Top 10: June 7

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By Christian Hoffmann &
Bernd S. Kamps

7 June

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Li Z, Chen Q, Feng L, et al.  Active case finding with case management: the key to tackling the COVID-19 pandemic. The Lancet, June 4, 2020.

Learning from China. Case finding and management, with identification and quarantine of close contacts: the authors describe the next steps planned in China following the containment effort.



Cyranoski D. The biggest mystery: what it will take to trace the coronavirus source. Nature 2020, June 05. Full-text:

Elegant article summarizing the current (and limited) knowledge of the origin of SARS-CoV-2. Most researchers say the more likely explanation is that bats passed it to an intermediate animal, which then spread it to people. However, this finding will be tricky, as will calming speculations of a “lab escape”. This would require a forensic investigation, looking for viruses that matched the genetic sequence of SARS-CoV-2 and. Authorities would need to take samples from the lab, interview staff, review lab books and records of safety incidents, and see what types of experiment researchers had done.



Han MS, Seong MW, Kim N, et al. Viral RNA Load in Mildly Symptomatic and Asymptomatic Children with COVID-19, Seoul. Emerg Infect Dis. 2020 Jun 4;26(10). PubMed: . Full-text:

This study raises doubts on the hypothesis that children are less infectious. Of 12 children (median 6.5 years), 9 were mildly symptomatic and 3 were asymptomatic. Viral RNA load in the nasopharyngeal swabs (and saliva) peaked early at high levels, achieving a median of 7.56 (range 6.19–10.56) log10 copies/mL. Along with positive SARS-CoV-2 RNA in nasopharyngeal swabs, viral RNA was detectable at high concentration for > 3 weeks in fecal samples.



Hung DL, Li X, Chiu KH, et al. Early Morning Versus Spot Posterior Oropharyngeal Saliva for Diagnosis of SARS-CoV-2 Infection: Implication of Timing of Specimen Collection for Community-wide Screening. Open Forum Infectious Diseases, June 7. Full-text:

The cycle threshold (Ct) PCR values (low = more virus) were compared in posterior oropharyngeal saliva, collected at five different time points within the same day from 18 COVID-19 patients. There was an overall trend of lower Ct values from specimens collected in the early morning, with a gradual decrease of viral load towards night time. Eight out of 13 subjects had highest viral load in the early morning than the rest of the four time points. The results suggest a diurnal variation of viral shedding from the upper respiratory tract.



Belli LC, Duvoux C, Karam V, et al. COVID-19 in liver transplant recipients: preliminary data from the ELITA/ELTR registry. Lancet Gastroenterology & Hepatology, June 4, 2020.  Full-text:

First large analysis on liver transplant recipients. At a median follow-up of 18 days, 16/100 died from COVID-19. Of note, mortality was observed only in patients aged 60 years or older (16/73) and was more common in male recipients than in female recipients. Although not statistically significant, more patients who were transplanted at least 2 years earlier died than did those who received their transplant within the past 2 years (15/82, 18% vs 1/21, 5%).


Severe COVID

Ferreyro BL, Angriman F, Munshi L, et al. Association of Noninvasive Oxygenation Strategies With All-Cause Mortality in Adults With Acute Hypoxemic Respiratory Failure. JAMA June 4, 2020. Full-text:

For this network meta-analysis of trials of adult patients with acute hypoxemic respiratory failure, the authors included 25 studies with 3,804 patients. Compared with standard oxygen therapy, helmet NIV (3 trials with 330 patients), face mask NIV (14 trials with 1725 patients) and HFNC (5 trials with 1479 patients) were associated with a lower risk of endotracheal intubation. Both forms of NIV, helmet and face mask, were also associated with a lower risk of death.


Patel BK, Kress JP, Hall JB. Alternatives to Invasive Ventilation in the COVID-19 Pandemic. JAMA June 4, 2020. Full-text:

This article reviews the meta-analysis and describes how COVID-19 has accelerated the need to add clarity to the ongoing debate of whether to intubate early and, if not, which type of non-invasive support (NIV, HFNC, or standard oxygen therapy) is the most efficacious. Future clinical trials comparing these strategies should not focus on declaring a “winner” per se but rather on identifying the patient phenotypes that stand to benefit from each non-invasive oxygenation support method. According to the authors, a heterogeneous syndrome like AHRF requires multiple options.


Von Weyhern C, Kaufmann I, Neff F, Kremer M. Early evidence of pronounced brain involvement in fatal COVID-19 outcomes.  The Lancet, June 4, 2020. Full-text:

Autopsy findings of six patients (four men and two women, aged 58–82 years) who died from COVID-19 in April 2020. A pronounced CNS involvement with pan-encephalitis, meningitis, and brainstem neuronal cell damage were key events in all cases. In patients younger than 65 years, CNS hemorrhage was a fatal complication of COVID-19.



Ucciferri C, Auricchio A, Di Nicola M, et al. Canakinumab in a subgroup of patients with COVID-19. Lancet Rheumatology, June 4, 2020.

Canakinumab is human monoclonal antibody against IL-1β, approved for the treatment of juvenile rheumatoid arthritis and other chronic autoinflammatory syndromes. In a pilot trial, 10 patients with hyperinflammation (defined as CRP ≥ 50 mg/L) and respiratory failure showed a rapid improvement in serum inflammatory biomarkers and an improvement in oxygenation.



Toubiana J, Poirault C, Corsia A, et al. Kawasaki-like multisystem inflammatory syndrome in children during the covid-19 pandemic in Paris, France: prospective observational study. BMJ. 2020 Jun 3;369:m2094. PubMed: . Full-text:

Of 21 children and adolescents (3.7-16.6 years, 19 with recent SARS-CoV-2 infection) with features of Kawasaki disease who were admitted between 27 April and 11 May 2020, 12 (57%) presented with Kawasaki disease shock syndrome and 16 (76%) with myocarditis. 17 (81%) required intensive care support. All 21 patients had noticeable gastrointestinal symptoms and high levels of inflammatory markers. All 21 patients received intravenous immunoglobulin and 10 (48%) also received corticosteroids. The clinical outcome was favourable in all patients.