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By Christian Hoffmann &
Bernd S. Kamps

16 July

Deutsch | Español | Français | Italiano | Português | Tiếng Việt | Turkish | Pусский | عربى | 中文
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Epidemiology

Islam N, Sharp SJ, Chowell G, et al. Physical distancing interventions and incidence of coronavirus disease 2019: natural experiment in 149 countries. BMJ. 2020 Jul 15;370:m2743. PubMed: https://pubmed.gov/32669358. Full-text: https://doi.org/10.1136/bmj.m2743

Be fast – but don’t close the metro. In this large empirical study, data from 149 countries were pooled, in order to estimate the relative effectiveness of different policy interventions within each country. Implementation of any physical distancing intervention was associated with an overall incidence reduction of 13% (IRR 0.87). Closure of public transport was not associated with any additional reduction when the other four physical distancing interventions were in place. Data from 11 countries also suggested similar overall effectiveness (IRR 0.85) when school closures, workplace closures, and restrictions on mass gatherings were in place. Earlier implementation of lockdown was associated with a larger reduction (IRR 0.86) compared with a delayed implementation of lockdown after other physical distancing interventions were in place (IRR 0.90).

 

Vaccine, Immunology

Jackson LA, Anderson EJ, Rouphael NG, et al. An mRNA Vaccine against SARS-CoV-2 – Preliminary Report. N Engl J Med. 2020 Jul 14. PubMed: https://pubmed.gov/32663912. Full-text: https://doi.org/10.1056/NEJMoa2022483

This study conducted in Washington and Atlanta evaluated the candidate vaccine mRNA-1273 that encodes the stabilized prefusion SARS-CoV-2 spike protein. In a Phase I open label trial, 45 healthy adults received two vaccinations, 28 days apart, at three different doses. Antibody responses were higher with a higher dose and further increased after the second vaccination, leading to serum-neutralizing activity in all participants. Values were similar to those in the upper half of the distribution of a panel of control convalescent serum specimens. Solicited adverse events that occurred in > 50% included fatigue, chills, headache, myalgia, and pain at the injection site.

 

Arnold C. How computational immunology changed the face of COVID-19 vaccine development. Nat Med. 2020 Jul 15. PubMed: https://pubmed.gov/32669667. Full-text: https://doi.org/10.1038/d41591-020-00027-9

After more than two decades of work, computational immunology now enables the development of a candidate vaccine in just a few hours. However, no in silico analysis, no matter how high-quality the input and how exacting the computational algorithms, will ever be a substitute for experimental data.

 

Mathew D, Giles JR, Baxter AE, et al. Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications. Science 2020 Jul 15. PubMed: https://pubmed.gov/32669297. Full-text: https://doi.org/10.1126/science.abc8511

Patients differ: Analysing 125 COVID-19 patients, the authors identified three “immunotypes” associated with poorer clinical trajectories versus improving health. A subgroup of patients had T cell activation characteristic of acute viral infection and plasmablast responses reaching > 30% of circulating B cells. However, another subgroup had lymphocyte activation comparable to uninfected subjects. Stable versus dynamic immunological signatures were identified and linked to trajectories of disease severity change. This study provides a compendium of immune response data and also an integrated framework as a “map” for connecting immune features to disease. By localizing patients on an immune topology map built on this dataset, we can begin to infer which types of therapeutic interventions may be most useful in specific patients.

 

Le Bert N, Tan AT, Kunasegaran K, et al. SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls. Nature. 2020 Jul 15. PubMed: https://pubmed.gov/32668444. Full-text: https://doi.org/10.1038/s41586-020-2550-z

Is there a natural immunity? In this study, T cell responses to structural (nucleocapsid protein, NP) and non-structural (NSP-7 and NSP13 of ORF1) regions of SARS-CoV-2 were analyzed in 36 COVID-19 convalescents. In all of them, CD4 and CD8 T cells recognizing multiple regions of the NP protein were found. Surprisingly, the authors also frequently detected SARS-CoV-2 specific T cells in 37 individuals with no history of SARS, COVID-19 or contact with SARS/COVID-19 patients. These T cells exhibited a different pattern of immunodominance, frequently targeting the ORF-1-coded proteins NSP7 and 13 as well as the NP structural protein. Epitope characterization of NSP7-specific T cells showed recognition of protein fragments with low homology to “common cold” human coronaviruses but conserved amongst animal betacoronaviruses. Thus, infection with betacoronaviruses induces multispecific and long-lasting T cell immunity to the structural protein NP.

 

Transmission

Vivanti AJ, Vauloup-Fellous C, Prevot S, et al. Transplacental transmission of SARS-CoV-2 infection. Nat Commun2020. Full-text: https://doi.org/10.1038/s41467-020-17436-6

Maybe the first documented case of transplacental transmission. French doctors report on a 23-year-old COVID-19 patient who gave birth by cesarean section to a baby found to have the infection. The viral load was much higher in the placental tissue than in the amniotic fluid or maternal blood: this suggests the presence of the virus in placental cells, which is consistent with findings of inflammation seen at histological examination. Good news: baby is fine.

 

Clinical

Yadav DK, Singh A, Zhang Q, et al. Involvement of liver in COVID-19: systematic review and meta-analysis. Gut. 2020 Jul 15:gutjnl-2020-322072. PubMed: https://pubmed.gov/32669289. Full-text: https://doi.org/10.1136/gutjnl-2020-322072

In this meta-analysis of 9 studies with a total of 2115 patients, patients with COVID-19 with liver injury were at an increased risk of severity (OR 2.57) and mortality (1.66). Thus, special attention should be given to any liver dysfunction while treating patients with COVID-19.

 

Belanger MJ, Hill MA, Angelidi AM, Dalamaga M, Sowers JR, Mantzoros CS. Covid-19 and Disparities in Nutrition and Obesity. N Engl J Med. 2020 Jul 15. PubMed: https://pubmed.gov/32668105. Full-text: https://doi.org/10.1056/NEJMp2021264

Nice perspective. Though the factors underlying racial and ethnic disparities in COVID-19 in the United States are multifaceted and complex, long-standing disparities in nutrition and obesity play a crucial role in the health inequities unfolding during the pandemic.

 

Zhang AJ, Lee AC, Chu H, et al. SARS-CoV-2 infects and damages the mature and immature olfactory sensory neurons of hamsters. Clin Infect Dis. 2020 Jul 15. PubMed: https://pubmed.gov/32667973. Full-text: https://doi.org/10.1093/cid/ciaa99532667967

Poor golden Syrian hamsters. But, this probably explains what happens in your nose. After intranasal inoculation with SARS-CoV-2, inflammatory cell infiltration and proinflammatory cytokine/chemokine responses were detected in the nasal turbinate tissues peaking between 2 to 4 days post-infection with the highest viral load detected at day 2 post-infection.

 

Treatment

Okafor EC, Pastick KA, Rajasingham R. Hydroxychloroquine as Postexposure Prophylaxis for Covid-19. Reply. N Engl J Med. 2020 Jul 15. PubMed: https://pubmed.gov/32668109. Full-text: https://doi.org/10.1056/NEJMc2023617

Some discussion on this trial in which HCQ did not work as a COVID-19 PEP. Main messages: absence of evidence is not evidence of absence. It is argued that the PEP was started too late, the trial too small and that testing capacity was limited.