invasion may be especially detrimental in people with baseline ACE2 deficiency associated with the above conditions. The additional ACE2 deficiency after viral invasion might amplify the dysregulation between the ‘adverse’ ACE→Angiotensin II→AT1 receptor axis and the ‘protective’ ACE2→Angiotensin1-7→Mas receptor axis. In the lungs, such dysregulation would favor the progression of inflammatory and thrombotic processes triggered by local angiotensin II hyperactivity unopposed by angiotensin1-7. In this setting, recombinant ACE2, angiotensin1-7 and angiotensin II type 1 receptor blockers could be promising therapeutic approaches in patients with SARS-CoV-2 infection.

Eur J Intern Med2020       LitCov and CORD-19
1456Adaptive immunity to SARS-CoV-2 and COVID-19  

The adaptive immune system is important for control of most viral infections. The three fundamental components of the adaptive immune system are B cells (the source of antibodies), CD4+ T cells, and CD8+ T cells. The armamentarium of B cells, CD4+ T cells, and CD8+ T cells has differing roles in different viral infections, and in vaccines, and thus it is critical to directly study adaptive immunity to SARS-CoV-2 to understand COVID-19. Knowledge is now available on relationships between antigen-specific immune responses and SARS-CoV-2 infection. While more studies are needed, a picture has begun to emerge that reveals that CD4+ T cells, CD8+ T cells, and neutralizing antibodies all contribute to control of SARS-CoV-2, in both non-hospitalized and hospitalized cases of COVID-19. The specific functions and kinetics of these adaptive immune responses are discussed, as well as their interplay with innate immunity and implications for COVID-19 vaccines and immune memory against re-infection.

Cell2021       LitCov and CORD-19
1457Differing kinetics of anti-spike protein IgGs and neutralizing antibodies against SARS-CoV-2 after Comirnaty (BNT162b2) immunization  

N/A

J Appl Microbiol2022       LitCov and CORD-19
1458Knowledge and practice regarding prevention of COVID-19 among the Saudi Arabian population  

N/A

Work2020       LitCov and CORD-19
1459Public mental health under the long-term influence of COVID-19 in China: Geographical and temporal distribution  

BACKGROUND: The mental health status caused by major epidemics is serious and lasting. At present, there are few studies about the lasting mental health effects of COVID-19 outbreak. The purpose of this study was to investigate the mental health of the Chinese public during the long-term COVID-19 outbreak. METHODS: A total of 1172 online questionnaires were collected, covering demographical information and 8 common psychological states: depression, anxiety, somatization, stress, psychological resilience, suicidal ideation and behavior, insomnia, and stress disorder. In addition, the geographical and temporal distributions of different mental states were plotted. RESULTS: Overall, 30.1% of smokers increased smoking, while 11.3% of drinkers increased alcohol consumption. The prevalence rates of depression, anxiety, mental health problems, high risk of suicidal and behavior, clinical insomnia, clinical post-traumatic stress disorder symptoms, moderate-to-high levels of perceived stress were 18.8%, 13.3%, 7.6%, 2.8%, 7.2%, 7.0%, and 67.9%, respectively. Further, the geographical distribution showed that the mental status in some provinces/autonomous regions/municipalities was relatively more serious. The temporal distribution showed that the psychological state of the participants was relatively poorer on February 20, 24 to 26 and March 25, especially on March 25. LIMITATIONS: This cross-sectional design cannot make causal inferences. And the snowball sampling was not representative enough. CONCLUSION: Our findings suggest that the prevalence rate of mental disorders in the Chinese public is relatively low in the second month of the COVID-19 pandemic. In addition, people's mental state is affected by the geographical and temporal distributions.

J Affect Disord2020       LitCov and CORD-19
1460Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus  

Estimation of the prevalence and contagiousness of undocumented novel coronavirus (SARS-CoV2) infections is critical for understanding the overall prevalence and pandemic potential of this disease. Here we use observations of reported infection within China, in conjunction with mobility data, a networked dynamic metapopulation model and Bayesian inference, to infer critical epidemiological characteristics associated with SARS-CoV2, including the fraction of undocumented infections and their contagiousness. We estimate 86% of all infections were undocumented (95% CI: [82%–90%]) prior to 23 January 2020 travel restrictions. Per person, the transmission rate of undocumented infections was 55% of documented infections ([46%–62%]), yet, due to their greater numbers, undocumented infections were the infection source for 79% of documented cases. These findings explain the rapid geographic spread of SARS-CoV2 and indicate containment of this virus will be particularly challenging.

Science2020       LitCov and CORD-19
1461Attributes and predictors of long COVID  

N/A

Nat Med2021       LitCov and CORD-19
1462Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages  

The COVID-19 pandemic caused by infection with SARS-CoV-2 has led to more than 200,000 deaths worldwide. Several studies have now established that the hyperinflammatory response induced by SARS-CoV-2 is a major cause of disease severity and death in infected patients. Macrophages are a population of innate immune cells that sense and respond to microbial threats by producing inflammatory molecules that eliminate pathogens and promote tissue repair. However, a dysregulated macrophage response can be damaging to the host, as is seen in the macrophage activation syndrome induced by severe infections, including in infections with the related virus SARS-CoV. Here we describe the potentially pathological roles of macrophages during SARS-CoV-2 infection and discuss ongoing and prospective therapeutic strategies to modulate macrophage activation in patients with COVID-19.

Nat Rev Immunol2020       LitCov and CORD-19
1463SARS and MERS: recent insights into emerging coronaviruses  

The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 marked the second introduction of a highly pathogenic coronavirus into the human population in the twenty-first century. The continuing introductions of MERS-CoV from dromedary camels, the subsequent travel-related viral spread, the unprecedented nosocomial outbreaks and the high case-fatality rates highlight the need for prophylactic and therapeutic measures. Scientific advancements since the 2002–2003 severe acute respiratory syndrome coronavirus (SARS-CoV) pandemic allowed for rapid progress in our understanding of the epidemiology and pathogenesis of MERS-CoV and the development of therapeutics. In this Review, we detail our present understanding of the transmission and pathogenesis of SARS-CoV and MERS-CoV, and discuss the current state of development of measures to combat emerging coronaviruses. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrmicro.2016.81) contains supplementary material, which is available to authorized users.

Nat Rev Microbiol2016       CORD-19
1464coinfections among patients with COVID-19: The need for combination therapy with non-anti-SARS-CoV-2 agents?  

Co-infection has been reported in patients with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, but there is limited knowledge on co-infection among patients with coronavirus disease 2019 (COVID-19). The prevalence of co-infection was variable among COVID-19 patients in different studies, however, it could be up to 50% among non-survivors. Co-pathogens included bacteria, such as Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumonia, Legionella pneumophila and Acinetobacter baumannii; Candida species and Aspergillus flavus; and viruses such as influenza, coronavirus, rhinovirus/enterovirus, parainfluenza, metapneumovirus, influenza B virus, and human immunodeficiency virus. Influenza A was one of the most common co-infective viruses, which may have caused initial false-negative results of real-time reverse-transcriptase polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Laboratory and imaging findings alone cannot help distinguish co-infection from SARS-CoV-2 infection. Newly developed syndromic multiplex panels that incorporate SARS-CoV-2 may facilitate the early detection of co-infection among COVID-19 patients. By contrast, clinicians cannot rule out SARS-CoV-2 infection by ruling in other respiratory pathogens through old syndromic multiplex panels at this stage of the COVID-19 pandemic. Therefore, clinicians must have a high index of suspicion for coinfection among COVID-19 patients. Clinicians can neither rule out other co-infections caused by respiratory pathogens by diagnosing SARS-CoV-2 infection nor rule out COVID-19 by detection of non-SARS-CoV-2 respiratory pathogens. After recognizing the possible pathogens causing co-infection among COVID-19 patients, appropriate antimicrobial agents can be recommended.

J Microbiol Immunol Infect2020       LitCov and CORD-19
1465Anxiety and depression symptoms in the same pregnant women before and during the COVID-19 pandemic  

N/A

J Perinat Med2020       LitCov and CORD-19
1466Facing SARS-CoV-2 Pandemic at a COVID-19 Regional Children's Hospital in Italy  

N/A

Pediatr Infect Dis J2020       LitCov and CORD-19
1467Patient and clinician experience with a rapidly implemented large-scale video consultation program during COVID-19  

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has forced health-care providers to find creative ways to allow continuity of care in times of lockdown. Telemedicine enables provision of care when in-person visits are not possible. Sheba Medical Center made a rapid transition of outpatient clinics to video consultations (VC) during the first wave of COVID-19 in Israel. OBJECTIVE: Results of a survey of patient and clinician user experience with VC are reported. METHODS: Satisfaction surveys were sent by text messages to patients, clinicians who practice VC (users) and clinicians who do not practice VC (non-users). Questions referred to general satisfaction, ease of use, technical issues and medical and communication quality. Questions and scales were based on surveys used regularly in outpatient clinics of Sheba Medical Center. RESULTS: More than 1200 clinicians (physicians, psychologists, nurses, social workers, dietitians, speech therapists, genetic consultants and others) provided VC during the study period. Five hundred and forty patients, 162 clinicians who were users and 50 clinicians who were non-users completed the survey. High level of satisfaction was reported by 89.8% of patients and 37.7% of clinician users. Technical problems were experienced by 21% of patients and 80% of clinician users. Almost 70% of patients but only 23.5% of clinicians found the platform very simple to use. Over 90% of patients were very satisfied with clinician’s courtesy, expressed a high sense of trust, thought that clinician’s explanations and recommendations were clear and estimated that the clinician understood their problems and 86.5% of them would recommend VC to family and friends. Eighty-seven percent of clinician users recognize the benefit of VC for patients during the COVID-19 pandemic but only 68% supported continuation of the service after the pandemic. CONCLUSION: Our study reports high levels of patient satisfaction from outpatient clinics VC during the COVID-19 pandemic. Lower levels of clinician satisfaction can mostly be attributed to technical and administrative challenges related to the newly implemented telemedicine platform. Our findings support the continued future use of VC as a means of providing patient-centered care. Future steps need to be taken to continuously improve the clinical and administrative application of telemedicine services.

Int J Qual Healthcare2020       LitCov and CORD-19
1468Surveillance of Vaccination Coverage Among Adult Populations -United States, 2018  

PROBLEM/CONDITION: Adults are at risk for illness, hospitalization, disability and, in some cases, death from vaccine-preventable diseases, particularly influenza and pneumococcal disease. CDC recommends vaccinations for adults on the basis of age, health conditions, prior vaccinations, and other considerations. Updated vaccination recommendations from CDC are published annually in the U.S. Adult Immunization Schedule. Despite longstanding recommendations for use of many vaccines, vaccination coverage among U.S. adults remains low. REPORTING PERIOD: August 2017–June 2018 (for influenza vaccination) and January–December 2018 (for pneumococcal, herpes zoster, tetanus and diphtheria [Td]/tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis [Tdap], hepatitis A, hepatitis B, and human papillomavirus [HPV] vaccination). DESCRIPTION OF SYSTEM: The National Health Interview Survey (NHIS) is a continuous, cross-sectional national household survey of the noninstitutionalized U.S. civilian population. In-person interviews are conducted throughout the year in a probability sample of households, and NHIS data are compiled and released annually. NHIS’s objective is to monitor the health of the U.S. population and provide estimates of health indicators, health care use and access, and health-related behaviors. Adult receipt of influenza, pneumococcal, herpes zoster, Td/Tdap, hepatitis A, hepatitis B, and at least 1 dose of HPV vaccines was assessed. Estimates were derived for a new composite adult vaccination quality measure and by selected demographic and access-to-care characteristics (e.g., age, race/ethnicity, indication for vaccination, travel history [travel to countries where hepatitis infections are endemic], health insurance status, contacts with physicians, nativity, and citizenship). Trends in adult vaccination were assessed during 2010−2018. RESULTS: Coverage for the adult age-appropriate composite measure was low in all age groups. Racial and ethnic differences in coverage persisted for all vaccinations, with lower coverage for most vaccinations among non-White compared with non-Hispanic White adults. Linear trend tests indicated coverage increased from 2010 to 2018 for most vaccines in this report. Few adults aged ≥19 years had received all age-appropriate vaccines, including influenza vaccination, regardless of whether inclusion of Tdap (13.5%) or inclusion of any tetanus toxoid–containing vaccine (20.2%) receipt was measured. Coverage among adults for influenza vaccination during the 2017−18 season (46.1%) was similar to the estimate for the 2016−17 season (45.4%), and coverage for pneumococcal (adults aged ≥65 years [69.0%]), herpes zoster (adults aged ≥50 years and aged ≥60 years [24.1% and 34.5%, respectively]), tetanus (adults aged ≥19 years [62.9%]), Tdap (adults aged ≥19 years [31.2%]), hepatitis A (adults aged ≥19 years [11.9%]), and HPV (females aged 19–26 years [52.8%]) vaccination in 2018 were similar to the estimates for 2017. Hepatitis B vaccination coverage among adults aged ≥19 years and health care personnel (HCP) aged ≥19 years increased 4.2 and 6.7 percentage points to 30.0% and 67.2%, respectively, from 2017. HPV vaccination coverage among males aged 19–26 years increased 5.2 percentage points to 26.3% from the 2017 estimate. Overall, HPV vaccination coverage among females aged 19–26 years did not increase, but coverage among Hispanic females aged 19–26 years increased 10.8 percentage points to 49.6% from the 2017 estimate. Coverage for the following vaccines was lower among adults without health insurance compared with those with health insurance: influenza vaccine (among adults aged ≥19 years, 19–49 years, and 50–64 years), pneumococcal vaccine (among adults aged 19–64 years at increased risk), Td vaccine (among all age groups), Tdap vaccine (among adults aged ≥19 years and 19–64 years), hepatitis A vaccine (among adults aged ≥19 years overall and among travelers aged ≥19 years), hepatitis B vaccine (among adults aged ≥19 years and 19–49 years and among travelers aged ≥19 years), herpes zoster vaccine (among adults aged ≥60 years), and HPV vaccine (among males and females aged 19–26 years). Adults who reported having a usual place for health care generally reported receipt of recommended vaccinations more often than those who did not have such a place, regardless of whether they had health insurance. Vaccination coverage was higher among adults reporting ≥1 physician contact during the preceding year compared with those who had not visited a physician during the preceding year, regardless of whether they had health insurance. Even among adults who had health insurance and ≥10 physician contacts during the preceding year, depending on the vaccine, 20.1%–87.5% reported not having received vaccinations that were recommended either for all persons or for those with specific indications. Overall, vaccination coverage among U.S.-born adults was significantly higher than that of foreign-born adults, including influenza vaccination (aged ≥19 years), pneumococcal vaccination (all ages), tetanus vaccination (all ages), Tdap vaccination (all ages), hepatitis B vaccination (aged ≥19 years and 19–49 years and travelers aged ≥19 years), herpes zoster vaccination (all ages), and HPV vaccination among females aged 19–26 years. Vaccination coverage also varied by citizenship status and years living in the United States. INTERPRETATION: NHIS data indicate that many adults remain unprotected against vaccine-preventable diseases. Coverage for the adult age-appropriate composite measures was low in all age groups. Individual adult vaccination coverage remained low as well, but modest gains occurred in vaccination coverage for hepatitis B (among adults aged ≥19 years and HCP aged ≥19 years), and HPV (among males aged 19–26 years and Hispanic females aged 19–26 years). Coverage for other vaccines and groups with Advisory Committee on Immunization Practices vaccination indications did not improve from 2017. Although HPV vaccination coverage among males aged 19–26 years and Hispanic females aged 19–26 years increased, approximately 50% of females aged 19–26 years and 70% of males aged 19–26 years remained unvaccinated. Racial/ethnic vaccination differences persisted for routinely recommended adult vaccines. Having health insurance coverage, having a usual place for health care, and having ≥1 physician contacts during the preceding 12 months were associated with higher vaccination coverage; however, these factors alone were not associated with optimal adult vaccination coverage, and findings indicate missed opportunities to vaccinate remained. PUBLIC HEALTH ACTIONS: Substantial improvement in adult vaccination uptake is needed to reduce the burden of vaccine-preventable diseases. Following the Standards for Adult Immunization Practice (https://www.cdc.gov/vaccines/hcp/adults/for-practice/standards/index.html), all providers should routinely assess adults’ vaccination status at every clinical encounter, strongly recommend appropriate vaccines, either offer needed vaccines or refer their patients to another provider who can administer the needed vaccines, and document vaccinations received by their patients in an immunization information system.

MMWR Surveill Summ2021       CORD-19
1469Severity of Disease Among Adults Hospitalized with Laboratory-Confirmed COVID-19 Before and During the Period of SARS-CoV-2 B.1.617.2 (Delta) Predominance-COVID-NET, 14 States, January-August 2021  

In mid-June 2021, B.1.671.2 (Delta) became the predominant variant of SARS-CoV-2, the virus that causes COVID-19, circulating in the United States. As of July 2021, the Delta variant was responsible for nearly all new SARS-CoV-2 infections in the United States.* The Delta variant is more transmissible than previously circulating SARS-CoV-2 variants (1); however, whether it causes more severe disease in adults has been uncertain. Data from the CDC COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), a population-based surveillance system for COVID-19-associated hospitalizations, were used to examine trends in severe outcomes in adults aged ≥18 years hospitalized with laboratory-confirmed COVID-19 during periods before (January-June 2021) and during (July-August 2021) Delta variant predominance. COVID-19-associated hospitalization rates among all adults declined during January-June 2021 (pre-Delta period), before increasing during July-August 2021 (Delta period). Among sampled nonpregnant hospitalized COVID-19 patients with completed medical record abstraction and a discharge disposition during the pre-Delta period, the proportion of patients who were admitted to an intensive care unit (ICU), received invasive mechanical ventilation (IMV), or died while hospitalized did not significantly change from the pre-Delta period to the Delta period. The proportion of hospitalized COVID-19 patients who were aged 18-49 years significantly increased, from 24.7% (95% confidence interval [CI] = 23.2%-26.3%) of all hospitalizations in the pre-Delta period, to 35.8% (95% CI = 32.1%-39.5%, p<0.01) during the Delta period. When examined by vaccination status, 71.8% of COVID-19-associated hospitalizations in the Delta period were in unvaccinated adults. Adults aged 18-49 years accounted for 43.6% (95% CI = 39.1%-48.2%) of all hospitalizations among unvaccinated adults during the Delta period. No difference was observed in ICU admission, receipt of IMV, or in-hospital death among nonpregnant hospitalized adults between the pre-Delta and Delta periods. However, the proportion of unvaccinated adults aged 18-49 years hospitalized with COVID-19 has increased as the Delta variant has become more predominant. Lower vaccination coverage in this age group likely contributed to the increase in hospitalized patients during the Delta period. COVID-19 vaccination is critical for all eligible adults, including those aged <50 years who have relatively low vaccination rates compared with older adults.

MMWR Morb Mortal Wkly Rep2021       LitCov and CORD-19
1470COVID-19 Vaccine Safety in Adolescents Aged 12-17 Years-United States, December 14, 2020-July 16, 2021  

As of July 30, 2021, among the three COVID-19 vaccines authorized for use in the United States, only the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine is authorized for adolescents aged 12-17 years. The Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for Pfizer-BioNTech vaccine for use in persons aged ≥16 years on December 11, 2020 (1); the EUA was expanded to include adolescents aged 12-15 years on May 10, 2021 (2), based on results from a Phase 3 clinical trial (3). Beginning in June 2021, cases of myocarditis and myopericarditis (hereafter, myocarditis) after receipt of Pfizer-BioNTech vaccine began to be reported, primarily among young males after receipt of the second dose (4,5). On June 23, 2021, CDC's Advisory Committee on Immunization Practices (ACIP) reviewed available data and concluded that the benefits of COVID-19 vaccination to individual persons and the population outweigh the risks for myocarditis and recommended continued use of the vaccine in persons aged ≥12 years (6). To further characterize safety of the vaccine, adverse events after receipt of Pfizer-BioNTech vaccine reported to the Vaccine Adverse Event Reporting System (VAERS) and adverse events and health impact assessments reported in v-safe (a smartphone-based safety surveillance system) were reviewed for U.S. adolescents aged 12-17 years during December 14, 2020-July 16, 2021. As of July 16, 2021, approximately 8.9 million U.S. adolescents aged 12-17 years had received Pfizer-BioNTech vaccine.* VAERS received 9,246 reports after Pfizer-BioNTech vaccination in this age group; 90.7% of these were for nonserious adverse events and 9.3% were for serious adverse events, including myocarditis (4.3%). Approximately 129,000 U.S. adolescents aged 12-17 years enrolled in v-safe after Pfizer-BioNTech vaccination; they reported local (63.4%) and systemic (48.9%) reactions with a frequency similar to that reported in preauthorization clinical trials. Systemic reactions were more common after dose 2. CDC and FDA continue to monitor vaccine safety and provide data to ACIP to guide COVID-19 vaccine recommendations.

MMWR Morb Mortal Wkly Rep2021       LitCov and CORD-19
1471SARS-CoV-2 infection in children, clinical characteristics, diagnostic findings and therapeutic interventions at a tertiary care center in Riyadh, Saudi Arabia  

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 was first identified in Wuhan, China. All ages are susceptible to SARS-CoV-2 infection. Few studies had reported milder course in children however, severe course of illness has been reported. We aimed to describe the clinical features of COVID-19 in pediatric patients including diagnostic findings and therapeutic interventions in sever disease manifestation. METHODS: We retrospectively reviewed 742 patients with SARS-CoV-2 proven infection at King Abdullah Specialist Children’s Hospital, from April 2020 and July 2020. Inpatients, outpatient, including those with sever manifestation treated at the Intensive Care Unit (ICU) were included. We collected data including demographic data, comorbidities, symptoms, imaging data, laboratory findings, treatments and clinical outcomes of patients with COVID-19. RESULTS: Among of 742 patients, 71 (9.6%) were hospitalized. The median age of patients was 75 months old and 53.6 were male. A total of 461 (62.1%) had close contact with confirmed cases, 45 (6.1%) had no contact history, and 236 (31.8%) with unknown exposure risk. The most common symptoms at the onset of illness were fever (32.5%), respiratory symptoms (21%) and gastrointestinal symptoms (10.3%). Among the entire cohort, 7 patients were admitted to PICU with COVID-19 related symptoms, five patients diagnosed with MIS-C, one patient with Kawasaki, and one patient with pneumonia. All patients received supportive therapy, no antiviral treatment had been used however, in MIS-C patients IVIG had been given to all patients, five patients received Anakinra; and one patient received tocilizumab. CONCLUSIONS: In this study, children infected with SARS-CoV-2 are less likely to develop symptomatic or serious diseases. Among symptomatic children, the most common clinical features were fever and respiratory symptoms followed by gastrointestinal manifestations. The majority of infected children have reported contact with an infected individual. MIS-C associated with COVID-19 is a severe presentation of SARS-CoV-2 infection and of a major concern as an overlapping features with other diseases could happen, making the diagnosis challenging.

J Infect Public Health2021       LitCov and CORD-19
1472Strange Days: Adult Physical Activity and Mental Health in the First Two Months of the COVID-19 Pandemic  

Background: In addition to its physical health benefits, physical activity is increasingly recognized as a means to support mental health. Regular moderate-to-vigorous physical activity (MVPA) is associated with improved mental well-being, reduced likelihood of developing mental illness, and improved symptom management. Despite these benefits, most people fail to achieve minimum recommended levels of MVPA. Population levels of physical activity have further declined since the onset of the COVID-19 pandemic and implementation of public health measures (e.g., shelter-in-place protocols). The potential impact of this decline on mental heath outcomes warrants ongoing investigation. Purpose: To investigate associations between changes in MVPA and mental health (depressive symptoms, anxiety symptoms, and life satisfaction) in adults impacted by the COVID-19 pandemic. Method: Research followed a cross-sectional design. English-speaking adults were invited to complete an online questionnaire. MVPA was assessed retrospectively (before COVID-19) and currently (during COVID-19) with the International Physical Activity Questionnaire. Mental health was assessed with the Patient Health Questionnaire, 9-Item (PHQ-9), the Generalized Anxiety Disorder, 7-Item (GAD-7), and the Satisfaction with Life Scale (SWLS). Regression was used to assess relationships between MVPA and mental health. ANOVA with follow-up tests examined whether participants who differed in mental health status (e.g., no symptoms vs. severe symptoms) differed in their change in MVPA. T-tests were used to examine differences in mental health symptomatology between participants who were sufficiently (i.e., achieving MVPA guidelines of ≥ 150 min/week) vs. insufficiently active. Results: Prior to COVID-19, 68.2% of participants were classified as being sufficiently active, vs. 60.6% during COVID-19. The majority of participants reported experiencing some level of depressive symptoms (62.0%) or anxiety symptoms (53.7%). After controlling for covariates, changes in MVPA accounted for significant variability in the PHQ-9 (7.7%), GAD-7 (2.5%), and SWLS (1.5 %). Participants with clinically significant mental health symptomatology reported greater declines in MVPA than those who reported no symptoms. Conversely, participants who were sufficiently active during COVID-19 reported significantly lower depression and anxiety, and higher life satisfaction. Conclusion: Participants who experienced the greatest declines in MVPA reported relatively greater psychological distress and lower life satisfaction. While preliminary, these findings suggest the importance of maintaining and promoting physical activity during a period of pandemic.

Front Public Health2021       LitCov and CORD-19
1473Mortality and critical care unit admission associated with the SARS-CoV-2 lineage B.1.1.7 in England: an observational cohort study  

BACKGROUND: A more transmissible variant of SARS-CoV-2, the variant of concern 202012/01 or lineage B.1.1.7, has emerged in the UK. We aimed to estimate the risk of critical care admission, mortality in patients who are critically ill, and overall mortality associated with lineage B.1.1.7 compared with non-B.1.1.7. We also compared clinical outcomes between these two groups. METHODS: For this observational cohort study, we linked large primary care (QResearch), national critical care (Intensive Care National Audit & Research Centre Case Mix Programme), and national COVID-19 testing (Public Health England) databases. We used SARS-CoV-2 positive samples with S-gene molecular diagnostic assay failure (SGTF) as a proxy for the presence of lineage B.1.1.7. We extracted two cohorts from the data: the primary care cohort, comprising patients in primary care with a positive community COVID-19 test reported between Nov 1, 2020, and Jan 26, 2021, and known SGTF status; and the critical care cohort, comprising patients admitted for critical care with a positive community COVID-19 test reported between Nov 1, 2020, and Jan 27, 2021, and known SGTF status. We explored the associations between SARS-CoV-2 infection with and without lineage B.1.1.7 and admission to a critical care unit (CCU), 28-day mortality, and 28-day mortality following CCU admission. We used Royston-Parmar models adjusted for age, sex, geographical region, other sociodemographic factors (deprivation index, ethnicity, household housing category, and smoking status for the primary care cohort; and ethnicity, body-mass index, deprivation index, and dependency before admission to acute hospital for the CCU cohort), and comorbidities (asthma, chronic obstructive pulmonary disease, type 1 and 2 diabetes, and hypertension for the primary care cohort; and cardiovascular disease, respiratory disease, metastatic disease, and immunocompromised conditions for the CCU cohort). We reported information on types and duration of organ support for the B.1.1.7 and non-B.1.1.7 groups. FINDINGS: The primary care cohort included 198 420 patients with SARS-CoV-2 infection. Of these, 117 926 (59·4%) had lineage B.1.1.7, 836 (0·4%) were admitted to CCU, and 899 (0·4%) died within 28 days. The critical care cohort included 4272 patients admitted to CCU. Of these, 2685 (62·8%) had lineage B.1.1.7 and 662 (15·5%) died at the end of critical care. In the primary care cohort, we estimated adjusted hazard ratios (HRs) of 2·15 (95% CI 1·75–2·65) for CCU admission and 1·65 (1·36–2·01) for 28-day mortality for patients with lineage B.1.1.7 compared with the non-B.1.1.7 group. The adjusted HR for mortality in critical care, estimated with the critical care cohort, was 0·91 (0·76–1·09) for patients with lineage B.1.1.7 compared with those with non-B.1.1.7 infection. INTERPRETATION: Patients with lineage B.1.1.7 were at increased risk of CCU admission and 28-day mortality compared with patients with non-B.1.1.7 SARS-CoV-2. For patients receiving critical care, mortality appeared to be independent of virus strain. Our findings emphasise the importance of measures to control exposure to and infection with COVID-19. FUNDING: Wellcome Trust, National Institute for Health Research Oxford Biomedical Research Centre, and the Medical Sciences Division of the University of Oxford.

Lancet Infect Dis2021       LitCov and CORD-19
1474Impact of the COVID-19 Pandemic on the Health Status and Behaviors of Adults in Korea: National Cross-sectional Web-Based Self-report Survey  

BACKGROUND: The COVID-19 pandemic has radically shifted living practices, thereby influencing changes in the health status and behaviors of every person. OBJECTIVE: The aim of this study was to investigate the impact of COVID-19 on the self-reported health status and health behaviors along with any associated factors in adults in the Republic of Korea wherein no stringent lockdown measures were implemented during the pandemic. METHODS: We conducted a web-based self-reported survey from November 2020 to December 2020. The study participants (N=2097) were identified through quota sampling by age, sex, and geographical regions among residents aged 19 years or older in Korea. The survey collected information on basic demographics, changes in self-reported health status, and health behaviors during the COVID-19 pandemic. Self-reported health status and health behaviors were categorized into 3 groups: unchanged, improved, or worsened. A chi-square test and logistic regression analyses were conducted. RESULTS: With regard to changes in the self-reported health status, the majority (1478/2097, 70.5%) of the participants reported that their health was unchanged, while 20% (420/2097) of the participants reported having worser health after the COVID-19 outbreak. With regard to changes in health behaviors, the proportion of participants who increased tobacco consumption was similar to that of those who decreased tobacco consumption (110/545, 20.2% vs 106/545, 19.5%, respectively), while the proportion of those who decreased their drinking frequency was more than twice as many as those who increased their drinking frequency (578/1603, 36.1% vs 270/1603, 16.8%, respectively). Further, those who decreased their exercising frequency were more than those who increased their exercising frequency (333/823, 15.9% vs 211/823, 10%, respectively). The factor that had the greatest influence on lifestyle was age. In the subgroup analysis, the group aged 20-29 years had the highest number of individuals with both a worsened (100/377, 26.5%) and an improved (218/377, 15.7%) health status. Further, individuals aged 20-29 years had greater odds of increased smoking (6.44, 95% CI 2.15-19.32), increased alcohol use (4.64, 95% CI 2.60-8.28), and decreased moderate or higher intensity aerobic exercise (3.39, 95% CI 1.82-6.33) compared to individuals aged 60 years and older. Younger adults showed deteriorated health behaviors, while older adults showed improved health behaviors. CONCLUSIONS: The health status and the behavior of the majority of the Koreans were not found to be heavily affected by the COVID-19 outbreak. However, in some cases, changes in health status or health behavior were identified. This study highlighted that some groups were overwhelmingly affected by COVID-19 compared to others. Certain groups reported experiencing both worsening and improving health, while other groups reported unchanged health status. Age was the most influential factor for behavior change; in particular, the younger generation’s negative health behaviors need more attention in terms of public health. As COVID-19 prolongs, public health interventions for vulnerable groups may be needed.

JMIR Public Health Surveill2021       LitCov and CORD-19
1475Persistence of immunity against Omicron BA.1 and BA.2 variants following homologous and heterologous COVID-19 booster vaccines in healthy adults after a two-dose AZD1222 vaccination  

N/A

Int J Infect Dis2022       LitCov
1476Depression, anxiety and stress symptoms in Brazilian university students during the COVID-19 pandemic: Predictors and association with life satisfaction, psychological well-being and coping strategies  

BACKGROUND: The COVID-19 pandemic raises concerns about the mental health of the world population. Protection measures to prevention the disease impacted education and undergraduate students were exposed to additional stressors. OBJECTIVES: Analyze depression, anxiety and stress symptoms in undergraduates, their respective predictors and the association with satisfaction with life, psychological well-being and coping strategies. METHODS: An online cross-sectional study was conducted from September 14 to October 19, 2020, involving undergraduate students enrolled in 33 courses from 5 public university campuses in the state of Parana, Brazil, using: questionnaire with sociodemographic, academic, health and pandemic effects variables; Depression, Anxiety and Stress Scale-21 (DASS-21); Satisfaction with Life Scale (SWLS); Psychological Well-Being (PWB); BriefCOPE. The convenience sample was composed of 1,224 participants, with 18 years old or older, that completed all research instruments. Spearman correlation and logistic analysis (univariate and multivariate) were applied to the collected data. RESULTS: Most of the undergraduates presented symptoms of depression (60.5%), anxiety (52.5%) and stress (57.5%). Depression, anxiety and stress presented significant correlations in common: negative with satisfaction with life, all dimensions of psychological well-being, and 3 adaptive copings (active coping, planning, positive reframing); positive with 5 maladaptive copings (behavioral disengagement, denial, self-blame, self-distraction, substance use). In addition, there were 7 common predictors for symptoms of depression, anxiety and stress: female; age 18–24 years old; having a chronic disease; lower scores in 2 dimensions of psychological well-being (positive relations with others, self-acceptance); higher scores in 2 maladaptive copings (self-blame, substance use). CONCLUSIONS: The data indicate a high prevalence of symptoms of depression, anxiety and stress, and suggest that higher scores of satisfaction with life, psychological well-being dimensions and adaptive copings may present protective effects in undergraduates during a pandemic crisis.

PLoS One2021       LitCov and CORD-19
1477Loneliness during a strict lockdown: Trajectories and predictors during the COVID-19 pandemic in 38,217 United Kingdom adults  

RATIONALE: There are increasing worries that lockdowns and ‘stay-at-home’ orders due to the COVID-19 pandemic could lead to a rise in loneliness, which is recognised as a major public health concern. But profiles of loneliness during the pandemic and risk factors remain unclear. OBJECTIVE: The current study aimed to examine if and how loneliness levels changed during the strict lockdown and to explore the clustering of loneliness growth trajectories. METHODS: Data from 38,217 UK adults in the UCL COVID -19 Social Study (a panel study collecting data weekly during the pandemic) were analysed during the strict lockdown period in the UK (23/03/2020–10/05/2020). The sample was well-stratified and weighted to population proportions of gender, age, ethnicity, education and geographical location. Growth mixture modelling was used to identify the latent classes of loneliness growth trajectories and their predictors. RESULTS: Analyses revealed four classes, with the baseline loneliness level ranging from low to high. In the first a few weeks of lockdown, loneliness levels increased in the highest loneliness group, decreased in the lowest loneliness group, and stayed relatively constant in the middle two groups. Younger adults (OR = 2.17–6.81), women (OR = 1.59), people with low income (OR = 1.3), the economically inactive (OR = 1.3–2.04) and people with mental health conditions (OR = 5.32) were more likely to be in highest loneliness class relative to the lowest. Further, living with others or in a rural area, and having more close friends or greater social support were protective. CONCLUSIONS: Perceived levels of loneliness under strict lockdown measures due to COVID-19 were relatively stable in the UK, but for many people these levels were high with no signs of improvement. Results suggest that more efforts are needed to address loneliness.

Soc Sci Med2020       LitCov and CORD-19
1478An evolutionary insight into SARS-CoV-2 Omicron variant of concern  

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel virus that belongs to the family Coronaviridae. This virus produces a respiratory illness known as coronavirus disease 2019 (COVID-19) and is to blame for the pandemic of COVID-19. Due to its massive circulation around the world and the capacity of mutation of this virus, genomic studies are much needed in to order to reveal new variants of concern (VOCs). On November 26th, 2021, the WHO announced that a new SARS-CoV-2 VOC, named Omicron, had emerged. In order to get insight into the emergence, spread and evolution of Omicron SARS-CoV-2 variants, a comprehensive phylogenetic study was performed. The results of these studies revealed significant differences in codon usage among the S genes of SARS-CoV-2 VOCs Alfa, Beta, Gamma, Delta and Omicron, which can be linked to SARS-CoV-2 genotypes. Omicron variant did not evolve out of one of the early VOCs, but instead it belongs to a complete different genetic lineage from previous ones. Strains classified as Omicron variants evolved from ancestors that existed around May 15th, 2020, suggesting that this VOC may have been circulating undetected for a period of time until its emergence was observed in South Africa. A rate of evolution of 5.61 × 10(−4) substitutions/site/year was found for Omicron strains enrolled in these analyses. The results of these studies demonstrate that S genes have suitable genetic information for clear assignment of emerging VOCs to its specific genotypes.

Virus Res2022       LitCov and CORD-19
1479From chaos to control-experiences of healthcare workers during the early phase of the COVID-19 pandemic: a focus group study  

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic has caused overwhelming challenges to healthcare systems worldwide. Healthcare workers (HCWs) have faced particular challenges: being exposed to the coronavirus SARS-CoV-2 and caring for patients having a new and potentially life-threatening disease. The aim of this study was to explore how HCWs in the Swedish healthcare system perceived their work situation during the first phase of the COVID-19 pandemic in 2020. METHODS: Focus group discussions and interviews with HCWs were performed from June to October 2020 in one Swedish healthcare region. A purposeful sampling approach was used to select a variety of professions (physicians, nurses, nurse aides and cleaners) and workplaces (hospital inpatient wards, emergency department, nursing home and home care service). Qualitative content analysis was used for data analysis. RESULTS: In total, 51 HCWs participated in eight focus group discussions and one HCW participated in an individual interview. The content analysis identified two main categories: ‘Concerns about the risk of infection and transmission of infection to others’, and ‘Transition from chaos to managing in a new and challenging work situation’. The findings revealed how HCWs perceived working conditions, including experiences of fear for personal health, confusion and uncertainty regarding personal protective equipment and infection prevention and control (PPE/IPC), and fear of infecting others. Both fearful and appreciating attitudes were achieved from the surrounding community. Helpful strategies for transition from chaos to control were lifted i.e. present and supportive leadership, and finding comfort and strength in the working team. Both helplessness and meaningfulness were described when caring for COVID-19 patients. CONCLUSIONS: This study provides unique insights into HCWs experiences of an extremely challenging work situation during the first phase of the COVID-19 pandemic, including feelings of stress and insecurity in a chaotic and hazardous working environment. But there is also mitigation of these challenges and even positive experiences including feelings of safety and meaningfulness. To enhance safety among HCWs in healthcare crises such as the COVID-19 pandemic, the findings highlight the importance of avoiding confusion about PPE/IPC, having a supportive healthcare leadership and ensuring accurate information provision about virus transmission to the public. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12913-021-07248-9.

BMC Health Serv Res2021       LitCov and CORD-19
1480Effectiveness of a third dose of the BNT162b2 mRNA COVID-19 vaccine for preventing severe outcomes in Israel: an observational study  

BACKGROUND: Many countries are experiencing a resurgence of COVID-19, driven predominantly by the delta (B.1.617.2) variant of SARS-CoV-2. In response, these countries are considering the administration of a third dose of mRNA COVID-19 vaccine as a booster dose to address potential waning immunity over time and reduced effectiveness against the delta variant. We aimed to use the data repositories of Israel's largest health-care organisation to evaluate the effectiveness of a third dose of the BNT162b2 mRNA vaccine for preventing severe COVID-19 outcomes. METHODS: Using data from Clalit Health Services, which provides mandatory health-care coverage for over half of the Israeli population, individuals receiving a third vaccine dose between July 30, 2020, and Sept 23, 2021, were matched (1:1) to demographically and clinically similar controls who did not receive a third dose. Eligible participants had received the second vaccine dose at least 5 months before the recruitment date, had no previous documented SARS-CoV-2 infection, and had no contact with the health-care system in the 3 days before recruitment. Individuals who are health-care workers, live in long-term care facilities, or are medically confined to their homes were excluded. Primary outcomes were COVID-19-related admission to hospital, severe disease, and COVID-19-related death. The third dose effectiveness for each outcome was estimated as 1 – risk ratio using the Kaplan-Meier estimator. FINDINGS: 1 158 269 individuals were eligible to be included in the third dose group. Following matching, the third dose and control groups each included 728 321 individuals. Participants had a median age of 52 years (IQR 37–68) and 51% were female. The median follow-up time was 13 days (IQR 6–21) in both groups. Vaccine effectiveness evaluated at least 7 days after receipt of the third dose, compared with receiving only two doses at least 5 months ago, was estimated to be 93% (231 events for two doses vs 29 events for three doses; 95% CI 88–97) for admission to hospital, 92% (157 vs 17 events; 82–97) for severe disease, and 81% (44 vs seven events; 59–97) for COVID-19-related death. INTERPRETATION: Our findings suggest that a third dose of the BNT162b2 mRNA vaccine is effective in protecting individuals against severe COVID-19-related outcomes, compared with receiving only two doses at least 5 months ago. FUNDING: The Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.

Lancet2021       LitCov and CORD-19
1481Cellular and humoral immune responses and breakthrough infections after three SARS-CoV-2 mRNA vaccine doses  

N/A

Front Immunol2022       LitCov
1482Previous psychopathology predicted severe COVID-19 concern, anxiety and PTSD symptoms in pregnant women during "lockdown" in Italy  

Italy was the first COVID-19 pandemic epicenter among European countries and established a period of full “lockdown”, consisting of travel bans, mandatory staying at home, and temporary closure of nonessential businesses. Similar measures are known risk factors for psychological disturbances in the general population; still, little is known about their impact on pregnant women’s mental health during COVID-19 pandemic. The cross-sectional, web-based, national survey “COVID-19 related Anxiety and StreSs in prEgnancy, poSt-partum and breaStfeeding” (COVID-ASSESS) was conducted during the first month of full “lockdown” in Italy. Participants were recruited via social networks with a snowball technique. The questionnaire was specifically developed to examine COVID-19 concerns and included the psychometric tests National Stressful Events Survey (NSESSS) for posttraumatic stress disorder (PTSD) and State-Trait Anxiety Inventory. A multivariable logistic regression model was fitted to explore the association of the concern, anxiety and PTSD symptoms with age, gestational weeks, parity, days of “lockdown”, assisted reproductive technology use, psychopathological history, and previous perinatal losses. Out of 1015 pregnant women reached, 737 (72.6%) fully answered the questionnaire; no woman reported a COVID-19 infection. Median age was 34.4 years [quartiles 31.7, 37.2], median days in “lockdown” were 13.1 [11.0, 17.0], median gestational weeks were 27.8 [19.8, 34.0]. Clinically significant PTSD symptoms were present in 75 women (10.2%, NSESSS cutoff 24) and clinically significant anxiety symptoms were present in 160 women (21.7%, STAI-Y1 cutoff 50). Women were particularly worried about the health of their baby and of their elderly relatives, as well as of the possible impact of pandemic in the future of society. Previous anxiety predicted higher concern and PTSD symptoms; previous depression and anxiety were independently associated with current PTSD symptoms.

Arch Womens Ment Health2020       LitCov and CORD-19
1483Knowledge, attitudes and perceptions of COVID-19 vaccine and refusal to receive COVID-19 vaccine among healthcare workers in northeastern Ethiopia  

BACKGROUND: Major efforts are being made to control the spread and impacts of the coronavirus pandemic using vaccines. Ethiopia began on March 13, 2021, to vaccinate healthcare workers (HCWs) for COVID-19 with the AstraZeneca vaccine. However, willingness to be vaccinated depends to a large extent on factors beyond the availability of vaccines. This study aimed to determine the rate of intention to refuse COVID-19 vaccination and associated factors among HCWs in northeastern Ethiopia. northeastern, Ethiopia. METHOD: An institution-based cross-sectional study was employed among 404 HCWs in Dessie City, northeastern Ethiopia in May, 2021. Data were collected, checked, coded, entered into EpiData Version 4.6 and exported to Statistical Package of Social Sciences (SPSS) Version 25.0 for cleaning and analysis. The dependent variable was refuse to receive COVID-19 vaccination and the independent variables included socio-demographic factors, knowledge, attitudes and perceptions. A Binary logistic regression model was used to determine the association between vaccine refusal and the independent variables. From bivariate analysis, variables with p-values < 0.25 were retained for multivariable analysis. From multivariable analysis, variables with adjusted odds ratio (AOR), p-values <0.05 at 95% confidence interval (CI) were declared as factors significantly associated with refusal to be vaccinated among HCWs in Dessie City, northeastern Ethiopia. RESULTS: The proportion of HCWs with overall good knowledge, good perception, and positive attitudes about COVID-19 vaccination were 62.5%, 60.5%, and 52.3%, respectively; 64.0% of the HCWs wanted to be vaccinated while 36.0% said that they would refuse to do so. Multivariable analysis identified negative attitudes (AOR: 3.057; 95%CI [1.860 - 5.026]) and poor perceptions (AOR: 4.73; 95%CI [2.911 - 7.684]) about COVID-19 vaccines were significantly associated with refusal to be vaccinated for COVID-19. Nearly half (46.9%) of the HCWs stated that vaccines could worsen any pre-existing medical conditions and 39.5% of them thought that vaccines could cause COVID-19 infections. CONCLUSION: The willingness of HCWs to get vaccinated against COVID-19 was relatively high among HCWs. Negative attitudes and poor perceptions towards the anticipated COVID-19 vaccination were significant factors to refuse to be vaccinated. Our findings may provide information for the management authorities and stakeholders to promote and improve attitudes, knowledge and perceptions towards COVID-19 vaccination uptake among HCWs.

BMC Public Health2022       LitCov and CORD-19
1484Telehealth transformation: COVID-19 and the rise of virtual care  

The novel coronavirus disease-19 (COVID-19) pandemic has altered our economy, society and healthcare system. While this crisis has presented the US healthcare delivery system with unprecedented challenges, the pandemic has catalyzed rapid adoption of telehealth or the entire spectrum of activities used to deliver care at a distance. Using examples reported by US healthcare organizations including ours, we describe the role telehealth has played in transforming healthcare delivery during the three phases of the US COVID-19 pandemic: 1) Stay-at-Home Outpatient Care; 2) Initial COVID-19 Hospital Surge, and 3) Post-Pandemic Recovery. Within each of these three phases, we examine how people, process and technology work together to support a successful telehealth transformation. Whether healthcare enterprises are ready or not, the new reality is that virtual care has arrived.

J Am Med Inform Assoc2020       LitCov and CORD-19
1485Epidemiology, clinical profile, management and outcome of COVID-19-associated rhino-orbital-cerebral mucormycosis in 2826 patients in India-Collaborative OPAI-IJO Study on Mucormycosis in COVID-19 (COSMIC), Report 1  

PURPOSE: COVID-19-associated rhino-orbital-cerebral mucormycosis (ROCM) has reached epidemic proportion during India’s second wave of COVID-19 pandemic, with several risk factors being implicated in its pathogenesis. This study aimed to determine the patient demographics, risk factors including comorbidities, and medications used to treat COVID-19, presenting symptoms and signs, and the outcome of management. METHODS: This was a retrospective, observational study of patients with COVID-19-associated ROCM managed or co-managed by ophthalmologists in India from January 1, 2020 to May 26, 2021. RESULTS: Of the 2826 patients, the states of Gujarat (22%) and Maharashtra (21%) reported the highest number of ROCM. The mean age of patients was 51.9 years with a male preponderance (71%). While 57% of the patients needed oxygen support for COVID-19 infection, 87% of the patients were treated with corticosteroids, (21% for > 10 days). Diabetes mellitus (DM) was present in 78% of all patients. Most of the cases showed onset of symptoms of ROCM between day 10 and day 15 from the diagnosis of COVID-19, 56% developed within 14 days after COVID-19 diagnosis, while 44% had delayed onset beyond 14 days. Orbit was involved in 72% of patients, with stage 3c forming the bulk (27%). Overall treatment included intravenous amphotericin B in 73%, functional endoscopic sinus surgery (FESS)/paranasal sinus (PNS) debridement in 56%, orbital exenteration in 15%, and both FESS/PNS debridement and orbital exenteration in 17%. Intraorbital injection of amphotericin B was administered in 22%. At final follow-up, mortality was 14%. Disease stage >3b had poorer prognosis. Paranasal sinus debridement and orbital exenteration reduced the mortality rate from 52% to 39% in patients with stage 4 disease with intracranial extension (p < 0.05). CONCLUSION: Corticosteroids and DM are the most important predisposing factors in the development of COVID-19-associated ROCM. COVID-19 patients must be followed up beyond recovery. Awareness of red flag symptoms and signs, high index of clinical suspicion, prompt diagnosis, and early initiation of treatment with amphotericin B, aggressive surgical debridement of the PNS, and orbital exenteration, where indicated, are essential for successful outcome.

Indian J Ophthalmol2021       LitCov and CORD-19
1486Has Omicron Changed the Evolution of the Pandemic?  

BACKGROUND: Variants of the SARS-CoV-2 virus carry differential risks to public health. The Omicron (B.1.1.529) variant, first identified in Botswana on November 11, 2021, has spread globally faster than any previous variant of concern. Understanding the transmissibility of Omicron is vital in the development of public health policy. OBJECTIVE: The aim of this study is to compare SARS-CoV-2 outbreaks driven by Omicron to those driven by prior variants of concern in terms of both the speed and magnitude of an outbreak. METHODS: We analyzed trends in outbreaks by variant of concern with validated surveillance metrics in several southern African countries. The region offers an ideal setting for a natural experiment given that most outbreaks thus far have been driven primarily by a single variant at a time. With a daily longitudinal data set of new infections, total vaccinations, and cumulative infections in countries in sub-Saharan Africa, we estimated how the emergence of Omicron has altered the trajectory of SARS-CoV-2 outbreaks. We used the Arellano-Bond method to estimate regression coefficients from a dynamic panel model, in which new infections are a function of infections yesterday and last week. We controlled for vaccinations and prior infections in the population. To test whether Omicron has changed the average trajectory of a SARS-CoV-2 outbreak, we included an interaction between an indicator variable for the emergence of Omicron and lagged infections. RESULTS: The observed Omicron outbreaks in this study reach the outbreak threshold within 5-10 days after first detection, whereas other variants of concern have taken at least 14 days and up to as many as 35 days. The Omicron outbreaks also reach peak rates of new cases that are roughly 1.5-2 times those of prior variants of concern. Dynamic panel regression estimates confirm Omicron has created a statistically significant shift in viral spread. CONCLUSIONS: The transmissibility of Omicron is markedly higher than prior variants of concern. At the population level, the Omicron outbreaks occurred more quickly and with larger magnitude, despite substantial increases in vaccinations and prior infections, which should have otherwise reduced susceptibility to new infections. Unless public health policies are substantially altered, Omicron outbreaks in other countries are likely to occur with little warning.

JMIR Public Health Surveill2022       LitCov and CORD-19
1487Development and clinical application of a rapid IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosis  

The outbreak of the novel coronavirus disease (COVID‐19) quickly spread all over China and to more than 20 other countries. Although the virus (severe acute respiratory syndrome coronavirus [SARS‐Cov‐2]) nucleic acid real‐time polymerase chain reaction (PCR) test has become the standard method for diagnosis of SARS‐CoV‐2 infection, these real‐time PCR test kits have many limitations. In addition, high false‐negative rates were reported. There is an urgent need for an accurate and rapid test method to quickly identify a large number of infected patients and asymptomatic carriers to prevent virus transmission and assure timely treatment of patients. We have developed a rapid and simple point‐of‐care lateral flow immunoassay that can detect immunoglobulin M (IgM) and IgG antibodies simultaneously against SARS‐CoV‐2 virus in human blood within 15 minutes which can detect patients at different infection stages. With this test kit, we carried out clinical studies to validate its clinical efficacy uses. The clinical detection sensitivity and specificity of this test were measured using blood samples collected from 397 PCR confirmed COVID‐19 patients and 128 negative patients at eight different clinical sites. The overall testing sensitivity was 88.66% and specificity was 90.63%. In addition, we evaluated clinical diagnosis results obtained from different types of venous and fingerstick blood samples. The results indicated great detection consistency among samples from fingerstick blood, serum and plasma of venous blood. The IgM‐IgG combined assay has better utility and sensitivity compared with a single IgM or IgG test. It can be used for the rapid screening of SARS‐CoV‐2 carriers, symptomatic or asymptomatic, in hospitals, clinics, and test laboratories.

J Med Virol2020       LitCov and CORD-19
1488An Observational Laboratory-Based Assessment of SARS-CoV-2 Molecular Diagnostics in Benin, Western Africa  

Information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread in Africa is limited by insufficient diagnostic capacity. Here, we assessed the coronavirus disease (COVID-19)-related diagnostic workload during the onset of the pandemic in the central laboratory of Benin, Western Africa; characterized 12 SARS-CoV-2 genomes from returning travelers; and validated the Da An RT-PCR-based diagnostic kit that is widely used across Africa. We found a 15-fold increase in the monthly laboratory workload due to COVID-19, dealt with at the cost of routine activities. Genomic surveillance showed near-simultaneous introduction of distinct SARS-CoV-2 lineages termed A.4 and B.1, including the D614G spike protein variant potentially associated with higher transmissibility from travelers from six different European and African countries during March-April 2020. We decoded the target regions within the ORF1ab and N genes of the Da An dual-target kit by MinION-based amplicon sequencing. Despite relatively high similarity between SARS-CoV-2 and endemic human coronaviruses (HCoVs) within the ORF1ab target domain, no cross-detection of high-titered cell culture supernatants of HCoVs was observed, suggesting high analytical specificity. The Da An kit was highly sensitive, detecting 3.2 to 9.0 copies of target-specific in vitro transcripts/reaction. Although discrepant test results were observed in low-titered clinical samples, clinical sensitivity of the Da An kit was at least comparable to that of commercial kits from affluent settings. In sum, virologic diagnostics are achievable in a resource-limited setting, but unprecedented pressure resulting from COVID-19-related diagnostics requires rapid and sustainable support of national and supranational stakeholders addressing limited laboratory capacity. IMPORTANCE Months after the start of the COVID-19 pandemic, case numbers from Africa are surprisingly low, potentially because the number of SARS-CoV-2 tests performed in Africa is lower than in other regions. Here, we show an overload of COVID-19-related diagnostics in the central laboratory of Benin, Western Africa, with a stagnating average number of positive samples irrespective of daily sample counts. SARS-CoV-2 genomic surveillance confirmed a high genomic diversity in Benin introduced by travelers returning from Europe and other African countries, including early circulation of the D614G spike mutation associated with potentially higher transmissibility. We validated a widely used RT-PCR kit donated by the Chinese Jack Ma Foundation and confirmed high analytical specificity and clinical sensitivity equivalent to tests used in affluent settings. Our assessment shows that although achievable in an African setting, the burden from COVID-19-related diagnostics on national reference laboratories is very high.

mSphere2021       LitCov and CORD-19
1489Enoxaparin for primary thromboprophylaxis in ambulatory patients with coronavirus disease-2019 (the OVID study): a structured summary of a study protocol for a randomized controlled trial  

OBJECTIVES: The OVID study will demonstrate whether prophylactic-dose enoxaparin improves survival and reduces hospitalizations in symptomatic ambulatory patients aged 50 or older diagnosed with COVID-19, a novel viral disease characterized by severe systemic, pulmonary, and vessel inflammation and coagulation activation. TRIAL DESIGN: The OVID study is conducted as a multicentre open-label superiority randomised controlled trial. PARTICIPANTS: Inclusion Criteria 1. Signed patient informed consent after being fully informed about the study’s background. 2. Patients aged 50 years or older with a positive test for SARS-CoV2 in the past 5 days and eligible for ambulatory treatment. 3. Presence of respiratory symptoms (i.e. cough, sore throat, or shortness of breath) or body temperature >37.5° C. 4. Ability of the patient to travel to the study centre by private transportation, performed either by an accompanying person from the same household or by the patient themselves 5. Ability to comply with standard hygiene requirements at the time of in-hospital visit, including a face mask and hand disinfectant. 6. Ability to walk from car to study centre or reach it by wheelchair transport with the help of an accompanying person from the same household also complying with standard hygiene requirements. 7. Ability to self-administer prefilled enoxaparin injections after instructions received at the study centre or availability of a person living with the patient to administer enoxaparin. Exclusion Criteria 1. Any acute or chronic condition posing an indication for anticoagulant treatment, e.g. atrial fibrillation, prior venous thromboembolism (VTE), acute confirmed symptomatic VTE, acute coronary syndrome. 2. Anticoagulant thromboprophylaxis deemed necessary in view of the patient's history, comorbidity or predisposing strong risk factors for thrombosis: a. Any of the following events occurring in the prior 30 days: fracture of lower limb, hospitalization for heart failure, hip/knee replacement, major trauma, spinal cord injury, stroke, b. previous VTE, c. histologically confirmed malignancy, which was diagnosed or treated (surgery, chemotherapy, radiotherapy) in the past 6 months, or recurrent, or metastatic, or inoperable. 3. Any clinically relevant bleeding (defined as bleeding requiring hospitalization, transfusion, surgical intervention, invasive procedures, occurring in a critical anatomical site, or causing disability) within 30 days prior to randomization or sign of acute bleeding. 4. Intracerebral bleeding at any time in the past or signs/symptoms consistent with acute intracranial haemorrhage. 5. Haemoglobin <8 g/dL and platelet count <50 x 10(9) cells/L confirmed by recent laboratory test (<90 days). 6. Subjects with any known coagulopathy or bleeding diathesis, including known significant liver disease associated with coagulopathy. 7. Severe renal insufficiency (baseline creatinine clearance <30 mL/min calculated using the Cockcroft-Gault formula) confirmed by recent laboratory test (<90 days). 8. Contraindications to enoxaparin therapy, including prior heparin-induced thrombocytopenia and known hypersensitivity. 9. Current use of dual antiplatelet therapy. 10. Participation in other interventional studies over the past 30 days. 11. Non-compliance or inability to adhere to treatment or lack of a family environment or support system for home treatment. 12. Cognitive impairment and/or inability to understand information provided in the study information. Patient enrolment will take place at seven Swiss centres, including five university hospitals and two large cantonal hospitals. INTERVENTION AND COMPARATOR: Patients randomized to the intervention group will receive subcutaneous enoxaparin at the recommended dose of 4,000 IU anti-Xa activity (40 mg/0.4 ml) once daily for 14 days. Patients randomized to the comparator group will receive no anticoagulation. MAIN OUTCOMES: Primary outcome: a composite of any hospitalization or all-cause death occurring within 30 days of randomization. Secondary outcomes: (i) a composite of cardiovascular events, including deep vein thrombosis (including catheter-associated), pulmonary embolism, myocardial infarction/myocarditis, arterial ischemia including mesenteric and extremities, acute splanchnic vein thrombosis, or ischemic stroke within 14 days, 30 days, and 90 days of randomization; (ii) each component of the primary efficacy outcome, within 14 days, 30 days, and 90 days of randomization; (iii) net clinical benefit (accounting for the primary efficacy outcome, composite cardiovascular events, and major bleeding), within 14 days, 30 days, and 90 days of enrolment; (iv) primary efficacy outcome, within 14 days, and 90 days of enrolment; (v) disseminated intravascular coagulation (ISTH criteria, in-hospital diagnosis) within 14 days, 30 days, and 90 days of enrolment. RANDOMISATION: Patients will undergo block stratified randomization (by age: 50-70 vs. >70 years; and by study centre) with a randomization ratio of 1:1 with block sizes varying between 4 and 8. Randomization will be performed after the signature of the informed consent for participation and the verification of the eligibility criteria using the electronic data capture software (REDCAP, Vanderbilt University, v9.1.24). BLINDING (MASKING): In this open-label study, no blinding procedures will be used. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The sample size calculation is based on the parameters α = 0.05 (2-sided), power: 1−β = 0.8, event rate in experimental group, pexp = 0.09 and event rate in control group, pcon = 0.15. The resulting total sample size is 920. To account for potential dropouts, the total sample size was fixed to 1000 with 500 patients in the intervention group and 500 in the control group. TRIAL STATUS: Protocol version 1.0, 14 April 2020. Protocol version 3.0, 18 May 2020 Recruiting start date: June 2020. Last Patient Last Visit: March 2021. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04400799 First Posted: May 26, 2020 Last Update Posted: July 16, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Trials2020       LitCov and CORD-19
1490Dysregulated Interferon Response and Immune Hyperactivation in Severe COVID-19: Targeting STATs as a Novel Therapeutic Strategy  

N/A

Front Immunol2022       LitCov
1491Healthcare providers experience of working during the COVID-19 pandemic: A qualitative study  

BACKGROUND: The COVID-19 pandemic has had a far-reaching negative impact on healthcare systems worldwide and has placed healthcare providers under immense physiological and psychological pressures. OBJECTIVE: The aim of current study was to undertake an in-depth exploration of the experiences of health-care staff working during the COVID-19 crisis. METHODS: Using a thematic analysis approach, a qualitative study was conducted using semi-structured interviews with 97 health care professionals. Participants were health care professionals including pre-hospital emergency services (EMS), physicians, nurses, pharmacists, laboratory personnel, radiology technicians, hospital managers and managers in the ministry of health who work directly or indirectly with COVID-19 cases. RESULTS: Data analysis highlighted four main themes, namely: ‘Working in the pandemic era’, ‘Changes in personal life and enhanced negative affect’, ‘Gaining experience, normalization and adaptation to the pandemic’ and ‘Mental Health Considerations’ which indicated that mental ill deteriorations unfolded through a stage-wise process as the pandemic unfolded. CONCLUSIONS: Participants experienced a wide range of emotions and development during the unfolding of the pandemic. Providing mental health aid should thus be an essential part of services for healthcare providers during the pandemic. Based on our results the aid should be focused on the various stages and should be individual-centred. Such interventions are crucial to sustain workers in their ability to cope throughout the duration of the pandemic.

Am J Infect Control2020       LitCov and CORD-19
1492Risk factors for severe illness in hospitalized Covid-19 patients at a regional hospital  

BACKGROUND: The Covid-19 pandemic threatens to overwhelm scarce clinical resources. Risk factors for severe illness must be identified to make efficient resource allocations. OBJECTIVE: To evaluate risk factors for severe illness. DESIGN: Retrospective, observational case series. SETTING: Single-institution. PARTICIPANTS: First 117 consecutive patients hospitalized for Covid-19 from March 1 to April 12, 2020. EXPOSURE: None. MAIN OUTCOMES AND MEASURES: Intensive care unit admission or death. RESULTS: In-hospital mortality was 24.8% and average total length of stay was 11.82 days (95% CI: 10.01 to 13.63 days). 30.8% of patients required intensive care unit admission and 29.1% required mechanical ventilation. Multivariate regression identified the amount of supplemental oxygen required at admission (OR: 1.208, 95% CI: 1.011–1.443, p = .037), sputum production (OR: 6.734, 95% CI: 1.630–27.812, p = .008), insulin dependent diabetes mellitus (OR: 11.873, 95% CI: 2.218–63.555, p = .004) and chronic kidney disease (OR: 4.793, 95% CI: 1.528–15.037, p = .007) as significant risk factors for intensive care unit admission or death. Of the 48 patients who were admitted to the intensive care unit or died, this occurred within 3 days of arrival in 42%, within 6 days in 71%, and within 9 days in 88% of patients. CONCLUSIONS: At our regional medical center, patients with Covid-19 had an average length of stay just under 12 days, required ICU care in 31% of cases, and had a 25% mortality rate. Patients with increased sputum production and higher supplemental oxygen requirements at admission, and insulin dependent diabetes or chronic kidney disease may be at increased risk for severe illness. A model for predicting intensive care unit admission or death with excellent discrimination was created that may aid in treatment decisions and resource allocation. Early identification of patients at increased risk for severe illness may lead to improved outcomes in patients hospitalized with Covid-19.

PLoS One2020       LitCov and CORD-19
1493Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19  

Coronavirus disease 2019 is a newly emerging infectious disease currently spreading across the world. It is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The spike (S) protein of SARS-CoV-2, which plays a key role in the receptor recognition and cell membrane fusion process, is composed of two subunits, S1 and S2. The S1 subunit contains a receptor-binding domain that recognizes and binds to the host receptor angiotensin-converting enzyme 2, while the S2 subunit mediates viral cell membrane fusion by forming a six-helical bundle via the two-heptad repeat domain. In this review, we highlight recent research advance in the structure, function and development of antivirus drugs targeting the S protein.

Acta Pharmacol Sin2020       LitCov and CORD-19
1494Early cases of SARS-CoV-2 infection in Uganda: epidemiology and lessons learned from risk-based testing approaches-March-April 2020  

BACKGROUND: On March 13, 2020, Uganda instituted COVID-19 symptom screening at its international airport, isolation and SARS-CoV-2 testing for symptomatic persons, and mandatory 14-day quarantine and testing of persons traveling through or from high-risk countries. On March 21, 2020, Uganda reported its first SARS-CoV-2 infection in a symptomatic traveler from Dubai. By April 12, 2020, 54 cases and 1257 contacts were identified. We describe the epidemiological, clinical, and transmission characteristics of these cases. METHODS: A confirmed case was laboratory-confirmed SARS-CoV-2 infection during March 21–April 12, 2020 in a resident of or traveler to Uganda. We reviewed case-person files and interviewed case-persons at isolation centers. We identified infected contacts from contact tracing records. RESULTS: Mean case-person age was 35 (±16) years; 34 (63%) were male. Forty-five (83%) had recently traveled internationally (‘imported cases’), five (9.3%) were known contacts of travelers, and four (7.4%) were community cases. Of the 45 imported cases, only one (2.2%) was symptomatic at entry. Among all case-persons, 29 (54%) were symptomatic at testing and five (9.3%) were pre-symptomatic. Among the 34 (63%) case-persons who were ever symptomatic, all had mild disease: 16 (47%) had fever, 13 (38%) reported headache, and 10 (29%) reported cough. Fifteen (28%) case-persons had underlying conditions, including three persons with HIV. An average of 31 contacts (range, 4–130) were identified per case-person. Five (10%) case-persons, all symptomatic, infected one contact each. CONCLUSION: The first 54 case-persons with SARS-CoV-2 infection in Uganda primarily comprised incoming air travelers with asymptomatic or mild disease. Disease would likely not have been detected in these persons without the targeted testing interventions implemented in Uganda. Transmission was low among symptomatic persons and nonexistent from asymptomatic persons. Routine, systematic screening of travelers and at-risk persons, and thorough contact tracing will be needed for Uganda to maintain epidemic control.

Global Health2020       LitCov and CORD-19
1495Seroprevalence of SARS-CoV-2 antibodies in people with an acute loss in their sense of smell and/or taste in a community-based population in London, UK: An observational cohort study  

BACKGROUND: Loss of smell and taste are commonly reported symptoms associated with coronavirus disease 2019 (COVID-19); however, the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in people with acute loss of smell and/or taste is unknown. The study aimed to determine the seroprevalence of SARS-CoV-2 antibodies in a community-based population with acute loss of smell and/or taste and to compare the frequency of COVID-19 associated symptoms in participants with and without SARS-CoV-2 antibodies. It also evaluated whether smell or taste loss are indicative of COVID-19 infection. METHODS AND FINDINGS: Text messages, sent via primary care centers in London, United Kingdom, invited people with loss of smell and/or taste in the preceding month, to participate. Recruitment took place between 23 April 2020 and 14 May 2020. A total of 590 participants enrolled via a web-based platform and responded to questions about loss of smell and taste and other COVID-19–related symptoms. Mean age was 39.4 years (SD ± 12.0) and 69.1% (n = 392) of participants were female. A total of 567 (96.1%) had a telemedicine consultation during which their COVID-19–related symptoms were verified and a lateral flow immunoassay test that detected SARS-CoV-2 immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies was undertaken under medical supervision. A total of 77.6% of 567 participants with acute smell and/or taste loss had SARS-CoV-2 antibodies; of these, 39.8% (n = 175) had neither cough nor fever. New loss of smell was more prevalent in participants with SARS-CoV-2 antibodies, compared with those without antibodies (93.4% versus 78.7%, p < 0.001), whereas taste loss was equally prevalent (90.2% versus 89.0%, p = 0.738). Seropositivity for SARS-CoV-2 was 3 times more likely in participants with smell loss (OR 2.86; 95% CI 1.27–6.36; p < 0.001) compared with those with taste loss. The limitations of this study are the lack of a general population control group, the self-reported nature of the smell and taste changes, and the fact our methodology does not take into account the possibility that a population subset may not seroconvert to develop SARS-CoV-2 antibodies post-COVID-19. CONCLUSIONS: Our findings suggest that recent loss of smell is a highly specific COVID-19 symptom and should be considered more generally in guiding case isolation, testing, and treatment of COVID-19. TRIALS REGISTRATION: ClinicalTrials.gov NCT04377815

PLoS Med2020       LitCov and CORD-19
1496Rationally Designed ACE2-Derived Peptides Inhibit SARS-CoV-2  

[Image: see text] Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 is a novel and highly pathogenic coronavirus and is the causative agent of the coronavirus disease 2019 (COVID-19). The high morbidity and mortality associated with COVID-19 and the lack of an approved drug or vaccine for SARS-CoV-2 underscores the urgent need for developing effective antiviral therapies. Therapeutics that target essential viral proteins are effective at controlling virus replication and spread. Coronavirus Spike glycoproteins mediate viral entry and fusion with the host cell, and thus are essential for viral replication. To enter host cells, the Spike proteins of SARS-CoV-2 and related coronavirus, SARS-CoV, bind the host angiotensin-converting enzyme 2 (ACE2) receptor through their receptor binding domains (RBDs). Here, we rationally designed a panel of ACE2-derived peptides based on the RBD-ACE2 binding interfaces of SARS-CoV-2 and SARS-CoV. Using SARS-CoV-2 and SARS-CoV Spike-pseudotyped viruses, we found that a subset of peptides inhibits Spike-mediated infection with IC(50) values in the low millimolar range. We identified two peptides that bound Spike RBD in affinity precipitation assays and inhibited infection with genuine SARS-CoV-2. Moreover, these peptides inhibited the replication of a common cold causing coronavirus, which also uses ACE2 as its entry receptor. Results from the infection experiments and modeling of the peptides with Spike RBD identified a 6-amino-acid (Glu37-Gln42) ACE2 motif that is important for SARS-CoV-2 inhibition. Our work demonstrates the feasibility of inhibiting SARS-CoV-2 with peptide-based inhibitors. These findings will allow for the successful development of engineered peptides and peptidomimetic-based compounds for the treatment of COVID-19.

Bioconjug Chem2020       LitCov and CORD-19
1497Ivermectin to prevent hospitalizations in patients with COVID-19 (IVERCOR-COVID-19): a structured summary of a study protocol for a randomized controlled trial  

OBJECTIVES: To assess the efficacy of ivermectin in addition to standard treatment compared to standard treatment alone in reducing hospitalizations in the COVID-19 patient population. TRIAL DESIGN: IVERCOR-COVID19 will be a single-center, prospective, randomized, double-blind, parallel group (1:1 ratio), placebo-controlled study. PARTICIPANTS: Patients who meet the following criteria will be invited to participate: Inclusion criteria: (1) Over 18 years of age who reside in the province of Corrientes at the time of diagnosis. (2) Confirmed diagnosis of COVID-19 by polymerase chain reaction (PCR) test for detection of SARS-CoV2 in the last 48 h. (3) In the case of women of childbearing age, they must be using a contraceptive method of proven efficacy and safety (barrier, hormonal, or permanent contraceptives) for at least 3 months prior to inclusion in the present study and for the entire period of time for the duration of the study and until at least 30 days after the end of this study. A woman will be considered to have no reproductive capacity if she is postmenopausal (at least 2 years without her menstrual cycles) or if she has undergone surgical sterilization (at least 1 month before the time of inviting her to participate in this study). (4) Weight at the time of inclusion greater than 48 kg. (5) That they sign the informed consent for participation in the study. Exclusion criteria: (1) pregnant or breastfeeding women; (2) known allergy to ivermectin or some of the components of ivermectin tablets or placebo; (3) current use of home oxygen; (4) require hospitalization due to COVID-19 at the time of diagnosis or history of hospitalization for COVID-19; (5) presence of mal-absorptive syndrome; (6) presence of any other concomitant acute infectious disease; (7) known history of severe liver disease, for example liver cirrhosis; (8) need or use of antiviral drugs at the time of admission for another viral pathology other than COVID-19; (9) need or use of hydroxychloroquine or chloroquine; (10) use of ivermectin up to 7 days prior to randomization; (11) patients on dialysis or who have required it in the last 2 months or who plan to do it in the next 2 months; and (12) current participation or in the last 30 days in a research study that has included the administration of a drug (Table 1). The study will be carried out by the Ministry of Public Health of the Province of Corrientes (Argentina) in coordination with the Institute of Cardiology of Corrientes in the Province of Corrientes, Argentina. INTERVENTION AND COMPARATOR: Intervention group: patients who are randomized to ivermectin will receive the dose according to their weight (patients up to 80 kg will receive 2 tablets of 6 mg ivermectin; patients with more than 80 kg and up to 110 kg will receive 3 tablets of 6 mg of ivermectin; patients weighing more than 110 kg will receive 4 tablets of 6 mg ivermectin) the day they enter the study and the same dose 24 h after the first dose. Control group: patients who are randomized to placebo will receive the dose according to their weight (patients up to 80 kg will receive 2 tablets of 6 mg placebo; patients with more than 80 kg and up to 110 kg will receive 3 tablets of 6 mg of placebo; patients weighing more than 110 kg will receive 4 tablets of 6 mg placebo) on the day they enter the study and the same dose 24 h after the first dose (Table 2). MAIN OUTCOMES: Primary outcome will be the percentage of hospitalizations in patients with COVID-19 in the intervention and control groups. Secondary outcomes: time to hospitalization in each of the arms of the study: number of days elapsed from the inclusion in the study until the hospitalization of the patient; percentage of use of invasive mechanical ventilation in each of the study arms: every patient who is connected to invasive mechanical ventilation after signing the informed consent and before the final study visit; time to invasive mechanical ventilation in each of the arms of the study: number of days elapsed from inclusion in the study to connection to invasive mechanical ventilation of the patient; percentage of patients requiring dialysis in each of the study arms: all patients who require renal replacement therapy of any kind, temporary or permanent, and which begins after signing the informed consent and before the final visit; mortality from all causes in each of the two trial groups: death of the patient, from any cause. Negative PCR swab at 3 ± 1 and 12 ± 2 days after entering the study. Ivermectin safety: it will be analyzed according to the incidence of adverse events that patients present in the intervention and control groups. The end of study (EOS) is recorded as the day the patient is discharged or death. Discharge will be granted according to the current recommendations of the Ministry of Public Health of the Province of Corrientes. A follow-up visit (EOF) will be made by phone 30 days after the EOS when vital status will be verified. RANDOMIZATION: Randomization will be done through a web system with randomly permuted blocks. Randomization will be carried out by one of the investigators who will not participate in the inclusion of patients or in the delivery of medication (Table 3). BLINDING (MASKING): The participants, investigators, care providers, and outcome assessors will be blinded. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): We will include a total of 500 patients (250 patients in each group). TRIAL STATUS: This is version 1.0, 17 August 2020. The recruitment started on 19 August 2020, and we anticipate the trial will finish recruitment on 31 December 2020. TRIAL REGISTRATION: ClinicalTrials.gov NCT04529525. Registered on 26 August 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-020-04813-1.

Trials2020       LitCov and CORD-19
1498Neurologic Features in Severe SARS-CoV-2 Infection  

N Engl J Med2020       LitCov and CORD-19
1499COVID-19: Coronavirus Vaccine Development Updates  

Coronavirus Disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a newly emerged coronavirus, and has been pandemic since March 2020 and led to many fatalities. Vaccines represent the most efficient means to control and stop the pandemic of COVID-19. However, currently there is no effective COVID-19 vaccine approved to use worldwide except for two human adenovirus vector vaccines, three inactivated vaccines, and one peptide vaccine for early or limited use in China and Russia. Safe and effective vaccines against COVID-19 are in urgent need. Researchers around the world are developing 213 COVID-19 candidate vaccines, among which 44 are in human trials. In this review, we summarize and analyze vaccine progress against SARS-CoV, Middle-East respiratory syndrome Coronavirus (MERS-CoV), and SARS-CoV-2, including inactivated vaccines, live attenuated vaccines, subunit vaccines, virus like particles, nucleic acid vaccines, and viral vector vaccines. As SARS-CoV-2, SARS-CoV, and MERS-CoV share the common genus, Betacoronavirus, this review of the major research progress will provide a reference and new insights into the COVID-19 vaccine design and development.

Front Immunol2020       LitCov and CORD-19
1500Life in lockdown: A telephone survey to investigate the impact of COVID-19 lockdown measures on the lives of older people (≥75 years)  

Background: In response to the COVID-19 coronavirus pandemic, the UK government introduced social distancing measures and identified specific populations at high risk from the virus. People ≥70 were deemed “Clinically Vulnerable.” Distancing measures were introduced to reduce the risk of contracting COVID-19. However, these may have a negative impact on older people who are vulnerable to social isolation and may have challenges accessing services and provisions. Objectives: To investigate the impact of COVID-19 lockdown measures on the lives of older people. Study design and setting: Cross-sectional telephone survey. Participants: Community-dwelling older people, 76–97 years. Outcomes: Health anxiety; General health (RAND Short-form 36 Survey); Physical activity; Depression (PHQ-8); Anxiety (GAD-2); Loneliness; Access to services; Challenges, concerns and positive experiences. Data analysis: Counts (%), means (SDs). Thematic analysis was used to identify themes from open questions. Results: n = 142. 52% did not worry about their health; 76% rated their health as “good”, “very good” or “excellent”. < 10% met the criteria indicative of depression (PHQ-8), or anxiety (GAD-2). 42% were less active than before lockdown. 27% were lonely at least some of the time. Over half of participants identified positive aspects. Conclusions: Most participants reported good health with low levels of health anxiety, anxiety and depression. Many were able to identify positive aspects to lockdown and may be better equipped to deal with lockdown than anticipated. Strategies may be required to ameliorate the negative impact of loneliness for a minority of older people, and help some resume previous activity levels and pursuits.

Age Ageing2020       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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