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By Christian Hoffmann &
Bernd S. Kamps

6 September

Prevention

Lazzari S. Prevention. In: COVID Reference 2020.04, 4th updated edition, published 6 September. Full-text: https://covidreference.com/prevention

Lazzari S. Prevenzione. In: COVID Reference Italy 2020.04, Quarta edizione attualizzata, pubblicato il 6 settembre 2020. Testo integrale: https://covidreference.com/prevention_it

Stefano Lazzari, specialist in Public Health and Preventive Medicine, gives a 5000-word overview of the most important topic in a world without a COVID-19 vaccine: Prevention. See also the PDF of the updated 4th CR Edition (330 pages).

 

Epidemiology

Barbarossa MV, Fuhrmann J, Meinke JH, et al. Modeling the spread of COVID-19 in Germany: Early assessment and possible scenarios. PLoS One. 2020 Sep 4;15(9):e0238559. PubMed: https://pubmed.gov/32886696. Full-text: https://doi.org/10.1371/journal.pone.0238559

Maria Vittoria Barbarossa and colleagues have used complex mathematical models to reproduce data of the early evolution of the COVID-19 outbreak in Germany, taking into account the effect of actual and hypothetical non-pharmaceutical interventions. Interesting finding: a partial (and gradual) lifting of introduced control measures could soon be possible if accompanied by further increased testing activity, strict isolation of detected cases, and reduced contact to risk groups. However, in scenarios without appropriate measures, simulations predict incredibly high peaks in active cases and alarmingly high numbers of deaths far into the future. If no restrictive measures and interventions were to be (re)introduced, the simulation of the model results in about 32 million total infections and 730,000 deaths over the course of the epidemic, which seems to occur only by the end of the summer 2021 under the assumption that no reliable treatment becomes available before then. Just saying.

 

Marossy A, Rakowicz S, Bhan A, et al. A study of universal SARS-CoV-2 RNA testing of residents and staff in a large group of care homes in South London. J Infect Dis. 2020 Sep 5:jiaa565. PubMed: https://pubmed.gov/32889532. Full-text: https://doi.org/10.1093/infdis/jiaa565

One of the largest studies of care homes in Europe, involving 2,455 individuals tested irrespective of symptoms. Combined nose and throat swab testing for SARS-CoV-2 RNA was carried out in residents and staff across 37 care homes in the London Borough of Bromley across a three-week period. Overall, the point prevalence of SARS-CoV-2 infection was 6.5% with a higher rate in residents (9.0%) than in staff (4.7%). A key finding was the high proportion of asymptomatic infection detected in staff (69%) and residents (51%) with evidence of under-detection of symptoms by care home staff.

 

Immunology

Nielsen SC, Yang F, Jackson KJ, et al. Human B cell clonal expansion and convergent antibody responses to SARS-CoV-2. Cell Host Microbe September 03, 2020. Full-text: https://doi.org/10.1016/j.chom.2020.09.002

Sandra C.A. Nielsen and colleagues from Stanford analyzed the evolution of the human antibody response to SARS-CoV-2 in detail and over time in 13 COVID-19 patients. They sequenced the immune globulin heavy chain (IGHVs) genes of the B cell antigen receptors (BCRs) and captured the hallmarks of clonal evolution, such as somatic hypermutation (SHM, a programmed process of mutation in the variable regions of immunoglobulin by which the immune system adapts to new foreign elements). After early recruitment of B cells expressing a limited subset of IGHV genes, immune response progresses to a robust polyclonal response of B cells with broader IGHV gene usage and extensive class switching to IgG and IgA sub-classes with limited SHM in the initial weeks of infection. Antibody sequences across SARS-CoV-2 infected patients were convergent, highlighting stereotyped naïve responses to this virus. Notably, some patients had B cell clones expressing convergent IGH to other CoV RBD antibodies. These patients had the highest SARS-CoV RBD antibody IgG levels, suggesting that IGH sequencing data are able to predict the fine specificity of human serological response.

 

Chan KK, Dorosky D, Sharma P, et al. Engineering human ACE2 to optimize binding to the spike protein of SARS coronavirus 2. Science  04 Sep 2020: Vol. 369, Issue 6508, pp. 1261-1265. Full-text: https://doi.org/10.1126/science.abc0870

By using deep mutagenesis, Kui K. Chan and colleagues have identified mutations in angiotensin-converting enzyme 2 (ACE2, critical for binding of SARS-CoV-2) that increase spike binding across the interaction surface. Their mutational landscape provides a blueprint for understanding the specificity of the interaction between ACE2 and spike. Combining mutations gave ACE2 variants with high affinities that rival those of monoclonal antibodies and a stable dimeric variant showed potent SARS-CoV-2 and -1 neutralization in vitro. In addition, the similarity to the natural receptor may limit the possibility of viral escape.

 

Kox M, Waalders NJB, Kooistra EJ, Gerretsen J, Pickkers P. Cytokine Levels in Critically Ill Patients With COVID-19 and Other Conditions. JAMA. 2020 Sep 3. PubMed: https://pubmed.gov/32880615. Full-text: https://doi.org/10.1001/jama.2020.17052

Time to rethink the “cytokine storm”? Matthijs Kox and colleagues from Nijmegen have compared 46 COVID-19 patients with ARDS admitted to their ICU, 66 with septic shock with or without ARDS, 30 out-of-hospital cardiac arrest and 62 patients with multiple trauma. Of note, most cytokine levels were significantly lower in COVID-19 than in septic shock and not higher than in OHCA and trauma patients, suggesting that COVID-19 may not be characterized by the cytokine storm.

 

Van Elslande J, Vermeersch P, Vandervoort K, et al. Symptomatic SARS-CoV-2 reinfection by a phylogenetically distinct strain. Clinical Infectious Diseases, September 5. Full-text:  https://doi.org/10.1093/cid/ciaa1330

A handful of accounts of reinfection — people who recovered from COVID-19, only to test positive for the disease again later — has fed concerns that immunity might be short-lived. Jan Van Elslande and colleagues from Leuven, Belgium present another case. In this 51-year-old woman, re-infection occurred three months later and the illness was milder than the first episode.

 

Vaccine

Tostanoski LH, Wegmann F, Martinot AJ, et al. Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters. Nat Med. 2020 Sep 3. PubMed: https://pubmed.gov/32884153. Full-text: https://doi.org/10.1038/s41591-020-1070-6

It’s not only protection from infection but also from severe disease. In hamsters, a single immunization with an adenovirus serotype 26 vector-based vaccine expressing a stabilized SARS-CoV-2 spike protein elicited binding and neutralizing antibody responses and protected against weight loss, pneumonia and mortality.

 

Comorbidities

Meltzer DO, Best TJ, Zhang H, et al. Association of Vitamin D Status and Other Clinical Characteristics With COVID-19 Test Results. JAMA Netw Open September 3, 2020;3(9):e2019722. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.19722

Is treatment for vitamin D deficiency associated with reductions in the risk of COVID-19? Maybe. In this retrospective cohort study of 489 patients who had a vitamin D level measured in the year before COVID-19 testing, the relative risk of testing positive for COVID-19 was 1.77 times greater for patients with likely deficient vitamin D status compared with patients with likely sufficient vitamin D status. However, as with all retrospective studies, be aware of confounding: vitamin D deficiency may be a consequence associated with a range of chronic health conditions or behavioral or environmental factors that increase COVID-19 risk.

 

Severe COVID-19

Schultz MJ, Teng MS, Brenner MJ. Timing of Tracheostomy for Patients With COVID-19 in the ICU—Setting Precedent in Unprecedented Times. JAMA Otolaryngol Head Neck Surg September 3, 2020. Full-text: https://doi.org/10.1001/jamaoto.2020.2630

When to perform tracheostomy (and how)? Marcus J. Schultz and colleagues review the current evidence and give a nice overview of misconceptions that predispose to uncontrolled variation in tracheostomy among COVID-19 patients. However, the bottom line is: Decisions on tracheostomy must be personalized; some patients may be awake but cannot yet be extubated (favoring tracheostomy), whereas other patients may have immediate, severe hypoxemia when lying supine or with any period of apnea (favoring deferral).

 

Charre C, Icard V, Pradat P, et al. Coronavirus disease 2019 attack rate in HIV-infected patients and in preexposure prophylaxis users. AIDS. 2020 Oct 1;34(12):1765-1770. PubMed: https://pubmed.gov/32889852. Full-text: https://doi.org/10.1097/QAD.0000000000002639

Caroline Charre analyzed the COVID-19 attack rate in a small group of HIV-infected patients and in PrEP users in the Rhône county, France, and compared it with the general population. No differences were observed.