Top 10: July 2

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By Christian Hoffmann &
Bernd S. Kamps

2 July

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Schultheiß C, Paschold L, Simnica D, et al. Next Generation Sequencing of T and B cell receptor repertoires from COVID-19 patients showed signatures associated with severity of disease. Cell June 29, 2020. Full-text:

Insights on adaptive immunity. The authors analyzed COVID-19 patients with active, severe infection (n=20) or after recovery of mild disease (n=19) and created a repository of currently > 14 million B and T cell receptor (BCR, TCR) sequences from the blood of these patients. The B cell response showed converging IGHV3-driven BCR clusters closely associated with SARS-CoV-2 antibodies. The T cell pools of patients with active disease were considerably diminished and showed shifts towards CD4+ and expanded Treg cells. Clonality and skewing of TCR repertoires was associated with interferon type I and III responses and early CD4+ and CD8+ T cell activation.



Deming ME, Michael NL, Robb M, et al. Accelerating Development of SARS-CoV-2 Vaccines — The Role for Controlled Human Infection Models. NEJM July 1, 2020. Full-text: . Full-text:

The authors review practical considerations relevant to the development of a SARS-CoV-2 controlled human infection models (CHIMs) and the prerequisites for using such a model. Large, randomized, controlled trials of SARS-CoV-2 vaccines are still the most efficient, generalizable, and scientifically robust path to establishing vaccine efficacy. However, SARS-CoV-2 CHIM development might be able to accelerate the development of later rounds of vaccine candidates.



Paden CR, Tao Y, Queen K, et al. Rapid, sensitive, full-genome sequencing of severe acute respiratory syndrome coronavirus 2. Emerg Infect Dis. 2020, Jul 1, 2020.

Validated protocols are described for generating high-quality, full-length genomes from primary samples. One protocol uses multiplex reverse transcription PCR, followed by MinION or MiSeq sequencing; the other uses singleplex, nested reverse transcription PCR and Sanger sequencing. These protocols enable sensitive virus sequencing in different laboratory environments.



Ikeuchi K, Saito M, Yamamoto S, Nagai H, Adachi E. Relative bradycardia in patients with mild-to-moderate coronavirus disease, Japan. Emerg Infect Dis 2020, July 1. Full-text:

Relative bradycardia is a characteristic physical finding in some intracellular bacterial infections, viral infections, and non-infectious diseases. In this case series of 54 patients with mild-to-moderate COVID-19 in Japan, it was also a common finding. This clinical sign could help clinicians to diagnose this disease. Only body temperature was independently associated with pulse rate by multivariate analysis. The predicted change in pulse rate was 7.37 beats/min for each 1°C increase in body temperature.


Weinberger DM, Chen J, Cohen T, et al. Estimation of Excess Deaths Associated With the COVID-19 Pandemic in the United States, March to May 2020. JAMA Intern Med July 1, 2020. Full-text:

There were approximately 781,000 deaths in the US from March 1 to May 30, 2020, representing 122,300 (95% prediction interval, 116,800 – 127,000) more deaths than would typically be expected. The number of excess all-cause deaths was 28% higher than the official tally of COVID-19–reported deaths during that period. There was substantial variability between states in the difference between official COVID-19 deaths and the estimated burden of excess deaths.


Woolf SH, Chapman DA, Sabo RT. Excess Deaths From COVID-19 and Other Causes, March-April 2020. JAMA July 1, 2020. Full-text:

Same idea: the weekly death data for the 50 US states and the District of Columbia were obtained from the National Center for Health Statistics for January through April 2020 and the preceding 6 years. The authors provide state-by-state estimates of excess deaths and a more detailed account of the 5 states most affected by COVID-19. It was estimated that the number of COVID-19 deaths reported in the first weeks of the pandemic captured only two-thirds of excess deaths in the US.


Severe COVID-19

Sinha P, Matthay MA, Calfee CS. Is a “Cytokine Storm” Relevant to COVID-19? JAMA Intern Med June 30, 2020. Full-text:

“Cytokine storm” has no definition. Broadly speaking, it denotes a hyperactive immune response characterized by the release of interferons, interleukins, tumor necrosis factors, chemokines, and several other mediators. In this editorial, a critical evaluation of the term cytokine storm and its relevance is given. The authors point out that although the term “cytokine storm” conjures up dramatic imagery and has captured the attention of the mainstream and scientific media, the current data do not support its use. Until new data establish otherwise, the linkage of cytokine storm to COVID-19 may be nothing more than a tempest in a teapot.



Armeni E, Aziz U, Qamar S, et al. Protracted ketonaemia in hyperglycaemic emergencies in COVID-19: a retrospective case series. Lancet Diabetol Endocrinol July 01, 2020. Full-text:

COVID-19 is associated with hyperglycemic emergencies in COVID-19. In this case series of 35 patients from three hospitals in north London, UK, March 1–30, 2020, an over-representation of type 2 diabetes in patients presenting with diabetic ketoacidosis and long-lasting ketosis was observed. Findings suggest acute insulinopenia in patients with COVID-19 and with type 2 diabetes, which persisted up until the time of discharge in 30% of patients previously not insulin-treated. Moreover, the study sample, with almost half of patients of African background, had protracted ketonemia and ketoacidosis.



Dufort EM, Koumans EH, Chow EJ, et al. Multisystem Inflammatory Syndrome in Children in New York State. NEJM June 29, 2020. Full-text:  Full-text:

Another large cohort of 95 patients with a multi-system inflammatory syndrome in children (MIS-C), reported to the New York State Department of Health. Detailed analysis of the characteristics: Elevated levels of C-reactive protein, d-dimer, and troponin were found in 100%, 91%, and 71% of the patients, respectively; 53% had evidence of myocarditis, 80% were admitted to an intensive care unit, and 2 died.


Abdel-Mannan O, Eyre M, Löbel U. Neurologic and Radiographic Findings Associated With COVID-19 Infection in Children. JAMA Neurol July 1, 2020. Full-text:

A case series of 4 children with COVID-19 and neurological symptoms is described. Symptoms included encephalopathy, headaches, brainstem and cerebellar signs, muscle weakness, and reduced reflexes. All 4 patients had signal changes in the splenium of the corpus callosum on neuroimaging and required intensive care admission for the treatment of COVID-19 pediatric multisystem inflammatory syndrome.