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By Christian Hoffmann &
Bernd S. Kamps

3 May

Epidemiology

Zhang J, Litvinova M, Liang Y, et al. Changes in contact patterns shape the dynamics of the COVID-19 outbreak in China. Science  29 Apr 2020: Full-text: https://science.sciencemag.org/content/early/2020/04/28/science.abb8001

Elegant model, demonstrating the impact of lockdown by using contact survey data for Wuhan and Shanghai before and during the outbreak. Daily contacts were reduced 7-8-fold during the social distancing period, with most interactions restricted to the household. Of note, children 0-14 years were less susceptible to infection than adults (however, numbers were low). Social distancing alone, as implemented during the outbreak, was sufficient to control COVID-19. While proactive school closures cannot interrupt transmission on their own, they can reduce peak incidence by 40-60% and delay the epidemic.

 

Lu J, du Plessis L, Liu Z. Genomic Epidemiology of SARS-CoV-2 in Guangdong Province, China. Cell April 30, 2020. Full-text: https://www.cell.com/cell/fulltext/S0092-8674(20)30486-4

A comprehensive study on genomic epidemiology of SARS-CoV-2 in Guangdong province. The authors generated 53 genomes from infected individuals in Guangdong and deduce that following the first COVID-19 case detected in early January, most infections were the result of virus importation from elsewhere, and that chains of local transmission were limited in size and duration.

 

Virology, Immunology

Gordon DE, Jang GM, Bouhaddou M, et al. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. 2020 Apr 30. PubMed: https://pubmed.gov/32353859 . Full-text: https://doi.org/10.1038/s41586-020-2286-9

A blueprint for future therapies. This heroic work, emerging from a world-wide collaboration (>100 co-authors!), systematically maps the interaction landscape between SARS-CoV-2 proteins and human proteins. Authors cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and analyzed the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs).  In total 66 human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds) were found. Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 receptors.

 

Yin W, Mao C, Luan X. Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by Remdesivir. Science 01 May 2020. Full-text: https://science.sciencemag.org/content/early/2020/04/30/science.abc1560

Convincing data from clinical trials are still lacking (mostly rumours and press conferences). However, this work shows how remdesivir inhibit the SARS-CoV-2 RdRp activity in theory. Authors describe the structure of the SARS-CoV-2 RdRp complex in the apo form and in the complex with a template-primer RNA and the active form of remdesivir. The cryo-EM structures reveal how the template-primer RNA is recognized by the enzyme and how chain elongation is inhibited by remdesivir (and why other nucleotides such as EIDD-2801 may be more potent).

 

Lamers MM, Beumer J, van der Vaart J, et al. SARS-CoV-2 productively infects human gut enterocytes. Science 01 May 2020. Full-text: https://science.sciencemag.org/content/early/2020/04/30/science.abc1669

SARS-CoV and SARS-CoV-2 infected enterocyte lineage cells in a human intestinal organoid model. Similar infection rates of enterocyte-precursors and enterocytes were observed and low levels of ACE2 may be sufficient for viral entry. This study explains why gastrointestinal symptoms are observed in a subset of patients and why viral RNA can be found in rectal swabs, even after nasopharyngeal testing has turned negative.

 

Diagnostics

Zhang K, Liu X, Shen J, et al. Clinically Applicable AI System for Accurate Diagnosis, Quantitative Measurements and Prognosis of COVID-19 Pneumonia Using Computed Tomography. Cell April 29. Full-text: https://www.cell.com/cell/fulltext/S0092-8674(20)30551-1

A CT-based artificial intelligence (AI) system was shown to have the potential to assist in the early diagnosis and monitoring of pneumonia. For the classification model, 361,221 CT images from 2,246 patients including 752 NCP, 797 common pneumonia patients and 697 normal control patients were used for training. In brief, the AI system performance was overall superior to that of junior radiologists and comparable to mid-senior radiologists.

 

Clinical

von der Thusen J, van der Eerden M. Histopathology and genetic susceptibility in COVID-19 pneumonia. Eur J Clin Invest. 2020 Apr 30. PubMed: https://pubmed.gov/32353898 . Full-text: https://doi.org/10.1111/eci.13259

Brief review on current knowledge on the remarkable heterogeneity of disease patterns from a clinical, radiological, and histopathological point of view. The idiosyncratic responses of individual patients may be in part related to underlying genetic variations.

 

Comorbidities

Zhu L, She ZG, Cheng X. Association of Blood Glucose Control and Outcomes in Patients with COVID-19 and Pre-existing Type 2 Diabetes. Cell Metabolism, April 30, 2020. Full-text: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30238-2

Check your HbA1c! The hitherto largest retrospective study on the impact of typ 2 diabetes (T2D) has carefully analyzed 7,337 cases of COVID-19 in Hubei Province, China, among them 952 with pre-existing T2D. Authors found that subjects with T2D required more medical interventions and had a significantly higher mortality (7.8% versus 2.7%; adjusted hazard ratio, 1.49) and multiple organ injury than the non-diabetic individuals. Well-controlled blood glucose was associated with markedly lower mortality (in-hospital death rate 1.1% versus 11.0%) compared to individuals with poorly controlled BG.

 

Piccolo R, Bruzzese D, Mauro C, et al. Population Trends in Rates of Percutaneous Coronary Revascularization for Acute Coronary Syndromes Associated with the COVID-19 Outbreak. Circulation. 2020 Apr 30. PubMed: https://pubmed.gov/32352318 . Full-text: https://doi.org/10.1161/CIRCULATIONAHA.120.047457

Collateral damage of the current pandemic: Data from Italy, providing evidence that the outbreak of COVID-19 was associated with a decline by 32% in the number of percutaneous coronary intervention for acute coronary syndromes.

 

Treatment

Bonam SR, Kaveri SV, Saluntabhai A, et al. Adjunct immunotherapies for the management of severely ill COVID-19 patients. Cell Rep Med April 29, 2020. DOI:https://doi.org/10.1016/j.xcrm.2020.100016. Full-text: https://www.cell.com/action/showPdf?pii=S2666-3791%2820%2930021-5

Comprehensive review on current immunotherapies which either neutralize cytokines, SARS-CoV-2 or exert immunomodulation. Immunotherapies may not only reduce inflammation, inflammation-associated lung damage, or viral load, but could also prevent intensive care unit hospitalization.