Top 10: July 14

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By Christian Hoffmann &
Bernd S. Kamps

14 July

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Epidemiology

Rincón  A, Moreso F, López-Herradón A. The keys to control a coronavirus disease 2019 outbreak in a haemodialysis unit.  Clinical Kidney Journal, 13 July 2020. Full-text:  https://doi.org/10.1093/ckj/sfaa119

Outbreak in an hemodialysis unit in Barcelona, involving 18% of patients receiving treatment in this facility. In total, 22 symptomatic and 14 of the 170 asymptomatic patients became infected. The main risk factors for SARS-CoV-2 infection were sharing health-care transportation, living in a nursing home and having been admitted to the reference hospital within the previous 2 weeks.

 

Virology

Pollock DD, Castoe TA, Perry BW, et al. Viral CpG deficiency provides no evidence that dogs were intermediate hosts for SARS-CoV-2. Mol Biol Evol. 2020 Jul 13. PubMed: https://pubmed.gov/32658964 . Full-text: https://doi.org/10.1093/molbev/msaa178

No, dogs are not intermediate hosts. The authors clearly refute the conclusions of another group that dogs are a likely intermediate host of a SARS-CoV-2 ancestor, highlighting major flaws in the inference process and analysis.

 

Immunology

Hadjadj J, Yatim N, Barnabei L. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science 13 Jul 2020. Full-text:  https://doi.org/10.1126/science.abc6027

Not the first, but the largest study to date, analyzing the integrated immune analysis on a cohort of 50 COVID-19 patients with various disease severity. The picture is clearer now: SARS-CoV-2 infection is characterized by an absence of circulating IFN-β with all disease-severity grades. In addition, most severe COVID-19 patients display impaired IFN-α production that is associated with lower viral clearance and an exacerbated inflammatory response. Inflammation is partially driven by the transcriptional factor NF-κB and characterized by increased tumor necrosis factor (TNF)-α and interleukin (IL)-6 production and signaling.

 

Ovsyannikova IG, Haralambieva IH, Crooke SN, Poland GA, Kennedy RB. The role of host genetics in the immune response to SARS-CoV-2 and COVID-19 susceptibility and severity. Immunol Rev. 2020 Jul 13. PubMed: https://pubmed.gov/32658335 . Full-text: https://doi.org/10.1111/imr.12897

Individuals in the population harbor single nucleotide polymorphisms (SNPs) across a variety of genes (eg, ACE2, TMPRSS2, HLA, CD147, MIF, IFNG, IL6) that have been implicated in the pathology and immunology of SARS-CoV-2 and other pathogenic coronaviruses. This well-written review gives an overview on current knowledge on host factors involved in coronavirus infections and proposes a large research agenda.

 

Yan M, Liu H, Wu NC, et al. Structural basis of a shared antibody response to SARS-CoV-2. Science  13 Jul 2020. Full-text:  https://doi.org/10.1126/science.abd2321

Among 294 anti-SARS-CoV-2 antibodies, IGHV3-53 was the most frequently used IGHV gene for targeting the receptor-binding domain (RBD) of the spike protein. Co-crystal structures of two IGHV3-53 neutralizing antibodies with RBD revealed that the germline-encoded residues dominate recognition of the ACE2 binding site. These IGHV3-53 antibodies show minimal affinity for maturation and high potency, which is promising for vaccine design.

 

Diagnostics

Mallapaty S. The mathematical strategy that could transform coronavirus testing. Nature 10 July 2020. Full-text:  https://www.nature.com/articles/d41586-020-02053-6

If you are interested in math, then this article is for you (everyone else should avoid it). Beautiful mental exercise about how to best pool samples from as many people as possible, in order to save time and/or resources. It’s not that trivial. Some sophisticated strategies are discussed.

 

Clinical

Fauvel C, Weizman O, Trimaille A. Pulmonary embolism in COVID-19 patients: a French multicentre cohort study. European Heart Journal, 13 July 2020. Full-text:  https://doi.org/10.1093/eurheartj/ehaa500

In this retrospective multicentre study, 103/1,240 (8.3%) consecutive patients hospitalized for COVID-19 (patients who were directly admitted to an ICU were excluded) had evidence for PE. In a multivariable analysis, male gender, anticoagulation with a prophylactic or therapeutic dose, elevated C-reactive protein, and time from symptom onset to hospitalization were associated with PE risk. PE risk factors in the COVID-19 context do not include traditional thromboembolic risk factors but rather independent clinical and biological findings at admission, including a major contribution of inflammation.

 

Bäuerle A, Teufel N, Musche V. Increased generalized anxiety, depression and distress during the COVID-19 pandemic: a cross-sectional study in Germany. Journal of Public Health, 13 July 2020. Full-text:  https://doi.org/10.1093/pubmed/fdaa106

The more you know, the more afraid you’ll be of COVID-19. In this cross-sectional study on 15,704 German residents, trust in governmental actions to face COVID-19 and the subjective level of information regarding COVID-19 were negatively associated with mental health burden. However, the subjective level of information regarding COVID-19 was positively associated with increased COVID-19-related fear.

 

Comorbidities

Hogan AB, Jewel BL, Sherrard-Smith E, et al. Potential impact of the COVID-19 pandemic on HIV, tuberculosis, and malaria in low-income and middle-income countries: a modelling study. Lancet July 13, 2020. Full-text:  https://doi.org/10.1016/S2214-109X(20)30288-6

The collateral damage is just as great. Using established transmission models, data indicate that in countries with a high burden of malaria, HIV and tuberculosis, COVID-19 related disruptions in care could lead to a loss of life-years of over 5 years, that is of the same order of magnitude as the direct impact from COVID-19. The authors estimate that deaths due to HIV, tuberculosis, and malaria over 5 years could increase by up to 10% due to HIV (mainly due to treatment interruptions), 20% to TB (less timely diagnosis and treatment of new cases), and 36% to malaria (interruption of planned net campaigns), respectively.

 

Treatment

Mak YM, Chan FK, Ng SC. Probiotics and COVID-19 – Authors’ reply. Lancet Gastroenterology Hepatology Volume 5, ISSUE 8, P722-723, August 01, 2020. Full-text:  https://doi.org/10.1016/S2468-1253(20)30197-7

COVID-19 patients have an altered gut microbiome. Well, okay, but who doesn’t? Several letters discuss whether probiotics represent a complementary approach for the prevention and restoration of SARS-CoV-2-induced mucosal damage or inflammation through the modulation of gut microbiota. Some groups are optimistic, others aren’t.