Top 10: July 12

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By Christian Hoffmann &
Bernd S. Kamps

12 July

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­­­Epidemiology

Verdery AM, Smith-Greenaway E, Margolis R, Daw J. Tracking the reach of COVID-19 kin loss with a bereavement multiplier applied to the United States. Proc Natl Acad Sci U S A. 2020 Jul 10:202007476. PubMed: https://pubmed.gov/32651279. Full-text: https://doi.org/10.1073/pnas.2007476117

Multiply deaths by nine. These authors created a “bereavement multiplier”, an indicator that clarifies the downstream impact of COVID-19 mortality and can be applied to different epidemiological projections of death counts: how many people are at risk for losing a grandparent, parent, sibling, spouse, or child for each COVID-19 death. In the US, every death from COVID-19 will leave approximately nine bereaved.

 

Fenton MB. Bats navigate with cognitive maps. Science 10 Jul 2020: Vol. 369, Issue 6500, pp. 142. Full-text: https://doi.org/10.1126/science.abd1213

Interested in bats these days? They are smart. And they know where they are. This article summarizes current research on the path-finding strategies of fruit bats. Bats do not systematically follow known routes, nor do they directly sense cues such as landmarks or beacons: they rely on a cognitive map frame of reference for their current positions in relation to a goal that they had not yet detected.

 

Clinical

Wortham JM, Lee JT, Althomsons S, et al. Characteristics of Persons Who Died with COVID-19 — United States, February 12–May 18, 2020. MMWR Morb Mortal Wkly Rep. ePub: 10 July 2020. Full-text: http://dx.doi.org/10.15585/mmwr.mm6928e1

Using national case-based surveillance and supplementary data reported from 16 jurisdictions, detailed characteristics of 10,647 COVID-19 deaths that occurred during February 12–April 24, 2020 are described. More than one third of Hispanic decedents (34.9%) and nearly one third (29.5%) of non-white decedents were aged < 65 years, but only 13.2% of white decedents were aged < 65 years. Most decedents had one or more underlying medical conditions reported (76.4%) or were aged ≥ 65 years (74.8%). Among reported underlying medical conditions, cardiovascular disease and diabetes were the most common.

 

Kirschenbaum D, Imbach LL, Ulrich S, et al. Inflammatory olfactory neuropathy in two patients with COVID-19. Lancet July 10, 2020. Full-text: https://doi.org/10.1016/S0140-6736(20)31525-7

Post-mortem histological analysis of the olfactory epithelium in two COVID-19 patients showed prominent leukocytic infiltrates in the lamina propria and focal atrophy of the mucosa. However, it is unclear whether the observed inflammatory neuropathy is a result of direct viral damage or is mediated by damage to supporting non-neural cells.

 

Hengeveld PJ, Omar Khader A, de Bruin LHA, et al. Blood cell counts and lymphocyte subsets of patients admitted during the COVID-19 pandemic: a prospective cohort study. Br J Haematol. 2020 Jul 11. PubMed: https://pubmed.gov/32652585. Full-text: https://doi.org/10.1111/bjh.16983

Based on ICU admission or death during hospital admission, 197 COVID-19 patients were compared with 354 patients in whom COVID-19 was ruled out (controls). At admission, anemia, leukocytosis and neutrophilia were more prevalent in controls than in COVID-19 patients. In agreement with recent reports, thrombocyte counts were lower in COVID-19 patients, and thrombocytopenia was associated with an increased risk of in-hospital mortality.

 

Diagnostics

Fung B, Gopez A, Servellita V, et al. Direct Comparison of SARS-CoV-2 Analytical Limits of Detection across Seven Molecular Assays. J Clin Microbiol. 2020 Jul 10:JCM.01535-20. PubMed: https://pubmed.gov/32651238. Full-text: https://jcm.asm.org/content/early/2020/07/09/JCM.01535-20

The authors have determined analytical limits of detection for seven SARS-CoV-2 assays using serial dilutions of pooled patient material quantified with droplet digital PCR. Limits of detection ranged from ≤ 10-74 copies/mL for commercial high-throughput laboratory analyzers (Roche Cobas, Abbott m2000, Hologic Panther Fusion) and 167-511 copies/mL for sample to answer (Diasorin Simplexa, Genmark ePlex) and point-of-care instruments (Abbott ID NOW). The CDC assay yielded limits of detection ranging from 85-499 copies/mL, depending on the extraction method and thermocycler used.

 

Treatment

Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the Treatment of Covid-19 – Preliminary Report. Reply. N Engl J Med 2020 Jul 10;383. Full-text: https://doi.org/10.1056/NEJMc2022236

Discussion about the preliminary report on the large Phase III US trial of remdesivir (remember the Fauci press conference). Several letters elucidate the challenges arising from the dissemination of early results. The authors promise solemly that they have begun to analyze the final data and will revise the report after that analysis is complete, including a more detailed analyses of the duration of illness and its relationship to baseline disease severity and outcomes, as well as concomitant medications during the trial. Why this seemingly takes months (perceived years), remains unclear. We are very curious.

 

Somers EC, Eschenauer GA, Troost JP, et al. Tocilizumab for treatment of mechanically ventilated patients with COVID-19. Clin Infect Dis. 2020 Jul 11. PubMed: https://pubmed.gov/32651997. Full-text: https://doi.org/10.1093/cid/ciaa954

Comparison of 78 patients who received tocilizumab (TCZ) and 76 who did not. TCZ-treated patients were younger, less likely to have chronic pulmonary disease, and had lower D-dimer values at time of intubation. In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death and improved status on the ordinal outcome scale. Though tocilizumab was associated with an increased proportion of patients with superinfections (54% vs. 26%, mainly S. aureus), there was no difference in 28-day case fatality rate among TCZ-treated patients with versus without superinfection. We urgently need adequately powered RCT.

 

Wise J, Coombes R. Covid-19: The inside story of the RECOVERY trial. BMJ 2020; 370 Full-text: https://doi.org/10.1136/bmj.m2670

The UK’s flagship COVID-19 clinical trial may help in this regard. Patients enrolled in the open label RECOVERY trial are randomised to standard care or to one of six treatment arms: hydroxychloroquine (now closed), dexamethasone (also closed, press release June 16), lopinavir/ritonavir, azithromycin, convalescent plasma, and, in a second randomisation for patients who deteriorate, the anti-inflammatory drug tocilizumab. The authors unpack the criticisms that still surround this mammoth task, of mounting a large scale trial amid the first major pandemic in 100 years in record time.

 

Pregnancy

Khalil A, von Dadelszen P, Draycott T, et al. Change in the Incidence of Stillbirth and Preterm Delivery During the COVID-19 Pandemic. JAMA July 10, 2020. Full-text: https://doi.org/10.1001/jama.2020.12746

Pregnancy outcomes at St George’s University Hospital, London, were evaluated in two periods: from October 2019 to January 2020 and from February to June 2020. The incidence of stillbirth was significantly higher during the pandemic period (9.31 per 1000) than during the pre-pandemic period (2.38 per 1000). Of note, the increase in stillbirths may have also resulted from indirect effects such as reluctance to attend hospital when needed, fear of contracting infection, or not wanting to add to the National Health Service burden. Changes in obstetric services may have played a role secondary to staff shortages or reduced antenatal visits, ultrasound scans, and/or screening.