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By Christian Hoffmann &
Bernd S. Kamps

28 July

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Epidemiology

Vahidy FS, Bernard DW, Boom ML, et al. Prevalence of SARS-CoV-2 Infection Among Asymptomatic Health Care Workers in the Greater Houston, Texas, Area. JAMA Netw Open 2020;3(7):e2016451. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.16451

 

Transmission

Riediker M, Tsai D. Estimation of Viral Aerosol Emissions From Simulated Individuals With Asymptomatic to Moderate Coronavirus Disease 2019. JAMA Netw Open 2020;3(7):e2013807. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.13807

In this modeling study, Michael Riediker from the Swiss Centre for Occupational and Environmental Health in Winterthur and Dai-Hua Tsai from the University Hospital of Psychiatry in Zurich, Switzerland, it is estimated that viral load concentrations in a room with an individual who was coughing frequently were very high, with a maximum of 7.44 million copies/m³ from an individual who was a high emitter. However, regular breathing from an individual who was a high emitter was modeled to result in lower room concentrations of up to 1248 copies/m³. They conclude that the estimated infectious risk posed by a person with typical viral load who breathes normally was low and that only a few people with very high viral load posed an infection risk in the poorly ventilated closed environment simulated in this study.

 

Vahidy FS, Bernard DW, Boom ML, et al. Prevalence of SARS-CoV-2 Infection Among Asymptomatic Health Care Workers in the Greater Houston, Texas, Area. JAMA Netw Open 2020;3(7):e2016451. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.16451

Facing patients or not facing patients, that’s the question. Roberta L. Schwartz and colleagues from the Houston Methodist Academic Institute, US, report a 4.8% difference between COVID-19–facing (5.4%) and non–COVID-19–facing (0.6%) HCWs. The cross-sectional study presents data on SARS-CoV-2 seropositivity in 2872 self-reported asymptomatic individuals, including 2787 HCWs and 85 community residents. In all, 3.9% tested positive for SARS-CoV-2. Among clinical HCWs, 5.4% from COVID-19 units and 0.6% from non–COVID-19 units had a positive RT-PCR test. None of the non-clinical HCWs or community residents tested positive.

Among 1992 HCWs in units caring for patients with COVID-19, the rate of SARS-CoV-2 positivity ranged between 3.6% for support staff to 6.5% for allied health and 6.5% for administrative staff. However, the proportions of participants with positive results for SARS-CoV-2 were not significantly different across five job categories of COVID-19–facing HCWs.

 

Vaccine

Graham SP, McLean RK, Spencer AJ et al. Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19. npj Vaccines 5, 69 (2020). Full-text: https://doi.org/10.1038/s41541-020-00221-3

Simon P. Graham, Teresa Lambe and colleagues compare the immunogenicity of one or two doses of ChAdOx1 nCoV-19 in both mice and pigs. Whilst a single dose induced antigen-specific antibody and T cell responses, a booster immunization enhanced antibody responses, particularly in pigs, with a significant increase in SARS-CoV-2 neutralizing titers. See also the ChAdOx1 Phase 1/2 randomized trial of a chimpanzee adenovirus-vector vaccine (nCoV-19) published a week ago: https://covidreference.com/top-10-july-20.

 

Martin C, Lowery D. mRNA vaccines: intellectual property landscape.  Nat Rev Drug Discov 2020, 27 July. Full-text: https://www.nature.com/articles/d41573-020-00119-8

Cecilia Martin and Drew Lowery generate an intellectual property landscape surrounding mRNA vaccine development. Overall filing activity aims at protecting methods to improve mRNA delivery efficiency as well as pharmacological modifications to reduce mRNA instability and innate immunogenicity. Moderna, CureVac, BioNTech and GSK own nearly half of the mRNA vaccine patent applications.

 

Immunology

Lucas C, Wong P, Klein J, et al. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature. 2020 Jul 27. PubMed: https://pubmed.gov/32717743. Full-text: https://doi.org/10.1038/s41586-020-2588-y

Akiko Iwasaki and colleagues serially analyzed the immune responses in 113 COVID-19 patients with moderate (non-ICU) and severe (ICU) disease. Following an early increase in cytokines, COVID-19 patients with moderate disease displayed a progressive reduction in type 1 (antiviral) and type 3 (antifungal) responses. In contrast, patients with severe disease maintained these elevated responses throughout the course of disease. Moreover, severe disease was accompanied by an increase in multiple type 2 (anti-helminths) effectors including, IL-5, IL-13, IgE and eosinophils.  The authors identified four immune signatures, representing

1. growth factors
2. type 2/3 cytokines
3. mixed type 1/2/3 cytokines
4. chemokines

which correlated with three distinct disease trajectories in patients. These differences in the expression of inflammatory markers along disease progression between patients who exhibit moderate vs. severe COVID-19 symptoms may provide opportunities for targeted treatment.

 

Weisblum Y, Schmidt F, Zhang F, et al. Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. bioRxiv 2020, posted 22 July. Full-text: https://doi.org/10.1101/2020.07.21.214759 | Not yet peer reviewed.

Will SARS-CoV-2 adapt over time and evade neutralizing antibodies? Theodora Hatziioannou, Paul Bieniasz and colleagues at Rockefeller University made an animal virus produce the SARS-CoV-2 spike protein. When grown in the presence of neutralizing antibodies, functional SARS-CoV-2 spike protein variants with mutations in the receptor binding domain (RBD) and N-terminal domain that conferred resistance to monoclonal antibodies or convalescent plasma could be readily selected. Monoclonal antibodies, if one day used as treatment for COVID-19, will probably need to be designed as cocktails of multiple neutralizing antibodies which target distinct neutralizing epitopes.

 

Comorbidities

Puntmann VO, Carerj ML, Wieters I, et al. Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19). JAMA Cardiol 2020, published online July 27. Full-text: https://doi.org/10.1001/jamacardio.2020.3557

Are COVID-19 patients at risk of heart problems after surviving an illness? In a prospective observational cohort study, Eike Nagel and colleagues from the University of Frankfurt, Germany, evaluated cardiovascular magnetic resonance (CMR) images of 100 patients who were recovering from COVID-19 disease. A total of 78 patients (78%) had abnormal CMR findings, including raised myocardial native T1 (n = 73), raised myocardial native T2 (n = 60), myocardial late gadolinium enhancement (n = 32), and pericardial enhancement (n = 22). Endomyocardial biopsy in patients with severe findings revealed active lymphocytic inflammation. At the time of CMR, high-sensitivity troponin T was detectable (3 pg/mL or greater) in 71 patients recently recovered from COVID-19 (71%) and significantly elevated (13.9 pg/mL or greater) in 5 patients (5%). Of note, the median time interval between COVID-19 diagnosis and CMR was 71 (IQR: 64-92) days. The authors stress the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.

Read also the editorial by Clyde W. Yancy and Gregg C. Fonarow: Coronavirus Disease 2019 (COVID-19) and the Heart—Is Heart Failure the Next Chapter? JAMA Cardiol 2020, published online July 27. Full-text: https://doi.org/doi:10.1001/jamacardio.2020.3575

 

Lindner D, Fitzek A, Bräuninger H, et al. Association of Cardiac Infection With SARS-CoV-2 in Confirmed COVID-19 Autopsy Cases. JAMA Cardiol 2020, published online July 27. Full-text: https://doi.org/10.1001/jamacardio.2020.3551

How much is COVID-19 associated with myocardial injury, possibly as the result of viral infection of the heart? Dirk Westermann and colleagues from the University Heart and Vascular Center in Hamburg, Germany, report on a series of 39 autopsies of patients with COVID-19 in whom pneumonia was the clinical cause of death in 35 of 39. SARS-CoV-2 was documented in 24 of 39 patients (61.5%) and viral load above 1000 copies per μg RNA in 16 of 39 patients (41.0%). A cytokine response panel consisting of 6 proinflammatory genes was increased in those 16 patients compared with 15 patients without any SARS-CoV-2 in the heart. In situ hybridization suggested that the most likely localization of SARS-CoV-2 was not in the cardiomyocytes but in interstitial cells or macrophages invading the myocardial tissue.

Read also the editorial by Clyde W. Yancy and Gregg C. Fonarow: Coronavirus Disease 2019 (COVID-19) and the Heart—Is Heart Failure the Next Chapter? JAMA Cardiol 2020, published online July 27. Full-text: https://doi.org/doi:10.1001/jamacardio.2020.3575

 

Pediatrics

Bonnet M, Champagnac A, Lantelme P, Harbaoui B. Endomyocardial biopsy findings in Kawasaki-like disease associated with SARS-CoV-2. European Heart Journal 2020, published 25 July. Full-text: https://doi.org/10.1093/eurheartj/ehaa588

 

Beyond the planet’s borders

Witze A. How space missions snatch pieces of other worlds and bring them back to Earth. Nature 2020, published 27 July. Full-text: https://www.nature.com/articles/d41586-020-02185-9

NASA is going to launch a spacecraft to collect samples from Mars. Andrea Witze looks back at missions that have grabbed extraterrestrial material. Visit the Moon, asteroids, a comet, solar wind and Mars.