\ 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
1101Antibody response to SARS-CoV-2 vaccination is extremely vivacious in subjects with previous SARS-CoV-2 infection  

The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic calls for rapid actions, now principally oriented to a world‐wide vaccination campaign. In this study we verified if, in individuals with a previous SARS‐CoV‐2 infection, a single dose of messenger RNA (mRNA) vaccine would be immunologically equivalent to a full vaccine schedule in naïve individuals. Health care workers (184) with a previous SARS‐CoV‐2 infection were sampled soon before the second dose of vaccine and between 7 and 10 days after the second dose, the last sampling time was applied to SARS‐CoV‐2 naïve individuals, too. Antibodies against SARS‐CoV‐2 were measured using Elecsys Anti‐SARS‐CoV‐2 S immunoassay. The study was powered for non‐inferiority. We used non parametric tests and Pearson correlation test to perform inferential analysis. After a single vaccine injection, the median titer of specific antibodies in individuals with previous coronavirus disease 2019 was 30.527 U/ml (interquartile range [IQR]: 19.992–39.288) and in subjects with previous SARS‐CoV‐2 asymptomatic infection was 19.367.5 U/ml (IQR: 14.688–31.353) (p = .032). Both results were far above the median titer in naïve individuals after a full vaccination schedule: 1974.5 U/ml (IQR: 895–3455) (p < .0001). Adverse events after vaccine injection were more frequent after the second dose of vaccine (mean: 0.95; 95% confidence interval [CI]: 0.75–1.14 vs. mean: 1.91; 95% CI: 1.63–2.19) (p < .0001) and in exposed compared to naïve (mean: 1.63; 95% CI: 1.28–1.98 vs. mean: 2.35; 95% CI: 1.87–2.82) (p = .015). In SARS‐CoV‐2 naturally infected individuals a single mRNA vaccine dose seems sufficient to reach immunity. Modifying current dosing schedules would speed‐up vaccination campaigns.

J Med Virol2021       LitCov and CORD-19
1102Neutralizing antibody response against the B.1.617.2 (delta) and the B.1.1.529 (omicron) variants after a third mRNA SARS-CoV-2 vaccine dose in kidney transplant recipients  

Seroconversion after COVID‐19 vaccination is impaired in kidney transplant recipients. Emerging variants of concern such as the B.1.617.2 (delta) and the B.1.1.529 (omicron) variants pose an increasing threat to these patients. In this observational cohort study, we measured anti‐S1 IgG, surrogate neutralizing, and anti‐receptor‐binding domain antibodies three weeks after a third mRNA vaccine dose in 49 kidney transplant recipients and compared results to 25 age‐matched healthy controls. In addition, vaccine‐induced neutralization of SARS‐CoV‐2 wild‐type, the B.1.617.2 (delta), and the B.1.1.529 (omicron) variants was assessed using a live‐virus assay. After a third vaccine dose, anti‐S1 IgG, surrogate neutralizing, and anti‐receptor‐binding domain antibodies were significantly lower in kidney transplant recipients compared to healthy controls. Only 29/49 (59%) sera of kidney transplant recipients contained neutralizing antibodies against the SARS‐CoV‐2 wild‐type or the B.1.617.2 (delta) variant and neutralization titers were significantly reduced compared to healthy controls (p < 0.001). Vaccine‐induced cross‐neutralization of the B.1.1.529 (omicron) variants was detectable in 15/35 (43%) kidney transplant recipients with seropositivity for anti‐S1 IgG, surrogate neutralizing, and/or anti‐RBD antibodies. Neutralization of the B.1.1.529 (omicron) variants was significantly reduced compared to neutralization of SARS‐CoV‐2 wild‐type or the B.1.617.2 (delta) variant for both, kidney transplant recipients and healthy controls (p < .001 for all).

Am J Transplant2022       LitCov and CORD-19
1103Association of Socioeconomic Changes due to the COVID-19 Pandemic With Health Outcomes in Patients With Skin Diseases: Cross-Sectional Survey Study  

BACKGROUND: The outbreak of COVID-19 has profoundly influenced people’s lifestyles; these impacts have varied across subgroups of people. The pandemic-related impacts on the health outcomes of people with dermatological conditions are unknown. OBJECTIVE: The aim of this paper was to study the association of COVID-19 pandemic–related impacts with health-related quality of life in patients with skin diseases. METHODS: This was a cross-sectional study among Chinese patients with skin diseases. A self-administered web-based questionnaire was distributed through social media. Demographic and clinical data and pandemic-related impacts (isolation status, income changes, and employment status) were collected. The main outcomes included perceived stress (Visual Analog Scale), symptoms of anxiety (Generalized Anxiety Disorder-7) and depression (9-Item Patient Health Questionnaire), quality of life (Dermatology Life Quality Index), and health utility mapping based on the EQ-5D-3L descriptive system. Multivariable logistic regression was used to investigate the associations. RESULTS: A total of 506 patients with skin diseases completed the survey. The mean age of the patients was 33.5 years (SD 14.0), and 217/506 patients (42.9%) were male. Among the 506 respondents, 128 (25.3%) were quarantined, 102 (20.2%) reported unemployment, and 317 (62.6%) reported decrease or loss of income since the pandemic. The pandemic-related impacts were significantly associated with impaired mental well-being and quality of life with different effects. Unemployment and complete loss of income were associated with the highest risks of adverse outcomes, with increases of 110% to 162% in the prevalence of anxiety, depression, and impaired quality of life. CONCLUSIONS: Isolation, income loss, and unemployment are associated with impaired health-related quality of life in patients with skin diseases during the COVID-19 pandemic.

J Med Internet Res2020       LitCov and CORD-19
1104Previous Infection Combined with Vaccination Produces Neutralizing Antibodies with Potency against SARS-CoV-2 Variants  

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve in humans. Spike protein mutations increase transmission and potentially evade antibodies raised against the original sequence used in current vaccines. Our evaluation of serum neutralizing activity in both persons soon after SARS-CoV-2 infection (in April 2020 or earlier) or vaccination without prior infection confirmed that common spike mutations can reduce antibody antiviral activity. However, when the persons with prior infection were subsequently vaccinated, their antibodies attained an apparent biologic ceiling of neutralizing potency against all tested variants, equivalent to the original spike sequence. These findings indicate that additional antigenic exposure further improves antibody efficacy against variants.

mBio2021       LitCov and CORD-19
1105Interdependencies of cellular and humoral immune responses in heterologous and homologous SARS-CoV-2 vaccination  

BACKGROUND: Homologous and heterologous SARS‐CoV‐2 vaccinations yield different spike protein‐directed humoral and cellular immune responses. This study aimed to explore their currently unknown interdependencies. METHODS: COV‐ADAPT is a prospective, observational cohort study of 417 healthcare workers who received vaccination with homologous ChAdOx1 nCoV‐19, homologous BNT162b2 or with heterologous ChAdOx1 nCoV‐19/BNT162b2. We assessed humoral (anti‐spike‐RBD‐IgG, neutralizing antibodies, and avidity) and cellular (spike‐induced T‐cell interferon‐γ release) immune responses in blood samples up to 2 weeks before (T1) and 2–12 weeks following secondary immunization (T2). RESULTS: Initial vaccination with ChAdOx1 nCoV‐19 resulted in lower anti‐spike‐RBD‐IgG compared with BNT162b2 (70 ± 114 vs. 226 ± 279 BAU/ml, p < .01) at T1. Booster vaccination with BNT162b2 proved superior to ChAdOx1 nCoV‐19 at T2 (anti‐spike‐RBD‐IgG: ChAdOx1 nCoV‐19/BNT162b2 2387 ± 1627 and homologous BNT162b2 3202 ± 2184 vs. homologous ChAdOx1 nCoV‐19 413 ± 461 BAU/ml, both p < .001; spike‐induced T‐cell interferon‐γ release: ChAdOx1 nCoV‐19/BNT162b2 5069 ± 6733 and homologous BNT162b2 4880 ± 7570 vs. homologous ChAdOx1 nCoV‐19 1152 ± 2243 mIU/ml, both p < .001). No significant differences were detected between BNT162b2‐boostered groups at T2. For ChAdOx1 nCoV‐19, no booster effect on T‐cell activation could be observed. We found associations between anti‐spike‐RBD‐IgG levels (ChAdOx1 nCoV‐19/BNT162b2 and homologous BNT162b2) and T‐cell responses (homologous ChAdOx1 nCoV‐19 and ChAdOx1 nCoV‐19/BNT162b2) from T1 to T2. Additionally, anti‐spike‐RBD‐IgG and T‐cell response were linked at both time points (all groups combined). All regimes yielded neutralizing antibodies and increased antibody avidity at T2. CONCLUSIONS: Interdependencies between humoral and cellular immune responses differ between common SARS‐CoV‐2 vaccination regimes. T‐cell activation is unlikely to compensate for poor humoral responses.

Allergy2022       LitCov and CORD-19
1106Nasal delivery of broadly neutralizing antibodies protects mice from lethal challenge with SARS-CoV-2 delta and omicron variants  

Multiple new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have constantly emerged, as the delta and omicron variants, which have developed resistance to currently gained neutralizing antibodies. This highlights a critical need to discover new therapeutic agents to overcome the variants mutations. Despite the availability of vaccines against coronavirus disease 2019 (COVID-19), the use of broadly neutralizing antibodies has been considered as an alternative way for the prevention or treatment of SARS-CoV-2 variants infection. Here, we show that the nasal delivery of two previously characterized broadly neutralizing antibodies (F61 and H121) protected K18-hACE2 mice against lethal challenge with SARS-CoV-2 variants. The broadly protective efficacy of the F61 or F61/F121 cocktail antibodies was evaluated by lethal challenge with the wild strain (WIV04) and multiple variants, including beta (B.1.351), delta (B.1.617.2), and omicron (B.1.1.529) at 200 or 1000 TCID(50), and the minimum antibody administration doses (5–1.25 mg/kg body weight) were also evaluated with delta and omicron challenge. Fully prophylactic protections were found in all challenged groups with both F61 and F61/H121 combination at the administration dose of 20 mg/kg body weight, and corresponding mice lung viral RNA showed negative, with almost all alveolar septa and cavities remaining normal. Furthermore, low-dose antibody treatment induced significant prophylactic protection against lethal challenge with delta and omicron variants, whereas the F61/H121 combination showed excellent results against omicron infection. Our findings indicated the potential use of broadly neutralizing monoclonal antibodies as prophylactic and therapeutic agent for protection of current emerged SARS-CoV-2 variants infection.

Virol Sin2022       LitCov and CORD-19
1107COVID-19 vaccine hesitancy and vaccine passports: a cross-sectional conjoint experiment in Japan  

N/A

BMJ Open2022       LitCov
1108Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study  

BACKGROUND: The SARS-CoV-2 omicron variant of concern was identified in South Africa in November, 2021, and was associated with an increase in COVID-19 cases. We aimed to assess the clinical severity of infections with the omicron variant using S gene target failure (SGTF) on the Thermo Fisher Scientific TaqPath COVID-19 PCR test as a proxy. METHODS: We did data linkages for national, South African COVID-19 case data, SARS-CoV-2 laboratory test data, SARS-CoV-2 genome data, and COVID-19 hospital admissions data. For individuals diagnosed with COVID-19 via TaqPath PCR tests, infections were designated as either SGTF or non-SGTF. The delta variant was identified by genome sequencing. Using multivariable logistic regression models, we assessed disease severity and hospitalisations by comparing individuals with SGTF versus non-SGTF infections diagnosed between Oct 1 and Nov 30, 2021, and we further assessed disease severity by comparing SGTF-infected individuals diagnosed between Oct 1 and Nov 30, 2021, with delta variant-infected individuals diagnosed between April 1 and Nov 9, 2021. FINDINGS: From Oct 1 (week 39), 2021, to Dec 6 (week 49), 2021, 161 328 cases of COVID-19 were reported in South Africa. 38 282 people were diagnosed via TaqPath PCR tests and 29 721 SGTF infections and 1412 non-SGTF infections were identified. The proportion of SGTF infections increased from two (3·2%) of 63 in week 39 to 21 978 (97·9%) of 22 455 in week 48. After controlling for factors associated with hospitalisation, individuals with SGTF infections had significantly lower odds of admission than did those with non-SGTF infections (256 [2·4%] of 10 547 vs 121 [12·8%] of 948; adjusted odds ratio [aOR] 0·2, 95% CI 0·1–0·3). After controlling for factors associated with disease severity, the odds of severe disease were similar between hospitalised individuals with SGTF versus non-SGTF infections (42 [21%] of 204 vs 45 [40%] of 113; aOR 0·7, 95% CI 0·3–1·4). Compared with individuals with earlier delta variant infections, SGTF-infected individuals had a significantly lower odds of severe disease (496 [62·5%] of 793 vs 57 [23·4%] of 244; aOR 0·3, 95% CI 0·2–0·5), after controlling for factors associated with disease severity. INTERPRETATION: Our early analyses suggest a significantly reduced odds of hospitalisation among individuals with SGTF versus non-SGTF infections diagnosed during the same time period. SGTF-infected individuals had a significantly reduced odds of severe disease compared with individuals infected earlier with the delta variant. Some of this reduced severity is probably a result of previous immunity. FUNDING: The South African Medical Research Council, the South African National Department of Health, US Centers for Disease Control and Prevention, the African Society of Laboratory Medicine, Africa Centers for Disease Control and Prevention, the Bill & Melinda Gates Foundation, the Wellcome Trust, and the Fleming Fund.

Lancet2022       LitCov and CORD-19
1109Low SARS-CoV-2 infection rates and high vaccine induced immunity among German healthcare workers at the end of the third wave of the COVID-19 pandemic  

In this longitudinal cohort study, we assessed the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) seroconversion rates and analyzed the coronavirus disease 2019 (COVID-19) vaccine-induced immunity of 872 hospital workers at the University Medical Center Hamburg-Eppendorf between May 11 and May 31, 2021. The overall seroprevalence of anti–NC–SARS-CoV-2 antibodies was 4.7% (n = 41), indicating low SARS-CoV-2 infection rates and persistent effectiveness of hospital-wide infection control interventions during the second and third wave of the pandemic. In total, 92.7% (n = 808) out of the entire study cohort, 98.2% (n = 325) of those who had been vaccinated once and all 393 individuals who had been vaccinated twice had detectable anti-S1-RBD-SARS-CoV-2 antibody titers and no significant differences in vaccine-induced immune response were detected between male and female individuals and between different age groups. Vaccinated study participants with detectable anti–NC–SARS-CoV-2 antibody titers (n = 30) developed generally higher anti-S1-RBD-SARS-CoV-2 antibody titers compared to anti–NC–SARS-CoV-2 negative individuals (n = 694) (median titer: 7812 vs. 345 BAU/ml, p < 0.0001). Furthermore, study participants who received heterologous vaccination with AZD1222 followed by an mRNA vaccine showed markedly higher anti-S1-RBD-SARS-CoV-2 antibody titers than individuals who received two doses of an mRNA vaccine or two doses of AZD1222 (median titer: AZD1222/AZD1222: 1069 BAU/ml, mRNA/mRNA: 1388 BAU/ml, AZD1222/mRNA: 9450 BAU/ml; p < 0.0001). Our results indicate that infection control interventions were generally effective in preventing nosocomial transmission of SARS-CoV-2 and that COVID-19 vaccines can elicit strong humoral responses in the majority of a real-world cohort of hospital workers.

Int J Hyg Environ Health2021       LitCov and CORD-19
1110Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved alpha-ketoamide inhibitors  

The COVID-19 pandemic caused by SARS-CoV-2 is a global health emergency. An attractive drug target among coronaviruses is the main protease (M(pro), 3CL(pro)), due to its essential role in processing the polyproteins that are translated from the viral RNA. We report the X-ray structures of the unliganded SARS-CoV-2 M(pro) and its complex with an α-ketoamide inhibitor. This was derived from a previously designed inhibitor but with the P3-P2 amide bond incorporated into a pyridone ring to enhance the half-life of the compound in plasma. Based on the structure, we developed the lead compound into a potent inhibitor of the SARS-CoV-2 M(pro). The pharmacokinetic characterization of the optimized inhibitor reveals a pronounced lung tropism and suitability for administration by the inhalative route.

Science2020       LitCov and CORD-19
1111Differences of SARS-CoV-2 Shedding Duration in Sputum and Nasopharyngeal Swab Specimens Among Adult Inpatients With COVID-19  

Abstract Background The viral shedding duration of SARS-CoV-2 has not been fully defined. Consecutive detection of SARS-CoV-2 RNA from respiratory tract specimens is essential for determining duration of virus shedding and providing evidence to optimize the clinical management of COVID-19. Research Question What are the shedding durations of SARS-CoV-2 RNA in upper and lower respiratory tract specimens respectively? What are their associated risk factors? Study Design and Methods: A total of 68 patients with COVID-19 admitted to Wuhan Taikang Tongji Hospital and Huoshenshan Hospital from February 10, 2020 to March 20, 2020 were recruited. Consecutive SARS-CoV-2 RNA detection from paired specimens of nasopharyngeal swab (NPS) and sputum were carried out. The clinical characteristics of patients were recorded for further analysis. Results SARS-CoV-2 RNA was detected from NPS in 48 (70.6%) patients, and from sputum specimens in 30 (44.1%) patients. The median duration of viral shedding from sputum specimens (34 days, IQR 24-40 days) was significantly longer than from NPS (19 days, IQR 14-25 days; P<0.001). Elderly age was an independent factor associated with prolonged virus shedding time of SARS-CoV-2 (HR 1.71, 1.01-2.93). It was noteworthy that in 9 patients the viral RNA was detected in sputum after NPS turned negative. Chronic lung disease and steroids were associated with virus detection in sputum, and diabetes mellitus was associated with virus detection in both NPS and sputum. Interpretation These findings may impact a test based clearance discharge criteria given patients with COVID-19 may shed virus longer in their lower respiratory tracts, with potential implication for prolonged transmission risk. In addition, more attention should be given to elderly patients who might have prolonged viral shedding duration.

Chest2020       LitCov and CORD-19
1112Online education at the medical School of Tongji University during the COVID-19 pandemic: a cross-sectional study  

BACKGROUND: The global reputation of coronavirus disease (COVID-19) has led universities in China to conduct online teaching. However, the actual feedback from medical teachers and students regarding online education remains unclear. METHODS: A prospective questionnaire survey examined the current opinions of online education from teachers and students at the Medical School of Tongji University. RESULTS: A total of 488 valid questionnaires were collected (223 males, 45.7%; 265 females, 54.3%), including 394 students (80.7%) and 94 teachers (19.3%). Most teachers and students were “in favor of online teaching,” had “positive views for online education,” were “satisfied with online teaching,” and “expected for regular online education,” although students thought that “too much learning tasks had been assigned” (90.4% teachers vs. 43.1% students, P < 0.001) and “less teaching effect than in offline classes” (68.1% teachers vs. 43.4% students). Compared to female counterpart, male students had higher “learning interest” (27.6% vs. 14.9%), “learning attention” (29.2% vs. 14.4%), “learning efficiency” (30.2% vs. 16.7%), and “better learning effect” (27.6% vs. 15.3%). Furthermore, male students had a significantly rise in attendance rate. Compared with male teachers, female teachers had less “experience in online educational course recording” (25.9% vs. 50%) and “past training for online teaching” (53.7% vs. 77.5%). Furthermore, they tended to be more “resistant to online teaching” (44.4% vs. 22.5%) and less “ready for online teaching” (70.4% vs. 87.5%). There was no significant difference in the acceptance of online teaching among teachers in different age groups. CONCLUSIONS: Most teachers and students supported and were satisfied with the implementation of online education during the pandemic. Although teachers were less adaptable to online education, they still had positive opinions. Sex influenced the acceptance of online teaching. Male teachers and students showed better adaptability than their female counterparts. Although online teaching has advantages, it still cannot completely replace traditional offline teaching. As online education is a trend for future learning, universities should make more efforts to improve it, especially to provide more attention to female teachers and students.

BMC Med Educ2021       LitCov and CORD-19
1113Prevalence of Sars-Cov-2 Infection in Health Workers (HWs) and Diagnostic Test Performance: The Experience of a Teaching Hospital in Central Italy  

(1) Background: Health workers (HWs) are at high risk of acquiring SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infections. Therefore, health authorities further recommend screening strategies for SARS-CoV-2 infection in exposed or high-risk HWs. Nevertheless, to date, the best/optimal method to screen HWs for SARS-CoV-2 infection is still under debate, and data on the prevalence of SARS-CoV-2 infection in HWs are still scarce. The present study aims to assess the SARS-CoV-2 infection rate amongst HWs in a teaching hospital in Central Italy and the diagnostic performance of SARS-CoV-2 serology (index test) in comparison with the SARS-CoV-2 RNA PCR assay (reference standard). (2) Methods: A cross-sectional study on the retrospective data of HWs tested for SARS-CoV-2 by RNA-RT-PCR on nasopharyngeal swabs and by an IgM/IgG serology assay on venous blood samples, irrespective of exposure and/or symptoms, was carried out. (3) Results: A total of 2057 HWs (median age 46, 19–69 years, females 60.2%) were assessed by the RNA RT-PCR assay and 58 (2.7%) tested positive for SARS-CoV-2 infection. Compared with negative HWs, SARS-CoV-2-positives were younger (mean age 41.7 versus 45.2, p < 0.01; 50% versus 31% under or equal to 40 years old, p < 0.002) and had a shorter duration of employment (64 versus 125 months, p = 0.02). Exposure to SARS-CoV-2 was more frequent in positive HWs than in negatives (55.2% versus 27.5%, p < 0.0001). In 44.8% of positive HWs, no exposure was traced. None of the positive HWs had a fatal outcome, none of them had acute respiratory distress syndrome, and only one required hospitalization for mild/moderate pneumonia. In 1084 (51.2%) HWs, nasopharyngeal swabs and an IgM/IgG serology assay were performed. With regard to IgM serology, sensitivity was 0% at a specificity of 98.99% (positive predictive value, PPV 0%, negative predictive value, NPV 99.2%). Concerning IgG serology and irrespective of the time interval between nasopharyngeal swab and serology, sensitivity was 50% at a specificity of 99.1% (PPV 28.6%, NPV 99.6%). IgG serology showed a higher diagnostic performance when performed at least two weeks after testing SARS-CoV-2-positive at the RNA RT-PCR assay by a nasopharyngeal swab. (4) Conclusions: Our experience in Central Italy demonstrated a low prevalence of SARS-CoV-2 infection amongst HWs, but higher than in the general population. Nearly half of the positive HWs reported no previous exposure to SARS-CoV-2-infected subjects and were diagnosed thanks to the proactive screening strategy implemented. IgG serology seems useful when performed at least two weeks after an RNA RT-PCR assay. IgM serology does not seem to be a useful test for the diagnosis of active SARS-CoV-2 infection. High awareness of SARS-CoV-2 infection is mandatory for all people, but especially for HWs, irrespective of symptoms, to safeguard their health and that of patients.

Int J Environ Res Public Healt2020       LitCov and CORD-19
1114Relationship between viral load, infection-to-delivery interval and mother-to-child transfer of anti-SARS-CoV-2 antibodies  

OBJECTIVE: To investigate the association of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) viral load and infection‐to‐delivery interval with maternal and cord serum concentrations of anti‐SARS‐CoV‐2 immunoglobulin G (IgG) antibodies and transplacental transfer ratio in pregnant women with active or recovered SARS‐CoV‐2 infection. METHODS: This was a prospective case series of consecutive pregnant women with laboratory‐confirmed SARS‐CoV‐2 infection between 27 March 2020 and 24 January 2021. We collected information regarding deep throat saliva or nasopharyngeal swab (NPS) reverse transcription polymerase chain reaction (RT‐PCR) test results, serial cycle threshold (Ct) values at and after diagnosis, demographic, clinical and outcome data, and neonatal NPS RT‐PCR results. Qualitative and quantitative analysis of IgG and immunoglobulin M (IgM) antibodies against SARS‐CoV‐2 was performed in maternal and cord blood serum samples obtained at delivery. Correlation of maternal Ct values, infection‐to‐delivery interval, infection duration and viral load area under the curve (AUC) with gestational age (GA) at diagnosis, maternal and cord serum IgG concentrations and transplacental transfer ratio of IgG were evaluated using Pearson's correlation. RESULTS: Twenty pregnant women who consented to participate and who had delivered their babies by 31 January 2021 were included in the study, comprising 14 who had recovered from coronavirus disease 2019 (COVID‐19) and six with active infection at delivery. The median GA at clinical manifestation was 32.7 (range, 11.9–39.4) weeks. The median infection‐to‐delivery interval and infection duration were 41.5 (range, 2–187) days and 10.0 (range, 1–48) days, respectively. The median GA at delivery was 39.1 (range, 32.4–40.7) weeks and the median seroconversion interval was 14 (range, 1–19) days. Of 13 neonates born to seropositive mothers with recovered infection at delivery, 12 tested positive for anti‐SARS‐CoV‐2 IgG. All neonatal NPS samples were negative for SARS‐CoV‐2 and all cord sera tested negative for IgM. The median transplacental transfer ratio of IgG was 1.3 (interquartile range, 0.9–1.6). There was a negative correlation between infection‐to‐delivery interval and anti‐SARS‐CoV‐2 IgG concentrations in maternal (r = –0.6693, P = 0.0087) and cord (r = –0.6554, P = 0.0068) serum and a positive correlation between IgG concentration in maternal serum and viral load AUC (r = 0.5109, P = 0.0310). A negative correlation was observed between transfer ratio and viral load AUC (r = –0.4757, P = 0.0409). CONCLUSIONS: In pregnant women who have recovered from COVID‐19, anti‐SARS‐CoV‐2 IgG concentrations at delivery increased with increasing viral load during infection and decreased with increasing infection‐to‐delivery interval. The median transplacental transfer ratio of IgG was 1.3 and it decreased with increasing viral load during infection. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Ultrasound Obstet Gynecol2021       LitCov and CORD-19
1115Humoral and Cellular Immune Responses to SARS-CoV-2 mRNA Vaccination in Patients with Multiple Sclerosis: An Israeli Multicenter Experience Following 3 Vaccine Doses  

BACKGROUND: Immunomodulatory/immunosuppressive activity of multiple sclerosis (MS) disease modifying therapies (DMTs) might affect immune responses to SARS-CoV-2 exposure or vaccination in patients with MS (PwMS). We evaluated the effect of DMTs on humoral and cell-mediated immune responses to 2 and 3 vaccinations and the longevity of SARS-Cov-2 IgG levels in PwMS. METHODS: 522 PwMS and 68 healthy controls vaccinated with BNT162b2-Pfizer mRNA vaccine against SARS-CoV-2, or recovering from COVID-19, were recruited in a nation-wide multi-center study. Blood was collected at 3 time-points: 2-16 weeks and ~6 months post 2(nd) vaccination and 1-16 weeks following 3(rd) vaccination. Serological responses were measured by quantifying IgG levels against the spike-receptor-binding-domain of SARS-CoV-2, and cellular responses (in a subgroup analysis) by quantifying IFNγ secretion in blood incubated with COVID-19 spike-antigen. RESULTS: 75% PwMS were seropositive post 2(nd) or 3(rd) vaccination. IgG levels decreased by 82% within 6 months from vaccination (p<0.0001), but were boosted 10.3 fold by the 3(rd) vaccination (p<0.0001), and 1.8 fold compared to ≤3m post 2(nd) vaccination (p=0.025). Patients treated with most DMTs were seropositive post 2(nd) and 3(rd) vaccinations, however only 38% and 44% of ocrelizumab-treated patients and 54% and 46% of fingolimod-treated patients, respectively, were seropositive. Similarly, in COVID-19-recovered patients only 54% of ocrelizumab-treated, 75% of fingolimod-treated and 67% of cladribine-treated patients were seropositive. A time interval of ≥5 months between ocrelizumab infusion and vaccination was associated with higher IgG levels (p=0.039 post-2(nd) vaccination; p=0.036 post-3(rd) vaccination), and with higher proportions of seropositive patients. Most fingolimod- and ocrelizumab-treated patients responded similarly to 2(nd) and 3(rd) vaccination. IFNγ-T-cell responses were detected in 89% and 63% of PwMS post 2(nd) and 3(rd) vaccination, however in only 25% and 0% of fingolimod-treated patients, while in 100% and 86% of ocrelizumab-treated patients, respectively. CONCLUSION: PwMS treated with most DMTs developed humoral and T-cell responses following 2 and 3 mRNA SARS-CoV-2 vaccinations. Fingolimod- or ocrelizumab-treated patients had diminished humoral responses, and fingolimod compromised the cellular responses, with no improvement after a 3(rd) booster. Vaccination following >5 months since ocrelizumab infusion was associated with better sero-positivity. These findings may contribute to the development of treatment-stratified vaccination guidelines for PwMS.

Front Immunol2022       LitCov and CORD-19
1116Work and social functioning in frontline healthcare workers during the covid-19 pandemic in Italy: role of acute post-traumatic stress, depressive and anxiety symptoms  

N/A

Riv Psichiatr2021       LitCov and CORD-19
1117Presumed Asymptomatic Carrier Transmission of COVID-19  

N/A

JAMA2020       LitCov and CORD-19
1118A crucial role of angiotensin-converting enzyme 2 (ACE2) in SARS coronavirus induced lung injury  

During several months of 2003, a newly identified illness termed severe acute respiratory syndrome (SARS) spread rapidly through the world(1,2,3). A new coronavirus (SARS-CoV) was identified as the SARS pathogen(4,5,6,7), which triggered severe pneumonia and acute, often lethal, lung failure(8). Moreover, among infected individuals influenza such as the Spanish flu(9,10) and the emergence of new respiratory disease viruses(11,12) have caused high lethality resulting from acute lung failure(13). In cell lines, angiotensin-converting enzyme 2 (ACE2) has been identified as a potential SARS-CoV receptor(14). The high lethality of SARS-CoV infections, its enormous economic and social impact, fears of renewed outbreaks as well as the potential misuse of such viruses as biologic weapons make it paramount to understand the pathogenesis of SARS-CoV. Here we provide the first genetic proof that ACE2 is a crucial SARS-CoV receptor in vivo. SARS-CoV infections and the Spike protein of the SARS-CoV reduce ACE2 expression. Notably, injection of SARS-CoV Spike into mice worsens acute lung failure in vivo that can be attenuated by blocking the renin-angiotensin pathway. These results provide a molecular explanation why SARS-CoV infections cause severe and often lethal lung failure and suggest a rational therapy for SARS and possibly other respiratory disease viruses. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nm1267) contains supplementary material, which is available to authorized users.

Nat Med2005       CORD-19
1119Compassionate Use of Remdesivir for Patients with Severe Covid-19  

BACKGROUND: Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has shown in vitro activity against SARS-CoV-2. METHODS: We provided remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, the illness caused by infection with SARS-CoV-2. Patients were those with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support. Patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment. This report is based on data from patients who received remdesivir during the period from January 25, 2020, through March 7, 2020, and have clinical data for at least 1 subsequent day. RESULTS: Of the 61 patients who received at least one dose of remdesivir, data from 8 could not be analyzed (including 7 patients with no post-treatment data and 1 with a dosing error). Of the 53 patients whose data were analyzed, 22 were in the United States, 22 in Europe or Canada, and 9 in Japan. At baseline, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving extracorporeal membrane oxygenation. During a median follow-up of 18 days, 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated. A total of 25 patients (47%) were discharged, and 7 patients (13%) died; mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation. CONCLUSIONS: In this cohort of patients hospitalized for severe Covid-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%). Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy. (Funded by Gilead Sciences.)

N Engl J Med2020       LitCov and CORD-19
1120Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma  

N/A

JAMA2020       LitCov and CORD-19
1121COVID-19 Vaccine Hesitancy Worldwide: A Concise Systematic Review of Vaccine Acceptance Rates  

Utility of vaccine campaigns to control coronavirus 2019 disease (COVID-19) is not merely dependent on vaccine efficacy and safety. Vaccine acceptance among the general public and healthcare workers appears to have a decisive role in the successful control of the pandemic. The aim of this review was to provide an up-to-date assessment of COVID-19 vaccination acceptance rates worldwide. A systematic search of the peer-reviewed English survey literature indexed in PubMed was done on 25 December 2020. Results from 31 peer-reviewed published studies met the inclusion criteria and formed the basis for the final COVID-19 vaccine acceptance estimates. Survey studies on COVID-19 vaccine acceptance rates were found from 33 different countries. Among adults representing the general public, the highest COVID-19 vaccine acceptance rates were found in Ecuador (97.0%), Malaysia (94.3%), Indonesia (93.3%) and China (91.3%). However, the lowest COVID-19 vaccine acceptance rates were found in Kuwait (23.6%), Jordan (28.4%), Italy (53.7), Russia (54.9%), Poland (56.3%), US (56.9%), and France (58.9%). Only eight surveys among healthcare workers (doctors and nurses) were found, with vaccine acceptance rates ranging from 27.7% in the Democratic Republic of the Congo to 78.1% in Israel. In the majority of survey studies among the general public stratified per country (29/47, 62%), the acceptance of COVID-19 vaccination showed a level of ≥70%. Low rates of COVID-19 vaccine acceptance were reported in the Middle East, Russia, Africa and several European countries. This could represent a major problem in the global efforts to control the current COVID-19 pandemic. More studies are recommended to address the scope of COVID-19 vaccine hesitancy. Such studies are particularly needed in the Middle East and North Africa, Sub-Saharan Africa, Eastern Europe, Central Asia, Middle and South America. Addressing the scope of COVID-19 vaccine hesitancy in various countries is recommended as an initial step for building trust in COVID-19 vaccination efforts.

Vaccines (Basel)2021       LitCov and CORD-19
1122Cardiac Complications After SARS-CoV-2 Infection and mRNA COVID-19 Vaccination-PCORnet, United States, January 2021-January 2022  

Cardiac complications, particularly myocarditis and pericarditis, have been associated with SARS-CoV-2 (the virus that causes COVID-19) infection (1-3) and mRNA COVID-19 vaccination (2-5). Multisystem inflammatory syndrome (MIS) is a rare but serious complication of SARS-CoV-2 infection with frequent cardiac involvement (6). Using electronic health record (EHR) data from 40 U.S. health care systems during January 1, 2021-January 31, 2022, investigators calculated incidences of cardiac outcomes (myocarditis; myocarditis or pericarditis; and myocarditis, pericarditis, or MIS) among persons aged ≥5 years who had SARS-CoV-2 infection, stratified by sex (male or female) and age group (5-11, 12-17, 18-29, and ≥30 years). Incidences of myocarditis and myocarditis or pericarditis were calculated after first, second, unspecified, or any (first, second, or unspecified) dose of mRNA COVID-19 (BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]) vaccines, stratified by sex and age group. Risk ratios (RR) were calculated to compare risk for cardiac outcomes after SARS-CoV-2 infection to that after mRNA COVID-19 vaccination. The incidence of cardiac outcomes after mRNA COVID-19 vaccination was highest for males aged 12-17 years after the second vaccine dose; however, within this demographic group, the risk for cardiac outcomes was 1.8-5.6 times as high after SARS-CoV-2 infection than after the second vaccine dose. The risk for cardiac outcomes was likewise significantly higher after SARS-CoV-2 infection than after first, second, or unspecified dose of mRNA COVID-19 vaccination for all other groups by sex and age (RR 2.2-115.2). These findings support continued use of mRNA COVID-19 vaccines among all eligible persons aged ≥5 years.

MMWR Morb Mortal Wkly Rep2022       LitCov and CORD-19
1123Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis  

BACKGROUND: The coronavirus disease 2019 (Covid-19) outbreak is evolving rapidly worldwide. OBJECTIVE: To evaluate the risk of serious adverse outcomes in patients with coronavirus disease 2019 (Covid-19) by stratifying the comorbidity status. METHODS: We analysed the data from 1590 laboratory-confirmed hospitalised patients 575 hospitals in 31 province/autonomous regions/provincial municipalities across mainland China between December 11(th), 2019 and January 31(st), 2020. We analyse the composite endpoints, which consisted of admission to intensive care unit, or invasive ventilation, or death. The risk of reaching to the composite endpoints was compared according to the presence and number of comorbidities. RESULTS: The mean age was 48.9 years. 686 patients (42.7%) were females. Severe cases accounted for 16.0% of the study population. 131 (8.2%) patients reached to the composite endpoints. 399 (25.1%) reported having at least one comorbidity. The most prevalent comorbidity was hypertension (16.9%), followed by diabetes (8.2%). 130 (8.2%) patients reported having two or more comorbidities. After adjusting for age and smoking status, COPD [hazards ratio (HR) 2.681, 95% confidence interval (95%CI) 1.424–5.048], diabetes (HR 1.59, 95%CI 1.03–2.45), hypertension (HR 1.58, 95%CI 1.07–2.32) and malignancy (HR 3.50, 95%CI 1.60–7.64) were risk factors of reaching to the composite endpoints. The HR was 1.79 (95%CI 1.16–2.77) among patients with at least one comorbidity and 2.59 (95%CI 1.61–4.17) among patients with two or more comorbidities. CONCLUSION: Among laboratory-confirmed cases of Covid-19, patients with any comorbidity yielded poorer clinical outcomes than those without. A greater number of comorbidities also correlated with poorer clinical outcomes.

Eur Respir J2020       LitCov and CORD-19
1124Asymptomatic carrier state, acute respiratory disease and pneumonia due to SARS-CoV-2: Facts and myths  

Since the emergence of coronavirus disease 2019 (COVID-19) (formerly known as the 2019 novel coronavirus [2019-nCoV]) in Wuhan, China in December 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), more than 75,000 cases have been reported in 32 countries/regions, resulting in more than 2000 deaths worldwide. Despite the fact that most COVID-19 cases and mortalities were reported in China, the WHO has declared this outbreak as the sixth public health emergency of international concern. The COVID-19 can present as an asymptomatic carrier state, acute respiratory disease, and pneumonia. Adults represent the population with the highest infection rate; however, neonates, children, and elderly patients can also be infected by SARS-CoV-2. In addition, nosocomial infection of hospitalized patients and healthcare workers, and viral transmission from asymptomatic carriers are possible. The most common finding on chest imaging among patients with pneumonia was ground-glass opacity with bilateral involvement. Severe cases are more likely to be older patients with underlying comorbidities compared to mild cases. Indeed, age and disease severity may be correlated with the outcomes of COVID-19. To date, effective treatment is lacking; however, clinical trials investigating the efficacy of several agents, including remdesivir and chloroquine, are underway in China. Currently, effective infection control intervention is the only way to prevent the spread of SARS-CoV-2.

J Microbiol Immunol Infect2020       LitCov and CORD-19
1125Estimating global, regional and national daily and cumulative infections with SARS-CoV-2 through Nov 14, 2021: a statistical analysis  

BACKGROUND: Timely, accurate, and comprehensive estimates of SARS-CoV-2 daily infection rates, cumulative infections, the proportion of the population that has been infected at least once, and the effective reproductive number (R(effective)) are essential for understanding the determinants of past infection, current transmission patterns, and a population's susceptibility to future infection with the same variant. Although several studies have estimated cumulative SARS-CoV-2 infections in select locations at specific points in time, all of these analyses have relied on biased data inputs that were not adequately corrected for. In this study, we aimed to provide a novel approach to estimating past SARS-CoV-2 daily infections, cumulative infections, and the proportion of the population infected, for 190 countries and territories from the start of the pandemic to Nov 14, 2021. This approach combines data from reported cases, reported deaths, excess deaths attributable to COVID-19, hospitalisations, and seroprevalence surveys to produce more robust estimates that minimise constituent biases. METHODS: We produced a comprehensive set of global and location-specific estimates of daily and cumulative SARS-CoV-2 infections through Nov 14, 2021, using data largely from Johns Hopkins University (Baltimore, MD, USA) and national databases for reported cases, hospital admissions, and reported deaths, as well as seroprevalence surveys identified through previous reviews, SeroTracker, and governmental organisations. We corrected these data for known biases such as lags in reporting, accounted for under-reporting of deaths by use of a statistical model of the proportion of excess mortality attributable to SARS-CoV-2, and adjusted seroprevalence surveys for waning antibody sensitivity, vaccinations, and reinfection from SARS-CoV-2 escape variants. We then created an empirical database of infection–detection ratios (IDRs), infection–hospitalisation ratios (IHRs), and infection–fatality ratios (IFRs). To estimate a complete time series for each location, we developed statistical models to predict the IDR, IHR, and IFR by location and day, testing a set of predictors justified through published systematic reviews. Next, we combined three series of estimates of daily infections (cases divided by IDR, hospitalisations divided by IHR, and deaths divided by IFR), into a more robust estimate of daily infections. We then used daily infections to estimate cumulative infections and the cumulative proportion of the population with one or more infections, and we then calculated posterior estimates of cumulative IDR, IHR, and IFR using cumulative infections and the corrected data on reported cases, hospitalisations, and deaths. Finally, we converted daily infections into a historical time series of R(effective) by location and day based on assumptions of duration from infection to infectiousness and time an individual spent being infectious. For each of these quantities, we estimated a distribution based on an ensemble framework that captured uncertainty in data sources, model design, and parameter assumptions. FINDINGS: Global daily SARS-CoV-2 infections fluctuated between 3 million and 17 million new infections per day between April, 2020, and October, 2021, peaking in mid-April, 2021, primarily as a result of surges in India. Between the start of the pandemic and Nov 14, 2021, there were an estimated 3·80 billion (95% uncertainty interval 3·44–4·08) total SARS-CoV-2 infections and reinfections combined, and an estimated 3·39 billion (3·08–3·63) individuals, or 43·9% (39·9–46·9) of the global population, had been infected one or more times. 1·34 billion (1·20–1·49) of these infections occurred in south Asia, the highest among the seven super-regions, although the sub-Saharan Africa super-region had the highest infection rate (79·3 per 100 population [69·0–86·4]). The high-income super-region had the fewest infections (239 million [226–252]), and southeast Asia, east Asia, and Oceania had the lowest infection rate (13·0 per 100 population [8·4–17·7]). The cumulative proportion of the population ever infected varied greatly between countries and territories, with rates higher than 70% in 40 countries and lower than 20% in 39 countries. There was no discernible relationship between R(effective) and total immunity, and even at total immunity levels of 80%, we observed no indication of an abrupt drop in R(effective), indicating that there is not a clear herd immunity threshold observed in the data. INTERPRETATION: COVID-19 has already had a staggering impact on the world up to the beginning of the omicron (B.1.1.529) wave, with over 40% of the global population infected at least once by Nov 14, 2021. The vast differences in cumulative proportion of the population infected across locations could help policy makers identify the transmission-prevention strategies that have been most effective, as well as the populations at greatest risk for future infection. This information might also be useful for targeted transmission-prevention interventions, including vaccine prioritisation. Our statistical approach to estimating SARS-CoV-2 infection allows estimates to be updated and disseminated rapidly on the basis of newly available data, which has and will be crucially important for timely COVID-19 research, science, and policy responses. FUNDING: Bill & Melinda Gates Foundation, J Stanton, T Gillespie, and J and E Nordstrom.

Lancet2022       LitCov and CORD-19
1126Antiviral and immunomodulatory interferon-beta in high-risk COVID-19 patients: a structured summary of a study protocol for a randomised controlled trial  

OBJECTIVES: The primary objective of the study is to demonstrate the efficacy of low-dose IFN-β in reducing the risk of SARS-CoV-2 recently infected elderly patients to progress towards severe COVID-19 versus 1. To assess the reduction in Intensive Care Unit (ICU) admission in patients treated with IFN-β versus control group within 28 days of randomization. 2. To assess the reduction in number of deaths in IFN- β compared to control group (day 28). 3. To evaluate the increase in proportion of participants returning to negative SARS-CoV-2 RT-PCR in IFN-β -treated versus control group at Day 14 and Day 28. 4. To assess the increase in SARS-CoV-2-specific binding antibody titers in IFN-β compared to control group (day 28). 5. To assess the safety of IFN-β -treated patients versus control group. TRIAL DESIGN: Randomized, Open-Label, Controlled, Superiority Phase II Study. Patients, who satisfy all inclusion criteria and no exclusion criteria, will be randomly assigned to one of the two treatment groups in a ratio 2:1 (IFN-treated versus control patients). Randomization will be stratified by gender. Stratified randomization will balance the presence of male and female in both study arms. PARTICIPANTS: Male and female adults aged 65 years or older with newly diagnosed SARS-CoV-2 infection and mild COVID-19 symptoms are eligible for the study. The trial is being conducted in Rome. Participants will be either hospitalized or home isolated. A group of physicians belonging to the Special Unit for Regional Continued Care (USCAR), specifically trained for the study and under the supervision of the National Institute for Infectious Diseases “Lazzaro Spallanzani”, will be responsible for the screening, enrolment, treatment and clinical monitoring of patients, thus acting as a bridge between clinical centers and territorial health management. ≥ 65 years of age at time of enrolment; Laboratory-confirmed SARS-CoV-2 infection as determined by PCR, in any specimen < 72 hours prior to randomization; Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures; Understands and agrees to comply with planned study procedures; Agrees to the collection of nasopharyngeal swabs and venous blood samples per protocol; Being symptomatic for less than 7 days before starting therapy; NEWS2 score ≤2. Clinical assessment (evidence of rales/crackles on exam) and SpO2 ≤ 94% on room air at rest or after walking test, OR. Acute respiratory failure requiring mechanical ventilation and/or supplemental oxygen; Patients currently using IFN-β (e.g., multiple sclerosis patients); Patients undergoing chemotherapy or other immunosuppressive treatments; Patients with chronic kidney diseases; Known allergy or hypersensitivity to IFN (including asthma); Any autoimmune disease (resulting from patient anamnesis); Patients with signs of dementia or neurocognitive disorders; Patients with current severe depression and/or suicidal ideations; Being concurrently involved in another clinical trial; HIV infection (based on the anamnesis); Use of any antiretroviral medication; Impaired renal function (eGFR calculated by CKD-EPI Creatinine equation < 30 ml/min); Presence of other severe diseases impairing life expectancy (e.g. patients are not expected to survive 28 days given their pre-existing medical condition); Any physical or psychological impediment in a patient that could let the investigator to suspect his/her poor compliance; Lack or withdrawal of informed consent. INTERVENTION AND COMPARATOR: Control arm: No specific antiviral treatment besides standard of care. Treatment arm: 11μg (3MIU) of IFN-β1a will be injected subcutaneously at day 1, 3, 7, and 10 in addition to standard of care. The drug solution, contained in a pre-filled cartridge, will be injected by means of the RebiSmart® electronic injection device. Interferon β1a (Rebif®, Merck KGaA, Darmstadt, Germany) is a disease-modifying drug used to treat relapsing forms of multiple sclerosis (MS). The dose selected for this study is expected to exploit the antiviral and immunomodulatory properties of the cytokine without causing relevant toxicity or inducing refractoriness phenomena sometimes observed after high-dose and/or chronic IFNβ treatments. MAIN OUTCOMES: Primary endpoint of the study is the proportion of patients experiencing a disease progression, during at least 5 days, according to the National Early Warning Score (NEWS2). The NEWS2 score is a standardized approach aimed at promptly detecting signs of clinical deterioration in acutely ill patients and establishing the potential need for higher level of care. It is based on the evaluation of vital signs, including respiratory rate, oxygen saturation, temperature, blood pressure, pulse/heart rate, AVPU response. The resulting observations, compared to a normal range, are combined in a single composite “alarm” score. Any other clinical sign clearly indicating a disease worsening will be considered as disease progression. RANDOMIZATION: Sixty patients will be randomized 2:1 to receive IFN-β1a plus the standard of care or the standard of care only. Eligible patients will be randomized (no later than 36 h after enrolment) by means of a computerized central randomization system. All patients will receive a unique patient identification number at enrolling visit when signing the informed consent and before any study procedure is performed. This number remains constant throughout the entire study. The randomization of patients will be closed when 60 patients have been enrolled. The randomization will be stratified by sex; for each stratum a sequence of treatments randomly permuted in blocks of variable length (3 or 6) will be generated. BLINDING (MASKING): This is an open-label study. After the randomization, patients will be notified whether they will be in the experimental arm or in the control arm. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The study plans to enrol 60 patients: 40 in the IFN-β1a arm, 20 in the control arm, according to a 2:1 - treated: untreated ratio. TRIAL STATUS: Protocol Version: 3.0 Version Date: 18/03/2021 The study is open for recruitment since 16/04/2021.Recruitment is expected to l be completed before 15/08/2021. TRIAL REGISTRATION: EudraCT N°: 2020-003872-42, registration date: 19/10/2020. 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.” SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-021-05367-6.

Trials2021       LitCov and CORD-19
1127Myopericarditis after messenger RNA COVID-19 Vaccination in Adolescents 12 to 18 Years of Age  

OBJECTIVES: To characterize the clinical course and outcomes of children who developed probable myopericarditis after vaccination with the Pfizer- BioNTech (BNT162b2) COVID-19 mRNA vaccine. STUDY DESIGN: A cross-sectional study of 32 children, aged 12 through 18 years, diagnosed with probable myopericarditis following COVID-19 mRNA vaccination as per the CDC criteria for myopericarditis at 9 US centers between May 10, 2021 and June 20, 2021. We retrospectively collected the following data: demographics, SARS-CoV-2 virus detection or serologic testing, clinical manifestations, laboratory test results, imaging study results, treatment and time to resolutions of symptoms. RESULTS: Most (90%) cases followed the second dose of vaccine, and chest pain (100%) was the most common presenting symptom. Patients came to medical attention a median of 2 days (range: <1-20 days) after receipt of Pfizer mRNA COVID-19 vaccination. All adolescents had an elevated plasma troponin concentration. Echocardiographic abnormalities were infrequent, and 84% showed normal cardiac function at presentation. However, cardiac magnetic resonance imaging (CMR), obtained in 16 patients (50%), revealed that 15 (94%) had late gadolinium enhancement consistent with myopericarditis. Most were treated with ibuprofen or an equivalent NSAID for symptomatic relief, one patient was treated primarily with a corticosteroid orally and three patients were given a corticosteroid orally after initial administration of ibuprofen or NSAID; two patients also received intravenous immune globulin. Symptom resolution was observed within 7 days in all patients. CONCLUSIONS: Our data suggest that symptoms due to myopericarditis following mRNA COVID-19 vaccination tend to be mild and transient. Approximately one half of patients underwent CMR, which revealed evidence of myocardial inflammation despite a lack of echocardiographic abnormalities.

J Pediatr2021       LitCov and CORD-19
1128Impact of the COVID-19 pandemic and lockdown restrictions on psychosocial and behavioural outcomes among Australian adults with type 2 diabetes: Findings from the PREDICT cohort study  

AIM: To examine psychosocial and behavioural impacts of the novel coronavirus disease 2019 (COVID‐19) pandemic and lockdown restrictions among adults with type 2 diabetes. METHODS: Participants enrolled in the PRogrEssion of DIabetic ComplicaTions (PREDICT) cohort study in Melbourne, Australia (n = 489 with a baseline assessment pre‐2020) were invited to complete a phone/online follow‐up assessment in mid‐2020 (i.e., amidst COVID‐19 lockdown restrictions). Repeated assessments that were compared with pre‐COVID‐19 baseline levels included anxiety symptoms (7‐item Generalised Anxiety Disorder scale [GAD‐7]), depressive symptoms (8‐item Patient Health Questionnaire [PHQ‐8]), diabetes distress (Problem Areas in Diabetes scale [PAID]), physical activity/sedentary behaviour, alcohol consumption and diabetes self‐management behaviours. Additional once‐off measures at follow‐up included COVID‐19‐specific worry, quality of life (QoL), and healthcare appointment changes (telehealth engagement and appointment cancellations/avoidance). RESULTS: Among 470 respondents (96%; aged 66 ± 9 years, 69% men), at least ‘moderate’ worry about COVID‐19 infection was reported by 31%, and 29%–73% reported negative impacts on QoL dimensions (greatest for: leisure activities, feelings about the future, emotional well‐being). Younger participants reported more negative impacts (p < 0.05). Overall, anxiety/depressive symptoms were similar at follow‐up compared with pre‐COVID‐19, but diabetes distress reduced (p < 0.001). Worse trajectories of anxiety/depressive symptoms were observed among those who reported COVID‐19‐specific worry or negative QoL impacts (p < 0.05). Physical activity trended lower (~10%), but sitting time, alcohol consumption and glucose‐monitoring frequency remained unchanged. 73% of participants used telehealth, but 43% cancelled a healthcare appointment and 39% avoided new appointments despite perceived need. CONCLUSIONS: COVID‐19 lockdown restrictions negatively impacted QoL, some behavioural risk factors and healthcare utilisation in adults with type 2 diabetes. However, generalised anxiety and depressive symptoms remained relatively stable.

Diabet Med2021       LitCov and CORD-19
1129In silico identification of potential inhibitors of key SARS-CoV-2 3CL hydrolase (Mpro) via molecular docking, MMGBSA predictive binding energy calculations and molecular dynamics simulation  

The incidence of 2019 novel corona virus (SARS-CoV-2) has created a medical emergency throughout the world. Various efforts have been made to develop the vaccine or effective treatments against the disease. The discovery of crystal structure of SARS-CoV-2 main protease has made the in silico identification of its inhibitors possible. Based on its critical role in viral replication, the viral protease can prove to be a promising “target” for antiviral drug therapy. We have systematically screened an in-house library of 15,754 natural and synthetic compounds, established at International Center for Chemical and Biological Sciences, University of Karachi. The in silico search for potential viral protease inhibitors resulted in nine top ranked ligands (compounds 1–9) against SARS-CoV-2 main protease (PDB ID: 6LU7) based on docking scores, and predictive binding energies. The in silico studies were updated via carrying out the docking, and predictive binding energy estimation, with a recently reported crystal structure of main protease (PDB ID: 6Y2F) at a better resolution i.e., 1.95 Å. Compound 2 (molecular bank code AAA396) was found to have highest negative binding energy of −71.63 kcal/mol for 6LU7. While compound 3 (molecular bank code AAD146) exhibited highest negative binding energy of -81.92 kcal/mol for 6Y2F. The stability of the compounds- in complex with viral protease was analyzed by Molecular Dynamics simulation studies, and was found to be stable over the course of 20 ns simulation time. Compound 2, and 3 were predicted to be the significant inhibitors of SARS-CoV-2 3CL hydrolase (Mpro) among the nine short listed compounds.

PLoS One2020       LitCov and CORD-19
1130Antibody responses to SARS-CoV-2 in patients with COVID-19  

N/A

Nat Med2020       LitCov and CORD-19
1131Impact of prior infection status on antibody response to the BNT162b2 mRNA COVID-19 vaccine in healthcare workers at a COVID-19 referral hospital in Milan, Italy  

In Italy, SARS-CoV-2 vaccination campaign prioritized healthcare workers (HCWs) to receive two doses of BNT162b2 vaccine, irrespective of a previous SARS-CoV-2 infection. In this real-life study, we compared the humoral response to BNT162b2 vaccine in HCWs with and without a previous SARS-CoV-2 infection. Of the 407 HCWs enrolled, 334 (82.1%) were SARS-CoV-2-naive and 73 (17.9%) SARS-CoV-2-experienced. Post-vaccine humoral response was detectable in more than 98% of HCWs. Overall, the median level of anti-S IgG in SARS-COV-2-experienced HCWs was twice as high as those of SARS-CoV-2-naive subjects (24641.0 AU/mL [IQR: 15273.0–>40000.0] versus 13053.8 [IQR: 7303.3–20105.8]; p < .001), irrespective of the time elapsed from SARS-CoV-2 previous infection. In a subgroup of SARS-CoV-2-naive and -experienced subjects who received only one dose of the vaccine, the latter showed 32 times higher levels of anti-S IgG compared to the former. Although no serious adverse events have been reported, mild to moderate side effects occurred more frequently after the first dose in the SARS-CoV-2-experienced than in naive subjects (67% versus 42%, respectively; p < .001). Notably, post-vaccination anti-SARS-CoV-2 spike IgG levels ≥20,000 AU/mL were independently associated with the risk of fever ≥38°C (adjusted odds ratio [aOR] 5.122, 95% CI 2.368–11.080, p < .0001). Our study showed high responsiveness of BNT162b2 vaccine and a relationship between levels of antibody response and reactogenicity. It suggests that a single dose of mRNA vaccine might evoke effective protection in SARS-CoV-2-experienced subjects.

Hum Vaccin Immunother2021       LitCov and CORD-19
1132Willingness to get the COVID-19 vaccine among patients with rheumatic diseases, healthcare workers and general population in Turkey: a web-based survey  

OBJECTIVES: Vaccination against COVID-19 emerges as an effective strategy for combating the pandemic. While many of our patients with rheumatic diseases (RD) wonder whether it is safe to get the vaccine, vaccine hesitancy is rising among the general population. We assessed the willingness to get vaccination and its probable predictors among patients with RD compared to healthcare workers and a sample from the general population. METHODS: We conducted a web-based questionnaire survey in a cross-sectional design in 3 groups of participants just before the mass vaccination program in Istanbul, Turkey. The questionnaire sought socio-demographic variables, COVID-19 related risk factors, willingness to get vaccination, and concerns and thoughts about vaccine. COVID-19 anxiety scale (CAS) was also evaluated. RESULTS: We studied in total 732 patients with RD (Group 1), 763 individuals representing general population (Group 2) and 320 hospital workers (Group 3). Dysfunctional anxiety related to COVID-19 was found in 4.9%, 3.8% and 4.1%, in Group 1, 2 and 3, respectively. Of the patients with RD, 29.2% were willing to be vaccinated, 19.0% were unwilling and 51.8% were undecided. These were somewhat similar among the general population (yes: 34.6%, no: 23.3% and unsure: 42.1%), with significantly less undecided individuals (p < 0.001). On the other hand, hospital workers were significantly more willing (yes: 52.5%, no: 20.9% and unsure: 26.6%) (p < 0.001). Main concerns were probable side effects, unknown scientific results and having no trust. Being male, older age, working in a hospital, not having contracted COVID-19 and high scores on CAS were found to be independently associated with willingness. CONCLUSIONS: The low rate of vaccine acceptance among patients with RD, as well as general population sampling is worrying. Healthcare policies should aim to implement communication, promote confidence and increase demand for COVID-19 vaccine. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00296-021-04841-3.

Rheumatol Int2021       LitCov and CORD-19
1133Effects of adjusting public health, travel and social measures during the roll-out of COVID-19 vaccination: a modelling study  

BACKGROUND: Since the emergence of the COVID-19 pandemic in late 2019, various public health and social measures (PHSMs) have been used to suppress and mitigate the spread of SARS-CoV-2. With mass vaccination programmes against COVID-19 being rolled out in many countries in early 2021, we aimed to evaluate to what extent travel restrictions and other PHSMs can be relaxed without exacerbating the local and global spread of COVID-19. METHODS: We adapted an existing age-structured susceptible-infectious-removed model of SARS-CoV-2 transmission dynamics that can be parameterised with country-specific age demographics and contact patterns to simulate the effect of vaccination and PHSM relaxation on transmission. We varied assumptions by age-specific susceptibility and infectiousness, vaccine uptake, contact patterns, and age structures. We used Hong Kong as a case study and assumed that, before vaccination, the population is completely susceptible to SARS-CoV-2 infection. We applied our model to 304 jurisdictions (27 countries and 277 sub-national administrative regions from eight countries). We assumed that PHSMs have suppressed the effective reproductive number (R(e)) to fall between 1·0 and 9·0 locally before the commencement of vaccination programmes. We evaluated the levels of PHSMs that should be maintained during the roll-out of COVID-19 vaccination to avoid a large local outbreak of COVID-19, with different assumptions about vaccine efficacy, vaccination coverage, and travel restrictions. We assumed that the maximum capacity of the health system, in terms of daily hospital admissions, is 0·005% of the population size. FINDINGS: At vaccine efficacy of 0·80 in reducing susceptibility to SARS-CoV-2 infection, 0·50 in reducing SARS-CoV-2 infectivity, and 0·95 in reducing symptomatic COVID-19 diseases, vaccination coverage would have to be 100% for all individuals aged 30 or older to avoid an outbreak, when relaxing PHSMs, that would overload the local health-care system, assuming a pre-vaccination R(e) of 2·5. Testing and quarantine of at least 5 days would have to be maintained for inbound travellers to minimise the risk of reintroducing a local outbreak until high vaccination coverages are attained locally and overseas in most countries. INTERPRETATION: Gradual relaxation of PHSMs should be carefully planned during the roll-out of vaccination programmes, and easing of travel restrictions weighed against risk of reintroducing outbreaks, to avoid overwhelming health systems and minimise deaths related to COVID-19. FUNDING: Health and Medical Research Fund and the General Research Fund.

Lancet Public Health2021       LitCov and CORD-19
1134Psychological distress associated with COVID-19 quarantine: Latent profile analysis, outcome prediction and mediation analysis  

BACKGROUND: Mental health of the population during COVID-19 quarantine could be at risk. Previous studies in short quarantines, found mood-related and anxiety symptomatology. Here we aimed to characterize the subtypes of psychological distress associated with quarantine, assess its prevalence, explore risk/protective factors, and possible mechanisms. METHODS: Online cross-sectional data (n=4408) was collected during the Argentine quarantine, between 1(st)-17(th) April 2020 along a small replication study (n=644). Psychological distress clusters were determined using latent profile analysis on a wide-range of symptoms using the complete Brief-Symptom Inventory-53. Multinomial and Elastic-net regression were performed to identify risk/protective factors among trait-measures (Personality and Resilience) and state-measures (COVID-19 related fear and coping-skills). RESULTS: Three latent-classes defined by symptom severity level were identified. The majority of individuals were classified in the mild (40.9%) and severe classes (41.0%). Participants reported elevated symptoms of Phobic-Anxiety (41.3%), Anxiety (31.8%), Depression (27.5%), General-Distress (27.1%), Obsession-Compulsion (25.1%) and Hostility (13.7%). Logistic-regressions analyses mainly revealed that women, young individuals, having a previous psychiatric diagnosis or trauma, having high levels of trait-neuroticism and COVID-related fear, were those at greater risk of psychological distress. In contrast, adults, being married, exercising, having upper-class income, having high levels of trait-resilience and coping-skills, were the most protected. Mediation analysis, showed that state-measures mediated the association between trait-measures and class-membership. CONCLUSIONS: Quarantine was associated intense psychological distress. Attention should be given to COVID-19-related fear and coping-skills as they act as potential mediators in emotional suffering during quarantine.

J Affect Disord2020       LitCov and CORD-19
1135Humoral and T-cell responses to SARS-CoV-2 vaccination in patients receiving immunosuppression  

OBJECTIVE: There is an urgent need to assess the impact of immunosuppressive therapies on the immunogenicity and efficacy of SARS-CoV-2 vaccination. METHODS: Serological and T-cell ELISpot assays were used to assess the response to first-dose and second-dose SARS-CoV-2 vaccine (with either BNT162b2 mRNA or ChAdOx1 nCoV-19 vaccines) in 140 participants receiving immunosuppression for autoimmune rheumatic and glomerular diseases. RESULTS: Following first-dose vaccine, 28.6% (34/119) of infection-naïve participants seroconverted and 26.0% (13/50) had detectable T-cell responses to SARS-CoV-2. Immune responses were augmented by second-dose vaccine, increasing seroconversion and T-cell response rates to 59.3% (54/91) and 82.6% (38/46), respectively. B-cell depletion at the time of vaccination was associated with failure to seroconvert, and tacrolimus therapy was associated with diminished T-cell responses. Reassuringly, only 8.7% of infection-naïve patients had neither antibody nor T-cell responses detected following second-dose vaccine. In patients with evidence of prior SARS-CoV-2 infection (19/140), all mounted high-titre antibody responses after first-dose vaccine, regardless of immunosuppressive therapy. CONCLUSION: SARS-CoV-2 vaccines are immunogenic in patients receiving immunosuppression, when assessed by a combination of serology and cell-based assays, although the response is impaired compared with healthy individuals. B-cell depletion following rituximab impairs serological responses, but T-cell responses are preserved in this group. We suggest that repeat vaccine doses for serological non-responders should be investigated as means to induce more robust immunological response.

Ann Rheum Dis2021       LitCov and CORD-19
1136Neutralizing Antibody Response to Pseudotype SARS-CoV-2 Differs between mRNA-1273 and BNT162b2 COVID-19 Vaccines and by History of SARS-CoV-2 Infection  

BACKGROUND: Data on the development of neutralizing antibodies against SARS-CoV-2 after SARS-CoV-2 infection and after vaccination with messenger RNA (mRNA) COVID-19 vaccines are limited. METHODS: From a prospective cohort of 3,975 adult essential and frontline workers tested weekly from August 2020 to March 2021 for SARS-CoV-2 infection by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) assay irrespective of symptoms, 497 participants had sera drawn after infection (170), vaccination (327), and after both infection and vaccination (50 from the infection population). Serum was collected after infection and each vaccine dose. Serum-neutralizing antibody titers against USA-WA1/2020-spike pseudotype virus were determined by the 50% inhibitory dilution. Geometric mean titers (GMTs) and corresponding fold increases were calculated using t-tests and linear mixed effects models. RESULTS: Among 170 unvaccinated participants with SARS-CoV-2 infection, 158 (93%) developed neutralizing antibodies (nAb) with a GMT of 1,003 (95% CI=766-1,315). Among 139 previously uninfected participants, 138 (99%) developed nAb after mRNA vaccine dose-2 with a GMT of 3,257 (95% CI = 2,596-4,052). GMT was higher among those receiving mRNA-1273 vaccine (GMT =4,698, 95%CI= 3,186-6,926) compared to BNT162b2 vaccine (GMT=2,309, 95%CI=1,825-2,919). Among 32 participants with prior SARS-CoV-2 infection, GMT was 21,655 (95%CI=14,766-31,756) after mRNA vaccine dose-1, without further increase after dose-2. CONCLUSIONS: A single dose of mRNA vaccine after SARS-CoV-2 infection resulted in the highest observed nAb response. Two doses of mRNA vaccine in previously uninfected participants resulted in higher nAb to SARS-CoV-2 than after one dose of vaccine or SARS-CoV-2 infection alone. Neutralizing antibody response also differed by mRNA vaccine product.

Clin Infect Dis2021       LitCov and CORD-19
1137COVID-19 coronavirus: recommended personal protective equipment for the orthopedic and trauma surgeon  

PURPOSE: With the COVID-19 crisis, recommendations for personal protective equipment (PPE) are necessary for protection in orthopaedics and traumatology. The primary purpose of this study is to review and present current evidence and recommendations for personal protective equipment and safety recommendations for orthopaedic surgeons and trauma surgeons. METHODS: A systematic review of the available literature was performed using the keyword terms “COVID-19”, “Coronavirus”, “surgeon”, “health-care workers”, “protection”, “masks”, “gloves”, “gowns”, “helmets”, and “aerosol” in several combinations. The following databases were assessed: Pubmed, Cochrane Reviews, Google Scholar. Due to the paucity of available data, it was decided to present it in a narrative manner. In addition, participating doctors were asked to provide their guidelines for PPE in their countries (Austria, Luxembourg, Switzerland, Germany, UK) for consideration in the presented practice recommendations. RESULTS: World Health Organization guidance for respiratory aerosol-generating procedures (AGPs) such as intubation in a COVID19 environment was clear and included the use of an FFP3 (filtering face piece level 3) mask and face protection. However, the recommendation for surgical AGPs, such as the use of high-speed power tools in the operating theatre, was not clear until the UK Public Health England (PHE) guidance of 27 March 2020. This guidance included FFP3 masks and face protection, which UK surgeons quickly adopted. The recommended PPE for orthopaedic surgeons, working in a COVID19 environment, should consist of level 4 surgical gowns, face shields or goggles, double gloves, FFP2-3 or N95-99 respirator masks. An alternative to the mask, face shield and goggles is a powered air-purifying respirator, particularly if the surgeons fail the mask fit test or are required to undertake a long procedure. However, there is a high cost and limited availabilty of these devices at present. Currently available surgical helmets and toga systems may not be the solution due to a permeable top for air intake. During the current COVID-19 crisis, it appeared that telemedicine can be considered as an electronic personal protective equipment by reducing the number of physical contacts and risk contamination. CONCLUSION: Orthopaedic and trauma surgery using power tools, pulsatile lavage and electrocautery are surgical aerosol-generating procedures and all body fluids contain virus particles. Raising awareness of these issues will help avoid occupational transmission of COVID-19 to the surgical team by aerosolization of blood or other body fluids and hence adequate PPE should be available and used during orthopaedic surgery. In addition, efforts have to be made to improve the current evidence in this regard. LEVEL OF EVIDENCE: IV.

Knee Surg Sports Traumatol Art2020       LitCov and CORD-19
1138The Association of COVID-19 With Acute Kidney Injury Independent of Severity of Illness: A Multicenter Cohort Study  

RATIONALE AND OBJECTIVE: While COVID-19 infection has been associated with acute kidney injury (AKI), it is unclear whether this association is independent of traditional risk factors such as hypotension, nephrotoxin exposure, and inflammation. We tested the independent association of COVID-19 with AKI. STUDY DESIGN: Multicenter, observational, cohort study. SETTING AND PARTICIPANTS: Patients admitted to one of six hospitals within the Yale-New Haven Health System between 3/10/2020 and 8/31/2020 and tested for SARS-CoV-2 via nasopharyngeal PCR test. EXPOSURE: Positive test for SARS-CoV-2. OUTCOME: AKI by Kidney Disease: Improving Global Outcomes criteria. ANALYTIC APPROACH: Evaluated the association of COVID-19 with AKI after controlling for time-invariant factors at admission (e.g., demographics, comorbidities) and time-varying factors updated continuously during hospitalization (e.g., vital signs, medications, laboratory results, respiratory failure) using time-updated Cox proportional hazard models. RESULTS: Of the 22,122 patients hospitalized between, 2,600 tested positive and 19,522 tested negative for SARS-CoV-2. Compared to patients who tested negative, patients with COVID-19 had more AKI [30.6% vs. 18.2%, absolute risk difference 12.5 (95% CI, 10.6, 14.3)%] and dialysis-requiring AKI (8.5% vs. 3.6%) and lower recovery from AKI (58% vs. 69.8%]. Compared to patients who tested negative, patients with COVID-19 had higher inflammatory markers (C-reactive protein, ferritin), and greater use of vasopressors and diuretics. Compared to patients who tested negative, patients with COVID-19 had higher rate of AKI in univariable analysis (HR, 1.84 [1.73, 1.95]). In fully adjusted model controlling for demographics, comorbidities, vital signs, medications, and laboratory results, COVID-19 remained associated with a high rate of AKI (adjusted HR, 1.40 [1.29-1.53]). LIMITATIONS: Possibility of residual confounding. CONCLUSIONS: COVID-19 is associated with high rates of AKI not fully explained by adjustment for known risk factors. This suggests the presence of mechanisms of AKI not accounted for in this analysis, which may include a direct effect of COVID-19 on the kidney or other unmeasured mediators. Future studies should evaluate the possible unique pathways by which COVID-19 may cause AKI.

Am J Kidney Dis2021       LitCov and CORD-19
1139Mental health of medical personnel during the COVID-19 pandemic  

INTRODUCTION: The coronavirus disease 2019 (COVID‐19) pandemic caused significant changes in the everyday functioning of the general population, as well as medical workers. Medical personnel, especially those in direct contact with COVID‐19 patients, could have increased levels of stress, anxiety, and depression. The objective of this study was to explore the mental health status of medical personnel in Serbia during the pandemic by assessing stress levels, symptoms of anxiety, and depression. METHODS: This cross‐sectional study was conducted as an online‐based survey, in the period from 8 April to 14 April 2020, during the COVID‐19 pandemic. The study included 1678 participants, and the snowball sampling technique was used to reach healthcare professionals. The level of stress and symptoms of depression and anxiety were assessed among medical personnel in Serbia by the 10‐item Perceived Stress Scale (PSS), the Beck Depression Inventory IA (BDI‐IA), and the 7‐item Generalized Anxiety Disorder Scale (GAD‐7), respectively. RESULTS: A total of 1678 participants completed the survey, with a mean age of 40.38 ± 10.32 years, of which 1,315 (78.4%) were women, and 363 (21.6%) were men. Out of these, 684 (40.8%) participants were medical personnel, and 994 (59.2%) were people of other professions. Frontline medical personnel reported higher scores on all measurement tools than second‐line medical personnel (e.g., mean PSS scores: 19.12 ± 5.66 versus 17.53 ± 5.71; p = .006; mean GAD‐7 scores: 8.57 ± 6.26 versus 6.73 ± 5.76; p = .001; mean BDI‐IA scores: 9.25 ± 8.26 versus 7.36 ± 7.28; p = .006). Binary logistic regression showed that the probability of developing more severe anxiety symptoms doubles in frontline medical personnel. CONCLUSION: Our findings suggest that frontline medical personnel is under an increased psychological burden during the COVID‐19 pandemic, having higher levels of stress, anxiety, and depression than second‐line medical personnel. Adequate measures should be taken to relieve this burden and preserve the mental health of frontline medical personnel.

Brain Behav2020       LitCov and CORD-19
1140A global database of COVID-19 vaccinations  

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Nat Hum Behav2021       LitCov and CORD-19
1141Depression, anxiety, stress and their associated factors among Ethiopian University students during an early stage of COVID-19 pandemic: An online-based cross-sectional survey  

BACKGROUND: The occurrence of the Coronavirus Disease 2019 (COVID-19) affects the mental health situation of almost everyone, including University students who spent most of their time at home due to the closure of the Universities. Therefore, this study aimed at assessing depression, anxiety, stress and identifying their associated factors among university students in Ethiopia during the early stage of the COVID-19 pandemic. METHODS: We invited students to complete an online survey using Google forms comprising consent, socio-demographic characteristics, and the standard validated depression, anxiety, and stress scale (DASS-21) questionnaire. After completion of the survey from June 30 to July 30, 2020, we exported the data into SPSS 22. Both descriptive and analytical statistics were computed. Associated factors were identified using binary logistic regression and variables with a p-value <0.05 were declared as statistically significant factors with the outcome variables. RESULTS: A total of 423 students completed the online survey. The prevalence of depression, anxiety, and stress in this study was 46.3%, 52%, and 28.6%, respectively. In the multivariable model, female sex, poor self-efficacy to prevent COVID-19, those who do not read any material about COVID-19 prevention, lack of access to reading materials about their profession, and lack of access to uninterrupted internet access were significantly associated with depression. Female sex, lower ages, students with non-health-related departments, those who do not think that COVID-19 is preventable, and those who do not read any materials about COVID-19 prevention were significantly associated with anxiety. Whereas, being female, students attending 1(st) and 2(nd) years, those who do not think that COVID-19 is preventable, presence of confirmed COVID-19 patient at the town they are living in, and lack of access to reading materials about their profession were significantly associated with stress. CONCLUSIONS: Depression, anxiety, and stress level among University students calls for addressing these problems by controlling the modifiable factors identified and promoting psychological wellbeing of students.

PLoS One2021       LitCov and CORD-19
1142Time Course of Lung Changes at Chest CT during Recovery from COVID-19  

BACKGROUND: Chest CT is used to assess the severity of lung involvement in COVID-19 pneumonia. PURPOSE: To determine the change in chest CT findings associated with COVID-19 pneumonia from initial diagnosis until patient recovery. MATERIALS AND METHODS: This retrospective review included patients with RT-PCR confirmed COVID-19 infection presenting between 12 January 2020 to 6 February 2020. Patients with severe respiratory distress and/ or oxygen requirement at any time during the disease course were excluded. Repeat Chest CT was obtained at approximately 4 day intervals. The total CT score was the sum of lung involvement (5 lobes, score 1-5 for each lobe, range, 0 none, 25 maximum) was determined. RESULTS: Twenty one patients (6 males and 15 females, age 25-63 years) with confirmed COVID-19 pneumonia were evaluated. These patients under went a total of 82 pulmonary CT scans with a mean interval of 4±1 days (range: 1-8 days). All patients were discharged after a mean hospitalized period of 17±4 days (range: 11-26 days). Maximum lung involved peaked at approximately 10 days (with the calculated total CT score of 6) from the onset of initial symptoms (R2=0.25), p<0.001). Based on quartiles of patients from day 0 to day 26 involvement, 4 stages of lung CT were defined: Stage 1 (0-4 days): ground glass opacities (GGO) in 18/24 (75%) patients with the total CT score of 2±2; (2)Stage-2 (5-8d days): increased crazy-paving pattern 9/17 patients (53%) with a increase in total CT score (6±4, p=0.002); (3) Stage-3 (9-13days): consolidation 19/21 (91%) patients with the peak of total CT score (7±4); (4) Stage-4 (≥14 days): gradual resolution of consolidation 15/20 (75%) patients with a decreased total CT score (6±4) without crazy-paving pattern. CONCLUSION: In patients recovering from COVID-19 pneumonia (without severe respiratory distress during the disease course), lung abnormalities on chest CT showed greatest severity approximately 10 days after initial onset of symptoms.

Radiology2020       LitCov and CORD-19
1143Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity  

Limited knowledge is available on the relationship between antigen-specific immune responses and COVID-19 disease severity. We completed a combined examination of all three branches of adaptive immunity at the level of SARS-CoV-2-specific CD4+ and CD8+ T cell and neutralizing antibody responses in acute and convalescent subjects. SARS-CoV-2-specific CD4+ and CD8+ T cells were each associated with milder disease. Coordinated SARS-CoV-2-specific adaptive immune responses were associated with milder disease, suggesting roles for both CD4+ and CD8+ T cells in protective immunity in COVID-19. Notably, coordination of SARS-CoV-2 antigen-specific responses was disrupted in individuals > 65 years old. Scarcity of naive T cells was also associated with ageing and poor disease outcomes. A parsimonious explanation is that coordinated CD4+ T cell, CD8+ T cell, and antibody responses are protective, but uncoordinated responses frequently fail to control disease, with a connection between ageing and impaired adaptive immune responses to SARS-CoV-2.

Cell2020       LitCov and CORD-19
1144Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19  

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Nat Med2020       LitCov and CORD-19
1145Depression, anxiety and the COVID-19 pandemic: Severity of symptoms and associated factors among university students after the end of the movement lockdown  

BACKGROUND AND AIMS: This online cross-sectional study investigated the severity of depressive, anxiety, and stress symptoms among university students and determined the association between various factors and the levels of depressive and anxiety symptoms in response to the coronavirus disease 2019 (COVID-19) pandemic after the movement control order (MCO) was lifted. METHODS: A total of 316 participants were administered a self-report questionnaire that collected data on sociodemographic attributes, personal characteristics, COVID-19-related stressors, religious coping, and clinical characteristics. In addition, the Multidimensional Scale of Perceived Social Support (MSPSS) and the 21-item Depression, Anxiety and Stress Scale (DASS-21) were administered. RESULTS: Regarding depression, 15.5%, 11.7%, and 9.2% of the participants reported mild, moderate, and severe to extremely severe depression, respectively. For anxiety, 7.0%, 16.5%, and 13.2% of the respondents had mild, moderate, and severe to extremely severe anxiety, respectively. Moreover, 26.3% of participants had mild stress, 9.5% had moderate stress, and 6.6% had severe to extremely severe stress. The multiple linear regression model revealed that frustration because of loss of daily routine and study disruption and having preexisting medical, depressive, and anxiety disorders were associated with elevated depressive symptoms, while a greater degree of family and friends social support was associated with less depressive symptoms after adjusting for age, gender, and marital status. It was also found that frustration because of study disruption and having preexisting medical, depressive, and anxiety disorders were associated with elevated anxiety symptoms, while being enrolled in medicine-based courses and having a greater degree of family support were factors associated with less anxiety symptoms after adjusting for age, gender, and marital status. CONCLUSION: There is a need to conduct a longitudinal study in the future to confirm the causal relationship between the significant predictive factors and depression and anxiety identified in this study, and maintenance of a persistent flow of academic activities and social interaction may be of utmost importance to safeguard the mental wellbeing of university students.

PLoS One2021       LitCov and CORD-19
1146mRNA vaccination drives differential mucosal neutralizing antibody profiles in naïve and SARS-CoV-2 previously-infected individuals  

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Front Immunol2022       LitCov
1147Global Telemedicine Implementation and Integration Within Health Systems to Fight the COVID-19 Pandemic: A Call to Action  

On March 11, 2020, the World Health Organization declared the coronavirus disease 2019 (COVID-19) outbreak as a pandemic, with over 720,000 cases reported in more than 203 countries as of 31 March. The response strategy included early diagnosis, patient isolation, symptomatic monitoring of contacts as well as suspected and confirmed cases, and public health quarantine. In this context, telemedicine, particularly video consultations, has been promoted and scaled up to reduce the risk of transmission, especially in the United Kingdom and the United States of America. Based on a literature review, the first conceptual framework for telemedicine implementation during outbreaks was published in 2015. An updated framework for telemedicine in the COVID-19 pandemic has been defined. This framework could be applied at a large scale to improve the national public health response. Most countries, however, lack a regulatory framework to authorize, integrate, and reimburse telemedicine services, including in emergency and outbreak situations. In this context, Italy does not include telemedicine in the essential levels of care granted to all citizens within the National Health Service, while France authorized, reimbursed, and actively promoted the use of telemedicine. Several challenges remain for the global use and integration of telemedicine into the public health response to COVID-19 and future outbreaks. All stakeholders are encouraged to address the challenges and collaborate to promote the safe and evidence-based use of telemedicine during the current pandemic and future outbreaks. For countries without integrated telemedicine in their national health care system, the COVID-19 pandemic is a call to adopt the necessary regulatory frameworks for supporting wide adoption of telemedicine.

JMIR Public Health Surveill2020       LitCov and CORD-19
1148Investigating and Improving the Accuracy of US Citizens' Beliefs About the COVID-19 Pandemic: Longitudinal Survey Study  

BACKGROUND: The COVID-19 infodemic, a surge of information and misinformation, has sparked worry about the public’s perception of the coronavirus pandemic. Excessive information and misinformation can lead to belief in false information as well as reduce the accurate interpretation of true information. Such incorrect beliefs about the COVID-19 pandemic might lead to behavior that puts people at risk of both contracting and spreading the virus. OBJECTIVE: The objective of this study was two-fold. First, we attempted to gain insight into public beliefs about the novel coronavirus and COVID-19 in one of the worst hit countries: the United States. Second, we aimed to test whether a short intervention could improve people’s belief accuracy by empowering them to consider scientific consensus when evaluating claims related to the pandemic. METHODS: We conducted a 4-week longitudinal study among US citizens, starting on April 27, 2020, just after daily COVID-19 deaths in the United States had peaked. Each week, we measured participants’ belief accuracy related to the coronavirus and COVID-19 by asking them to indicate to what extent they believed a number of true and false statements (split 50/50). Furthermore, each new survey wave included both the original statements and four new statements: two false and two true statements. Half of the participants were exposed to an intervention aimed at increasing belief accuracy. The intervention consisted of a short infographic that set out three steps to verify information by searching for and verifying a scientific consensus. RESULTS: A total of 1202 US citizens, balanced regarding age, gender, and ethnicity to approximate the US general public, completed the baseline (T0) wave survey. Retention rate for the follow-up waves— first follow-up wave (T1), second follow-up wave (T2), and final wave (T3)—was high (≥85%). Mean scores of belief accuracy were high for all waves, with scores reflecting low belief in false statements and high belief in true statements; the belief accuracy scale ranged from –1, indicating completely inaccurate beliefs, to 1, indicating completely accurate beliefs (T0 mean 0.75, T1 mean 0.78, T2 mean 0.77, and T3 mean 0.75). Accurate beliefs were correlated with self-reported behavior aimed at preventing the coronavirus from spreading (eg, social distancing) (r at all waves was between 0.26 and 0.29 and all P values were less than .001) and were associated with trust in scientists (ie, higher trust was associated with more accurate beliefs), political orientation (ie, liberal, Democratic participants held more accurate beliefs than conservative, Republican participants), and the primary news source (ie, participants reporting CNN or Fox News as the main news source held less accurate beliefs than others). The intervention did not significantly improve belief accuracy. CONCLUSIONS: The supposed infodemic was not reflected in US citizens’ beliefs about the COVID-19 pandemic. Most people were quite able to figure out the facts in these relatively early days of the crisis, calling into question the prevalence of misinformation and the public’s susceptibility to misinformation.

J Med Internet Res2021       LitCov and CORD-19
1149Beliefs, barriers and hesitancy towards the COVID-19 vaccine among Bangladeshi residents: Findings from a cross-sectional study  

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PLoS One2022       LitCov
1150Comprehensive assessment of humoral response after Pfizer BNT162b2 mRNA Covid-19 vaccination: a three-case series  

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Clin Chem Lab Med2021       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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