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SARS-CoV-2 proteins

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    Emergence of multiple SARS-CoV-2 antibody escape variants in an immunocompromised host undergoing convalescent plasma treatment

    Authors: Liang Chen; Michael C Zody; Jose R Mediavilla; Marcus H Cunningham; Kaelea Composto; Kar Fai Chow; Milena Kordalewska; Andre Corvelo; Dayna M Oschwald; Samantha Fennessey; Marygrace Zetkulic; Sophia Dar; Yael Kramer; Barun Mathema; Tom Maniatis; David S Perlin; Barry N Kreiswirth

    doi:10.1101/2021.04.08.21254791 Date: 2021-04-11 Source: medRxiv

    SARS-CoV-2 Variants of Concerns (VOC), e.g., B.1.351 (20H/501Y.V2) and P1 (20J/501Y.V3), harboring N-terminal domain ( NTD HGNC) or the receptor-binding domain (RBD) (e.g., E484K) mutations, exhibit reduced in vitro susceptibility to convalescent serum, commercial antibody cocktails, and vaccine neutralization, and have been associated with reinfection. The accumulation of these mutations could be the consequence of intra-host viral evolution due to prolonged infection MESHD in immunocompromised hosts. In this study, we document the microevolution of SARS-CoV-2 recovered from sequential tracheal aspirates from an immunosuppressed patient on tacrolimus, steroids and convalescent plasma therapy, and identify the emergence of multiple NTD HGNC and RBD mutations associated with reduced antibody neutralization as early as three weeks after infection. SARS-CoV-2 genomes from the first swab (Day 0) and three tracheal aspirates (Day 7, 21 and 27) were compared at the sequence level. We identified five different S protein PROTEIN mutations at the NTD HGNC or RBD regions from the second tracheal aspirate sample (21 Day). The S:Q493R substitution and S:243-244LA deletion had ~70% frequency, while ORF1a PROTEIN:A138T, S:141-144LGVY deletion, S:E484K and S:Q493K substitutions demonstrated ~30%, ~30%, ~20% and ~10% mutation frequency, respectively. However, the third tracheal aspirate sample collected one week later (Day 27) was predominated by the haplotype of ORF1a PROTEIN:A138T, S:141-144LGVY deletion and S:E484K (> 95% mutation frequency). Notably, S protein PROTEIN deletions (141-144LGVY and 243-244LA deletions in NTD HGNC region) and substitutions (Q493K/R and E484K in the RBD region) previously showed reduced susceptibly to monoclonal antibody or convalescent plasma. The observation supports the hypothesis that VOCs can independently arise and that immunocompromised patients on convalescent plasma therapy are potential breeding grounds for immune-escape mutants.

    Characteristics of Long Covid: findings from a social media surve

    Authors: Nida Ziauddeen; Deepti Gurdasani; Margaret E O'Hara; Claire Hastie; Paul Roderick; Guiqing Yao; Nisreen A Alwan

    doi:10.1101/2021.03.21.21253968 Date: 2021-03-26 Source: medRxiv

    Many people are not recovering for months after being infected with SARS-CoV-2. Long Covid has emerged as a major public health concern that needs defining, quantifying, and describing. We aimed to explore the initial and ongoing symptoms of Long Covid following SARS-CoV-2 infection MESHD and describe its impact on daily life in people who were not admitted to hospital during the first two weeks of the illness. We co-produced a survey with people living with Long Covid. We collected the data through an online survey using convenience non-probability sampling, with the survey posted both specifically on Long Covid support groups and generally on social media. The criteria for inclusion were adults with lab-confirmed (PCR or antibody) or suspected COVID-19 MESHD managed in the community (non-hospitalised) in the first two weeks of illness. We used agglomerative hierarchical clustering to identify specific symptom clusters, and their demographic and functional correlates. We analysed data from 2550 participants with a median duration of illness of 7.7 months (interquartile range (IQR) 7.4-8.0). The mean age was 46.5 years (standard deviation 11 years) with 82.8% females and 79.9% of participants based in the UK. 89.5% described their health as good, very good or excellent before COVID-19 MESHD. The most common initial symptoms that persisted were exhaustion, chest pressure/tightness, shortness of breath MESHD and headache MESHD. Cough, fever MESHD, and chills were common initial symptoms that became less prevalent later in the illness, whereas cognitive dysfunction MESHD and palpitations became more prevalent later in the illness. 26.5% reported lab-confirmation of infection. The biggest difference in ongoing symptoms between those who reported testing positive and those who did not was loss of smell/taste. Ongoing symptoms affected at least 3 organ systems in 83.5% of participants. Most participants described fluctuating (57.7%) or relapsing symptoms (17.6%). Physical activity, stress and sleep disturbance commonly triggered symptoms. A third (32%) reported they were unable to live alone without any assistance at six weeks from start of illness. 16.9% reported being unable to work solely due to COVID-19 MESHD illness. 66.4% reported taking time off sick (median of 60 days, IQR 20, 129). 37.0% reported loss of income due to illness, and 64.4% said they were unable to perform usual activities/duties. Acute systems clustered broadly into two groups: a majority cluster (n=2235, 88%) with cardiopulmonary predominant symptoms, and a minority cluster (n=305, 12%) with multisystem symptoms. Similarly, ongoing symptoms broadly clustered in two groups; a majority cluster (n=2243, 88.8%) exhibiting mainly cardiopulmonary, cognitive symptoms MESHD and exhaustion, and a minority cluster (n=283, 11.2%) exhibited more multisystem symptoms. Belonging to the more severe multisystem cluster MESHD was associated with more severe functional impact, lower income, younger age, being female, worse baseline health, and inadequate rest in the first two weeks of the illness, with no major differences in the cluster patterns when restricting analysis to the lab-confirmed subgroup. This is an exploratory survey of Long Covid characteristics. Whilst it is important to acknowledge that it is a non-representative population sample, it highlights the heterogeneity of persistent symptoms, and the significant functional impact of prolonged illness MESHD following confirmed or suspected SARS-CoV-2 infection MESHD. To study prevalence, predictors and prognosis, research is needed in a representative population sample using standardised case definitions (to include those not lab-confirmed in the first pandemic wave).

    Who suffered most after deaths due to COVID-19 MESHD? Prevalence and correlates of prolonged grief disorder in COVID-19 MESHD related bereaved adults

    Authors: Suqin Tang; Zhendong Xiang

    doi:10.21203/rs.3.rs-118229/v2 Date: 2020-11-29 Source: ResearchSquare

    Background: Deaths by COVID-19 MESHD have left behind nearly 12 million recent bereaved individuals worldwide and researchers have raised concerns that the circumstances of COVID-19 MESHD related deaths will lead to a rise prevalence of prolonged grief disorder MESHD ( PGD MESHD PGD HGNC) cases. However, to date, no studies have examined the prevalence of PGD HGNC PGD MESHD among people bereaved due to COVID-19 MESHD. This study aimed to estimate the prevalence of PGD HGNC PGD MESHD and investigated demographic and loss-related factors associated with prolonged grief symptoms among Chinese individuals bereaved due to COVID-19 MESHD.Methods: This was a cross-sectional online survey conducted between September 1 and October 3, 2020. A total of 422 Chinese participants (55.5% males; 32.73 [9.31] years old) who lost a close person due to COVID-19 MESHD participated in the study. Demographic and loss-related information was collected, and self-reported prolonged grief symptoms were measured by a 13-item International Prolonged Grief Disorder Scale (IPGDS: 1–65) and a 17- item Traumatic MESHD Grief Inventory Self Report (TGI-SR: 1–85). Multiple linear regression analysis was used to determine the associated factors of levels of grief symptoms.Results: Prevalence of PGD HGNC PGD MESHD was 37.8% screened by IPGDS and 29.3% by TGI-SR. No difference was found in levels of grief symptoms between participants whose close one died more than 6 months ago and those who experienced the loss less than 6 months ago. More severe prolonged grief symptoms assessed by IPGDS was associated with losing a close person by COVID-19 MESHD rather than complications (B: 5.35; 95% CI: 0.54–10.05), losing a partner (B: 7.80; 95% CI: 3.24–12.37), child (B: 8.15; 95% CI: 1.03–15.26), and parent (B: 5.49; 95% CI: 1.49–9.48) rather than losing a relative or a person with other relationship, feeling more traumatic MESHD about the loss (B: 1.71; 95% CI: 0.52–2.90), being closer with the deceased (B: 1.60; 95% CI: 0.34–2.86). Moreover, Losing a grandparent (B: 6.62; 95% CI: 0.53–12.71) and having more conflicts with the deceased (B: 1.05; 95% CI: -0.008–2.11) were related to higher levels of grief symptoms assessed by TGI-SR. Conclusions: Echoing to researchers’ concerns, prevalence of PGD HGNC PGD MESHD is high among people bereaved due to COVID-19 MESHD. Individuals with higher risk of developing PGD HGNC PGD MESHD should be identified and bereavement support should be offered as early as possible.

    Analysis of the Effect of Proton Pump Inhibitors on the Course of Common COVID-19 MESHD

    Authors: xiaoyu ZHANG; Haibing Wu; Yun Ling; Liang Chen

    doi:10.21203/rs.3.rs-90738/v1 Date: 2020-10-10 Source: ResearchSquare

    Background/aims: This study is to evaluate the effect of proton pump inhibitors on the course of common COVID-19 MESHD.Methods: Clinical data of common COVID-19 MESHD patients admitted to the Shanghai Public Health Clinical Center for treatment from January 20, 2020 to March 16, 2020 were collected. A retrospective study was conducted and the patients were divided into two groups according to whether they used proton pump inhibitors or not. The differences in SARS-CoV-2 clearance and hospital stay between the two groups were compared by univariate and multivariate analyses.Results: A total of 154 COVID-19 MESHD common cases were included in this study, including 80 males (51.9%), 35 patients (22.7%) in the proton pump inhibitors group, and 119 patients (77.3%) in the control group. In the proton pump inhibitors group and the control group, the duration of the SARS-CoV-2 clearance were 7(6-9) and 7(6-11) days, and the duration of the hospital stay was 21(16-25) and 20(15-26) days, respectively. There was no significant difference between the two groups in the cumulative incidence of the SARS-CoV-2 clearance and the discharge, all P > 0.05. Multivariate analysis showed that chronic gastropathy prolonged MESHD the duration of SARS-CoV-2 clearance, the HR was 20.924(3.547-123.447). Hypertension MESHD, chronic obstructive pulmonary disease MESHD, chronic liver disease MESHD and malignant tumor MESHD all increased the duration of hospital stay for COVID-19 MESHD, and the HR were 1.820 (1.073-3.085), 4.370 (1.205-15.844), 9.011 (2.681-30.290) and 5.270 (1.237-22.456), respectively; the duration of the hospital stay in COVID-19 MESHD patients was shortened by the SARS-CoV-2 clearance, and the HR was 0.907 (0.869-0.947); all P < 0.05.Conclusion:  Proton pump inhibitors use has no effect on the prolonging or shortening of the course of adults hospitalized with COVID-19 MESHD.

    Analysis of the effect of proton pump inhibitors on the course of common COVID-19 MESHD

    Authors: Xiao-Yu Zhang; Hai-Bing Wu; Yun Ling; Zhi-Ping Qian; Liang Chen

    doi:10.1101/2020.06.07.20124776 Date: 2020-06-09 Source: medRxiv

    Background/aims: To evaluate the effect of proton pump inhibitors on the course of common COVID-19 MESHD. Methods: Clinical data of common COVID-19 MESHD patients admitted to the Shanghai public health clinical center for treatment from January 20, 2020 to March 16, 2020 were collected. A retrospective study was conducted and the patients were divided into two groups according to whether they used proton pump inhibitors or not. The differences in SARS-CoV-2 clearance and hospital stay between the two groups were compared by univariate and multivariate analyses. Results: A total of 154 COVID-19 MESHD common cases were included in this study, including 80 males (51.9%), 35 patients (22.7%) in the proton pump inhibitors group, and 119 patients (77.3%) in the control group. In the proton pump inhibitors group and the control group, the duration of SARS-CoV-2 clearance were 7(6-9) and 7(6-11) days, and the duration of hospital stay was 21(16-25) and 20(15-26) days, respectively. There was no significant difference between the two groups in the cumulative incidence of SARS-CoV-2 clearance and the cumulative incidence of discharge, and the same after Propensity Score Match, all P > 0.05. Multivariate analysis suggested that chronic gastropathy prolonged MESHD the duration of SARS-CoV-2 clearance, the HR was 20.924(3.547-123.447). Hypertension MESHD, chronic obstructive pulmonary disease MESHD, chronic liver disease MESHD and malignant tumor MESHD all increased the duration of hospital stay for COVID-19 MESHD, and the HR were 1.820 (1.073-3.085), 4.370 (1.205-15.844), 9.011 (2.681-30.290) and 5.270 (1.237-22.456), respectively; the duration of hospital stay in COVID-19 MESHD patients was shortened by SARS-CoV-2 clearance, and the HR was 0.907 (0.869-0.947); all P < 0.05. Conclusion: Proton pump inhibitors use have no effect on the prolonging or shortening of the course of adults hospitalized with COVID-19 MESHD.

    Experience with Hydroxychloroquine and Azithromycin in the COVID-19 Pandemic MESHD COVID-19 Pandemic MESHD: Implications for QT Interval Monitoring

    Authors: Archana Ramireddy; Harpriya S. Chugh; Kyndaron Reinier; Joseph Ebinger; Eunice Park; Michael Thompson; Eugenio Cingolani; Susan Cheng; Eduardo Marban; Christine Albert; Sumeet S. Chugh

    doi:10.1101/2020.04.22.20075671 Date: 2020-04-25 Source: medRxiv

    Background: Despite a paucity of clinical evidence, hydroxychloroquine and azithromycin are being administered widely to patients with verified or suspected COVID-19 MESHD. Both drugs may increase risk of lethal arrhythmias MESHD associated with QT interval prolongation MESHD. Methods: We performed a case series of COVID-19 MESHD positive/suspected patients admitted between 2/1/2020 and 4/4/2020 who were treated with azithromycin, hydroxychloroquine or a combination. We evaluated baseline and post-medication QT interval (QTc, Bazett) using 12-lead ECGs. Critical QTc prolongation MESHD was defined as: a) maximum QTc [≥]500 ms (if QRS <120 ms) or QTc [≥]550 (if QRS [≥]120 ms) and b) increased QTc of [≥]60 ms. Tisdale score and Elixhauser comorbidity index were calculated. Results: Of 490 COVID-19 MESHD positive/suspected patients, 314 (64%) received either/both drugs, and 98 (73 COVID-19 MESHD positive, 25 suspected) met study criteria (age 62{+/-}17 yrs, 61% male). Azithromycin was prescribed in 28%, hydroxychloroquine in 10%, and both in 62%. Baseline mean QTc was 448{+/-}29 ms and increased to 459{+/-}36ms (p=0.005) with medications. Significant prolongation MESHD was observed only in men (18{+/-}43 ms vs -0.2{+/-}28 ms in women, p=0.02). 12% of patients reached critical QTc prolongation MESHD. In a multivariable logistic regression, age, sex, Tisdale score, Elixhauser score, and baseline QTc were not associated with critical QTc prolongation MESHD (p>0.14). Changes in QTc were highest with the combination compared to either drug, with many-fold greater prolongation with the combination vs. azithromycin alone (17{+/-}39 vs. 0.5{+/-}40 ms, p=0.07). No patients manifested torsades de pointes MESHD. Conclusions: Overall, 12% of patients manifested critical QTc interval prolongation MESHD, and traditional risk indices failed to flag these patients. With the drug combination, QTc prolongation MESHD was several-fold higher compared to azithromycin alone. The balance between uncertain benefit and potential risk when treating COVID-19 MESHD patients with these drugs should be carefully assessed prior to use.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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