Top 10: January 23

Copy-editor: Rob Camp


* * * Paper of the Day * * *

Anesi GL, Jablonski J, Harhay MO, et al. Characteristics, Outcomes, and Trends of Patients With COVID-19-Related Critical Illness at a Learning Health System in the United States. Ann Intern Med. 2021 Jan 19. PubMed: Full-text:

Is there a learning curve? Among 468 patients with COVID-19–related critical illness admitted to ICUs during the initial surge of the pandemic in the US (from 1 March to 11 May 2020), mortality seemed to decrease over time despite stable patient characteristics. Mortality decreased over time, from 43,5% (95% CI: 31,3% to 53,8%) to 19,2% (CI: 11,6% to 26,7%) between the first and last 15-day periods in the core adjusted model, whereas patient acuity and other factors did not change. Further studies are necessary to investigate causal mechanisms.


Vahidy FS, Pan AP, Ahnstedt H, et al. Sex differences in susceptibility, severity, and outcomes of coronavirus disease 2019: Cross-sectional analysis from a diverse US metropolitan area. PLoS One. 2021 Jan 13;16(1):e0245556. PubMed: . Full-text: eCollection 2021

In this large US cohort, males were more likely to test positive for COVID-19. In hospitalized patients, males were more likely to have complications, require ICU admission and mechanical ventilation, and had higher mortality than females, independent of age.


Song E, Zhang C, Israelow B, et al. Neuroinvasion of SARS-CoV-2 in human and mouse brain. J Exp Med. 2021 Mar 1;218(3):e20202135. PubMed: Full-text:

Evidence for the neuro-invasive capacity of SARS-CoV-2. Akiko Iwasaki, Eric Song and colleagues demonstrate that neuronal infection can be prevented by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient. In autopsies, they also detected SARS-CoV-2 in cortical neurons and noted pathological features associated with infection with minimal immune cell infiltrates.



Callaway E. Fast-spreading COVID variant can elude immune responses. Nature News 21 January 2021. Full-text:

Ewen Callaway discusses the growing evidence that the SARS-CoV-2 variant identified in South Africa might compromise immunity sparks concerns about vaccine effectiveness.


Ella E, Vadreva KM, Jogdand H, et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomised, phase 1 trial. Lancet Infect Dis January 21, 2021. Full-text:

In this double-blind, multi-center, randomized Phase I trial from India, the inactivated vaccine BBV152 led to tolerable safety outcomes and enhanced immune responses. Different adjuvants were also evaluated (chemosorbed imidazoquinoline onto the aluminum hydroxide gel or not). In 375 participants who were assigned to receive two doses separated by 2 weeks of BBV152 3 μg with Algel-IMDG (n = 100), 6 μg with Algel-IMDG (n = 100), or 6 μg with Algel (n = 100), or an Algel-only control (n = 75), 80% of patients in each vaccine group seroconverted, with at least a four-fold increase in binding antibody titers. Seroconversion occurred by microneutralization in 88% and 92% of the 3 and 6 μg Algel-IMDG groups but also in 8% of the control group, suggesting SARS-CoV-2 infections occurred in some participants.


Rostad CA, Anderson EJ. Optimism and caution for an inactivated COVID-19 vaccine. Lancet Inf Dis January 21, 2021. Full-text:

Christina Rostad and Evan Anderson see an inactivated vaccine as a welcome addition to the COVID-19 vaccine landscape. However, they discuss the open questions and concerns regarding inactivated vaccines (i.e. antibody-dependent enhancement of infection and vaccine-associated enhanced respiratory disease). Until then, they “will wait with cautious optimism on this vaccine candidate poised to bolster worldwide equitable access to COVID-19 prevention”. Ok, let’s wait. But for how long?


Siegel CA, Melmed GY, McGovern DP, et al. SARS-CoV-2 vaccination for patients with inflammatory bowel diseases: recommendations from an international consensus meeting. Gut. 2021 Jan 20:gutjnl-2020-324000. PubMed: Full-text:

The panel recommends vaccinating all patients with IBD as soon as they are able to receive the vaccine, regardless of immune-modifying therapies. The exception is for any live-attenuated virus vaccines or replication-competent viral vector vaccines that come to market.



Doubleday A, Choe Y, Busch Isaksen T, Miles S, Errett NA. How did outdoor biking and walking change during COVID-19?: A case study of three U.S. cities. PLoS One. 2021 Jan 20;16(1):e0245514. PubMed: Full-text:

In Houston, bicycle use increased during lockdown. In New York, less people used their bikes. In Seattle, the results varied by trail use type. Read here why.



Veiga VC, Prats JAGG, Farias DLC, et al. Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical coronavirus disease 2019: randomised controlled trial. BMJ. 2021 Jan 20;372:n84. PubMed: Full-text:

Bad news from this randomized, open-label trial in nine hospitals in Brazil. Patients who were receiving supplemental oxygen or mechanical ventilation and had abnormal levels of at least two serum biomarkers were randomized to receive standard of care (SOC) plus tocilizumab (TCZ) or SOC alone. The data monitoring committee recommended stopping the trial early, after 129 patients had been enrolled, because of an increased number of deaths at 15 days in the SOC + TCZ group (17% vs 3%).


Chen JS, Alfajaro MM, Chow RD, et al. Non-steroidal anti-inflammatory drugs dampen the cytokine and antibody response to SARS-CoV-2 infection. J Virol. 2021 Jan 13:JVI.00014-21. PubMed: Full-text:

SARS-CoV-2 infection induces COX-2 expression in cell lines, primary airway epithelial cells, and mice. Inhibition of COX-2 by NSAIDs did not affect viral entry or replication in vitro or in vivo. However, NSAID treatment impaired the production of pro-inflammatory cytokines and neutralizing antibodies in response to SARS-CoV-2 infection in mice. NSAIDs could therefore have complex effects on the host response to SARS-CoV-2.


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