Top 10: May 18

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By Christian Hoffmann &
Bernd S. Kamps

18 May

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Summary

First, identify 14 potent neutralizing antibodies by high-throughput single B-cell RNA- sequencing; investigate the transmission rate from households with confirmed COVID-19 cases to their dogs; and tell your friends to stop making assumptions on the effect of sunlight on SARS-CoV-2 transmission.

Afterwards, design a rhesus macaque model that recapitulates COVID-19 in humans; transmit SARS-CoV-2 from inoculated Golden Syrian hamsters to naïve hamsters by direct contact and via aerosols; and determine changes in host-cell pathways upon SARS-CoV-2 infection.

Finally, make an in-depth enquiry of COVID-19-associated headache; discuss with your colleagues the hypothetical use of alisporivir; follow 21 transplanted patients (10 kidney, 5 liver, 1 pancreas, 1 lung, 1 heart and 3 combined transplantations); and describe a cohort of 168 children and adolescents with laboratory-confirmed COVID-19.

 

Virology

Munster  VJ, Feldmann F, Williamson BN, et al. Respiratory disease in rhesus macaques inoculated with SARS-CoV-2. Nature 2020. https://doi.org/10.1038/s41586-020-2324-7

SARS-CoV-2 caused respiratory disease in 8 infected rhesus macaques, lasting 8-16 days. Pulmonary infiltrates were visible in lung radiographs. High viral loads were detected in swabs as well as in bronchoalveolar lavages. Taken together, this rhesus macaque “model” recapitulates COVID-19, with regard to virus replication and shedding, the presence of pulmonary infiltrates, histological lesions and seroconversion.

 

Sia SF, Yan L, Chin AWH. et al. Pathogenesis and transmission of SARS-CoV-2 in golden hamsters. Nature 2020. https://doi.org/10.1038/s41586-020-2342-5

In most cases, you don’t need monkeys. Golden Syrian hamsters may also work as an animal model. SARS-CoV-2 transmitted efficiently from inoculated hamsters to naïve hamsters by direct contact and via aerosols. Transmission via fomites in soiled cages was less efficient. Inoculated and naturally-infected hamsters showed apparent weight loss, and all animals recovered with the detection of neutralizing antibodies.

 

Immunology

Bojkova D, Klann K, Koch B et al. Proteomics of SARS-CoV-2-infected host cells reveals therapy targets. Nature 2020, May 14. https://doi.org/10.1038/s41586-020-2332-7

The authors describe a SARS-CoV-2 cell infection system to determine changes in host-cell pathways upon infection, resulting from host-cell (antiviral) responses or viral effector proteins, and assess some potential inhibitors.

 

Transmission

Sit TH, Brackman CJ, Ip SM et al. Infection of dogs with SARS-CoV-2. Nature 2020. https://doi.org/10.1038/s41586-020-2334-5. Full-text: https://www.nature.com/articles/s41586-020-2334-5#citeas

Two out of fifteen dogs (one Pomeranian and one German Shepherd) from households with confirmed human cases of COVID-19 in Hong Kong were found to be infected. Both dogs remained asymptomatic but later developed antibody responses detected using plaque reduction neutralization assays. Genetic analysis suggested that the dogs caught the virus from their owners. It still remains unclear whether infected dogs can transmit the virus to other animals or back to humans.

 

Seyer A, Sanlidaf T. Solar ultraviolet radiation sensitivity of SARS-CoV-2. Lancet Microbe 2020, 1:e8-e9, May, 2020. Full-text: https://doi.org/10.1016/S2666-5247(20)30013-6

Sunlight reaching the ground lacks germicidal ultraviolet C radiation. According to the authors, scientists should avoid voicing assumptions on the effect of sunlight on viral transmission.

 

Clinical

Bolay H, Gul A, Baykan B. COVID-19 is a Real Headache! Headache 2020 May 15. PubMed: https://pubmed.gov/32412101 . Full-text: https://doi.org/10.1111/head.13856

Nice overview on a symptom which is frequently overlooked in clinical practice. Headache was observed in 11-34% of hospitalized patients (in 6-10% as presenting symptom). Significant features are moderate to severe, bilateral headache with pulsating or pressing quality in the temporo-parietal, forehead or periorbital region. The most striking features are sudden to gradual onset and poor response to common analgesics. Possible pathophysiological mechanisms include activation of peripheral trigeminal nerve endings by SARS-CoV2 directly or through vasculopathy and/or increased circulating pro-inflammatory cytokines and hypoxia.

 

Comorbidities

Tschopp J, L´Huillier AG, Mombelli M, et al. First experience of SARS-CoV-2 infections in solid organ transplant recipients in the Swiss Transplant Cohort Study. Am J Transplant 2020 May 15. PubMed: https://pubmed.gov/32412159 . Full-text: https://doi.org/10.1111/ajt.16062

Data from Switzerland. Overall, 21 patients were included with a median age of 56 years (10 kidney, 5 liver, 1 pancreas, 1 lung, 1 heart and 3 combined transplantations). Ninety‐five percent and 24% of patients required hospitalization and ICU admission, respectively. After a median of 33 days of follow‐up, 16 patients were discharged, 3 were still hospitalized and 2 patients died.

 

Treatment

Cao Y, Sui B, Guo X, et al. Potent neutralizing antibodies against SARS-CoV-2 identified by high-throughput single-cell sequencing of convalescent patients’ B cells. Cell 2020, May 17, 2020. Full-text: https://doi.org/10.1016/j.cell.2020.05.025

Fantastic work, identifying 14 potent neutralizing antibodies by high-throughput single B-cell RNA- sequencing  from 60 convalescent patients. The most potent one, BD-368-2, exhibited an IC50 of 15 ng/mL against SARS-CoV-2. This antibody displayed strong therapeutic and prophylactic efficacy in mice, the epitope overlaps with the ACE2 binding site. Time to go into the clinic!

 

Pawlotsky JM. SARS-CoV-2 pandemic : Time to revive the cyclophilin inhibitor alisporivir. Clin Infect Dis 2020 May 15. PubMed: https://pubmed.gov/32409832 . Full-text: https://doi.org/10.1093/cid/ciaa587

Some arguments supporting the use of alisporivir, a non-immunosuppressive analogue of cyclosporine A developed by Novartis. Arguments include the cyclophilin-dependency of the lifecycle of many coronaviruses and preclinical data on antiviral and cytoprotective properties.

 

Pediatrics

Garazzino S, Montagnani C, Dona D, et al. Multicentre Italian study of SARS-CoV-2 infection in children and adolescents, preliminary data as at 10 April 2020. Euro Surveill. 2020 May;25(18). PubMed: https://pubmed.gov/32400362. Full-text: https://doi.org/10.2807/1560-7917.ES.2020.25.18.2000600

The largest cohort of European children and adolescents, comprising 168 patients with laboratory-confirmed COVID-19. Nearly 40% were under 1 year of age and the majority of them were hospitalized. However, all patients, including those with comorbidities, recovered fully, and no sequelae were reported at the last follow-up.