Top 10: December 18

“Copy-editor: Rob Camp


Baric RS. Emergence of a Highly Fit SARS-CoV-2 Variant. NEJM December 16, 2020. Full-text:

Brief overview on the genetic and molecular evidence for enhanced fitness of the G614 variant over ancestral strains by Ralph S. Baric, one of the world‘s leading experts in the field. Fortunately, the new variant is as sensitive to the serum specimens as the D614 strain and thus should allay fears that it might escape vaccine-elicited immunity. However, there remains a critical need for proactive, rather than reactive, tracking of SARS-CoV-2 and other potential emerging coronaviruses.



Garcia-Beltran WF, Lam EC, Astudillo MG, et al. COVID-19 neutralizing antibodies predict disease severity and survival. Cell December 15, 2020. Full-text:

Wilfredo Garcia-Beltran from Boston and colleagues examined antibody responses in 113 COVID-19 patients and found that severe cases exhibited increased inflammatory markers, lymphopenia, pro-inflammatory cytokines, and high anti-RBD antibody levels. A new finding was that patient sera were also able to neutralize the recently emerged SARS-CoV-2 mutant D614G, suggesting cross-protection from re-infection by either strain. In contrast, SARS-CoV-2 sera lacked cross-neutralization to a highly homologous bat coronavirus, WIV1-CoV, that has not yet crossed the species barrier.


Ku MW, Bourgine M, Authié P. Intranasal Vaccination with a Lentiviral Vector Protects against SARS-CoV-2 in Preclinical Animal Models. Cell Host Microbe December 14, 2020. Full-text:

Min-Wen Ku from Paris and colleagues generated a lentiviral vector (LV) that elicits neutralizing antibodies against the Spike glycoprotein of SARS-CoV-2. Eliciting an immune response in the respiratory tract through an intranasal boost results in > 3 log10 decrease in the lung viral load and reduces local inflammation. The vaccine also worked well in golden hamsters, designating intranasal immunization as a powerful approach against COVID-19.


Pairo-Castineira E, Clohisey S, Klaric L et al. Genetic mechanisms of critical illness in Covid-19. Nature (2020). Full-text:

Erola Pairo-Castineira and colleagues report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study (GWAS) in 2244 critically ill COVID-19 patients from 208 UK intensive care units (ICUs). They scanned each person’s genes, which contain the instructions for every biological process, including how to fight a virus. They have identified some genetic differences (odds ratio of the tested risk alleles were 1.2-1.9) between patients with severe COVID-19 and the general population, revealing “robust genetic signals relating to key host antiviral defense mechanisms, and mediators of inflammatory organ damage”.



Salathé M, Althaus C, Anderegg N, et al. Early evidence of effectiveness of digital contact tracing for SARS-CoV-2 in Switzerland. Swiss Med Wkly. 2020 Dec 16;150:w20457. PubMed: Full-text:

COVID apps may work (at least in Switzerland!). By 10 September 2020, the SwissCovid app (it uses the EN framework to estimate proximity between phones) has been downloaded 2,36 million times. Marcel Salathé and colleagues estimate that digital contact tracing can show similar effectiveness at identifying infected partners of index cases as classic contact tracing, provided that both the index case and the exposed contacts use the app. These apps represent a helpful complementary tool for controlling the spread of SARS-CoV-2. Please download your local app.



Faust JS, Krumholz HM, Du C, et al. All-Cause Excess Mortality and COVID-19–Related Mortality Among US Adults Aged 25-44 Years, March-July 2020. JAMA December 16, 2020. Full-text:

According to provisional National Center for Health Statistics data, the COVID-19 pandemic was associated with increases in all-cause mortality among US adults aged 25 to 44 years from March through July of 2020. From March to July, a total of 76.088 all-cause deaths occurred among US adults aged 25 to 44 years, which was 11.899 more than expected (incident rate ratio, 1.19 [95% CI, 1.14-1.23]. Of note, only 38% of all-cause excess deaths were attributed directly to COVID-19, suggesting that COVID-19–related mortality may have been under-detected in this population.


Izurieta HS, Graham DJ, Jiao Y, et al. Natural history of COVID-19: Risk factors for hospitalizations and deaths among >26 million U.S. Medicare beneficiaries. J Infect Dis 16 December 2020. Full-text:

Retrospective cohort study covering Medicare fee-for-service beneficiaries, comparing 653.966 elderly residents in nursing homes (NH) and 292.302 with end-stage renal disease (ESRD) from the primary study population of > 25 million individuals aged ≥ 65. COVID-related death rates (per 10.000) were much higher among elderly NH residents (275,7) and ESRD patients (60,8) than the primary study population (5,0). Regression-adjusted clinical predictors of death among the primary population included immunocompromised status (OR: 1.43), frailty index conditions such as cognitive impairment (3.16) as well as other co-morbidities including congestive heart failure (1.30). Demographic-related risk factors included male sex (1.77), older age (OR: 3.09 for 80-year-old vs. 65-year-old), and racial/ethnic minority.


Severe COVID-19

Bharat Am Querrey M, Markov NS. Lung transplantation for patients with severe COVID-19. Science Translational Medicine 16 Dec 2020: Vol. 12, Issue 574, eabe4282. Full-text:

Ankit Bharat and colleagues from Chicago report the results of lung transplantation in three patients with non-resolving COVID-19–associated respiratory failure: a 28-year-old Latina female with neuromyelitis optica (who was treated with rituximab, patient A), a 62-year-old male with hypertension (B), and a 43-year-old man with medically controlled type 2 diabetes mellitus (C). About 4-5 months after transplantation, patients A and B reported independence in activities of daily living while patient C received care in an in-patient rehabilitation facility at month 3. SARS-CoV-2 RNA could not be detected in the explanted lungs of these patients, but fibrotic pathology and transcriptional changes resembling those of lungs from patients with pulmonary fibrosis were observed.



Agrawal M, Brenner EJ, Zhang X, et al. Characteristics and Outcomes of IBD Patients with COVID-19 on Tofacitinib Therapy in the SECURE-IBD Registry. Inflammatory Bowel Diseases 16 December 2020. Full-text:

Tofacitinib is a Janus kinase inhibitor (JAKi) approved for the treatment of ulcerative colitis (UC) and other immune-mediated diseases. As many JAKis, it is also evaluated in COVID-19 trials. Manasi Agrawal and colleagues here describe characteristics and outcomes of COVID-19 in 37 patients with IBD treated with tofacitinib compared with other medications in the SECURE-IBD registry. Overall, they found no difference in COVID-19 outcomes between the two groups. Good to see: though tofacitinib at the higher dose has been associated with venous thromboembolism, none of the tofacitinib-treated patients in this cohort experienced thrombotic complications.

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