Home | Daily Science: TOP 10 | TOP 10 BOOK (PDF)

By Christian Hoffmann &
Bernd S. Kamps

13 September

Epidemiology

Thomas LJ, Hunag O, Yin F, et al. Spatial heterogeneity can lead to substantial local variations in COVID-19 timing and severity. PNAS September 10, 2020. Full-text:  https://doi.org/10.1073/pnas.2011656117

Loring J. Thomas and colleagues examined the potential impact of local spatial heterogeneity on COVID-19, modelling the diffusion of SARS-CoV-2 in populations whose contacts are based on spatially plausible network structures. They focus here on the urban context, examining 19 different cities in the US. The main results: The spread of COVID-19 is much “burstier” than in standard epidemiological models, with substantial local disparities in timing and severity and long lags between local outbreaks. Spatial heterogeneity may produce dramatic differences in social exposures to those with the illness, and may stress health care delivery systems in ways that are not well captured by standard models.

 

Transmission

Bax A, Bax CE, Stadnytskyi V, Anfinrud P. SARS-CoV-2 transmission via speech-generated respiratory droplets. Lancet Inf Dis September 11, 2020. Full-text: https://doi.org/10.1016/S1473-3099(20)30726-X

Spit happens. This group published the impressive NEJM video, visualizing speech-generated oral fluid droplets and suggesting that normal speaking might be an important mode of transmission. Here, the four authors vigorously resist the criticism of other authors who argued that the video experiments were unrealistic. They also provide nice new videos showing speech droplets emitted by four people, when speaking the phrase “spit happens” with the face positioned about 10–15 cm behind a thin sheet of intense green laser light.

Anfinrud P, Stadnytskyi V, Bax CE, Bax A. Visualizing Speech-Generated Oral Fluid Droplets with Laser Light Scattering. N Engl J Med. 2020 May 21;382(21):2061-2063. PubMed: https://pubmed.gov/32294341. Full-text: https://doi.org/10.1056/NEJMc2007800

New video: https://www.youtube.com/watch?v=ooVjNth4ut8

 

Immunology

Habel JR, Nguyen TH, van de Sandt CE, et al. Suboptimal SARS-CoV-2−specific CD8+ T cell response associated with the prominent HLA-A*02:01 phenotype. PNAS September 10, 2020. Full-text: https://doi.org/10.1073/pnas.2015486117

Jennifer R. Habel and colleagues from Melbourne investigated circulating SARS-CoV-2−specific CD8 T cells from 18 COVID-19 patients. For two HLA-A*02:01 SARS-CoV-2−specific CD8 T cell epitopes, they found that, while ex vivo frequencies of responding T cells were approximately five-fold higher than for pre−COVID-19 samples, they were ∼10-fold lower than for influenza or EBV-specific memory CD8 T cells. Additionally, SARS-CoV-2−specific CD8 T cells recovered from convalescent COVID-19 patients had an atypically high prevalence of stem cell memory, central memory, and naïve phenotypes. This raises questions concerning the integrity of the epitope-specific CD8 T cell response in COVID-19.

 

Pathogenesis

Manne BK, Denorme F, Middleton EA, et al. Platelet gene expression and function in patients with COVID-19. Blood September 10, 2020, 136 (11): 1317–1329. Full-text: https://doi.org/10.1182/blood.2020007214

Platelet hyperreactivity may contribute to COVID-19 pathophysiology. Bhanu Kanth Manne and colleagues found distinct changes in the gene expression profile of circulating platelets of 25 COVID-19 patients, mainly in pathways associated with protein ubiquitination, antigen presentation, and mitochondrial dysfunction. Though ACE2 was not detected in platelets, mRNA from the SARS-CoV-2 N1 gene was detected in platelets from 2 of 25 COVID-19 patients, suggesting that platelets may take-up SARS-COV-2 mRNA independent of ACE2. Platelet activation and aggregation were increased and could partially be attributed to increased MAPK pathway activation and thromboxane generation.

 

Bunyavanich S, Grant C, Vicencio A, et al. Racial/Ethnic Variation in Nasal Gene Expression of Transmembrane Serine Protease 2 (TMPRSS2).  JAMA September 10, 2020. Full-text: https://doi.org/10.1001/jama.2020.17386

SARS-CoV-2 uses transmembrane serine protease 2 (TMPRSS2) to facilitate viral entry. Nasal TMPRSS2 expression was significantly higher in 47 black individuals compared with 25 Asian, 81 Latino, mixed race/ethnicity, and 123 White individuals based on linear regression. There were no significant associations between TMPRSS2 expression and sex, age, or asthma. Higher nasal expression of TMPRSS2 may contribute to the higher burden of COVID-19 among Black individuals.

 

Diagnostics

Procop GW, Shrestha NK, Vogel S, et al. A Direct Comparison of Enhanced Saliva to Nasopharyngeal Swab for the Detection of SARS-CoV-2 in Symptomatic Patients. J Clin Microbiol Sep 2020, JCM.01946-20. Full-text: https://doi.org/10.1128/JCM.01946-20

The next study showing that saliva works as well as NPS (although the overall viral load in saliva is somewhat lower). An “enhanced” saliva specimen (strong sniff, elicited cough, and collection of saliva/secretions) was collected without transport media prior to nasopharyngeal swab from 216 patients with symptoms deemed consistent with COVID-19. There was a 100% positive agreement (38/38 positive specimens) and 99.4% negative agreement (177/178 negative specimens). The one discrepant specimen had the presence of SARS-CoV-2 confirmed in the saliva specimen using an alternate FDA EUA assay. The overall mean difference in crossing threshold (Ct) values for the positive NPS and saliva specimens was -3.61 (remember: low Ct = higher viral load, 95% CI -5.78 to -1.44).

 

Van Praet JT, Coene A, Van De Moortele K et al. Comparison of four commercial SARS-CoV-2 IgG immuno-assays in RT-PCR negative patients with suspect CT findings. Infection (2020). Full-text: https://doi.org/10.1007/s15010-020-01523-3

If PCR is negative, serology testing may be helpful. Jens T. Van Praet and colleagues analyzed 17 patients with suspicious CT findings but (repeatedly) negative nasopharyngeal PCR screening. After disease duration of at least 14 days, 12/17 were found to be positive by different anti-SARS-CoV-2 IgG immunoassays. Clinical specificity was suboptimal in some N-based ELISA kits.

 

Treatment

Furlow B. COVACTA trial raises questions about tocilizumab’s benefit in COVID-19. Lancet Rheumatology. September 09, 2020. Full-text: https://doi.org/10.1016/S2665-9913(20)30313-1

At the end of the day, nothing but steroids? On July 29, Hoffmann-La Roche announced disappointing results from its much-anticipated phase 3 COVACTA trial of tocilizumab (TCZ), raising questions about the efficacy of IL-6 blockade in patients with severe COVID-19 pneumonia. TCZ did not improve patient mortality, although patients spent roughly a week less in hospital compared with those given placebo (the full results of the trial have not yet been published). Bryant Furlow argues that it may be too early to quit this strategy. Cautious interpretation of COVACTA is needed, in view of the study’s broad patient selection criteria and other study design factors. Tocilizumab continues to be evaluated in the RECOVERY trial. Let’s hope that it works.

 

Cheng LL, Guan WJ, Duan CY, et al. Effect of Recombinant Human Granulocyte Colony–Stimulating Factor for Patients With Coronavirus Disease 2019 (COVID-19) and Lymphopenia. A Randomized Clinical Trial. JAMA Intern Med September 10, 2020. Full-text: https://doi.org/10.1001/jamainternmed.2020.5503

G-CSF may be helpful in some patients. Lin-ling Cheng and colleagues performed an open-label trial at 3 participating centers in China, randomizing 200 patients with lymphopenia and no comorbidities to usual care alone or usual care plus 3 doses of recombinant human G-CSF (5 μg/kg, subcutaneously at days 0-2). Time to clinical improvement was similar between groups. However, the proportion of patients progressing to acute respiratory distress syndrome, sepsis, or septic shock was lower in the rhG-CSF group (2% vs 15%). Mortality was also lower (2% vs 10%). According to the authors, larger studies that include a broader range of patients with COVID-19 should be conducted.

 

Patell R, Bogue T, Koshy A, et al. Postdischarge thrombosis and hemorrhage in patients with COVID-19. Blood 2020, 136 (11): 1342–1346. Full-text: https://doi.org/10.1182/blood.2020007938

Rushad Patell and colleagues conducted a retrospective observational cohort study of 163 discharged COVID-19 patients not receiving anticoagulation (26% had required ICU care). The cumulative incidence of thrombosis (including arterial and venous events) at day 30 following discharge was 2.5% (95% CI, 0.8-7.6). The cumulative incidence of major hemorrhage was 0.7% and of clinically relevant non-major bleeds was 2.9%, emphasizing the need for randomized data to inform recommendations for universal post-discharge thromboprophylaxis.

 

Spanish

If you read Spanish, read Aunión JA. La escuela en la era covid: cómo sacar adelante a la generación que deberá pagar las deudas de la pandemia. El País 2020, published 12 September. Full-text: https://elpais.com/educacion/2020-09-12/la-escuela-en-la-era-covid-como-sacar-adelante-a-la-generacion-que-debera-pagar-las-deudas-de-la-pandemia.html

Expertos, alumnos y profesores de todo el mundo cuentan su experiencia y esbozan los retos a los que se enfrenta el sistema educativo.