\ 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
851Deciphering the Role of Humoral and Cellular Immune Responses in Different COVID-19 Vaccines-A Comparison of Vaccine Candidate Genes in Roborovski Dwarf Hamsters  

With the exception of inactivated vaccines, all SARS-CoV-2 vaccines currently used for clinical application focus on the spike envelope glycoprotein as a virus-specific antigen. Compared to other SARS-CoV-2 genes, mutations in the spike protein gene are more rapidly selected and spread within the population, which carries the risk of impairing the efficacy of spike-based vaccines. It is unclear to what extent the loss of neutralizing antibody epitopes can be compensated by cellular immune responses, and whether the use of other SARS-CoV-2 antigens might cause a more diverse immune response and better long-term protection, particularly in light of the continued evolution towards new SARS-CoV-2 variants. To address this question, we explored immunogenicity and protective effects of adenoviral vectors encoding either the full-length spike protein (S), the nucleocapsid protein (N), the receptor binding domain (RBD) or a hybrid construct of RBD and the membrane protein (M) in a highly susceptible COVID-19 hamster model. All adenoviral vaccines provided life-saving protection against SARS-CoV-2-infection. The most efficient protection was achieved after exposure to full-length spike. However, the nucleocapsid protein, which triggered a robust T-cell response but did not facilitate the formation of neutralizing antibodies, controlled early virus replication efficiently and prevented severe pneumonia. Although the full-length spike protein is an excellent target for vaccines, it does not appear to be the only option for future vaccine design.

Viruses2021       LitCov and CORD-19
852Immediate reactions after mRNA SARS-CoV-2 vaccination  

CMAJ2021       LitCov and CORD-19
853Analysis of Serological Biomarkers of SARS-CoV-2 Infection in Convalescent Samples From Severe, Moderate and Mild COVID-19 Cases  

Precision monitoring of antibody responses during the COVID-19 pandemic is increasingly important during large scale vaccine rollout and rise in prevalence of Severe Acute Respiratory Syndrome-related Coronavirus-2 (SARS-CoV-2) variants of concern (VOC). Equally important is defining Correlates of Protection (CoP) for SARS-CoV-2 infection and COVID-19 disease. Data from epidemiological studies and vaccine trials identified virus neutralising antibodies (Nab) and SARS-CoV-2 antigen-specific (notably RBD and S) binding antibodies as candidate CoP. In this study, we used the World Health Organisation (WHO) international standard to benchmark neutralising antibody responses and a large panel of binding antibody assays to compare convalescent sera obtained from: a) COVID-19 patients; b) SARS-CoV-2 seropositive healthcare workers (HCW) and c) seronegative HCW. The ultimate aim of this study is to identify biomarkers of humoral immunity that could be used to differentiate severe from mild or asymptomatic SARS-CoV-2 infections. Some of these biomarkers could be used to define CoP in further serological studies using samples from vaccination breakthrough and/or re-infection cases. Whenever suitable, the antibody levels of the samples studied were expressed in International Units (IU) for virus neutralisation assays or in Binding Antibody Units (BAU) for ELISA tests. In this work we used commercial and non-commercial antibody binding assays; a lateral flow test for detection of SARS-CoV-2-specific IgG/IgM; a high throughput multiplexed particle flow cytometry assay for SARS-CoV-2 Spike (S), Nucleocapsid (N) and Receptor Binding Domain (RBD) proteins); a multiplex antigen semi-automated immuno-blotting assay measuring IgM, IgA and IgG; a pseudotyped microneutralisation test (pMN) and an electroporation-dependent neutralisation assay (EDNA). Our results indicate that overall, severe COVID-19 patients showed statistically significantly higher levels of SARS-CoV-2-specific neutralising antibodies (average 1029 IU/ml) than those observed in seropositive HCW with mild or asymptomatic infections (379 IU/ml) and that clinical severity scoring, based on WHO guidelines was tightly correlated with neutralisation and RBD/S antibodies. In addition, there was a positive correlation between severity, N-antibody assays and intracellular virus neutralisation.

Front Immunol2021       LitCov and CORD-19
854Psychosocial impact of COVID-19  

BACKGROUND: Along with its high infectivity and fatality rates, the 2019 Corona Virus Disease (COVID-19) has caused universal psychosocial impact by causing mass hysteria, economic burden and financial losses. Mass fear of COVID-19, termed as “coronaphobia”, has generated a plethora of psychiatric manifestations across the different strata of the society. So, this review has been undertaken to define psychosocial impact of COVID-19. METHODS: Pubmed and GoogleScholar are searched with the following key terms- “COVID-19”, “SARS-CoV2”, “Pandemic”, “Psychology”, “Psychosocial”, “Psychitry”, “marginalized”, “telemedicine”, “mental health”, “quarantine”, “infodemic”, “social media” and” “internet”. Few news paper reports related to COVID-19 and psychosocial impacts have also been added as per context. RESULTS: Disease itself multitude by forced quarantine to combat COVID-19 applied by nationwide lockdowns can produce acute panic, anxiety, obsessive behaviors, hoarding, paranoia, and depression, and post-traumatic stress disorder (PTSD) in the long run. These have been fueled by an “infodemic” spread via different platforms social media. Outbursts of racism, stigmatization, and xenophobia against particular communities are also being widely reported. Nevertheless, frontline healthcare workers are at higher-risk of contracting the disease as well as experiencing adverse psychological outcomes in form of burnout, anxiety, fear of transmitting infection, feeling of incompatibility, depression, increased substance-dependence, and PTSD. Community-based mitigation programs to combat COVID-19 will disrupt children's usual lifestyle and may cause florid mental distress. The psychosocial aspects of older people, their caregivers, psychiatric patients and marginalized communities are affected by this pandemic in different ways and need special attention. CONCLUSION: For better dealing with these psychosocial issues of different strata of the society, psychosocial crisis prevention and intervention models should be urgently developed by the government, health care personnel and other stakeholders. Apt application of internet services, technology and social media to curb both pandemic and infodemic needs to be instigated. Psychosocial preparedness by setting up mental organizations specific for future pandemics is certainly necessary.

Diabetes Metab Syndr2020       LitCov and CORD-19
855Primary care preparedness for the SARS-CoV-2 pandemic: a survey of NHS GPs  

BACKGROUND: Primary care manages a significant proportion of healthcare in the United Kingdom and should be a key part of the SARS-CoV-2 pandemic response. AIM: To assess preparedness for the SARS-CoV-2 pandemic by understanding GPs’ perception of their ability to manage current and future service demand, set-up of triage processes, and training in Covid-19 infection prevention and control procedures. DESIGN AND SETTING: Cross-sectional survey of practicing GPs in the United Kingdom, with 2 rounds of data collection early in the pandemic. METHODS: Online survey, scripted and hosted by medeConnect Healthcare, comprising 6 closed prompts on 7-point Likert scales, and an optional free-text component. Quantitative data were analysed using descriptive statistics. Free-text data were analysed thematically. RESULTS: One thousand two GPs completed each round; 51 GPs completed free-text responses in March, and 64 in April. Quantitative data showed greatest confidence in triage of Covid-19 patients, and GPs were more confident managing current than future Covid-19 demand. GPs’ responses were more optimistic and aligned in April than March. Free-text data highlighted that GPs were concerned about lack of appropriate personal protective equipment and personal risk of Covid-19 infection in March, and unmet needs of non-Covid-19 patients in April. In both rounds, GPs expressed feeling overlooked by government and public health bodies. CONCLUSION: Guidance to support general practice clinicians to manage future waves of Covid-19 or other health emergencies must be tailored to general practice from the outset, to support clinicians to manage competing health demands, and mitigate impacts on primary care providers’ wellbeing.

Fam Pract2021       LitCov and CORD-19
856CovXNet: A multi-dilation convolutional neural network for automatic COVID-19 and other pneumonia detection from chest X-ray images with transferable multi-receptive feature optimization  

With the recent outbreak of COVID-19, fast diagnostic testing has become one of the major challenges due to the critical shortage of test kit. Pneumonia, a major effect of COVID-19, needs to be urgently diagnosed along with its underlying reasons. In this paper, deep learning aided automated COVID-19 and other pneumonia detection schemes are proposed utilizing a small amount of COVID-19 chest X-rays. A deep convolutional neural network (CNN) based architecture, named as CovXNet, is proposed that utilizes depthwise convolution with varying dilation rates for efficiently extracting diversified features from chest X-rays. Since the chest X-ray images corresponding to COVID-19 caused pneumonia and other traditional pneumonias have significant similarities, at first, a large number of chest X-rays corresponding to normal and (viral/bacterial) pneumonia patients are used to train the proposed CovXNet. Learning of this initial training phase is transferred with some additional fine-tuning layers that are further trained with a smaller number of chest X-rays corresponding to COVID-19 and other pneumonia patients. In the proposed method, different forms of CovXNets are designed and trained with X-ray images of various resolutions and for further optimization of their predictions, a stacking algorithm is employed. Finally, a gradient-based discriminative localization is integrated to distinguish the abnormal regions of X-ray images referring to different types of pneumonia. Extensive experimentations using two different datasets provide very satisfactory detection performance with accuracy of 97.4% for COVID/Normal, 96.9% for COVID/Viral pneumonia, 94.7% for COVID/Bacterial pneumonia, and 90.2% for multiclass COVID/normal/Viral/Bacterial pneumonias. Hence, the proposed schemes can serve as an efficient tool in the current state of COVID-19 pandemic. All the architectures are made publicly available at: https://github.com/Perceptron21/CovXNet.

Comput Biol Med2020       LitCov and CORD-19
857Neutralization of SARS-CoV-2 Omicron by BNT162b2 mRNA vaccine-elicited human sera  

N/A

Science2022       LitCov and CORD-19
858Clinical characteristics and day-90 outcomes of 4244 critically ill adults with COVID-19: a prospective cohort study  

PURPOSE: To describe acute respiratory distress syndrome (ARDS) severity, ventilation management, and the outcomes of ICU patients with laboratory-confirmed COVID-19 and to determine risk factors of 90-day mortality post-ICU admission. METHODS: COVID-ICU is a multi-center, prospective cohort study conducted in 138 hospitals in France, Belgium, and Switzerland. Demographic, clinical, respiratory support, adjunctive interventions, ICU length-of-stay, and survival data were collected. RESULTS: From February 25 to May 4, 2020, 4643 patients (median [IQR] age 63 [54–71] years and SAPS II 37 [28–50]) were admitted in ICU, with day-90 post-ICU admission status available for 4244. On ICU admission, standard oxygen therapy, high-flow oxygen, and non-invasive ventilation were applied to 29%, 19%, and 6% patients, respectively. 2635 (63%) patients were intubated during the first 24 h whereas overall 3376 (80%) received invasive mechanical ventilation (MV) at one point during their ICU stay. Median (IQR) positive end-expiratory and plateau pressures were 12 (10–14) cmH(2)O, and 24 (21–27) cmH(2)O, respectively. The mechanical power transmitted by the MV to the lung was 26.5 (18.6–34.9) J/min. Paralyzing agents and prone position were applied to 88% and 70% of patients intubated at Day-1, respectively. Pulmonary embolism and ventilator-associated pneumonia were diagnosed in 207 (9%) and 1209 (58%) of these patients. On day 90, 1298/4244 (31%) patients had died. Among patients who received invasive or non-invasive ventilation on the day of ICU admission, day-90 mortality increased with the severity of ARDS at ICU admission (30%, 34%, and 50% for mild, moderate, and severe ARDS, respectively) and decreased from 42 to 25% over the study period. Early independent predictors of 90-day mortality were older age, immunosuppression, severe obesity, diabetes, higher renal and cardiovascular SOFA score components, lower PaO(2)/FiO(2) ratio and a shorter time between first symptoms and ICU admission. CONCLUSION: Among more than 4000 critically ill patients with COVID-19 admitted to our ICUs, 90-day mortality was 31% and decreased from 42 to 25% over the study period. Mortality was higher in older, diabetic, obese and severe ARDS patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-06294-x) contains supplementary material, which is available to authorized users.

Intensive Care Med2020       LitCov and CORD-19
859Implementation of Telemedicine in a Tertiary Hospital-Based Ambulatory Practice in Detroit During the COVID-19 Pandemic: Observational Study  

BACKGROUND: The COVID-19 pandemic, caused by SARS-CoV-2, has forced the health care delivery structure to change rapidly. The pandemic has further widened the disparities in health care and exposed vulnerable populations. Health care services caring for such populations must not only continue to operate but create innovative methods of care delivery without compromising safety. We present our experience of incorporating telemedicine in our university hospital–based outpatient clinic in one of the worst-hit areas in the world. OBJECTIVE: Our goal is to assess the adoption of a telemedicine service in the first month of its implementation in outpatient practice during the COVID-19 pandemic. We also want to assess the need for transitioning to telemedicine, the benefits and challenges in doing so, and ongoing solutions during the initial phase of the implementation of telemedicine services for our patients. METHODS: We conducted a prospective review of clinic operations data from the first month of a telemedicine rollout in the outpatient adult ambulatory clinic from April 1, 2020, to April 30, 2020. A telemedicine visit was defined as synchronous audio-video communication between the provider and patient for clinical care longer than 5 minutes or if the video visit converted to a telephone visit after 5 minutes due to technical problems. We recorded the number of telemedicine visits scheduled, visits completed, and the time for each visit. We also noted the most frequent billing codes used based on the time spent in the patient care and the number of clinical tasks (eg, activity suggested through diagnosis or procedural code) that were addressed remotely by the physicians. RESULTS: During the study period, we had 110 telemedicine visits scheduled, of which 94 (85.4%) visits were completed. The average duration of the video visit was 35 minutes, with the most prolonged visit lasting 120 minutes. Of 94 patients, 24 (25.54%) patients were recently discharged from the hospital, and 70 (74.46%) patients were seen for urgent care needs. There was a 50% increase from the baseline in the number of clinical tasks that were addressed by the physicians during the pandemic. CONCLUSIONS: There was a high acceptance of telemedicine services by the patients, which was evident by a high show rate during the COVID-19 pandemic in Detroit. With limited staffing, restricted outpatient work hours, a shortage of providers, and increased outpatient needs, telemedicine was successfully implemented in our practice.

JMIR Public Health Surveill2021       LitCov and CORD-19
860Psychosocial and Socio-Economic Crisis in Bangladesh Due to COVID-19 Pandemic: A Perception-Based Assessment  

Background: The spread of the COVID-19 pandemic, the partial lockdown, the disease intensity, weak governance in the healthcare system, insufficient medical facilities, unawareness, and the sharing of misinformation in the mass media has led to people experiencing fear and anxiety. The present study intended to conduct a perception-based analysis to get an idea of people's psychosocial and socio-economic crisis, and the possible environmental crisis, amidst the COVID-19 pandemic in Bangladesh. Methods: A perception-based questionnaire was put online for Bangladeshi citizens of 18 years and/or older. The sample size was 1,066 respondents. Datasets were analyzed through a set of statistical techniques including principal component and hierarchical cluster analysis. Results: There was a positive significant association between fear of the COVID-19 outbreak with the struggling healthcare system (p < 0.05) of the country. Also, there was a negative association between the fragile health system of Bangladesh and the government's ability to deal with the pandemic (p < 0.05), revealing the poor governance in the healthcare system. A positive association of shutdown and social distancing with the fear of losing one's own or a family members' life, influenced by a lack of healthcare treatment (p < 0.05), reveals that, due to the decision of shutting down normal activities, people may be experiencing mental and economic stress. However, a positive association of the socio-economic impact of the shutdown with poor people's suffering, the price hike of basic essentials, the hindering of formal education (p < 0.05), and the possibility of a severe socio-economic and health crisis will be aggravated. Moreover, there is a possibility of a climate change-induced disaster and infectious diseases like dengue during/after the COVID-19 situation, which will create severe food insecurity (p < 0.01) and a further healthcare crisis. Conclusions: The partial lockdown in Bangladesh due to the COVID-19 pandemic increased community transmission and worsened the healthcare crisis, economic burden, and loss of GDP despite the resuming of industrial operations. In society, it has created psychosocial and socio-economic insecurity among people due to the loss of lives and livelihoods. The government should take proper inclusive steps for risk assessment, communications, and financial stimulus toward the public to alleviate their fear and anxiety, and to take proper action to boost mental health and well-being.

Front Public Health2020       LitCov and CORD-19
861Assessment of the Frequency and Variety of Persistent Symptoms Among Patients With COVID-19: A Systematic Review  

IMPORTANCE: Infection with COVID-19 has been associated with long-term symptoms, but the frequency, variety, and severity of these complications are not well understood. Many published commentaries have proposed plans for pandemic control that are primarily based on mortality rates among older individuals without considering long-term morbidity among individuals of all ages. Reliable estimates of such morbidity are important for patient care, prognosis, and development of public health policy. OBJECTIVE: To conduct a systematic review of studies examining the frequency and variety of persistent symptoms after COVID-19 infection. EVIDENCE REVIEW: A search of PubMed and Web of Science was conducted to identify studies published from January 1, 2020, to March 11, 2021, that examined persistent symptoms after COVID-19 infection. Persistent symptoms were defined as those persisting for at least 60 days after diagnosis, symptom onset, or hospitalization or at least 30 days after recovery from the acute illness or hospital discharge. Search terms included COVID-19, SARS-CoV-2, coronavirus, 2019-nCoV, long-term, after recovery, long-haul, persistent, outcome, symptom, follow-up, and longitudinal. All English-language articles that presented primary data from cohort studies that reported the prevalence of persistent symptoms among individuals with SARS-CoV-2 infection and that had clearly defined and sufficient follow-up were included. Case reports, case series, and studies that described symptoms only at the time of infection and/or hospitalization were excluded. A structured framework was applied to appraise study quality. FINDINGS: A total of 1974 records were identified; of those, 1247 article titles and abstracts were screened. After removal of duplicates and exclusions, 92 full-text articles were assessed for eligibility; 47 studies were deemed eligible, and 45 studies reporting 84 clinical signs or symptoms were included in the systematic review. Of 9751 total participants, 5266 (54.0%) were male; 30 of 45 studies reported mean or median ages younger than 60 years. Among 16 studies, most of which comprised participants who were previously hospitalized, the median proportion of individuals experiencing at least 1 persistent symptom was 72.5% (interquartile range [IQR], 55.0%-80.0%). Individual symptoms occurring most frequently included shortness of breath or dyspnea (26 studies; median frequency, 36.0%; IQR, 27.6%-50.0%), fatigue or exhaustion (25 studies; median frequency, 40.0%; IQR, 31.0%-57.0%), and sleep disorders or insomnia (8 studies; median 29.4%, IQR, 24.4%-33.0%). There were wide variations in the design and quality of the studies, which had implications for interpretation and often limited direct comparability and combinability. Major design differences included patient populations, definitions of time zero (ie, the beginning of the follow-up interval), follow-up lengths, and outcome definitions, including definitions of illness severity. CONCLUSIONS AND RELEVANCE: This systematic review found that COVID-19 symptoms commonly persisted beyond the acute phase of infection, with implications for health-associated functioning and quality of life. Current studies of symptom persistence are highly heterogeneous, and future studies need longer follow-up, improved quality, and more standardized designs to reliably quantify risks.

JAMA Netw Open2021       LitCov and CORD-19
862COVID-19 pandemic: A review of the global lockdown and its far-reaching effects  

N/A

Sci Prog2021       LitCov and CORD-19
863Heterogeneous SARS-CoV-2-Neutralizing Activities After Infection and Vaccination  

N/A

Front Immunol2022       LitCov
864Myocarditis Temporally Associated With COVID-19 Vaccination  

Supplemental Digital Content is available in the text.

Circulation2021       LitCov and CORD-19
865Phase 1-2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine  

BACKGROUND: NVX-CoV2373 is a recombinant severe acute respiratory syndrome coronavirus 2 (rSARS-CoV-2) nanoparticle vaccine composed of trimeric full-length SARS-CoV-2 spike glycoproteins and Matrix-M1 adjuvant. METHODS: We initiated a randomized, placebo-controlled, phase 1–2 trial to evaluate the safety and immunogenicity of the rSARS-CoV-2 vaccine (in 5-μg and 25-μg doses, with or without Matrix-M1 adjuvant, and with observers unaware of trial-group assignments) in 131 healthy adults. In phase 1, vaccination comprised two intramuscular injections, 21 days apart. The primary outcomes were reactogenicity; laboratory values (serum chemistry and hematology), according to Food and Drug Administration toxicity scoring, to assess safety; and IgG anti–spike protein response (in enzyme-linked immunosorbent assay [ELISA] units). Secondary outcomes included unsolicited adverse events, wild-type virus neutralization (microneutralization assay), and T-cell responses (cytokine staining). IgG and microneutralization assay results were compared with 32 (IgG) and 29 (neutralization) convalescent serum samples from patients with Covid-19, most of whom were symptomatic. We performed a primary analysis at day 35. RESULTS: After randomization, 83 participants were assigned to receive the vaccine with adjuvant and 25 without adjuvant, and 23 participants were assigned to receive placebo. No serious adverse events were noted. Reactogenicity was absent or mild in the majority of participants, more common with adjuvant, and of short duration (mean, ≤2 days). One participant had mild fever that lasted 1 day. Unsolicited adverse events were mild in most participants; there were no severe adverse events. The addition of adjuvant resulted in enhanced immune responses, was antigen dose–sparing, and induced a T helper 1 (Th1) response. The two-dose 5-μg adjuvanted regimen induced geometric mean anti-spike IgG (63,160 ELISA units) and neutralization (3906) responses that exceeded geometric mean responses in convalescent serum from mostly symptomatic Covid-19 patients (8344 and 983, respectively). CONCLUSIONS: At 35 days, NVX-CoV2373 appeared to be safe, and it elicited immune responses that exceeded levels in Covid-19 convalescent serum. The Matrix-M1 adjuvant induced CD4+ T-cell responses that were biased toward a Th1 phenotype. (Funded by the Coalition for Epidemic Preparedness Innovations; ClinicalTrials.gov number, NCT04368988).

N Engl J Med2020       LitCov and CORD-19
866Increased resistance of SARS-CoV-2 Omicron variant to neutralization by vaccine-elicited and therapeutic antibodies  

BACKGROUND: SARS-CoV-2 vaccines currently authorized for emergency use have been highly successful in preventing infection and lessening disease severity. The vaccines maintain effectiveness against earlier SARS-CoV-2 Variants of Concern but the heavily mutated, highly transmissible Omicron variant presents an obstacle both to vaccine protection and monoclonal antibody therapies. METHODS: Pseudotyped lentiviruses were incubated with serum from vaccinated and boosted donors or therapeutic monoclonal antibody and then applied to target cells. After 2 days, luciferase activity was measured in a microplate luminometer. Resistance mutations of the Omicron spike were identified using point-mutated spike protein pseudotypes and mapped onto the three-dimensional spike protein structure. FINDINGS: Virus with the Omicron spike protein was 26-fold resistant to neutralization by recovered donor sera and 26-34-fold resistance to Pfizer BNT162b2 and Moderna vaccine-elicited antibodies following two immunizations. A booster immunization increased neutralizing titres against Omicron. Neutralizing titres against Omicron were increased in the sera with a history of prior SARS-CoV-2 infection. Analysis of the therapeutic monoclonal antibodies showed that the Regeneron and Eli Lilly monoclonal antibodies were ineffective against the Omicron pseudotype while Sotrovimab and Evusheld were partially effective. INTERPRETATION: The results highlight the benefit of a booster immunization to protect against the Omicron variant and demonstrate the challenge to monoclonal antibody therapy. The decrease in neutralizing titres against Omicron suggest that much of the vaccine efficacy may rely on T cells. FUNDING: The work was funded by grants from the NIH to N.R.L. (DA046100, AI122390 and AI120898) and 55 to M.J.M. (UM1AI148574).

EBioMedicine2022       LitCov and CORD-19
867Anxiety and depression in COVID-19 survivors: Role of inflammatory and clinical predictors  

Infection-triggered perturbation of the immune system could induce psychopathology, and psychiatric sequelae were observed after previous coronavirus outbreaks. The spreading of the Severe Acute Respiratory Syndrome Coronavirus (COVID-19) pandemic could be associated with psychiatric implications. We investigated the psychopathological impact of COVID-19 in survivors, also considering the effect of clinical and inflammatory predictors. We screened for psychiatric symptoms 402 adults surviving COVID-19 (265male,meanage58), at one month follow-up after hospital treatment. A clinical interview and a battery of self-report questionnaires were used to investigate post-traumatic stress disorder (PTSD), depression, anxiety, insomnia, and obsessive-compulsive (OC) symptomatology. We collected sociodemographic information, clinical data, baseline inflammatory markers and follow-up oxygen saturation levels. A significant proportion of patients self-rated in the psychopathological range: 28% for PTSD, 31% for depression, 42% for anxiety, 20% for OC symptoms, and 40% for insomnia. Overall, 56% scored in the pathological range in at least one clinical dimension. Despite significantly lower levels of baseline inflammatory markers, females suffered more for both anxiety and depression. Patients with a positive previous psychiatric diagnosis showed increased scores on most psychopathological measures, with similar baseline inflammation. Baseline systemic immune-inflammation index (SII), which reflects the immune response and systemic inflammation based on peripheral lymphocyte, neutrophil and platelet counts, positively associated with scores of depression and anxiety at follow-up. PTSD, major depression, and anxiety, are all high-burden non-communicable conditions associated with years of life lived with disability. Considering the alarming impact of COVID-19 infection on mental health, the current insights on inflammation in psychiatry, and the present obervation of worse inflammation leading to worse depression, we recommend to assess psychopathology of COVID-19 survivors and to deepen research on inflammatory biomarkers, in order to diagnose and treat emergent psychiatric conditions.

Brain Behav Immun2020       LitCov and CORD-19
868A pilot study of therapeutic plasma exchange for serious SARS CoV-2 disease: A structured summary of a randomized controlled trial study protocol  

OBJECTIVES: To evaluate the safety of therapeutic plasma exchange (TPE) in adult patients with serious/life-threatening COVID-19 requiring intensive care unit (ICU) admission, and associated 28-day mortality. Serious and life threatening COVID-19 are defined as per published literature (please, refer to the full protocol, Additional file 1). The rationale is that TPE can remove interleukins-3, 6, 8, 10, interferon-gamma and tumor necrosis factor-alpha. Thus, it may reduce the cytokine release syndrome associated with fulminant COVID-19 disease. TRIAL DESIGN: Pilot, interventional, open-label, randomized controlled multicenter trial. PARTICIPANTS: Inclusion criteria are: 1) age ≥ 18 years old; 2) intubation and intensive care unit (ICU) admission; 3) serious and/or life-threatening COVID-19 (please, refer to the full protocol, Additional file 1). SARS-CoV-2 infection is confirmed by Real-Time-Polymerase-Chain-Reaction (RT-PCR) assays using QuantiNova Probe RT-PCR kit (Qiagen) in a Light-Cycler 480 real-time PCR system (Roche, Basel, Switzerland). Exclusion criteria are: 1) previous allergic reaction to plasma exchange or its ingredients (i.e., sodium citrate), 2) two consecutive negative RT-PCR tests for SARS-CoV-2 at least 24 hours apart, 3) mild COVID-19 not requiring ICU admission and 4) terminally ill patients receiving palliative care. The primary site will be King Saud Medical City (KSMC), Riyadh, Kingdom of Saudi Arabia (KSA). Also, the study will run in ICUs (Ministry of Health Cluster 1; Riyadh) and other centers in KSA pending their institutional review board (IRB) approval. INTERVENTIONS AND COMPARATOR: The intervention group will receive TPE, plus empiric treatment for COVID-19. TPE is administered using the Spectra Optia TM Apheresis System equipped with the Depuro D2000 Adsorption Cartridge (Terumo BCT Inc., USA). The first dose is 1.5 plasma volumes, followed by one plasma volume on alternate days or daily for five to seven total treatments. Spectra Optia TM Apheresis System operates with acid-citrate dextrose anticoagulant (ACDA) as per Kidney Disease Improving Global Outcomes (KDIGO) 2019 guidelines. Plasma is replaced with albumin 5% or fresh frozen plasma in patients with coagulopathy (prothrombin time >37 seconds; international normalized ratio >3; activated partial thromboplastin time >100 or fibrinogen level <100 mg/d). TPE sessions are performed daily over four hours and laboratory markers measured daily. The comparators are controls not receiving TPE but usual empiric treatment for COVID-19 as per institutional, national and international recommendations. Both groups will receive standard ICU supportive care. MAIN OUTCOMES: Primary study end-point is 28-day mortality and safety of TPE in serious and/or life-threatening COVID-19. Safety will be evaluated by the documentation of any pertinent adverse and/or serious adverse effects related to TPE as per institutional, national and international (Food and Drug Administration) guidelines. Secondary outcomes are: i) improvement in Sequential Organ Function Assessment (SOFA) score ; ii) changes in inflammatory markers: serum C-reactive protein, lactate dehydrogenase, ferritin, d-dimers and interleukin-6; iii) days on mechanical ventilation and ICU length of stay. RANDOMIZATION: Eligible consented patients are randomized (1:1 allocation) after stratification by ICU center and two PaO2/FIO2 ratio categories (> 150 and ≤ 150). Randomization occurs in variable block sizes of four to eight patients. A web-based randomization service, randomize.net, is used to allocate patients to their respective strata prior to the intervention or control therapy. BLINDING (MASKING): Given the visibility of TPE machinery, the intervention will be unblinded; hence, no enrollment concealment will be expedited. The lack of allocation concealment will be mitigated by several measures (please, refer to the full protocol, Additional file 1). NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): This pilot randomized trial aims to recruit a convenience sample of patients with serious and/or life-threatening COVID-19. Therefore, at least 20 patients are to be randomized to each group per participating center. We are hoping to consent and randomize approximately 60 patients in each group over a 3 to 6 months period giving a total of 120 participants. TRIAL STATUS: The protocol version 1 was approved 29/04/2020. Recruitment is ongoing, and began on 01/05/2020. We estimate completion by 29/10/2020. TRIAL REGISTRATION: Registered at ISRCTN on 18/05/2020 (ISRCTN21363594; doi.10.1186/ ISRCTN21363594). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.

Trials2020       LitCov and CORD-19
869Uptrend in distress and psychiatric symptomatology in pregnant women during the COVID-19 pandemic  

N/A

Acta Obstet Gynecol Scand2020       LitCov and CORD-19
870Acute Kidney Injury in COVID-19 Patients: An Inner City Hospital Experience and Policy Implications  

BACKGROUND: Although diffuse alveolar damage and respiratory failure are the key features of coronavirus disease 2019 (COVID-19), the involvement of other organs such as the kidney has also been reported. The reports of the incidence of acute kidney injury (AKI) in COVID-19 patients vary widely. In this study, we report our unique experience with AKI in COVID-19 patients in a low socioeconomic and predominantly ethnic minority group and provide its incidence, risk factors, and prognosis to expand the current understanding of this complication. METHODS: In this single-center, retrospective cohort study, we analyzed the data of 469 COVID-19 patients admitted to the Brookdale University Hospital in Brooklyn, NY, from March 18 through April 23, 2020. Information regarding demographics, comorbidities, medications, clinical and laboratory data, and outcomes was collected from the electronic medical records. Both univariate and multivariate analyses were performed to determine the association of AKI with in-hospital mortality. RESULTS: The median age was 66 years (interquartile range [IQR] 25–75; range 19–101 years), and 268 (57.14%) patients were male. Estimated glomerular filtration rate (eGFR) as determined by the Modification of Diet in Renal Disease Study Equation was low (<60 mL/min/1.73 m(2)) in 207 (44.1%) patients. During hospitalization, 128 (27.3%) patients developed AKI, and the incidence was significantly higher in those patients presenting with a low eGFR (N = 81, 39.1%; p < 0.001). Male sex, hypertension, the use of angiotensin-converting enzyme inhibitors and non-steroidal anti-inflammatories, hemodynamic instability, mechanical ventilation, acute respiratory distress syndrome, and admission elevated ferritin, creatinine kinase, brain natriuretic peptide, and troponin 1 were identified as the risk factors for in-hospital AKI. Ninety-seven (28.45%) patients died in the non-AKI group versus 91 (71.1%) in the AKI group (p < 0.001). The Cox proportional hazard model after adjusting for age, gender, comorbidities, hemodynamic status, and PF ratio (arterial oxygen partial pressure [PaO2]/fractional inspired oxygen [FiO2]) determined that on admission, an elevated blood urea nitrogen (hazard ratio [HR]: 1.75; 95% confidence interval [CI] 1.23–2.48), a low eGFR (HR 1.43; CI 1.1–2.03), AKI stage 1 (HR 1.14; CI 0.64–2.03), AKI stage 2 (HR 1.86; CI 1.03–3.56), and AKI stage 3 (HR 2.1; CI 1.3–2.81) were independent risk factors for in-hospital mortality. Renal replacement therapy (RRT) did not improve survival in stage III AKI. CONCLUSION: AKI in our hospitalized COVID-19 patients was common and carried a high mortality, especially in patients with AKI stage 3. RRT did not improve survival. Policy changes and planning for this high incidence of AKI in COVID-19 patients and its associated high mortality are necessary at the local and national levels.

Am J Nephrol2020       LitCov and CORD-19
871Impact of COVID-19 and other pandemics and epidemics on people with pre-existing mental disorders: a systematic review protocol and suggestions for clinical care  

INTRODUCTION: The current COVID-19 pandemic has resulted in high rates of infection and death, as well as widespread social disruption and a reduction in access to healthcare services and support. There is growing concern over how the pandemic, as well as measures put in place to curb the pandemic, will impact people with mental disorders. We aim to study the effect of pandemics and epidemics on mental health outcomes for people with premorbid mental disorders. METHODS AND ANALYSIS: With our predefined search strategy, we will search five databases for studies reporting on mental health outcomes in people with pre-existing mental disorders during pandemic and epidemic settings. Search dates are planned as follows: 5 May 2020 and 23 July 2020. The following databases will be searched: MEDLINE/PubMed, CINAHL, PsycINFO, MedRxiv and EMBASE. Data will be screened and extracted in duplicate by two independent reviewers. Studies involving non-clinical populations or patients diagnosed with a mental disorder during a pandemic/epidemic will be excluded. We will include data collected from all pandemics and epidemics throughout history, including the present COVID-19 pandemic. If possible, study findings will be combined in meta-analyses, and subgroup analyses will be performed. We hope that this review will shed light on the impact of pandemics and epidemics on those with pre-existing mental disorders. Knowledge generated may inform future intervention studies as well as healthcare policies. Given the potential implications of the current pandemic measures (ie, disruption of healthcare services) on mental health, we will also compile a list of existing mental health resources. ETHICS AND DISSEMINATION: No ethical approval is required for this protocol and proposed systematic review as we will only use data from previously published papers that have themselves received ethics clearance and used proper informed consent procedures. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number: CRD42020179611.

BMJ Open2020       LitCov and CORD-19
872Infections, hospitalisations and deaths averted via a nationwide vaccination campaign using the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine in Israel: a retrospective surveillance study  

BACKGROUND: On Dec 20, 2020, Israel initiated a nationwide COVID-19 vaccination campaign for people aged 16 years and older and exclusively used the Pfizer–BioNTech BNT162b2 mRNA COVID-19 vaccine (tozinameran). We provide estimates of the number of SARS-CoV-2 infections and COVID-19-related admissions to hospital (ie, hospitalisations) and deaths averted by the nationwide vaccination campaign. METHODS: In this retrospective surveillance study, we used national surveillance data routinely collected by the Israeli Ministry of Health from the first 112 days (Dec 20, 2020, up to our data cutoff of April 10, 2021) of Israel's vaccination campaign to estimate the averted burden of four outcomes: SARS-CoV-2 infections and COVID-19-related hospitalisations, severe or critical hospitalisations, and deaths. As part of the campaign, all individuals aged 16 years and older were eligible for inoculation with the BNT162b2 vaccine in a two-dose schedule 21 days apart. We estimated the direct effects of the immunisation programme for all susceptible individuals (ie, with no previous evidence of laboratory-confirmed SARS-CoV-2 infection) who were at least partly vaccinated (at least one dose and at least 14 days of follow-up after the first dose). We estimated the number of SARS-CoV-2 infection-related outcomes averted on the basis of cumulative daily, age-specific rate differences, comparing rates among unvaccinated individuals with those of at least partly vaccinated individuals for each of the four outcomes and the (age-specific) size of the susceptible population and proportion that was at least partly vaccinated. FINDINGS: We estimated that Israel's vaccination campaign averted 158 665 (95% CI 144 640–172 690) SARS-CoV-2 infections, 24 597 (18 942–30 252) hospitalisations, 17 432 (12 770–22 094) severe or critical hospitalisations, and 5532 (3085–7982) deaths. 16 213 (65·9%) of 24 597 hospitalisations and 5035 (91·0%) of 5532 of deaths averted were estimated to be among those aged 65 years and older. We estimated 116 000 (73·1%) SARS-CoV-2 infections, 19 467 (79·1%) COVID-19-related hospitalisations, and 4351 (79%) deaths averted were accounted for by the fully vaccinated population. INTERPRETATION: Without the national vaccination campaign, Israel probably would have had triple the number of hospitalisations and deaths compared with what actually occurred during its largest wave of the pandemic to date, and the health-care system might have become overwhelmed. Indirect effects and long-term benefits of the programme, which could be substantial, were not included in these estimates and warrant future research. FUNDING: Israel Ministry of Health and Pfizer.

Lancet Infect Dis2021       LitCov and CORD-19
873COVID-19 and pregnancy: what obstetricians need to know  

Coronavirus disease 2019 is an emerging disease with a rapid increase in cases and deaths since its first identification in Wuhan, China, in December 2019. Limited data are available about coronavirus disease 2019 during pregnancy; however, information on illnesses associated with other highly pathogenic coronaviruses (ie, severe acute respiratory syndrome and the Middle East respiratory syndrome) might provide insights into coronavirus disease 2019’s effects during pregnancy. Coronaviruses cause illness ranging in severity from the common cold to severe respiratory illness and death. Currently the primary epidemiologic risk factors for coronavirus disease 2019 include travel from mainland China (especially Hubei Province) or close contact with infected individuals within 14 days of symptom onset. Data suggest an incubation period of ∼5 days (range, 2–14 days). Average age of hospitalized patients has been 49–56 years, with a third to half with an underlying illness. Children have been rarely reported. Men were more frequent among hospitalized cases (54–73%). Frequent manifestations include fever, cough, myalgia, headache, and diarrhea. Abnormal testing includes abnormalities on chest radiographic imaging, lymphopenia, leukopenia, and thrombocytopenia. Initial reports suggest that acute respiratory distress syndrome develops in 17–29% of hospitalized patients. Overall case fatality rate appears to be ∼1%; however, early data may overestimate this rate. In 2 reports describing 18 pregnancies with coronavirus disease 2019, all were infected in the third trimester, and clinical findings were similar to those in nonpregnant adults. Fetal distress and preterm delivery were seen in some cases. All but 2 pregnancies were cesarean deliveries and no evidence of in utero transmission was seen. Data on severe acute respiratory syndrome and Middle East respiratory syndrome in pregnancy are sparse. For severe acute respiratory syndrome, the largest series of 12 pregnancies had a case-fatality rate of 25%. Complications included acute respiratory distress syndrome in 4, disseminated intravascular coagulopathy in 3, renal failure in 3, secondary bacterial pneumonia in 2, and sepsis in 2 patients. Mechanical ventilation was 3 times more likely among pregnant compared with nonpregnant women. Among 7 first-trimester infections, 4 ended in spontaneous abortion. Four of 5 women with severe acute respiratory syndrome after 24 weeks’ gestation delivered preterm. For Middle East respiratory syndrome, there were 13 case reports in pregnant women, of which 2 were asymptomatic, identified as part of a contact investigation; 3 patients (23%) died. Two pregnancies ended in fetal demise and 2 were born preterm. No evidence of in utero transmission was seen in severe acute respiratory syndrome or Middle East respiratory syndrome. Currently no coronavirus-specific treatments have been approved by the US Food and Drug Administration. Because coronavirus disease 2019 might increase the risk for pregnancy complications, management should optimally be in a health care facility with close maternal and fetal monitoring. Principles of management of coronavirus disease 2019 in pregnancy include early isolation, aggressive infection control procedures, oxygen therapy, avoidance of fluid overload, consideration of empiric antibiotics (secondary to bacterial infection risk), laboratory testing for the virus and coinfection, fetal and uterine contraction monitoring, early mechanical ventilation for progressive respiratory failure, individualized delivery planning, and a team-based approach with multispecialty consultations. Information on coronavirus disease 2019 is increasing rapidly. Clinicians should continue to follow the Centers for Disease Control and Prevention website to stay up to date with the latest information (https://www.cdc.gov/coronavirus/2019-nCoV/hcp/index.html).

Am J Obstet Gynecol2020       LitCov and CORD-19
874COVID-19 vaccination intention and hesitancy: Mistrust on COVID-19 vaccine benefit a major driver for vaccine hesitancy among healthcare workers; a cross-sectional study in North India  

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J Prev Med Hyg2022       LitCov
875Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology  

Analysis of the specificity and kinetics of neutralizing antibodies (nAbs) elicited by SARS-CoV-2 infection is crucial for understanding immune protection and identifying targets for vaccine design. In a cohort of 647 SARS-CoV-2-infected subjects we found that both the magnitude of Ab responses to SARS-CoV-2 spike (S) and nucleoprotein and nAb titers correlate with clinical scores. The receptor-binding domain (RBD) is immunodominant and the target of 90% of the neutralizing activity present in SARS-CoV-2 immune sera. Whereas overall RBD-specific serum IgG titers waned with a half-life of 49 days, nAb titers and avidity increased over time for some individuals, consistent with affinity maturation. We structurally defined an RBD antigenic map and serologically quantified serum Abs specific for distinct RBD epitopes leading to the identification of two major receptor-binding motif antigenic sites. Our results explain the immunodominance of the receptor-binding motif and will guide the design of COVID-19 vaccines and therapeutics.

Cell2020       LitCov and CORD-19
876Effectiveness of BNT162b2 and mRNA-1273 covid-19 vaccines against symptomatic SARS-CoV-2 infection and severe covid-19 outcomes in Ontario, Canada: test negative design study  

OBJECTIVE: To estimate the effectiveness of mRNA covid-19 vaccines against symptomatic infection and severe outcomes (hospital admission or death). DESIGN: Test negative design study. SETTING: Ontario, Canada between 14 December 2020 and 19 April 2021. PARTICIPANTS: 324 033 community dwelling people aged ≥16 years who had symptoms of covid-19 and were tested for SARS-CoV-2. INTERVENTIONS: BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine. MAIN OUTCOME MEASURES: Laboratory confirmed SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) and hospital admissions and deaths associated with SARS-CoV-2 infection. Multivariable logistic regression was adjusted for personal and clinical characteristics associated with SARS-CoV-2 and vaccine receipt to estimate vaccine effectiveness against symptomatic infection and severe outcomes. RESULTS: Of 324 033 people with symptoms, 53 270 (16.4%) were positive for SARS-CoV-2 and 21 272 (6.6%) received at least one dose of vaccine. Among participants who tested positive, 2479 (4.7%) were admitted to hospital or died. Vaccine effectiveness against symptomatic infection observed ≥14 days after one dose was 60% (95% confidence interval 57% to 64%), increasing from 48% (41% to 54%) at 14-20 days after one dose to 71% (63% to 78%) at 35-41 days. Vaccine effectiveness observed ≥7 days after two doses was 91% (89% to 93%). Vaccine effectiveness against hospital admission or death observed ≥14 days after one dose was 70% (60% to 77%), increasing from 62% (44% to 75%) at 14-20 days to 91% (73% to 97%) at ≥35 days, whereas vaccine effectiveness observed ≥7 days after two doses was 98% (88% to 100%). For adults aged ≥70 years, vaccine effectiveness estimates were observed to be lower for intervals shortly after one dose but were comparable to those for younger people for all intervals after 28 days. After two doses, high vaccine effectiveness was observed against variants with the E484K mutation. CONCLUSIONS: Two doses of mRNA covid-19 vaccines were observed to be highly effective against symptomatic infection and severe outcomes. Vaccine effectiveness of one dose was observed to be lower, particularly for older adults shortly after the first dose.

BMJ2021       LitCov and CORD-19
877Individual preferences for COVID-19 vaccination in China  

Background Vaccinations are an effective choice to stop disease outbreaks, including COVID-19. There is little research on individuals' COVID-19 vaccination decision-making. Objective We aimed to determine individual preferences for COVID-19 vaccinations in China, and to assess the factors influencing vaccination decision-making to facilitate vaccination coverage. Methods A D-efficient discrete choice experiment was conducted across six Chinese provinces selected by the stratified random sampling method. Vaccine choice sets were constructed using seven attributes: vaccine effectiveness, side-effects, accessibility, number of doses, vaccination sites, duration of vaccine protection, and proportion of acquaintances vaccinated. Conditional logit and latent class models were used to identify preferences. Results Although all seven attributes were proved to significantly influence respondents’ vaccination decision, vaccine effectiveness, side-effects and proportion of acquaintances vaccinated were the most important. We also found a higher probability of vaccinating when the vaccine was more effective; risks of serious side effects were small; vaccinations were free and voluntary; the fewer the number of doses; the longer the protection duration; and the higher the proportion of acquaintances vaccinated. Higher local vaccine coverage created altruistic herd incentives to vaccinate rather than free-rider problems. The predicted vaccination uptake of the optimal vaccination scenario in our study was 84.77%. Preference heterogeneity was substantial. Individuals who were older, had a lower education level, lower income, higher trust in the vaccine and higher perceived risk of infection, displayed a higher probability to vaccinate. Conclusions Preference heterogeneity among individuals should lead health authorities to address the diversity of expectations about COVID-19 vaccinations. To maximize COVID-19 vaccine uptake, health authorities should promote vaccine effectiveness; pro-actively communicate the absence or presence of vaccine side effects; and ensure rapid and wide media communication about local vaccine coverage.

Vaccine2020       LitCov and CORD-19
878Perceptions of Covid-19 lockdowns and related public health measures in Austria: a longitudinal online survey  

BACKGROUND: Introducing national lockdown has been effective in containing Covid-19. However, several studies indicated negative impacts of lockdowns on the well-being and mental health of many people. In Austria, the first Covid-19-related lockdown was introduced on 16 March 2020 with most restrictions being lifted 1 month later. Seven months after that, in November 2020, the second full lockdown was implemented. The aim of this study was to compare the perceptions and experiences of the general population related to the first and second Covid-19 lockdowns in Austria. METHODS: Two waves of an online survey were conducted in May and December 2020 asking respondents about their concerns related to the Covid-19 illness, personal experiences of the lockdowns, perceptions of and compliance with imposed public health measures, and the impact of the Covid-19 pandemic on different aspects of life during the two lockdowns. Descriptive statistics including frequency analysis were used to compare respondents’ answers collected in the two waves of the survey. T-test and chi-square tests were used to test differences between the two lockdowns. RESULTS: Five hundred sixty participants were included in the first wave and a sub-sample of 134 participants in the second wave of data collection. During the second lockdown, study respondents were more concerned about their family members contracting Covid-19 when compared with the first lockdown. Compliance with public health measures was overall lower during the second lockdown, although it varied according to the type of the measure. Closure of schools was seen as the least essential restriction during the second lockdown, while wearing masks gained additional approval between the first and the second lockdown. Larger negative impacts of the Covid-19 pandemic on friendships, leisure activities, education and community were reported during the second lockdown. CONCLUSIONS: The study found that the extended duration of the pandemic and recurring lockdowns restricting freedom of movement and social contacts appear to have caused significant disruptions to many areas of life. Furthermore, declining adherence to most public health measures over time raises a question about the effectiveness of future lockdown measures. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-021-11476-3.

BMC Public Health2021       LitCov and CORD-19
879Clinical severity of COVID-19 in patients admitted to hospital during the omicron wave in South Africa: a retrospective observational study  

BACKGROUND: Up to the end of January, 2022, South Africa has had four recognisable COVID-19 pandemic waves, each predominantly dominated by one variant of concern: the ancestral strain with an Asp614Gly mutation during the first wave, the beta variant (B.1.351) during the second wave, the delta variant (B.1.617.2) during the third wave, and lastly, the omicron variant (B.1.1.529) during the fourth wave. We aimed to assess the clinical disease severity of patients admitted to hospital with SARS-CoV-2 infection during the omicron wave and compare the findings with those of the preceding three pandemic waves in South Africa. METHODS: We defined the start and end of each pandemic wave as the crossing of the threshold of weekly incidence of 30 laboratory-confirmed SARS-CoV-2 cases per 100 000 population. Hospital admission data were collected through an active national COVID-19-specific surveillance programme. We compared disease severity across waves by post-imputation random effect multivariable logistic regression models. Severe disease was defined as one or more of the following: acute respiratory distress, receipt of supplemental oxygen or mechanical ventilation, admission to intensive care, or death. FINDINGS: We analysed 335 219 laboratory-confirmed SARS-CoV-2 hospital admissions with a known outcome, constituting 10·4% of 3 216 179 cases recorded during the four waves. During the omicron wave, 52 038 (8·3%) of 629 617 cases were admitted to hospital, compared with 71 411 (12·9%) of 553 530 in the Asp614Gly wave, 91 843 (12·6%) of 726 772 in the beta wave, and 131 083 (10·0%) of 1 306 260 in the delta wave (p<0·0001). During the omicron wave, 15 421 (33·6%) of 45 927 patients admitted to hospital had severe disease, compared with 36 837 (52·3%) of 70 424 in the Asp614Gly wave, 57 247 (63·4%) of 90 310 in the beta wave, and 81 040 (63·0%) of 128 558 in the delta wave (p<0·0001). The in-hospital case-fatality ratio during the omicron wave was 10·7%, compared with 21·5% during the Asp614Gly wave, 28·8% during the beta wave, and 26·4% during the delta wave (p<0·0001). Compared with those admitted to hospital during the omicron wave, patients admitted during the other three waves had more severe clinical presentations (adjusted odds ratio 2·07 [95% CI 2·01–2·13] in the Asp614Gly wave, 3·59 [3·49–3·70] in the beta wave, and 3·47 [3·38–3·57] in the delta wave). INTERPRETATION: The trend of increasing cases and admissions across South Africa's first three waves shifted in the omicron wave, with a higher and quicker peak but fewer patients admitted to hospital, less clinically severe illness, and a lower case-fatality ratio compared with the preceding three waves. Omicron marked a change in the SARS-CoV-2 epidemic curve, clinical profile, and deaths in South Africa. Extrapolations to other populations should factor in differing vaccination and previous infection levels. FUNDING: National Institute for Communicable Diseases.

Lancet Glob Health2022       LitCov and CORD-19
880Socio-Demographics Correlate of COVID-19 Vaccine Hesitancy During the Second Wave of COVID-19 Pandemic: A Cross-Sectional Web-Based Survey in Saudi Arabia  

Background: The Coronavirus disease 2019 (COVID-19) pandemic is considered a major global public health threat affecting across the life course and socioeconomic aspects of life. Global acceptance to an effective vaccine is the most anticipated resolution. This study aims to evaluate intent to be vaccinated among public in Saudi Arabia during the second wave of the COVID-19 pandemic. Methods: A cross-sectional web-based study was designed in Saudi Arabia. Study participants (N = 658) were recruited through snowball sampling. The SurveyMonkey platform was used to record the response. Cross-tabulation was performed by participants' intention to vaccinate against COVID-19 virus with sociodemographic characteristics and respondents' risk perception toward COVID-19, trust in the healthcare system, and their history of vaccine hesitancy behavior. Multivariable logistic regression analysis was performed to compute the predictors of vaccination intention among the study participants. Results: Six hundred fifty-eight participants completed the survey (females = 47.4%). Of the 658 participants, 351 (53.3%) have shown intent to be vaccinated. Five hundred nineteen (78.8%) of the participants were reported to be at high risk of COVID-19, and 307 (46.6%) were reported to trust the healthcare system in the country. The multivariable analysis shows respondents with a high-risk perception (OR: 2.27, 95% CI: 1.49–3.48); higher trust in the healthcare system (OR: 3.24, 95% CI: 2.32–4.61) was found to be the significant factor affecting the decision in acceptance of the COVID-19 vaccine in Saudi Arabia. Conclusion: Participants reported high knowledge toward COVID-19 virus, and vaccine developments. About half (46.6%) of the study participants reported refusal/hesitancy toward the vaccine during the second wave of the pandemic in Saudi Arabia. The study highlighted that higher risk perception and higher trust in the healthcare system were found to be the main reasons for participants' intentions behind the vaccination.

Front Public Health2021       LitCov and CORD-19
881The experience of Australian general practice patients at high risk of poor health outcomes with telehealth during the COVID-19 pandemic: a qualitative study  

BACKGROUND: The emergence of the COVID-19 pandemic has raised concerns about the potential decrease in access and utilisation of general practice services and its impact on patient care. In March 2020, the Australian Government introduced telehealth services to ensure that people more vulnerable to COVID-19 do not delay routine care from their general practitioners. Evidence about patients’ experience of telehealth and its impact on patient care is scarce. This study aimed to investigate the experience with telehealth by Australian general practice patients at high risk of poor health outcomes during the COVID-19 pandemic. METHODS: Semi-structured telephone interviews were conducted with 30 patients from nine general practices in metropolitan Adelaide (May–June 2020). Participants were identified by their regular doctor as being at high risk of poor health outcomes. Interviews sought participants’ perspectives and experiences about telehealth services in the general practice setting during COVID-19, and the value of offering continued telehealth services post pandemic. Interviews were recorded and transcribed verbatim. Data were analysed using a coding structure developed based on deductive codes derived from the research questions and any additional concepts that emerged inductively from interviews. RESULTS: Participants expressed satisfaction with telehealth including convenient and timely access to general practice services. Yet, participants identified challenges including difficulties in expressing themselves and accessing physical exams. Prescription renewal, discussing test results and simple follow-ups were the most common reasons that telehealth was used. Telehealth was mainly via phone that better suited those with low digital literacy. Participants indicated that an existing doctor-patient relationship was important for telehealth services to be effective. Subjects believed that telehealth services should be continued but needed to be combined with opportunities for face-to-face consultations after the COVID-19 pandemic was over. CONCLUSIONS: The expansion of telehealth supported access to general practice including chronic disease management during the COVID-19 pandemic. In the future, telehealth in Australia is likely to have a stronger place in primary healthcare policy and practice and an increased acceptance amongst patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12875-021-01408-w.

BMC Fam Pract2021       LitCov and CORD-19
882Cellular and humoral functional responses after BNT162b2 mRNA vaccination differ longitudinally between naive and subjects recovered from COVID-19  

We have analyzed BNT162b2 vaccine-induced immune responses in naïve and individuals recovered from COVID-19, both early (fourteen days) and late (almost eight months) after vaccination. Plasma S-specific immunoglobulins peak after one vaccine shot in individuals recovered from COVID-19, while a second dose is needed in naïve subjects, although the latter group shows reduced levels all-along the analyzed period. Despite the neutralization capacity against SARS-CoV-2 mirrors this behavior early after vaccination, both groups show comparable neutralizing antibodies and S-specific B cells levels late post-vaccination. When studying cellular responses, naïve individuals exhibit higher SARS-CoV-2-specific cytokines production, CD4+ T cells activation and proliferation than individuals recovered from COVID-19, with patent inverse correlations between humoral and cellular variables early post-vaccination. However, almost eight months post-vaccination, SARS-CoV-2-specific responses are comparable between both groups. Our data indicate that previous history of COVID-19 differentially determines the functional T and B cell-mediated responses to BNT162b2 vaccination over time.

Cell Rep2021       LitCov and CORD-19
883Loneliness and mental well-being in the Polish population during the COVID-19 pandemic: a cross-sectional study  

OBJECTIVE: There is a growing concern that the restrictions imposed due to the COVID-19 pandemic could lead to increased loneliness and mental disorders, which are considered a major public health problem. The aim of the study was to assess loneliness, anxiety, depression and irritability in the Polish population during the COVID-19 pandemic. DESIGN: A cross-sectional study. The study participants completed an online questionnaire using the computer-assisted web interview technique. Data were collected using Revised UCLA Loneliness Scale and Hospital Anxiety and Depression Scale. SETTING: Poland. PARTICIPANTS: This study was conducted between 6 October and 12 October 2020, in a representative sample of 890 Polish residents. PRIMARY OUTCOME MEASURES: Self-reported loneliness; sociodemographic and COVID-19 pandemic factors associated with loneliness, anxiety, depression and irritability. RESULTS: The analyses showed a moderately high degree of loneliness in 22%, symptoms of anxiety in 27%, depression in 14% and irritability in 33% of the respondents. The increasing severity of anxiety, depression and irritation in the study group was accompanied by higher loneliness. Generally, younger people, both tested positive for SARS-CoV-2 and those who experienced home quarantine, scored higher in both scales. CONCLUSIONS: It is necessary to identify those most vulnerable to loneliness, anxiety and depression during a crisis to assess health needs and proactively allocate resources during and after the pandemic. Loneliness, anxiety, depression and irritability are important factors to consider in a population of younger, disadvantaged people, who tested positive for SARS-CoV-2, people who were quarantined at home, and people who believe that their physical and mental health is worse than in the pre-pandemic period. It is important to cater for the mental health of individuals during the COVID-19 pandemic and to promote psychological interventions to improve mental well-being in potentially vulnerable social groups.

BMJ Open2022       LitCov and CORD-19
884Mental Health, Social and Emotional Well-Being and Perceived Burdens of University Students During COVID-19 Pandemic Lockdown in Germany  

Background: The COVID-19 pandemic has been affecting everyone's daily life in unknown measures since its outbreak. Nearly all Universities around the globe were affected. Further, young people and University students in particular, are known to be vulnerable for developing mental disorders. This study aims to examine the mental health social and emotional well-being and perceived burdens of University students during COVID-19 pandemic lockdown in Germany. Materials and Methods: This cross-sectional and anonymous online survey among University students assessed mental health status with standardized measures (depressive symptoms, alcohol and drug consumption, and eating disorder symptoms), attitudes toward the COVID-19 pandemic and perceived burdens, and social and emotional aspects of the pandemic (social support, perceived stress, loneliness, and self-efficacy). Results: In total, N = 3,382 German University students participated. Nearly half of the students (49%) reported that they are worried or very much worried about the COVID-19 pandemic. The majority supports the governmental lockdown measures (85%). A Patient Health Questionnaire-9 (PHQ-9) sum score of 10 or above, indicating clinically relevant depressive symptoms, was reported by 37% (n = 1,249). The PHQ-9 sum score was on average 8.66 (SD = 5.46). Suicidal thoughts were indicated by 14.5% of the participants. Levels of depressive symptoms differed significantly for the different self-rated income changes during the pandemic (increase, decrease, no change in income). Further, levels of depressive symptoms and suicidal ideation differed significantly for students from different faculties. Multiple regression analyses revealed that not being a parent, having no indirect social contact one or two times a week, higher perceived stress, higher experienced loneliness, lower social support, and lower self-efficacy significantly predicted higher scores of depressive symptoms, also higher hazardous alcohol use, and higher levels of eating disorder symptoms. Other aspects of lifestyle such as social and cultural activities, dating, and hobbies were reported to be negatively affected during the pandemic. Conclusion: The present study implies that University students are vulnerable and due to elevated depressive symptoms at risk, being hit hard by the pandemic, but are in general coping adaptively. Low-threshold online interventions promoting help-seeking and also targeting various mental health conditions might bridge the gap the COVID-19 pandemic opened up recently.

Front Psychiatry2021       LitCov and CORD-19
885Mask-wearing and control of SARS-CoV-2 transmission in the USA: a cross-sectional study  

BACKGROUND: Face masks have become commonplace across the USA because of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic. Although evidence suggests that masks help to curb the spread of the disease, there is little empirical research at the population level. We investigate the association between self-reported mask-wearing, physical distancing, and SARS-CoV-2 transmission in the USA, along with the effect of statewide mandates on mask uptake. METHODS: Serial cross-sectional surveys were administered via a web platform to randomly surveyed US individuals aged 13 years and older, to query self-reports of face mask-wearing. Survey responses were combined with instantaneous reproductive number (R(t)) estimates from two publicly available sources, the outcome of interest. Measures of physical distancing, community demographics, and other potential sources of confounding (from publicly available sources) were also assessed. We fitted multivariate logistic regression models to estimate the association between mask-wearing and community transmission control (R(t)<1). Additionally, mask-wearing in 12 states was evaluated 2 weeks before and after statewide mandates. FINDINGS: 378 207 individuals responded to the survey between June 3 and July 27, 2020, of which 4186 were excluded for missing data. We observed an increasing trend in reported mask usage across the USA, although uptake varied by geography. A logistic model controlling for physical distancing, population demographics, and other variables found that a 10% increase in self-reported mask-wearing was associated with an increased odds of transmission control (odds ratio 3·53, 95% CI 2·03–6·43). We found that communities with high reported mask-wearing and physical distancing had the highest predicted probability of transmission control. Segmented regression analysis of reported mask-wearing showed no statistically significant change in the slope after mandates were introduced; however, the upward trend in reported mask-wearing was preserved. INTERPRETATION: The widespread reported use of face masks combined with physical distancing increases the odds of SARS-CoV-2 transmission control. Self-reported mask-wearing increased separately from government mask mandates, suggesting that supplemental public health interventions are needed to maximise adoption and help to curb the ongoing epidemic. FUNDING: Flu Lab, Google.org (via the Tides Foundation), National Institutes for Health, National Science Foundation, Morris-Singer Foundation, MOOD, Branco Weiss Fellowship, Ending Pandemics, Centers for Disease Control and Prevention (USA).

Lancet Digit Health2021       LitCov and CORD-19
886Covid-19 in Critically Ill Patients in the Seattle Region-Case Series  

BACKGROUND: Community transmission of coronavirus 2019 (Covid-19) was detected in the state of Washington in February 2020. METHODS: We identified patients from nine Seattle-area hospitals who were admitted to the intensive care unit (ICU) with confirmed infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Clinical data were obtained through review of medical records. The data reported here are those available through March 23, 2020. Each patient had at least 14 days of follow-up. RESULTS: We identified 24 patients with confirmed Covid-19. The mean (±SD) age of the patients was 64±18 years, 63% were men, and symptoms began 7±4 days before admission. The most common symptoms were cough and shortness of breath; 50% of patients had fever on admission, and 58% had diabetes mellitus. All the patients were admitted for hypoxemic respiratory failure; 75% (18 patients) needed mechanical ventilation. Most of the patients (17) also had hypotension and needed vasopressors. No patient tested positive for influenza A, influenza B, or other respiratory viruses. Half the patients (12) died between ICU day 1 and day 18, including 4 patients who had a do-not-resuscitate order on admission. Of the 12 surviving patients, 5 were discharged home, 4 were discharged from the ICU but remained in the hospital, and 3 continued to receive mechanical ventilation in the ICU. CONCLUSIONS: During the first 3 weeks of the Covid-19 outbreak in the Seattle area, the most common reasons for admission to the ICU were hypoxemic respiratory failure leading to mechanical ventilation, hypotension requiring vasopressor treatment, or both. Mortality among these critically ill patients was high. (Funded by the National Institutes of Health.)

N Engl J Med2020       LitCov and CORD-19
887Non-pharmacological measures implemented in the setting of long-term care facilities to prevent SARS-CoV-2 infections and their consequences: a rapid review  

N/A

Cochrane Database Syst Rev2021       LitCov and CORD-19
888Household secondary attack rate of COVID-19 and associated determinants in Guangzhou, China: a retrospective cohort study  

BACKGROUND: As of June 8, 2020, the global reported number of COVID-19 cases had reached more than 7 million with over 400 000 deaths. The household transmissibility of the causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains unclear. We aimed to estimate the secondary attack rate of SARS-CoV-2 among household and non-household close contacts in Guangzhou, China, using a statistical transmission model. METHODS: In this retrospective cohort study, we used a comprehensive contact tracing dataset from the Guangzhou Center for Disease Control and Prevention to estimate the secondary attack rate of COVID-19 (defined as the probability that an infected individual will transmit the disease to a susceptible individual) among household and non-household contacts, using a statistical transmission model. We considered two alternative definitions of household contacts in the analysis: individuals who were either family members or close relatives, such as parents and parents-in-law, regardless of residential address, and individuals living at the same address regardless of relationship. We assessed the demographic determinants of transmissibility and the infectivity of COVID-19 cases during their incubation period. FINDINGS: Between Jan 7, 2020, and Feb 18, 2020, we traced 195 unrelated close contact groups (215 primary cases, 134 secondary or tertiary cases, and 1964 uninfected close contacts). By identifying households from these groups, assuming a mean incubation period of 5 days, a maximum infectious period of 13 days, and no case isolation, the estimated secondary attack rate among household contacts was 12·4% (95% CI 9·8–15·4) when household contacts were defined on the basis of close relatives and 17·1% (13·3–21·8) when household contacts were defined on the basis of residential address. Compared with the oldest age group (≥60 years), the risk of household infection was lower in the youngest age group (<20 years; odds ratio [OR] 0·23 [95% CI 0·11–0·46]) and among adults aged 20–59 years (OR 0·64 [95% CI 0·43–0·97]). Our results suggest greater infectivity during the incubation period than during the symptomatic period, although differences were not statistically significant (OR 0·61 [95% CI 0·27–1·38]). The estimated local reproductive number (R) based on observed contact frequencies of primary cases was 0·5 (95% CI 0·41–0·62) in Guangzhou. The projected local R, had there been no isolation of cases or quarantine of their contacts, was 0·6 (95% CI 0·49–0·74) when household was defined on the basis of close relatives. INTERPRETATION: SARS-CoV-2 is more transmissible in households than SARS-CoV and Middle East respiratory syndrome coronavirus. Older individuals (aged ≥60 years) are the most susceptible to household transmission of SARS-CoV-2. In addition to case finding and isolation, timely tracing and quarantine of close contacts should be implemented to prevent onward transmission during the viral incubation period. FUNDING: US National Institutes of Health, Science and Technology Plan Project of Guangzhou, Project for Key Medicine Discipline Construction of Guangzhou Municipality, Key Research and Development Program of China.

Lancet Infect Dis2020       LitCov and CORD-19
889Reduced No-Show Rates and Sustained Patient Satisfaction of Telehealth During the COVID-19 Pandemic  

N/A

Telemed J E Health2021       LitCov and CORD-19
890T-cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial  

N/A

Nat Med2021       LitCov and CORD-19
891Real-Time RT-PCR Allelic Discrimination Assay for Detection of N501Y Mutation in the Spike Protein of SARS-CoV-2 Associated with B.1.1.7 Variant of Concern  

The N501Y amino acid mutation caused by a single point substitution A23063T in the spike gene of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is possessed by three variants of concern (VOCs), B.1.1.7, B.1.351, and P.1. A rapid screening tool using this mutation is important for surveillance during the coronavirus disease 2019 (COVID-19) pandemic. We developed and validated a single nucleotide polymorphism real-time reverse transcription PCR assay using allelic discrimination of the spike gene N501Y mutation to screen for potential variants of concern and differentiate them from SARS-CoV-2 lineages without the N501Y mutation. A total of 160 clinical specimens positive for SARS-CoV-2 were characterized as mutant (N501Y) or N501 wild type by Sanger sequencing and were subsequently tested with the N501Y single nucleotide polymorphism real-time reverse transcriptase PCR assay. Our assay, compared to Sanger sequencing for single nucleotide polymorphism detection, demonstrated positive percent agreement of 100% for all 57 specimens displaying the N501Y mutation, which were confirmed by Sanger sequencing to be typed as A23063T, including one specimen with mixed signal for wild type and mutant. Negative percent agreement was 100% in all 103 specimens typed as N501 wild type, with A23063 identified as wild type by Sanger sequencing. The identification of circulating SARS-CoV-2 lineages carrying an N501Y mutation is critical for surveillance purposes. Current identification methods rely primarily on Sanger sequencing or whole-genome sequencing, which are time consuming, labor intensive, and costly. The assay described herein is an efficient tool for high-volume specimen screening for SARS-CoV-2 VOCs and for selecting specimens for confirmatory Sanger or whole-genome sequencing. IMPORTANCE During the coronavirus disease 2019 (COVID-19) pandemic, several variants of concern (VOCs) have been detected, for example, B.1.1.7, B.1.351, P.1, and B.1.617.2. The VOCs pose a threat to public health efforts to control the spread of the virus. As such, surveillance and monitoring of these VOCs is of the utmost importance. Our real-time RT-PCR assay helps with surveillance by providing an easy method to quickly survey SARS-CoV-2 specimens for VOCs carrying the N501Y single nucleotide polymorphism (SNP). Samples that test positive for the N501Y mutation in the spike gene with our assay can be sequenced to identify the lineage. Thus, our assay helps to focus surveillance efforts and decrease turnaround times.

Microbiol Spectr2022       LitCov and CORD-19
892Prevention and Attenuation of Covid-19 with the BNT162b2 and mRNA-1273 Vaccines  

BACKGROUND: Information is limited regarding the effectiveness of the two-dose messenger RNA (mRNA) vaccines BNT162b2 (Pfizer–BioNTech) and mRNA-1273 (Moderna) in preventing infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and in attenuating coronavirus disease 2019 (Covid-19) when administered in real-world conditions. METHODS: We conducted a prospective cohort study involving 3975 health care personnel, first responders, and other essential and frontline workers. From December 14, 2020, to April 10, 2021, the participants completed weekly SARS-CoV-2 testing by providing mid-turbinate nasal swabs for qualitative and quantitative reverse-transcriptase–polymerase-chain-reaction (RT-PCR) analysis. The formula for calculating vaccine effectiveness was 100%×(1−hazard ratio for SARS-CoV-2 infection in vaccinated vs. unvaccinated participants), with adjustments for the propensity to be vaccinated, study site, occupation, and local viral circulation. RESULTS: SARS-CoV-2 was detected in 204 participants (5%), of whom 5 were fully vaccinated (≥14 days after dose 2), 11 partially vaccinated (≥14 days after dose 1 and <14 days after dose 2), and 156 unvaccinated; the 32 participants with indeterminate vaccination status (<14 days after dose 1) were excluded. Adjusted vaccine effectiveness was 91% (95% confidence interval [CI], 76 to 97) with full vaccination and 81% (95% CI, 64 to 90) with partial vaccination. Among participants with SARS-CoV-2 infection, the mean viral RNA load was 40% lower (95% CI, 16 to 57) in partially or fully vaccinated participants than in unvaccinated participants. In addition, the risk of febrile symptoms was 58% lower (relative risk, 0.42; 95% CI, 0.18 to 0.98) and the duration of illness was shorter, with 2.3 fewer days spent sick in bed (95% CI, 0.8 to 3.7). CONCLUSIONS: Authorized mRNA vaccines were highly effective among working-age adults in preventing SARS-CoV-2 infection when administered in real-world conditions, and the vaccines attenuated the viral RNA load, risk of febrile symptoms, and duration of illness among those who had breakthrough infection despite vaccination. (Funded by the National Center for Immunization and Respiratory Diseases and the Centers for Disease Control and Prevention.)

N Engl J Med2021       LitCov and CORD-19
893Telemedicine for contraceptive counseling: Patient experiences during the early phase of the COVID-19 pandemic in New York City  

OBJECTIVE: During theCOVID-19 pandemic, many clinicians increased provision of telemedicine services. This study describes patient experiences with telemedicine for contraceptive counseling during the COVID-19 pandemic in New York City. STUDY DESIGN: This is a mixed-methods study which includes a web-based or phone survey and in-depth phone interviews with patients who had telemedicine visits for contraception. RESULTS: A total of 169 patients had eligible telemedicine visits between April 1 and June 30, 2020. Of these, 86 (51%) responded to the survey, and 23 (14%) participated in the interviews. We found that 86% of survey respondents were very satisfied with the telemedicine visit, and 63% said it completely met their needs. A majority (73%) strongly agreed that these visits should be maintained after the COVID-19 pandemic, and half (51%) would be very likely to choose them over in-person visits. In-depth interviews highlighted the convenience of telemedicine, especially for those with work or parenting responsibilities. Although some patients had in-person visits after telehealth, many appreciated the counseling they received remotely, and found the subsequent in-person visits more efficient. Patients identified visits that do not require physical exams as ideal visits for telehealth, and some hoped that all or most of their future visits would be telehealth visits. Many patients (43%) expressed a preference for phone over video visits. CONCLUSIONS: Patients reported an overall positive experience with telemedicine visits for contraceptive counseling during the COVID-19 pandemic. They appreciated the convenience of telemedicine visits and valued the virtual counseling experience.

Contraception2021       LitCov and CORD-19
894Immunogenicity and safety after the third dose of BNT162b2 anti-SARS-CoV-2 vaccine in patients with solid tumors on active treatment: a prospective cohort study  

BACKGROUND: Although a full course of COVID-19 vaccine is effective in cancer patients, the duration of the protection and the efficacy of a booster dose against the new variants remain unknown. We prospectively evaluated the immunogenicity of the third dose of the SARS-CoV-2 BNT162b2 mRNA vaccine in cancer patients undergoing active treatment. PATIENTS AND METHODS: Patients with solid cancer, vaccinated with a booster dose during active treatment, were enrolled in this study. Patients were classified in SARS-CoV-2 naïve (without previous COVID-19 infection) and SARS-CoV-2 experienced (with previous COVID-19 infection). Neutralizing antibody (NT Abs) titer and total anti-Spike IgG concentration were quantified in serum. Heparinized whole blood samples were used for SARS-CoV-2 Interferon Gamma Release Assay (IGRA). The primary endpoint was to assess the increase of IgG antibody level between baseline and 3 weeks after the booster. RESULTS: 142 consecutive patients were recruited. In SARS-CoV-2 naïve subjects, median level of IgG was 157 BAU/mL (interquartile range (IQR) 62-423) at T0 and reached median of 2080 (IQR 2080-2080) at three weeks after booster administration (T1; p<0.0001). A median 16-fold increase of SARS-CoV-2 NT Abs titre (IQR 4-32) was observed in naïve subjects (from median 20 IQR 10-40 to median 640 IQR 160-640; p<0.0001). Median IFN-γ level at T1 was significantly higher than that measured at T0 in SARS-CoV-2 naïve subjects (p=0.0049) but not in SARS-CoV-2 experienced patients. The median level of SARS-CoV-2 NT Abs was 32-fold lower against Omicron compared to wild type strain (p=0.0004) and 12-fold lower compared to Delta strain (p=0.0110) CONCLUSIONS: The third dose is able to trigger both the humoral and the cell-mediated immune response in cancer patients on active treatment. Our preliminary data about the neutralization of the SARS-CoV-2 vaccine against variants of concern (VOCs) seem to confirm the vaccine lower activity.

ESMO Open2022       LitCov and CORD-19
895Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis  

N/A

JAMA2020       LitCov and CORD-19
896Elevated depression and anxiety symptoms among pregnant individuals during the COVID-19 pandemic  

BACKGROUND: Anxiety and depression symptoms in pregnancy typically affect between 10-25% of pregnant individuals. Elevated symptoms of depression and anxiety are associated with increased risk of preterm birth, postpartum depression, and behavioural difficulties in children. The current COVID-19 pandemic is a unique stressor with potentially wide-ranging consequences for pregnancy and beyond. METHODS: We assessed symptoms of anxiety and depression among pregnant individuals during the current COVID-19 pandemic and determined factors that were associated with psychological distress. 1987 pregnant participants in Canada were surveyed in April 2020. The assessment included questions about COVID-19-related stress and standardized measures of depression, anxiety, pregnancy-related anxiety, and social support. RESULTS: We found substantially elevated anxiety and depression symptoms compared to similar pre-pandemic pregnancy cohorts, with 37% reporting clinically relevant symptoms of depression and 57% reporting clinically relevant symptoms of anxiety. Higher symptoms of depression and anxiety were associated with more concern about threats of COVID-19 to the life of the mother and baby, as well as concerns about not getting the necessary prenatal care, relationship strain, and social isolation due to the COVID-19 pandemic. Higher levels of perceived social support and support effectiveness, as well as more physical activity, were associated with lower psychological symptoms. CONCLUSION: This study shows concerningly elevated symptoms of anxiety and depression among pregnant individuals during the COVID-19 pandemic, that may have long-term impacts on their children. Potential protective factors include increased social support and exercise, as these were associated with lower symptoms and thus may help mitigate long-term negative outcomes.

J Affect Disord2020       LitCov and CORD-19
897A human cell-based SARS-CoV-2 vaccine elicits potent neutralizing antibody responses and protects mice from SARS-CoV-2 challenge  

To curb the pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), multiple platforms have been employed toward a safe and highly effective vaccine. Here, we develop a novel cell-based vaccine candidate, namely K562-S, by utilizing human cell K562 as a cellular carrier to display Spike (S) protein of SARS-CoV-2 on the membrane. Analogous to the traditional inactivated vaccine, K562-S cells can be propagated to a large scale by culturing and completely lose their viability after exposure to X-ray irradiation or formalin. We in turn demonstrated high immunogenicity of formalin-inactivated K562-S vaccine in both mouse and non-human primates and its protective efficacy in mice. In mice, immunization with inactivated K562-S vaccines can elicit potent neutralizing antibody (nAb) responses persisting longer than 5 months. We consequently showed in a hACE2 mouse model of SARS-CoV-2 infection that a two-shot vaccination with adjuvanted K562-S rendered greater than 3 log reduction in viral lung load and concomitant ameliorated lung pathology. Of importance, the administration of the same regimen in non-human primates was able to induce a neutralizing antibody titer averaging three-fold higher relative to human convalescent serum. These results together support the promise of K562-based, S-protein-expressing vaccines as a novel vaccination approach against SARS-CoV-2. Importantly, with a powerful capacity to carry external genes for cell-based vectors, this platform could rapidly generate two- and multiple-valent vaccines by incorporating SARS-CoV-2 mutants, SARS-CoV, or MERS-CoV.

Emerg Microbes Infect2021       LitCov and CORD-19
898Clinical characteristics of 113 deceased patients with COVID-19: retrospective study  

OBJECTIVE: To delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died. DESIGN: Retrospective case series. SETTING: Tongji Hospital in Wuhan, China. PARTICIPANTS: Among a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed. Data were collected until 28 February 2020. MAIN OUTCOME MEASURES: Clinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms. RESULTS: The median age of deceased patients (68 years) was significantly older than recovered patients (51 years). Male sex was more predominant in deceased patients (83; 73%) than in recovered patients (88; 55%). Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)). Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)). The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days. Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively. Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients. Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113; 100%), type I respiratory failure (18/35; 51%), sepsis (113; 100%), acute cardiac injury (72/94; 77%), heart failure (41/83; 49%), alkalosis (14/35; 40%), hyperkalaemia (42; 37%), acute kidney injury (28; 25%), and hypoxic encephalopathy (23; 20%). Patients with cardiovascular comorbidity were more likely to develop cardiac complications. Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk. Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.

BMJ2020       LitCov and CORD-19
899Human neutralizing antibodies elicited by SARS-CoV-2 infection  

N/A

Nature2020       LitCov and CORD-19
900CovEMERALD: Assessing the feasibility and preliminary effectiveness of remotely delivered Eye Movement Desensitisation and Reprocessing following Covid-19 related critical illness: A structured summary of a study protocol for a randomised controlled trial  

OBJECTIVES: Primary Objective: To determine the feasibility of delivering a protocolised, remote, online, Eye Movement Desensitisation and Reprocessing (EMDR) intervention, within 12-weeks of hospital discharge, for adult survivors of Covid-19 related critical illness. Secondary objectives: To investigate whether remotely delivered EMDR can improve psychological outcome following Covid-19 related critical illness, specifically Post-Traumatic Stress Disorder (PTSD), anxiety and depression. TRIAL DESIGN: This is a single centre, randomised controlled cohort feasibility trial. PARTICIPANTS: Participants will be recruited following discharge from the Intensive Care Unit at University Hospital Southampton, United Kingdom. Eligible patients will have received mechanical ventilation for a minimum of 24 hours, tested Covid-19 positive by polymerase chain reaction, will be over the age of 18 years and have the capacity to provide informed consent. Patients will be excluded if they have pre-existing cognitive impairment, pre-existing psychotic diagnosis or are not expected to survive post-hospital discharge. INTERVENTION AND COMPARATOR: Group one: patients in the control arm will receive their standard package of prescribed care, following discharge home from hospital. If they experience any adverse physical or psychological health-conditions, they will access care through the usual available channels. Group two: patients randomly allocated to the intervention arm will receive their standard package of prescribed care, following discharge home from hospital. In addition, they will be referred to the Intensive Psychological Therapies Service in Poole, United Kingdom. They will receive an online appointment within 12-weeks of discharge home from hospital. They will receive a maximum of eight, weekly sessions of EMDR, delivered by a trained psychological therapist, following the Recent Traumatic Episode Protocol (R-TEP). Appendices 1 and 2 of the attached trial protocol contain a detailed description of the R-TEP intervention, written in accordance with the Template for Intervention Description and Replication (TIDieR) checklist and guide. MAIN OUTCOMES: The primary outcome from this trial will be feasibility. Feasibility will be determined by recruitment rates, expressed as a percentage of eligible patients approached, completion of the EMDR intervention, completion of final assessment at 6-months, incidence of attributable adverse events and protocol adherence by the psychological therapists. Secondary, exploratory outcomes will be assessed by comparison between the control and intervention groups at 6-months post-hospital discharge. Psychometric evaluation will consist of the PTSD Checklist-Civilian Version and Hospital Anxiety and Depression Scale. In addition, we will assess health-related quality of life using the EQ5D-5L, physical activity using wrist worn activity monitors and nutritional state using the Council of Nutrition Appetite Questionnaire. RANDOMISATION: Consenting participants will be randomly allocated to intervention or usual care using an internet-based system (ALEA(TM)). Participants will be randomly assigned, on a 1:1 ratio, to receive either standard care (control) or the standard care plus online EMDR R-TEP (Intervention) BLINDING (MASKING): Due to the nature of the intervention, participants cannot be blinded to group allocation. 6-month patient reported outcome measures will be completed using an online, electronic case report form. Group allocation will be masked during data analysis. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): This is a feasibility study, the results of which will be used to power a definitive study if appropriate. We anticipate a 25% mortality /loss to follow-up. A total of 26 patients will be recruited to this study, 13 patients in each arm. TRIAL STATUS: CovEMERALD opened to recruitment on 23(rd) September 2020 with an anticipated recruitment period of 6-months. We are using protocol version number 1.2 (1(st) June 2020) TRIAL REGISTRATION: CovEMERALD was registered on clinicaltrials.gov NCT04455360 on 2(nd) July 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. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Trials2020       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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