Top 10: June 12

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By Christian Hoffmann &
Bernd S. Kamps

12 June

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Epidemiology

Furuse Y, Sando E, Tsuchiya N, et al. Clusters of Coronavirus Disease in Communities, Japan, January-April 2020. Emerg Infect Dis. 2020 Jun 10;26(9). PubMed: https://pubmed.gov/32521222. Full-text: https://doi.org/10.3201/eid2609.202272

Bye, bye, karaoke. The Japanese authors defined a cluster as > 5 cases with primary exposure reported at a common event or venue, excluding within-household transmissions. In total, 61 COVID-19 clusters were found in various communities in the country: 18 (30%) in healthcare facilities; 10 (16%) in care facilities of other types, such as nursing homes and day care centers; 10 (16%) in restaurants or bars; 8 (13%) in workplaces; 7 (11%) in music-related events, such as live music concerts, chorus group rehearsals, and karaoke parties; 5 (8%) in gymnasiums; 2 (3%) in ceremonial functions; and 1 (2%) in transportation-related incident in an airplane. Of note, 41% of probable primary case-patients were pre-symptomatic or asymptomatic at the time of transmission. 45% had cough. Many clusters were associated with heavy breathing in close proximity.

 

Stringhini S, Wisniak A, Piumatti G, et al. The Lancet, June 11, 2020. Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Geneva, Switzerland (SEROCoV-POP): a population-based study. Full-text: https://doi.org/10.1016/S0140-6736(20)31304-0

Geneva was a COVID-19 hot spot in Switzerland (5000 cases over < 2,5 months in half a million people). Authors performed 5 consecutive weekly sero-surveys among 2,766 randomly selected participants from a previous population-representative survey, and 1,339 household members aged 5 years and older. Each participant was tested for anti-SARS-CoV-2-IgG antibodies. Seroprevalence increased from about 5% to about 11%. Of note, young children (5–9 years) and older people (≥ 65 years) had significantly lower seroprevalence than the other age groups. Authors estimated that there were 11 infections for every COVID-19 confirmed case.

 

Virology

Day T, Gandon S, Lion S, et al. On the evolutionary epidemiology of SARS-CoV-2. Cell 2020, June 11. Full-text: https://doi.org/10.1016/j.cub.2020.06.031

Outstanding essay about what little is currently known about the evolution of SARS-CoV-2. At present, there is a lack of compelling evidence that any existing variants impact the progression, severity, or transmission of COVID-19 in an adaptive manner. The authors discuss the potential evolutionary routes that SARS-CoV-2 might take and dispel some of the current misinformation that is circulating in the media.

 

Gussow AB, Auslander N, Faure G, Wolf YI, Zhang F, Koonin EV. Genomic determinants of pathogenicity in SARS-CoV-2 and other human coronaviruses. Proc Natl Acad Sci U S A. 2020 Jun 10:202008176. PubMed: https://pubmed.gov/32522874. Full-text: https://doi.org/10.1073/pnas.2008176117

This in-depth molecular analysis reconstructs key genomic features that differentiate SARS-CoV-2, SARS-CoV and MERS-CoV from less pathogenic coronaviruses. Exploring the regions identified within the nucleocapsid that predict the high case fatality rate of coronaviruses, the authors found that these deletions and insertions result in substantial enhancement of motifs that determine nuclear localization. The deletions, insertions, and substitutions in the N proteins of the high-CFR coronaviruses map to two monopartite nuclear localization signals. These findings imply an important role of the subcellular localization of the nucleocapsid protein in coronavirus pathogenicity.

 

Immunology

Hassan AO, Case JB, Winkler ES, et al. A SARS-CoV-2 infection model in mice demonstrates protection by neutralizing antibodies. Cell 2020, June 10. Full-text: https://doi.org/10.1016/j.cell.2020.06.011

Most mice are not readily infected by SARS-CoV-2 because of species-specific differences in their ACE2 receptors. US researchers transduced replication-defective adenoviruses encoding human ACE2 via intranasal administration into BALB/c mice and established receptor expression in lung tissues. hACE2-transduced mice were productively infected with SARS-CoV-2, and this resulted in high viral titers in the lung and lung pathology. Neutralizing mAbs protect from SARS-CoV-2 induced lung infection, and inflammation. This accessible mouse model will expedite the testing and deployment of therapeutics and vaccines.

 

Sun J, Zhuang, Zheng J, et al. Generation of a Broadly Useful Model for COVID-19 Pathogenesis Vaccination, and Treatment. Cell 2020, June 10. Full-text: https://doi.org/10.1016/j.cell.2020.06.010

Another murine model, but from China. After exogenous delivery of human ACE2 with a replication-deficient adenovirus, Ad5-hACE2-sensitized mice developed pneumonia and high-titer virus replication in lungs. Type I interferon, T cells and, most importantly, signal transducer and activator of transcription 1 (STAT1) were critical for virus clearance and disease resolution. This murine model of broad and immediate utility will help to investigate COVID-19 pathogenesis, and to evaluate new therapies and vaccines.

 

Transmission

Liu M, Cheng SZ, Xu KW, et al. Use of personal protective equipment against coronavirus disease 2019 by healthcare professionals in Wuhan, China: cross sectional study. BMJ. 2020 Jun 10;369:m2195. PubMed: https://pubmed.gov/32522737. Full-text: https://doi.org/10.1136/bmj.m2195

PPE works well: This study analyzed 420 healthcare professionals (116 doctors and 304 nurses) who were deployed to Wuhan by two affiliated hospitals of Sun Yatsen University and Nanfang Hospital of Southern Medical University for 6-8 weeks from 24 January to 7 April 2020. All were provided with appropriate personal protective equipment to deliver healthcare to patients admitted to hospital with COVID-19. Although all were involved in aerosol generating procedures (high risk of exposure), no-one contracted infection.

 

Schuit M, Ratnesar-Shumate S, Yolitz J, et al. Airborne SARS-CoV-2 is Rapidly Inactivated by Simulated Sunlight. J Infect Dis. 2020 Jun 11:jiaa334. PubMed: https://pubmed.gov/32525979. Full-text: https://doi.org/10.1093/infdis/jiaa334

Again, it’s sunlight! This study examined the effect of simulated sunlight and relative humidity on the stability of SARS-CoV-2 in aerosols. A 90% loss of virus in simulated saliva was 19 minutes under simulated sunlight levels representative of late winter/early fall, 6 minutes of summer levels and 125 minutes without simulated sunlight across all relative humidity levels. Aerosol transmission of SARS-CoV-2 may be dependent on environmental conditions, particularly sunlight.

 

Clinical

Destras G, Bal A, Excuret V, et al. Systematic SARS-CoV-2 screening in cerebrospinal fluid during the COVID-19 pandemic. The Lancet Microbe June 11, 2020. Full-text: https://doi.org/10.1016/S2666-5247(20)30066-5

Among 578 CSF samples analyzed at the virology laboratory of Lyon University Hospital during the COVID-19 epidemic (Feb 1 to May 11, 2020), all were negative, except for two samples that were slightly positive for SARS-CoV-2 corresponding to post-mortem samples from two adults with confirmed COVID-19. Importantly, the other 21 CSF samples from patients with confirmed COVID-19 were negative. These data suggest that, although SARS-CoV-2 is able to replicate in neuronal cells in vitro, SARS-CoV-2 testing in CSF is not relevant in the general population.

 

Comorbidities

Pinto BGG, Oliveira AER, Singh Y, et al. ACE2 Expression is Increased in the Lungs of Patients with Comorbidities Associated with Severe COVID-19. J Infect Dis. 2020 Jun 11:jiaa332. PubMed: https://pubmed.gov/32526012. Full-text: https://doi.org/10.1093/infdis/jiaa332

The authors analyzed over 700 lung transcriptome samples of patients with comorbidities associated with severe COVID-19 and found that ACE2 was highly expressed in these patients, compared to control individuals. Findings suggest that the higher expression of ACE2 in the lungs is associated with higher chances of developing a severe form of COVID-19, by facilitating SARS-CoV-2 entry into lung cells during the infection.