preVIEW: COVID-19

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Overview

MeSH Disease

Pneumonia (1322)

COVID-19 (1250)

Severe Acute Respiratory Syndrome (197)

Coronavirus Infections (175)

Death (167)


HGNC Genes

C-reactive protein (94)

interleukin 6 (70)

angiotensin I converting enzyme 2 (68)

solute carrier family 17 member 5 (15)

CD8a molecule (15)


SARS-CoV-2 proteins

ProteinS (51)

ProteinN (19)

NSP5 (11)

ComplexRdRp (9)

ProteinE (6)


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    High incidence of pulmonary thromboembolism MESHD in hospitalized SARS-CoV-2 infected MESHD patients

    Authors: DAVID EL-QUTOB Sr.; Laura Alvarez; Patricia Garcia; Montserrat Robustillo; Ines Barreda; MARIA NIETO; Maria Teresa Pin; Francisco Javier Carrera

    doi:10.1101/2021.03.23.21253258 Date: 2021-03-24 Source: medRxiv

    Introduction SARS-CoV-2 infected MESHD patients present thrombotic complications MESHD caused by direct endothelial cells injury of the microvessels. Pulmonary thromboembolism MESHD ( PE MESHD) has been reported by Computed Tomography pulmonary angiogram (CTPA) in patients with COVID-19 MESHD pneumonia MESHD with high D-dimer levels. Objectives We present the characteristics of SARS-CoV-2 infected MESHD patients diagnosed of PE MESHD by CTPA in our hospital. We also present the comparison of these findings with non-infected MESHD patients with PE MESHD data. Methods Patients 18 years of age or older with SARS-CoV2 virus infection MESHD, and patients with suspected infection at beginning of admission but with negative PCR, were studied with CTPA for suspicion of VTE MESHD, during their hospitalization. Results During the study period, 52 CTPA were performed in our hospital, sixteen in SARS-CoV-2 infected MESHD patients. No significant differences in age (p=0.43) and sex (p=0.31) were found between the two groups, infected and non-infected MESHD patients. In the infected group, the patients who had PE MESHD had a much lower median age (47.8 years) than those without PE MESHD (73.3 years). No differences between infected and non-infected MESHD patients were detected in the diagnosis of PE MESHD with CTPA, 28.6% versus 27.8% (p=1.00). Overall patient mortality was 1.9%; one patient died (6.3%) in the infected group, and none in the non-infected group (p=0.31). Conclusion A considerable incidence of PE MESHD diagnosed by CTPA in SARS-CoV-2 infected MESHD patients has been observed, despite thrombo-prophylaxis.

    Vascular Inflammation MESHD in Lungs of Patients with Fatal Coronavirus Disease 2019 MESHD ( COVID-19 MESHD) Infection: Possible role for the NLRP3 HGNC inflammasome

    Authors: Oindrila Paul; Jian Qin Tao; Leslie Litzky; Michael Feldman; Kathleen Montone; Chamith Rajapakse; Christian Bermudez; Shampa Chatterjee

    doi:10.1101/2021.03.19.21253815 Date: 2021-03-22 Source: medRxiv

    Hyperinflammation is a key event that occurs with SARS-CoV-2 infection MESHD. In the lung, hyperinflammation leads to structural damage to tissue. To date, numerous lung histological studies have shown extensive alveolar damage MESHD, but there is scarce documentation of vascular inflammation MESHD in postmortem lung tissue. Here we document histopathological features and monitor the NLRP3 HGNC inflammasome in fatal cases of disease caused by SARS Cov2 ( COVID-19 MESHD). We posit that inflammasome formation along the vessel wall is a characteristic of lung inflammation MESHD that accompanies COVID-19 MESHD and that it is a probable candidate that drives amplification of inflammation post infection MESHD.

    Circadian regulation of SARS-CoV-2 infection MESHD in lung epithelial cells

    Authors: Xiaodong Zhuang; Senko Tsukuda; Florian Wrensch; Peter AC Wing; Helene Borrmann; James M Harris; Sophie B Morgan; Laurent Mailly; Nazia Thakur; Carina Conceicao; Harshmeena Sanghani; Laura Heydmann; Charlotte Bach; Anna Ashton; Steven Walsh; Tiong Kit Tan; Lisa Schimanski; Kuan-Ying A Huang; Catherine Schuster; Koichi Watashi; Timothy SC Hinks; Aarti Jagannath; Sridhar R Vausdevan; Dalan Bailey; Thomas F Baumert; Jane A McKeating

    doi:10.1101/2021.03.20.436163 Date: 2021-03-21 Source: bioRxiv

    The COVID-19 pandemic MESHD, caused by SARS-CoV-2 coronavirus MESHD, is a global health issue with unprecedented challenges for public health. SARS-CoV-2 primarily infects cells of the respiratory tract, via binding human angiotensin-converting enzyme ( ACE2 HGNC), and infection can result in pneumonia MESHD and acute respiratory distress syndrome MESHD. Circadian rhythms coordinate an organisms response to its environment and recent studies report a role for the circadian clock to regulate host susceptibility to virus infection MESHD. Influenza A infection of arhythmic mice, lacking the circadian component BMAL1, results in higher viral replication and elevated inflammatory responses leading to more severe bronchitis MESHD, highlighting the impact of circadian pathways in respiratory function. We demonstrate circadian regulation of ACE2 in lung epithelial cells and show that silencing BMAL1 or treatment with the synthetic REV-ERB agonist SR9009 reduces ACE2 expression and inhibits SARS-CoV-2 entry MESHD and RNA replication. Treating infected cells with SR9009 limits viral replication and secretion of infectious particles, showing that post-entry steps in the viral life cycle are influenced by the circadian system. Our study suggests new approaches to understand and improve therapeutic targeting of COVID-19 MESHD.

    Predicting clinical outcomes in the Machine Learning era: The Piacenza score a purely data driven approach for mortality prediction in COVID-19 MESHD Pneumonia

    Authors: geza halasz; Michela Sperti; Matteo Villani; Umberto Michelucci; Piergiuseppe Agostoni; Andrea Biagi; Luca Rossi; Andrea Botti; Chiara Mari; Marco Maccarini; Filippo Pura; Loris Roveda; alessia nardecchia; Emanuele Mottola; Massimo Nolli; elisabetta salvioni; massimo mapelli; Marco Agostino deriu; Dario Piga; Massimo Piepoli

    doi:10.1101/2021.03.16.21253752 Date: 2021-03-20 Source: medRxiv

    Background Several models have been developed to predict mortality in patients with COVID-19 MESHD pneumonia MESHD, but only few have demonstrated enough discriminatory capacity. Machine-learning(ML) algorithms represent a novel approach for data-driven prediction of clinical outcomes with advantages over statistical modelling. We developed the Piacenza score, a ML-based score, to predict 30-day mortality in patients with COVID-19 MESHD pneumonia MESHD. Methods 852 patients (mean age 70years, 70%males) were enrolled from February to November 2020. The dataset was randomly splitted into derivation and test. The Piacenza score was obtained through the Naive Bayes classifier and externally validated on 86 patients. Using a forward-search algorithm the following six features were identified: age; mean corpuscular haemoglobin concentration; PaO2/FiO2 ratio; temperature; previous stroke MESHD; gender. In case one or more of the features are not available for a patient, the model can be re-trained using only the provided features. We also compared the Piacenza score with the 4C score and with a Naive Bayes algorithm with 14 variables chosen a-priori. Results The Piacenza score showed an AUC of 0.78(95% CI 0.74-0.84, Brier-score 0.19) in the internal validation cohort and 0.79(95% CI 0.68-0.89, Brier-score 0.16) in the external validation cohort showing a comparable accuracy respect to the 4C score and to the Naive Bayes model with a-priori chosen features, which achieved an AUC of 0.78(95% CI 0.73-0.83, Brier-score 0.26) and 0.80(95% CI 0.75-0.86, Brier-score 0.17) respectively. Conclusion A personalized ML-based score with a purely data driven features selection is feasible and effective to predict mortality in patients with COVID-19 MESHD pneumonia MESHD.

    Hospitalization of mild cases of community-acquired pneumonia MESHD decreased more than severe ones during the COVID-19 MESHD epidemic

    Authors: Hiroyuki Nagano; Daisuke Takada; Jung-ho Shin; Tetsuji Morishita; Susumu Kunisawa; Yuichi Imanaka

    doi:10.1101/2021.03.18.21253861 Date: 2021-03-20 Source: medRxiv

    ObjectiveThe epidemic of the coronavirus disease 2019 MESHD ( COVID-19 MESHD) has affected the entire health care systems. Our aim was to assess the impact of the COVID-19 MESHD epidemic on the number and severity of cases for community-acquired pneumonia MESHD (CAP) in Japan. MethodsUsing claims data from the Quality Indicator/Improvement Project (QIP) database, we included urgent cases of inpatients for CAP from August 1, 2018, to July 30, 2020. We compared the monthly ratio of inpatient cases from August 2018 to July 2019 and August 2019 to July 2020 as a year-over-year comparison. We also compared this ratio according to the severity score "A-DROP" and performed an interrupted time series analysis (ITS) to evaluate the impact of the COVID-19 MESHD epidemic on the monthly number of inpatient cases. ResultsA total of 67,900 inpatient cases for CAP in 262 hospitals were included. During the COVID-19 MESHD epidemic (defined as the period between March and July 2020), the number of inpatient cases for CAP drastically decreased during the epidemic compared with the same period in the past year (-48.1%), despite only a temporary reduction in the number of other urgent admissions. The number of inpatient cases decreased according to the severity of pneumonia MESHD. Milder cases showed a greater decrease in the year-over-year ratio than severe ones (mild -55.2%, moderate -45.8%, severe -39.4%, and extremely severe - 33.2%). The ITS analysis showed that the COVID-19 MESHD epidemic reduced the monthly number of inpatient cases for CAP significantly (estimated decrease: -1233 cases; 95% CI, -521 to -1955). ConclusionsOur study showed a significant reduction in the number of inpatient cases for CAP during the COVID-19 MESHD epidemic in Japan. The milder cases showed a greater decrease in the year-over-year ratio of the number of inpatient cases.

    Assessing the utility of lymphocyte count to diagnose COVID-19 MESHD

    Authors: Mike Fralick; Orly Bogler; Daniel Tamming; Lauren Lapointe-Shaw; Janice Kwan; Terence Tang; Shail Rawal; Jessica Liu; Fahad Razak; Amol A Verma

    doi:10.1101/2021.03.17.21252922 Date: 2021-03-20 Source: medRxiv

    Background: COronaVirus Disease 2019 MESHD ( COVID-19 MESHD) can be challenging to diagnose, because symptoms are non-specific, clinical presentations are heterogeneous, and false negative tests can occur. Our objective was to assess the utility of lymphocyte count to differentiate COVID-19 MESHD from influenza or community-acquired pneumonia MESHD (CAP). Methods: We conducted a cohort study of adults hospitalized with COVID-19 MESHD or another respiratory infection MESHD (i.e., influenza, CAP) at seven hospitals in Ontario, Canada.The first available lymphocyte count during the hospitalization was used. Standard test characteristics for lymphocyte count (x109/L) were calculated (i.e., sensitivity, specificity, area under the receiver operating curve [AUC]). All analyses were conducting using R. Results: There were 869 hospitalizations for COVID-19 MESHD, 669 for influenza, and 3009 for CAP. The mean age across the three groups was 67 and patients with pneumonia MESHD were older than those with influenza or COVID19 MESHD, and approximately 46% were woman. The median lymphocyte count was nearly identical for the three groups of patients: 1.0 x109/L (interquartile range [IQR]:0.7,2.0) for COVID-19 MESHD, 0.9 x109/L (IQR 0.6,1.0) for influenza, and 1.0 x109/L (IQR 0.6,2.0) for CAP. At a lymphocyte threshold of less than 2.0 x109/L, the sensitivity was 87% and the specificity was approximately 10%. As the lymphocyte threshold increased, the sensitivity of diagnosing COVID-19 MESHD increased while the specificity decreased. The AUC for lymphocyte count was approximately 50%. Interpretation: Lymphocyte count has poor diagnostic discrimination to differentiate between COVID-19 MESHD and other respiratory illnesses. The lymphopenia MESHD we consistently observed across the three illnesses in our study may reflect a non-specific sign of illness severity. However, lymphocyte count above 2.0 x109/L may be useful in ruling out COVID-19 MESHD (sensitivity = 87%).

    COVID-19 MESHD IN IRAQ, THE RURAL INITIATION (AL-MUTHANNA PROVINCE AS AN EXAMPLE)

    Authors: Hazim Talib Thwiny; Safa Ibrahim Jaber; Hekmat Kadhum Ateya; Ali Mosa Al-Yasari; Nawar Jasim Alsalih; Moyed A. AL- Saadawe; Emad Salih Jasim; Mohenned A Alsaadawi

    doi:10.1101/2021.03.16.21251969 Date: 2021-03-20 Source: medRxiv

    A sustained pneumonia MESHD outbreak associated with a novel coronavirus named acute respiratory coronavirus 2 syndrome MESHD (SARS-CoV-2) was identified in Wuhan, Hubei Province, China in December 2019 which was later called COVID-19 MESHD. The first confirmed case of COVID-19 MESHD was reported in Najaf/ Iraq on 24th February. This paper provided some information on COVID-19 MESHD infection in the Province of Al-Muthanna / South Iraq, which was then statistically analyzed and concluded. Confirmed cases of COVID-19 MESHD infections were reported by the Iraqi Ministry of Health in the Province of Al-Muthanna. The first foci started and the first dead infected individual was from Hilal which refers mainly to the role or rural places in starting and transmission of COVID-19 MESHD in Iraq. Many of the infections resulted in non-traveling persons because they were contaminated by contact (96%). Therefore, contact is perceived to be the best-recognized form of transmission. It was also reported that infections in Soweir District of Samawah City were the highest (45%) compared to other areas of the region. They should also be observed, however, that the steps to enforce and monitor the curfew are directly related to the direction of the City Centre because the more they drive away from the city centers, the less stringent the procedures. Infections were focused between the ages of 20 and 50 years old, as that is the expected result because these ranges are at the core of active age groups including social and sports events.

    Post-viral parenchymal lung disease of COVID-19 MESHD and viral pneumonitis MESHD: A systematic review and meta-analysis.

    Authors: Laura Fabbri; Samuel Moss; Fasihul Khan; Wenjie Chi; Jun Xia; Karen Robinson; Alan Smyth; Gisli Jenkins; Iain Stewart

    doi:10.1101/2021.03.15.21253593 Date: 2021-03-17 Source: medRxiv

    Background: Approximately half of patients discharged following COVID-19 MESHD related hospitalisation are reported to suffer from persisting respiratory symptoms. We assess the prevalence of long term radiological and functional pulmonary sequelae in survivors from COVID-19 MESHD and other viral pneumonia MESHD in published literature. Methods: We performed systematic review and meta-analysis of all original studies in adults admitted to hospital with SARS-CoV-2, SARS-CoV, MERS-CoV MESHD, or Influenza pneumonia MESHD and followed within 12 months from discharge. Searches were run on MEDLINE and Embase, with the last update on 1st March 2021. Primary outcomes were presence of 1) radiologic sequelae at CT scans; 2) restrictive impairment; 3) reduced diffusing capacity for carbon monoxide (DLCO). This review is registered on PROSPERO, CRD42020183139. Results: Sixty studies were included for qualitative synthesis, of which 41 were suitable for meta-analysis. On follow up CT scans, the overall estimated proportion was 0.56 (95%CI 0.44 to 0.66, I2= 94.44%) for inflammatory changes, and 0.40 (95%CI 0.29 to 0.52, I2=95.19%) for fibrotic findings. In SARS-CoV-2 specifically, proportions were estimated at 0.43 (95%CI 0.32 to 0.56, I2=94.60%) and 0.30 (95%CI 0.19 to 0.43, I2=94.89%) for inflammatory and fibrotic findings, respectively. Overall proportion for restrictive impairment was 0.19 (95%CI 0.12 to 0.27, I2=94.46%), DLCO reduction was estimated at 0.45 (95%CI 0.38 to 0.52, I2=90.10). Elevated radiological and functional estimates persisted across follow-up times. Confidence in the estimates was deemed very low as studies were largely observational without control groups, heterogeneity in estimates was high but was not clearly attributable to between-study differences of severity or design. Conclusion: Although estimates of prevalence are likely limited by differences in case mix and initial severity, a substantial proportion of radiological and functional sequelae are observed following viral pneumonitis MESHD, including COVID-19 MESHD. This highlights the importance of vigilant radiological and functional follow up.

    Tocilizumab Effect in COVID-19 MESHD Hospitalized Patients: A Systematic Review and Meta-Analysis of Randomized Control Trials

    Authors: Waleed Tharwat Aletreby; Basheer Abdulrahman; Ahmed Fouad Mady; Alfateh Mohammed Noor; Mohammed H Lhmdi; Fahad Faqihi; Abdulrahman M Alharthy; Mohammed A Al-Odat; Dimitrios Karakitsos; Ziad Memish

    doi:10.1101/2021.03.15.21253581 Date: 2021-03-17 Source: medRxiv

    Since the emergence of the first cases of COVID-19 MESHD viral pneumonia MESHD late 2019 several studies evaluated the benefits of different treatment modalities. Early in the pandemic, the interleukin 6 HGNC (IL-6) receptor antibody Tocilizumab was considered in view of the cytokine release syndrome associated with COVID-19 MESHD infection. Several early observational studies showed beneficial effect of treatment with Tocilizumab on mortality, however, results from well-designed randomized clinical trials (RCT) were contradicting. ObjectivesTo perform a systematic literature review and meta-analysis of RCTs utilizing Tocilizumab in the treatment of COVID-19 MESHD pneumonia MESHD, with in-hospital mortality as a primary objective, while secondary objectives included composite outcome of mortality, intubation, or ICU admission, another secondary outcome was super added infection. MethodThis was a random effects model (DerSimonian and Laird) model of relative risk (RR), along with corresponding 95% confidence intervals, p values, and forest plots of both primary and secondary outcomes. A fixed effect sensitivity test was performed for the primary outcome, in addition to subgroup and meta-regression analyses with predefined criteria. ResultsThe primary outcome of mortality showed statistically insignificant reduction of mortality with Tocilizumab (RR = 0.9, 95% CI: 0.8 - 1.01; p = 0.09) although with an unmistakable apparent clinical benefit. There was a significant reduction in the RR of the secondary composite outcome (RR = 0.83, 95% CI: 0.76 - 0.9; p < 0.001), and no difference between groups in super-added infection (RR = 0.77, 95% CI: 0.51 - 1.19; p = 0.24). Treatment protocol allowing a second dose was the only significant predictor of improved mortality in the meta-regression analysis. Certainty of evidence was reduced to moderate for the primary outcome and the secondary outcome of clinical deterioration, while it was reduced to low for the secondary outcome of super-added infection. ConclusionModerate certainty of evidence suggest no statistically significant improvement of 28-30 day all-cause mortality of hospitalized COVID-19 MESHD patients treated with TCZ, although there may be clinically important value. Moderate certainty of evidence suggest lowered relative risk of a composite outcome of death MESHD or clinical deterioration, while, low grade evidence indicate no increase in the risk of super-added infection associated with TCZ treatment. A protocol allowing two doses of TCZ shows evidence of improved mortality as compared to a strictly single dose protocol.

    SARS-CoV-2 Nsp5 HGNC Protein Causes Acute Lung Inflammation MESHD: A Dynamical Mathematical Model

    Authors: José Díaz; Elena R. Álvarez-Buylla; Antonio Bensussen

    id:10.20944/preprints202012.0749.v2 Date: 2021-03-15 Source: Preprints.org

    In the present work we propose a dynamical mathematical model of the lung cells inflammation process MESHD in response to SARS-CoV-2 infection MESHD. In this scenario the main protease PROTEIN Nsp5 HGNC enhances the inflammatory process, increasing the levels of NF kB, IL-6 HGNC, Cox2 HGNC, and PGE2 with respect to a reference state without the virus. In presence of the virus the translation rates of NF kB and IkB arise to a high constant value, and when the translation rate of IL-6 HGNC also increases above the threshold value of 7 pg mL-1 s-1 the model predicts a persistent over stimulated immune state with high levels of the cytokine IL-6 HGNC. Our model shows how such over stimulated immune state becomes autonomous of the signals from other immune cells such as macrophages and lymphocytes, and does not shut down by itself. We also show that in the context of the dynamical model presented here, Dexamethasone or Nimesulide have little effect on such inflammation MESHD state of the infected lung cell, and the only form to suppress it is with the inhibition of the activity of the viral protein Nsp5 HGNC.To that end, our model suggest that drugs like Saquinavir may be useful. In this form, our model suggests that Nsp5 HGNC is effectively a central node underlying the severe acute lung inflammation MESHD during SARS-CoV-2 infection MESHD. The persistent production of IL-6 HGNC by lung cells can be one of the causes of the cytokine storm observed in critical patients with COVID19 MESHD. Nsp5 HGNC seems to be the switch to start inflammation MESHD, the consequent overproduction of the ACE2 HGNC receptor, and an important underlying cause of the most severe cases of COVID19 MESHD.

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