16 January 2021

Copy-editor: Rob Camp

COVID Reference

Kamps BS, Hoffmann C, et al. COVID Reference 2021.6. Steinhäuser Verlag 2021, 6th edition, 453 pages, published 13 January. Download: https://covidreference.com/download

Since the publication of COVID Reference’s first edition on 29 March 2020, our website has lived an uneventful life. We have had our regular visitors – maybe you! – who read our presentation of the daily Top 10 papers or one or another PDF, in English, Spanish, Italian, Turkish or other languages. For more than 10 months, COVID Reference (CR) has been a steady source of daily, but mostly confidential information. Until last night, when the number of visitors to our website greatly increased. We don’t know why and why now, but the unusual activity may convince us to go ahead with our non-profit project. Thank you for staying with us! The CR Team.



Cyranoski D. Alarming COVID variants show vital role of genomic surveillance. Nature 2021, published 15 January. Full-text: https://www.nature.com/articles/d41586-021-00065-4

2021 is shaping up to be the year of COVID-19 variants. In the past two months, scientists have identified several fast-spreading variants that have prompted government restrictions in many countries — and new variants are being detected more frequently.

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van Kampen JJA, van de Vijver DAMC, Fraaij PLA, et al. Duration and key determinants of infectious virus shedding in hospitalized patients with coronavirus disease-2019 (COVID-19). Nat Commun. 2021 Jan 11;12(1):267. PubMed: https://pubmed.gov/33431879. Full-text: https://doi.org/10.1038/s41467-020-20568-4

Quantitative RNA viral load assays and serological assays might be used in testing based strategies to discontinue or de-escalate infection prevention and control precautions. This is the result of a study by Jeroen van Kampen and colleagues who report that infectious viral shedding is detected by virus cultures in 23 of 129 patients (17,8%) hospitalized with COVID-19. Of these, 89 patients (69,0%) were admitted to intensive care and the remaining 40 (31,0%) admitted to medium care. The median duration of shedding infectious virus was 8 days post-onset of symptoms (IQR 5–11) and dropped below 5% after 15,2 days post-onset of symptoms (95% confidence interval (CI) 13,4–17,2). Viral loads above 7 log10 RNA copies/mL were independently associated with isolation of infectious SARS-CoV-2 from the respiratory tract.

Figure 1. Viral loads and duration of symptoms for infectious virus shedding. | Viral RNA loads (Log10 RNA copies/mL) in the respiratory samples versus the duration of symptoms (days). Black boxes represent virus culture positive samples and open red circles represent the virus culture negative samples.


Figure 2. Probabilities of infectious virus shedding. | Probit analyses of the detection of infectious virus in respiratory samples with cell culture for duration of symptoms in… |Continue reading at  https://doi.org/10.1038/s41467-020-20568-4


Johansson MA, Quandelacy TM, Kada S, et al. SARS-CoV-2 Transmission From People Without COVID-19 Symptoms. JAMA Netw Open. 2021 Jan 4;4(1):e2035057. PubMed: https://pubmed.gov/33410879. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.35057

The identification and isolation of persons with symptomatic COVID-19 alone might not control the ongoing spread of SARS-CoV-2. This is the conclusion of a decision model by Jay Butler, Michael Johansson and colleagues who assessed multiple scenarios for the infectious period and the proportion of transmission from individuals who never had COVID-19 symptoms. Measures such as mask wearing and physical distancing might be needed to protect them and their communities for quite some time.

Figure 1.  The Contribution of Asymptomatic Transmission Under Different Infection Profiles | The top curve in each panel represents the average relative hourly infectiousness, such that while the lower curves change under different assumptions, the total hourly infectiousness equals 1 in all cases. Within each curve, the colored area indicates the… | Continue reading at https://doi.org/10.1001/jamanetworkopen.2020.35057.



Chambers ES, Vukmanovic-Stejic M, Shih BB, et al. Recruitment of inflammatory monocytes by senescent fibroblasts inhibits antigen-specific tissue immunity during human aging. Nat Aging 1, 101–113 (2021). Full-text: https://doi.org/10.1038/s43587-020-00010-6

Senescent fibroblasts in the skin of older participants secrete an array of chemokines including CCL2 in response to tissue injury, such as that induced by injection of saline, VZV or air. Arne Akbar, Emma Chambers and colleagues show how this phenomenon can be blocked pharmacologically to boost adaptive immunity. See also the comment by Kasler H, Verdin E. How inflammaging diminishes adaptive immunity. Nat Aging 1, 24–25 (2021). Full-text: https://doi.org/10.1038/s43587-020-00021-3

Figure 4. PGE2 production by monocytes inhibits CD4+ TRM cell proliferation in skin. | a, Representative staining of CD4 (green), CD69 (red) and EP4 (blue) in normal skin from eight independent donors; white arrows indicate CD4+ TRM cells that co-expressed EP4. b, Representative staining showing colocalization of… | Continue reading at https://doi.org/10.1038/s43587-020-00010-6.



Tian JH, Patel N, Haupt R, et al. SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice. Nat Commun 12, 372 (2021). Full-text: https://doi.org/10.1038/s41467-020-20653-8

In mice and baboons, low-dose levels of NVX-CoV2373 with Matrix-M was highly immunogenic. NVX-CoV2373, developed by Novavax, is a recombinant nanoparticle vaccine (rSARS-CoV-2) composed of trimeric full-length SARS-CoV-2 spike glycoproteins and Matrix-M1 adjuvant. Find more information about NVX-CoV2373 at https://covidreference.com/vaccines.

Figure 1. SARS-CoV-2 spike glycoprotein constructs. | a Linear diagram of the full-length SARS-CoV-2 spike (S) protein showing the S1 and S2 subunits. Structural elements include a cleavable signal sequence (SS, white), N-terminal domain (NTD, dark blue), receptor binding domain (RBD, green), subdomains 1 and 2 (SD1/SD2, light blue), fusion peptide (FP, red), heptad repeat 1 (HR1, yellow), central helix (CH, light green), heptad repeat 2 (HR2, purple), transmembrane domain (TM, black), and cytoplasmic tail (CT, white). The native furin cleavage site was… | Continue reading at https://doi.org/10.1038/s41467-020-20653-8.


Ledford H. How can countries stretch COVID vaccine supplies? Scientists are divided over dosing strategies. Nature 2021, published 11 January. Full-text: https://www.nature.com/articles/d41586-021-00001-6

On 30 December, the United Kingdom announced that it would allow doses of two coronavirus vaccines to be administered as many as 12 weeks apart, even though, in clinical trials, the two doses of the vaccine made by Pfizer of New York City and BioNTech of Mainz, Germany, were given to participants about three weeks apart. Not everyone agrees.



Resende C, Bezerra JF, Teixeira de Vasconcelos RH, et al. Spike E484K mutation in the first SARS-CoV-2 reinfection case confirmed in Brazil, 2020. Virological 2021, posted 10 January. Full-text: https://virological.org/t/spike-e484k-mutation-in-the-first-sars-cov-2-reinfection-case-confirmed-in-brazil-2020/584/1

SARS-CoV-2 strains containing the Spike E484K mutation may be a source of re-infection. The authors describe the case of a 37-year-old woman without pre-existing co-morbidities, a healthcare worker (medical doctor) who had two clinical episodes of COVID-19 (June and October 2020, interval: 116 days). The second infection (with the E484K strain) was mild and evolved without complications like the first episode.

Figure 1. Maximum Likelihood phylogenetic analysis of SARS-CoV-2 whole-genomes sequences from Paraiba. ML phylogenetic tree showing the branching pattern of SARS-CoV-2 whole genome sequences (29779 nt), from Paraiba (n = 77) classified within lineages B.1.1.28 (red), B1.1.33 (blue), and others B.1.1 (black). Sequences derived from the primo-infection and reinfection are both highlighted with different colors as indicate in the legend at left. Nodes with high statistical (aLRT ≥ 9.0) support are marked by circular shapes.



Anil SM, Shalev N, Vinayaka AC et al. Cannabis compounds exhibit anti-inflammatory activity in vitro in COVID-19-related inflammation in lung epithelial cells and pro-inflammatory activity in macrophages. Sci Rep 11, 1462 (2021). https://doi.org/10.1038/s41598-021-81049-2

Dope for SARS? Not yet. Although treatment with cannabis compounds CBD, CBG and THCV may have clinical value in reducing cytokine secretion in lung epithelial cells, Hinanit Koltai, Seegehalli Anil and colleagues from the Volcani Center in Rishon LeZion, Israel, caution that the increase of macrophage-secreted IL-6 and IL-8 levels by cannabis-based treatment may potentially lead to a worsening of the “cytokine storm” identified in severe COVID-19 patients. As for now, users and healthcare personnel should avoid the use of cannabis for COVID-19 prevention or treatment.

Figure 1. The levels of (a) IL-6 and (b) IL-8 in A549 cells treated with C. sativa Arbel crude and FCBD and FTHC extract fractions. Cells were treated with 300 ng/mL TNFα and C. sativa extract and fractions at a concentration of… | Continue reading at https://doi.org/10.1038/s41598-021-81049-2.


Collateral Effects

Morris JA, Goldacre R, Spata E, et al. Impact of the COVID-19 pandemic on the detection and management of colorectal cancer in England: a population-based study. Lancet Gastroenterol Hepatol 2021, published 14 January. Full-text: https://doi.org/10.1016/S2468-1253(21)00005-4

Pandemic COVID-19 waves lead to a sustained reduction in the number of people referred, diagnosed, and treated for colorectal cancer. As compared to the monthly average in 2019, in April 2020 there was a 63% reduction (from 36.274 to 13.440) in the monthly number of 2-week referrals for suspected cancer and a 92% reduction in the number of colonoscopies (from 46.441 to 3484).

Figure 1. Monthly number of referrals into the 2-week wait pathway (A) and the proportion meeting 2-week target in England (B)



If you read Spanish, read Vacunar al personal sanitario cuanto antes. El País 2021, publicated 15 January. Full-text: https://elpais.com/opinion/2021-01-14/proteger-al-personal-sanitario.html

Hay que flexibilizar los planes sin escatimar medios y preparar medidas extraordinarias.


Sampedro J. El futuro de un virus histórico. El País 2021, publicated 15 January. Full-text: https://elpais.com/opinion/2021-01-14/proteger-al-personal-sanitario.html

Los nuevos modelos indican que la COVID será en los próximos años una enfermedad leve de la infancia. Y los niños de hoy serán los adultos del futuro, y estarán inmunizados de un modo u otro.



If you read French, read Le Bars S. Les Etats-Unis subissent les ravages d’une pandémie de Covid-19 hors de contrôle. Le Monde 2021, published 15 January. Full-text : https://www.lemonde.fr/international/article/2021/01/15/covid-19-le-sombre-hiver-parti-pour-durer-aux-etats-unis_6066334_3210.html

Face aux chiffres de contaminations, d’hospitalisations et de morts et à une vaccination qui patine, Joe Biden s’est engagé à « agir vite ».


Rof G, Guillou C. Dans les restaurants clandestins : « Il fait gaffe quand même, y a toujours quelques poucaves ». Le Monde 2021, published 15 January. Full-text : https://www.lemonde.fr/economie/article/2021/01/15/dans-les-restaurants-clandestins-au-moins-ici-les-clients-voient-du-monde_6066309_3234.html

En Ile-de-France, le bouche-à-oreille permet vite de trouver quelques restaurants qui servent, rideaux baissés, leur clientèle d’habitués. Les voisins voient bien le manège puisqu’il y a derrière une terrasse où, aux beaux jours, on fait barbecue. Ils ne disent rien : l’ambiance est moins à la délation qu’à la commisération..



If you read German, read Hecking C. Deutschland braucht die FFP2-Maskenpflicht. Der Spiegel 2021, published 13 January. Full-text: https://www.spiegel.de/wissenschaft/mensch/deutschland-braucht-die-ffp2-maskenpflicht-a-0a6f4051-d3f6-4eb8-9aaf-e91ec2e9e13c

Die selbst genähte Alltagsmaske ist ein Relikt. Es wird höchste Zeit, dass wir alle professionelle Masken tragen, die auch uns selbst vor dem Virus schützen. Bezahlen muss sie der Staat.


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Bernd Sebastian Kamps


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