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By Christian Hoffmann &
Bernd S. Kamps

4 August

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Epidemiology

Kolthur-Seetharam U, Shah D, Shastri J, Juneja S, Kang G, Malani A, Mohanan M, Lobo GN, Velhal G, Gomare M. SARS-CoV2 Serological Survey in Mumbai by NITI-BMC-TIFR.  Tata Institute of Fundamental Research (TIFR) 2020, published 29 June. Full-text: https://www.tifr.res.in/TSN/article/Mumbai-Serosurvey%20Technical%20report-NITI.pdf

We usually prefer peer-reviewed studies and seldom present pre-published papers. We are even less readily inclined to present a PDF with just the technical details of an unpublished study. Today we make an exception. In a cross-sectional survey in Mumbai, India, Ullas Kolthur-Seetharam and colleagues estimated the prevalence of SARS-CoV-2 infection in three areas in Mumbai (called ‘wards’) in July 2020. The authors found, on average, a prevalence of around 57% in the slum areas of Chembur, Matunga and Dahisar, and 16% in neighboring non-slums. If these data are confirmed, some Mumbai areas would soon reach herd immunity and could return to a pre-COVID way of life. For many countries in the world, this would be the best piece of news since the beginning of the pandemic.

 

Virology

Huang Y, Yang C, Xu X et al. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol Sin 2020, published 3 August. Full-text: https://www.nature.com/articles/s41401-020-0485-4

The spike protein of SARS-CoV-2 plays a key role in the receptor recognition and cell membrane fusion process. In this review, Shu-wen Liu, Wei Xu and colleagues from Southern Medical University, Guangzhou, China, highlight recent research advances in the structure, function and development of antiviral drugs targeting the S protein. Six pages, 86 references.

 

Prevention

Krueger A, Gunn JK, Watson J, et al. Characteristics and Outcomes of Contacts of COVID-19 Patients Monitored Using an Automated Symptom Monitoring Tool — Maine, May–June 2020. MMWR Morb Mortal Wkly Rep 2020, published 3 August. Full-text: http://dx.doi.org/10.15585/mmwr.mm6931e2

A prompt case investigation can rapidly identify contacts and recommend quarantine, reducing additional exposures and transmission. Here Anna Krueger and colleagues present 1,622 contacts of 614 COVID-19 patients who were enrolled in an automated symptom monitoring system in May and June 2020. 190 (11.7%) eventually developed COVID-19. The authors conclude that using digital tools in support of a comprehensive contact tracing strategy can make the contact tracing and monitoring process faster and more efficient.

 

Immunology

Mateus J, Grifoni A, Tarke A, et al. Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans. Science 2020, published 4 August. Full-text: https://science.sciencemag.org/content/early/2020/08/03/science.abd3871

SARS-CoV-2 reactive CD4⁺ T cells have been reported in unexposed individuals, suggesting pre-existing cross-reactive T cell memory in 20-50% of people (see, for example, SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19, presented here on 29 July). To investigate this exciting topic, Daniela Weiskopf, Alessandro Sette and colleagues utilized PBMC samples from subjects collected between March 2015 and March 2018. They demonstrate a range of pre-existing memory CD4⁺ T cells that are cross-reactive with comparable affinity to SARS-CoV-2 and the common cold coronaviruses HCoV-OC43, HCoV-229E, HCoV-NL63, or HCoV-HKU1. Based on these data, the authors find plausible to hypothesize that pre-existing cross-reactive HCoV CD4⁺ T cell memory could explain different COVID-19 clinical outcomes and influence epidemiological models of herd immunity. However, their last sentence includes a warning: it’s still highly speculative.

 

Pathogenesis

Zhang B, Chu H, Han S et al. SARS-CoV-2 infects human neural progenitor cells and brain organoids. Cell Res 2020, published 4 August. Full-text:  https://doi.org/10.1038/s41422-020-0390-x

Jian-Dong Huang and colleagues assessed SARS-CoV-2 infection in induced pluripotent stem cells (iPSCs)-derived human neural progenitor cells (hNPCs), neurospheres, and brain organoids. They detected extensive viral protein expression and infectious viral particles in neurospheres and brain organoids infected with SARS-CoV-2, suggesting that SARS-CoV-2 can productively infect the human brain. In particular, they demonstrated that SARS-CoV-2 could also target the neuronal progenitor cell populations. Chronic or long-term consequences of SARS-CoV-2 infection in the CNS should be closely monitored.

 

Treatment

Touret F, Gilles M, Barral K et al. In vitro screening of a FDA approved chemical library reveals potential inhibitors of SARS-CoV-2 replication. Sci Rep 2020; 10, 13093. Full-text: https://doi.org/10.1038/s41598-020-70143-6

Do you remember Franck Touret? On 5 March, he published Of chloroquine and COVID-19 (Touret F, de Lamballerie X. Of chloroquine and COVID-19. Antiviral Res. 2020 May;177:104762. PubMed: https://pubmed.gov/32147496. Full-text: https://doi.org/10.1016/j.antiviral.2020.104762), a brilliant summary of chloroquine’s repeated failures in treating acute human viral diseases over the last decades. Now, Franck Touret, Bruno Coutard and colleagues screened 1,520 approved and off-patent drugs of the Prestwick Chemical Library in an infected cell-based assay. Eleven compounds such as macrolides antibiotics, proton pump inhibitors (omeprazole and vonoprazan), antiarrhythmic agents or CNS drugs emerged that show an antiviral potency with 2 of them < EC50 ≤ 20 µM.

 

Chan KK, Dorosky D, Sharma P, et al. Engineering human ACE2 to optimize binding to the spike protein of SARS coronavirus 2. Science 2020, published 4 August. Full-text: https://science.sciencemag.org/content/early/2020/08/03/science.abc0870

Soluble ACE2 (sACE2) has been proposed as a therapeutic candidate that neutralizes infection by acting as a decoy. Now Eric Procko and colleagues describe mutations in ACE2 that increase S binding across the interaction surface, in the N90 glycosylation motif and at buried sites. A stable dimeric sACE2 variant with improved properties for binding viral spike showed potent SARS-CoV-2 and -1 neutralization in vitro. The authors conclude that exceptional affinity for protein S can be engineered into the natural receptor for the virus, while also providing insights into the molecular basis for initial virus-host interactions.

 

Co-morbidities

Velez JCQ, Caza T, Larsen CP. COVAN is the new HIVAN: the re-emergence of collapsing glomerulopathy with COVID-19. Nat Rev Nephrol2020, published 4 August. Full-text: https://doi.org/10.1038/s41581-020-0332-3

Is COVAN the new HIVAN? Collapsing glomerulopathy was first characterized in the setting of HIV infection and termed HIV-associated nephropathy (HIVAN). In recent months, five case reports of collapsing glomerulopathy akin to those seen during the HIV epidemic have been published describing cases of collapsing glomerulopathy in association with SARS-CoV-2 infection. All of these cases were in patients of African ethnicity. Juan Carlos Velez and co-authors propose the term COVID-19-associated nephropathy (COVAN) to be used to describe this specific entity.