Top 10: June 25

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By Christian Hoffmann &
Bernd S. Kamps

25 June

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Epidemiology

Lewis M, Sanchez R, Auerbach S, et al. COVID-19 Outbreak Among College Students After a Spring Break Trip to Mexico — Austin, Texas, March 26–April 5, 2020. MMWR Morb Mortal Wkly Rep. ePub: 24 June 2020. Full-text: http://dx.doi.org/10.15585/mmwr.mm6926e1

A college spring break trip mid-March led to 64 cases (14 asymptomatic and 50 symptomatic at the time of testing), including 60 among 183 vacation travelers, one among 13 household contacts, and three among 35 community contacts. Asymptomatic persons or those with mild symptoms likely played an important role in sustaining transmission. Prompt epidemiologic investigation contributed to outbreak control.

 

Immunology/Pathogenesis

Song JW, Lam SM, Fan X, et al. Omics-driven systems interrogation of metabolic dysregulation in COVID-19 pathogenesis. Cell Metabolism June 24, 2020. Full-text: https://doi.org/10.1016/j.cmet.2020.06.016

To date, the largest quantitative repository on the plasma lipidome and metabolome distinctly associated with COVID-19. Evaluation of metabolic pathway alterations based on differential correlation network analyses, highlighting two lipid modules possibly implicated in COVID-19 pathogenesis.

 

Tong M, Jiang Y, Xia D, et al. Elevated Serum Endothelial Cell Adhesion Molecules Expression in COVID-19 Patients. J Inf Dis, 25 June 2020. Full-text: https://doi.org/10.1093/infdis/jiaa349

A small but important retrospective study of 39 COVID-19 patients and 32 control participants, examining the expression of endothelial cell adhesion molecules by enzyme-linked immunosorbent assays (ELISA). Serum levels of fractalkine, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and vascular adhesion protein-1 were elevated in mild patients, elevated dramatically in severe cases, while decreased in the convalescence phase. The increased expression may contribute to coagulation dysfunction.

 

Transmission

Chou R, Dana R, Jungbauer R, et al. Masks for Prevention of Respiratory Virus Infections, Including SARS-CoV-2, in Health Care and Community Settings. Ann Int Med 24 Jun 2020. Full-text: https://doi.org/10.7326/M20-3213

According to this “living rapid” review of 39 studies (18 randomized controlled trials and 21 observational studies; 33,867 participants), evidence on mask effectiveness for respiratory infection prevention is stronger in health care than community settings. N95 respirators might reduce SARS-CoV-1 risk versus surgical masks in health care settings, but applicability to SARS-CoV-2 is uncertain.

 

Clinical

Borras-Bermejo B, Martínez-Gómez X, Gutierrez-San Miguel M, et al. Asymptomatic SARS-CoV-2 infection in nursing homes, Barcelona, Spain, April 2020. Emerg Infect Dis. 2020 Sep [June 23, 2020]. https://doi.org/10.3201/eid2609.202603

High number of asymptomatic patients: the authors obtained a total of 5,869 samples, 3,214 from residents and 2,655 from facility staff in 69 nursing homes. Overall, 768 (23.9%) residents and 403 (15.2%) staff members tested positive for SARS-CoV-2. The presence of fever or respiratory symptoms during the preceding 14 days was recorded in 2,624 residents (81.6%) and 1,772 staff members (66.7%). Among those testing positive with information about symptoms, 69.7% of the residents and 55.8% of staff were asymptomatic. However, the ascertainment process could lead to misclassification due to atypical symptoms in the elderly. Moreover, cross-sectional symptom assessment did not allow the authors to differentiate between presymptomatic and asymptomatic cases.

 

Comorbidities

Zhang XJ, Quin JJ, Cheng X, et al. In-hospital Use of Statins is Associated with a Reduced Risk of Mortality among Individuals with COVID-19. Cell Metabolism June 24, 2020. Full-text: https://doi.org/10.1016/j.cmet.2020.06.015

Retrospective study on 13,981 patients in Hubei Province, China, among which 1,219 received statins. Based on a Cox model with time-varying exposure and after propensity score-matching, 28-day all-cause mortality was 5.2% and 9.4% in the matched statin and non-statin groups, respectively. Randomized controlled trials involving statin treatment for COVID-19 are needed.

 

Robilotti EV, Babady NE, Mead PA, et al. Determinants of COVID-19 disease severity in patients with cancer. Nat Med June 24, 2020. Full-text: https://doi.org/10.1038/s41591-020-0979-0

Among 423 cases of symptomatic COVID-19 who were diagnosed at Memorial Sloan Kettering Cancer Center, 40% were hospitalized for COVID-19 and 12% died within 30 days. Age older than 65 years and treatment with immune checkpoint inhibitors (ICIs) were predictors for hospitalization and severe disease, whereas receipt of chemotherapy and major surgery were not.

 

Treatment

Guaraldi G, Meschiari M, Cozzi-Lepri A, et al. Tocilizumab in patients with severe COVID-19: a retrospective cohort study. Lancet Rheumatology. June 24, 2020. Full-text: https://doi.org/10.1016/S2665-9913(20)30173-9

The largest retrospective, observational cohort study (from Italy) to date, reporting on IL-6 receptor blocker tocilizumab which was given either intravenously or subcutaneously. 57 (16%) of 365 patients in the standard of care (SOC) group needed mechanical ventilation, compared with 33 (18%) of 179 patients treated with tocilizumab (88 patients treated intravenously). 73 (20%) patients in the SOC group died, compared with 13 (7%; p<0·0001) patients treated with tocilizumab. After adjustment for sex, age, duration of symptoms, and SOFA (Sequential Organ Failure Assessment) score, tocilizumab treatment was associated with a reduced risk of invasive mechanical ventilation or death (adjusted hazard ratio 0.61, 95% CI 0.40–0.92). However, the precise group of patients who might benefit from tocilizumab and the optimal biomarkers for identifying the cytokine storm in the setting of COVID-19 remain unknown.

 

Deftereos SG, Giannopoulos G, Vrachatis DA, et al. Effect of Colchicine vs Standard Care on Cardiac and Inflammatory Biomarkers and Clinical Outcomes in Patients Hospitalized With Coronavirus Disease 2019The GRECCO-19 Randomized Clinical Trial. JAMA Netw Open June 24, 2020;3(6. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.13136

In this prospective, open-label, randomized clinical trial, 105 patients hospitalized with COVID-19 in Greece were randomized to either standard medical treatment or colchicine plus standard medical treatment. Participants who received colchicine had statistically “significantly improved time to clinical deterioration”. However, there were no significant differences in biomarkers and the observed difference was based on a narrow margin of clinical significance; according to the authors their observations “should be considered hypothesis generating” and “be interpreted with caution”.

 

Sarpatwari A, Kaltenboeck A, Kesselheim AS, et al. Missed Opportunities on Emergency Remdesivir Use. JAMA. June 24, 2020 Full-text: https://doi.org/10.1001/jama.2020.11932

Important viewpoint on monitoring remdesivir use, pricing, and drug supply. Gilead has yet to comment what the bounds of a reasonable price could be. According to the authors, the FDA should revise its current EUA for remdesivir to require the creation of a patient registry that includes information on patient demographics, treatment dose and duration, and safety outcomes.