Top 10: September 25

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By Christian Hoffmann &
Bernd S. Kamps


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25 September


Bastard P, Rosen LB, Zhang Q, et al. Auto-antibodies against type I IFNs in patients with life-threatening COVID-19. Science 2020, published 24 September. Full-text:

In an outstanding paper, Jean-Laurent Casanova, Paul Bastard and colleagues highlight the crucial role of type I IFNs in protective immunity against SARS-CoV-2. The authors report an analysis of 987 patients with life-threatening COVID-19 pneumonia, 663 subjects with asymptomatic or benign SARS-CoV-2 infection and a third group of 1,227 healthy volunteers. At least 10% of patients with life-threatening COVID-19 pneumonia had neutralizing auto-Abs against type I IFNs (IFN-ω: 13 patients; the 13 types of IFN-α: 36;  or both: 52) at the onset of critical disease.


Zhang Q, Bastard P, Liu Z, et al: Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science 2020, published 24 September. Full-text:

The title says it all: there are inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Jean-Laurent Casanova, Qian Zhang and colleagues report enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern TLR3- and IRF7-dependent type I interferon (IFN) immunity to influenza virus, in 659 patients with life-threatening COVID-19 pneumonia, relative to 534 subjects with asymptomatic or benign infection. The authors suggest that there may be mutations in other type I IFN-related genes in other patients with life-threatening COVID-19 pneumonia. They conclude that the administration of type I IFN might be of therapeutic benefit in selected patients, at least early in the course of SARS-CoV-2 infection.


Read also the comment by Meredith Wadman: Wadman M. Hidden immune weakness found in 14% of gravely ill COVID-19 patients. Science 2020, published 24 September. Full-text:



Schultze A, Walker AJ, MacKenna B, et al. Risk of COVID-19-related death among patients with chronic obstructive pulmonary disease or asthma prescribed inhaled corticosteroids: an observational cohort study using the OpenSAFELY platform. Lancet Resp Med September 24, 2020. Full-text:

Do treatments for respiratory disease, specifically inhaled corticosteroids (ICSs), have a protective effect? Probably not. Anna Schultze and colleagues from London have identified 148,557 people with COPD and 818,490 people with asthma who were given relevant respiratory medications in the 4 months before the index date (March 1). People with COPD who were prescribed ICSs were at increased risk of COVID-19-related death compared with those prescribed LABA–LAMA combinations (adjusted HR 1.39, 95% CI 1.10–1.76]). Compared with those prescribed short acting beta agonists only, people with asthma who were prescribed high-dose ICS were at an increased risk of death (1.55, 1.10–2.18]), whereas those given a low or medium dose were not. Sensitivity analyses showed that the apparent harmful association could be explained by relatively small health differences between people prescribed ICS and those not prescribed ICS.



Logunov DY, Dolzhikova IV, Zubkova OV, et al. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. Lancet. 2020 Sep 3:S0140-6736(20)31866-3. PubMed: Full-text:

On September 5, we commented that it was high time to see some data on an “approved” vaccine, consisting of two recombinant adenovirus vectors carrying the spike glycoprotein (Sputnik V, presented as a world’s “premiere”, like planting a tiny flag in the sea bed two and a half miles beneath the North Pole in 2007).

Bucci E, Andreev, Björkman A, et al. Safety and efficacy of the Russian COVID-19 vaccine: more information needed. Lancet September 21, 2020. Full-text:

A few days later, the study received these notes of serious concerns. Dozens of authors raised doubts about the reliability of the data. The main issue (among many others): there were several data patterns which appeared repeatedly for the reported experiments. A Photoshop fake? Enrico Bucci and colleagues conclude that “in lack of the original numerical data, no conclusions can be definitively drawn on the reliability of the data presented, especially regarding the apparent duplications detected”. For more details see also

Logunov DY, Dolzhikova IV, Tukhvatullin AI. Safety and efficacy of the Russian COVID-19 vaccine: more information needed – Authors’ reply. Lancet September 21, 2020. Full-text:

The author’s reply. They “confirm that individual participant data will be made available on request to DYL and that after approval of a proposal, data can be shared through a secure online platform”. We’ll see.



Buitrago-Garcia D, Egli-Gany D, Counotte MJ, et al. Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections: A living systematic review and meta-analysis. PLOS September 22, 2020. Full-text:

Diana Buitrago-Garcia and colleagues did a living systematic review through June 10, 2020. Overall, in 79 studies in a range of different settings, 20% (95% CI 17%–25%) of people with SARS-CoV-2 infection remained asymptomatic during follow-up, but biases in study designs limit the certainty of this estimate. In seven studies of defined populations screened for SARS-CoV-2 and then followed, 31% (95% CI 26%–37%) remained asymptomatic. There was some evidence that SARS-CoV-2 infection is less likely in contacts of people with asymptomatic infection.


Hughes MM, Groenewold MR, Lessem SE, et al. Update: Characteristics of Health Care Personnel with COVID-19 – United States, February 12-July 16, 2020. MMWR Morb Mortal Wkly Rep. 2020 Sep 25;69(38):1364-1368. PubMed: . Full-text:

This update describes demographic characteristics, underlying medical conditions, hospitalizations, and intensive care unit (ICU) admissions, stratified by vital status, among 100,570 HCP (median age 41 years, 79% females) with COVID-19 reported to CDC during February 12–July 16, 2020. Of persons with known hospitalization status, 8% (6,832 of 83,202) were hospitalized and 5% (1,684 of 33,694) were treated in an ICU. Vital status was known for 67% (67,746) of HCP with COVID-19; among those, 641 (1%) died. HCP with COVID-19 who died tended to be older, male, Asian, Black, and have an underlying medical condition when compared with HCP who did not die. Nursing and residential care facilities were the most commonly reported job setting and nursing the most common single occupation type of HCP with COVID-19.



Rauch A, Dupont A, Goutay J, et al. Endotheliopathy is induced by plasma from critically-ill patients and associated with organ failure in severe COVID-19. Circulation. 2020 Sep 24. PubMed: . Full-text:

Endotheliopathy is an essential part of the pathological response upon severe COVID-19, leading to respiratory failure, multi-organ dysfunction and thrombosis. Antoine Rauch and colleagues from Lille/France evaluated the cytotoxicity of plasma samples collected from COVID-19 patients on cultured human pulmonary microvascular endothelial cells (HPMVEC). They demonstrate a direct and rapid cytotoxic effect of plasma collected from critically-ill patients on vascular endothelial cells.



Zoufaly A, Poglitsch M, Aberle JH, et al. Human recombinant soluble ACE2 in severe COVID-19. Lancet Resp Med September 24, 2020. Full-text:

Human recombinant soluble ACE2 (hrsACE2) may act by binding the viral spike protein (thereby neutralizing SARS-CoV-2) and by interfering with the RAS system. Alex Zoufaly and colleagues from Vienna report on a case of a 45-year-old woman with severe COVID-19 who was treated with hrsACE2. The virus disappeared rapidly from the serum and the patient became afebrile within hours.  Phase II/III studies of hrsACE2 are ongoing.





European corrispondents. As Covid cases rise again, how are countries in Europe reacting? The Guardian 2020, published 23 September. Full-text:

Tighter measures are being imposed, but they vary across the continent



If you read Spanish, read Llaneras K, Sevillano EG. ¿Cómo son las zonas restringidas en Madrid? Más densas, con más inmigrantes y sobre todo más pobres. El País 2020, published 21 September. Full-text:

El Gobierno regional impone confinamientos perimetrales y otras medidas como el cierre de parques en las áreas más golpeadas por el virus, donde se aprecian patrones socioeconómicos.


Andrino B, Grasso D, Llaneras K. No es solo Madrid: el coronavirus golpea las áreas metropolitanas en la segunda ola. El País 2020, published 21 September. Full-text:

Talavera, Salamanca, Girona o Vitoria, entre otras, tienen cifras de incidencia del virus cercanas a la de la capital.


Babelia. Por qué los humanos somos presa fácil de las pandemias. El País 2020, published 22 September. Full-text:

El biólogo Juan Botas y el físico Juan José Gómez Cadenas aportan perspectiva histórica a la crisis sanitaria en ‘Virus. La guerra de los mil millones de años’, donde relatan por qué la epidemia es solo un episodio más en esa contienda. ‘Babelia’ publica un adelanto.

The Triumph of Death – Pieter Bruegel the Elder, painted c. 1562.


Beyond your plate borders

Garbe J, Albrecht T, Levermann A, et al. The hysteresis of the Antarctic Ice Sheet. Nature 585, 538–544 (2020). Full-text:

Antarctica’s long-term sea-level contribution might dramatically increase and exceed that of all other sources. Ricarda Winkelmann, Julius Garbe and colleagues show that at global warming levels around 2 degrees Celsius above pre-industrial levels, West Antarctica is committed to long-term partial collapse owing to the marine ice-sheet instability. Find out what will happen between 6 and 9 degrees of warming and beyond 10 degrees.

See also the comment by Harvey F. Melting Antarctic ice will raise sea level by 2.5 metres – even if Paris climate goals are met, study finds. The Guardian 2020, published 23 September. Full-text: