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Top 10: July 20

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By Christian Hoffmann &
Bernd S. Kamps

20 July

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Epidemiology

Ruktanonchai NW, Floyd JR, Lai S, et al. Assessing the impact of coordinated COVID-19 exit strategies across Europe. Science. 2020 Jul 17:eabc5096. PubMed: https://pubmed.gov/32680881. Full-text: https://doi.org/10.1126/science.abc5096

Collaboration is better than unilateralism (some people should have thought about that before voting pro-Brexit). Using mobile phone and case data to quantify how coordinated exit strategies can delay European resurgence of COVID-19, the authors conclude that synchronizing intermittent lockdowns would reduce the number of total lockdown periods. It doesn’t escape their notice that the implications of their study extend well beyond Europe and COVID-19.

 

Transmission and Prevention

Park YJ, Choe YJ, Park O, et al. Contact Tracing during Coronavirus Disease Outbreak, South Korea, 2020. Emerg Infect Dis October 2020. Full-text: https://wwwnc.cdc.gov/eid/article/26/10/20-1315_article

The authors analyzed 59,073 contacts of 5,706 COVID-19 index patients. Of 10,592 household contacts, 11.8% had COVID-19; rates were higher for contacts of children than adults. Of 48,481 non-household contacts, 1.9% had COVID-19. Interestingly, the highest COVID-19 rate (18.6%) was found for household contacts of school-aged children and the lowest (5.3%) for household contacts of children 0–9 years in the middle of school closure.

 

Vaccine

Folegatti PM, Ewer KJ, Aley PK, et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet, 20 July 2020. Full-text: https://www.thelancet.com/lancet/article/s0140-6736(20)31604-4

Andrew Pollard and colleagues report their Phase 1/2 randomized trial of a chimpanzee adenovirus-vector vaccine (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein. Study participants received either ChAdOx1 nCoV-19 (n = 543) or a meningococcal conjugate vaccine (MenACWY) as control (n = 534).  In ChAdOx1 vaccinees, T cell responses peaked on day 14, anti-spike IgG responses rose by day 28, and neutralizing antibody responses against SARS-CoV-2 were detected in > 90% (find more details in the paper, especially about results after a booster dose). Adverse events such as fatigue, headache, and local tenderness commonly occurred. There were no serious adverse events.

 

Zhu FC, Guan XH, Li YH, et al. Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet, 20 July 2020. Full-text: https://www.thelancet.com/lancet/article/s0140-6736(20)31605-6

Wei Chen and colleagues report results from a randomized Phase 2 trial of an Ad5-vector COVID-19 vaccine from a single center in Wuhan. More than 90% of participants had T cell responses, seroconversion of binding antibody occurred in more than 96%, and neutralizing antibodies were seen in about 85%. The authors found that compared with the younger population, older people had a significantly lower immune response, but higher tolerability, to the Ad5-vector COVID-19 vaccine. In a Phase 2b trial, an additional dose might therefore be needed to induce a better immune response in the older population. Adverse events such as fever, fatigue, headache, or local site pain were comparable to the ChAdOx1 study above.

 

Bar-Zeev N, Moss WJ. Encouraging results from phase 1/2 COVID-19 vaccine trials. Lancet, 20 July 2020. Full-text: https://www.thelancet.com/lancet/article/s0140-6736(20)31611-1

A comment on the two papers above as well as a list of questions to be addressed by the coming Phase 3 trials:

  • Will a single dose be sufficient in older adults, or is a booster dose required?
  • Does longevity of response or rates of waning differ with a two-dose regimen, and does longevity of clinical protection require cell-mediated responses?
  • Are there host-specific differences in immunogenicity by age, sex, or ethnicity?
  • Do T cell responses correlate with protection irrespective of humoral titers?
  • Are there specific adverse events in pregnant women?

 

Immunology

Zhu L, Yang P, Zhao Y, et al. Single-cell sequencing of peripheral blood mononuclear cells reveals distinct immune response landscapes of COVID-19 and influenza patients. Immunity, published July 19, 2020. Web: https://www.cell.com/immunity/fulltext/S1074-7613(20)30316-2. Full-text: https://doi.org/10.1016/j.immuni.2020.07.009

The authors report the single-cell transcriptional landscape of longitudinally collected peripheral blood mononuclear cells (PBMCs) in both COVID-19 and influenza A virus (IAV)-infected patients. COVID-19 (STAT1 and IRF3) and IAV (STAT3 and NFκB) activate distinct signaling.

 

Fischer B, Knabbe C, Vollmer T. SARS-CoV-2 IgG seroprevalence in blood donors located in three different federal states, Germany, March to June 2020. Euro Surveill. 2020;25(28), published 16 July 2020. Full-text: https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.28.2001285  

Bad news for German herd immunity. In 3,186 regular blood donors in three German federal states, the seroprevalence of IgG SARS-CoV-2 antibodies was 0.91% overall, ranging from 0.66% in Hesse to 1.22% in Lower-Saxony. 99% of Germans have no specific immunity against SARS-CoV-2 infection.

 

Comorbidities

Tan M, He FJ, MacGregor GA. Obesity and covid-19: the role of the food industry. BMJ. 2020 Jun 10;369:m2237. PubMed: https://pubmed.gov/32522740. Full-text: https://doi.org/10.1136/bmj.m2237

Sorry for being 40 days late to present this article published in June. As obesity is recognized as an independent risk factor for severe illness and death with COVID-19, a reminder of the players involved in the obesity pandemic is always helpful. The authors have a concise message: “Food industries around the world must immediately stop promoting, and governments must force reformulation of, unhealthy foods and drinks.” As food industries won’t stop promoting, governments must regulate them.

 

Apicella M, Campopiano MC, Mantuano M, et al. COVID-19 in people with diabetes: understanding the reasons for worse outcomes. Lancet Diabetes Endocrinol, 17 July 2020. Full-text: https://doi.org/10.1016/S2213-8587(20)30238-2

This review provides an assessment of prognostic factors in patients with diabetes and COVID-19. A poorer prognosis would be the consequence of the syndromic nature of diabetes: hyperglycemia, older age, comorbidities, and in particular hypertension, obesity, and cardiovascular disease. All would contribute to an increased risk.

 

Pediatrics

Derespina KR, Kaushik S, Plichta A, et al. Clinical Manifestations and Outcomes of Critically Ill Children and Adolescents with COVID-19 in New York City. J Pediatr. 2020 Jul 15:S0022-3476(20)30888-X. PubMed: https://pubmed.gov/32681989. Full-text: https://doi.org/10.1016/j.jpeds.2020.07.039

Retrospective observational study of 70 children who were admitted between mid-March and the beginning of May to 9 New York City pediatric intensive care units. About 75% presented with fever and cough, the most common presenting symptoms. Find out how many patients met severe sepsis criteria, required vasopressor support, developed ARDS, met acute kidney injury criteria, etc.