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By Christian Hoffmann &
Bernd S. Kamps

 

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23 September

Epidemiology

Lash RR, Donovan CV, Fleischauer AT, et al. COVID-19 Contact Tracing in Two Counties — North Carolina, June–July 2020. MMWR Morb Mortal Wkly Rep. ePub: 22 September 2020. Full-text: http://dx.doi.org/10.15585/mmwr.mm6938e3

Despite aggressive efforts by health departments, many COVID-19 patients do not report contacts, and many contacts cannot be reached. Staff members in North Carolina/US have investigated 5,514 (77%) persons with COVID-19 in Mecklenburg County and 584 (99%) in Randolph Counties: during periods of high COVID-19 incidence, 48% and 35% of patients reported no contacts, and 25% and 48 % of contacts were not reached. Median interval from index patient specimen collection to contact notification was 6 days. Improved timeliness of contact tracing, community engagement, and community-wide mitigation are needed to reduce SARS-CoV-2 transmission.

 

Virology

Toelzer C, Gupta K, Yadav SK, et al. Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein. Science  21 Sep 2020. Full-text: https://doi.org/10.1126/science.abd3255

This group from Bristol (UK) determined the structure of the SARS-CoV-2 S glycoprotein by cryo-EM. The receptor binding domains (RBDs) tightly bind the essential free fatty acid (FFA) linoleic acid (LA) in three composite binding pockets. At least four molecular features mediating LA binding to SARS-CoV-2 were identified. The LA-binding pocket presents a promising target for future development of small molecule inhibitors that, for example, could irreversibly lock S in the closed conformation and interfere with receptor interactions.

 

Pathogenesis

Jacob F, Pather SR, Huang WK, et al. Human Pluripotent Stem Cell-Derived Neural Cells and Brain Organoids Reveal SARS-CoV-2 Neurotropism Predominates in Choroid Plexus Epithelium. Cell Stem Cells September 21, 2020. Full-text: https://doi.org/10.1016/j.stem.2020.09.016

Fadi Jacob and colleagues have investigated the susceptibility of human induced pluripotent stem cell (hiPSC)-derived monolayer brain cells and region-specific brain organoids to SARS-CoV-2 infection. Neurons and astrocytes were sparsely infected, but choroid plexus epithelial cells underwent robust infection, indicating a selective SARS-CoV-2 neurotropism.

 

Immunology

Larson D, Brodniak SL, Voegtly LJ, et al. A Case of Early Re-infection with SARS-CoV-2. Clin Infect Dis. 2020 Sep 19:ciaa1436. PubMed: https://pubmed.gov/32949240. Full-text: https://doi.org/10.1093/cid/ciaa1436ed.gov/32950102

The next re-infection. A 42-year-old healthy male military healthcare provider became re-infected only 51 days after resolution of initial infection. Of note, his second infection was more severe, potentially due to immune enhancement, acquisition of a more pathogenic strain, or perhaps a greater inoculum of infection as the second exposure was from within household contacts.

 

Golinelli D, Boetto E, Maietti E, Fantini MP. The association between ABO blood group and SARS-CoV-2 infection: A meta-analysis. PLoS One 2020 Sep 18;15(9):e0239508. PubMed: https://pubmed.gov/32946531. Full-text: https://doi.org/10.1371/journal.pone.0239508

In this meta-analysis of 7 studies, the authors analyzed the odds of having each blood group among 7,503 SARS-CoV-2 positive patients compared with 2,962,160 (!) controls. SARS-CoV-2 positive individuals were more likely to have blood group A (pooled OR 1.23, 95%CI: 1.09–1.40) and less likely to have blood group O (pooled OR = 0.77, 95%CI: 0.67–0.88).

 

Clinical

Garibaldi BT, Fiksel J, Muschelli J, et al. Patient Trajectories Among Persons Hospitalized for COVID-19. A Cohort Study. Ann Intern Med, 22 September 2020. Full-text: https://doi.org/10.7326/M20-3905

Of 787 patients admitted with mild to moderate disease between March 4 and April 24 in five US hospitals at Maryland and Washington, 302 (38%) progressed to severe disease or death: 181 (60%) by day 2 and 238 (79%) by day 4. Patients had markedly different probabilities of disease progression on the basis of age, nursing home residence, comorbid conditions, obesity, respiratory symptoms, respiratory rate, fever, absolute lymphocyte count, hypoalbuminemia, troponin level, and C-reactive protein level and the interactions among these factors. Using only factors present on admission, a model to predict in-hospital disease progression had an area under the curve of 0.85, 0.79, and 0.79, at day 2, 4, and 7, respectively. An interactive version of a so called “COVID-19 Inpatient Risk Calculator” (CIRC) is available at https://rsconnect.biostat.jhsph.edu/covid_predict/.

The COVID Inpatient Risk Calculator: CIRC

 

Foy BH, Carlson JC, Reinertsen E, et al. Association of Red Blood Cell Distribution Width With Mortality Risk in Hospitalized Adults With SARS-CoV-2 Infection. JAMA Netw Open September 23, 2020;3(9):e2022058. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.22058

Red blood cell distribution width (RDW) as a nonspecific marker of illness? RDW is a component of complete blood counts that quantifies the variation of individual red blood cell (RBC) volumes and has been shown to be associated with elevated risk for morbidity and mortality in a wide range of diseases. In this large cohort study including 1,641 adults diagnosed with SARS-CoV-2 infection and admitted to 4 hospitals in Boston, RDW was associated with mortality risk in Cox models (hazard ratio of 1.09 per 0.5% RDW increase and 2.01 for an RDW >14.5% vs ≤14.5%).

 

Roncon L, Zuin M, Barco S, et al. Incidence of acute pulmonary embolism in COVID-19 patients: Systematic review and meta-analysis. Eur J Intern Med. 2020 Sep 17:S0953-6205(20)30349-6. PubMed: https://pubmed.gov/32958372. Full-text: https://doi.org/10.1016/j.ejim.2020.09.006

Loris Roncon and colleagues from Rovigo/Italy have analyzed data from 23 studies, including 7,178 COVID-19 patients. Among patients hospitalized in general wards and intensive care unit (ICU), the pooled in-hospital incidence of pulmonary embolism or lung thrombosis was 14.7% and 23.4%, respectively. Segmental/sub-segmental pulmonary arteries were more frequently involved compared to main/lobar arteries. (6.8% vs18.8%, p<0.001). Computer tomography pulmonary angiogram (CTPA) was used only in 35%, suggesting a potential underestimation of PE cases.

 

Treatment

De Alencar JC, Moreira CL, Müller AD, et al. Double-blind, randomized, placebo-controlled trial with N-acetylcysteine for treatment of severe acute respiratory syndrome caused by COVID-19. Clinical Infectious Diseases, 23 September 2020, ciaa1443. Full-text:  https://doi.org/10.1093/cid/ciaa1443

No effect of high-dose N-acetylcysteine. In this randomized clinical trial (RCT) from Brazil including 135 patients with severe COVID-19, 16 patients (24%) in the Placebo group were submitted to endotracheal intubation and mechanical ventilation, compared to 14 patients (21%) in the NAC group (p=0.675). No difference was observed in secondary endpoints.

 

Wang M, Zhao Y, Hu W, et al. Treatment of COVID-19 Patients with Prolonged Post-Symptomatic Viral Shedding with Leflunomide — a Single-Center, Randomized, Controlled Clinical Trial. Clin Infect Dis. 2020 Sep 21:ciaa1417. PubMed: https://pubmed.gov/32955081 . Full-text: https://doi.org/10.1093/cid/ciaa1417

No effect of leflunomide. Leflunomide is an approved antagonist of dihydroorotate dehydrogenase, has some antiviral and anti-inflammatory effects and has been widely used to treat patients with autoimmune diseases. In this small RCT from Wuhan on 50 COVID-19 patients with prolonged PCR positivity, no benefit in terms of the duration of viral shedding was observed with the combined treatment of leflunomide and IFN α-2a beyond IFN α-2a alone.