Top 10: June 26

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By Christian Hoffmann &
Bernd S. Kamps

26 June

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Virology

Barr IG, Rynehart C, Whitney P, et al. SARS-CoV-2 does not replicate in embryonated hen’s eggs or in MDCK cell lines. Eurosurveillance Volume 25, Issue 25, 25/Jun/2020. Full-text: https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.25.2001122

This study showed that even if a clinical sample, containing both human influenza and SARS-CoV-2, was inoculated into substrates used to prepare seeds for influenza vaccine production (embryonated chicken eggs or MDCK-based cell lines), SARS-CoV-2 would be unlikely to be propagated and would be undetectable after a small number of passages. This finding reassures influenza vaccine production staff and laboratory scientists who might be concerned about potential exposure to SARS-CoV-2 and also suggests that loss of potentially important influenza candidate vaccine viruses or final vaccine lots due to SARS-CoV-2 contamination is unlikely.

 

Immunology

Sokolowska M, Lukasik Z, Agache I, et al. Immunology of COVID-19: mechanisms, clinical outcome, diagnostics and perspectives – a report of the European Academy of Allergy and Clinical Immunology (EAACI). Allergy. 2020 Jun 25. PubMed: https://pubmed.gov/32584441 . Full-text: https://doi.org/10.1111/all.14462

Experts in basic and clinical immunology have joined forces to provide a consensus report on the basic molecular and immune mechanisms associated with susceptibility, clinical presentations and severity of COVID-19. This report summarizes current immunological data, including the differences between adequate innate and adaptive immune response in mild disease and the deep immune dysfunction in the more severe multi-organ disease.

 

Clinical

Roca-Ginés J, Torres-Navarro I, Sánchez-Arráez J, et al. Assessment of Acute Acral Lesions in a Case Series of Children and Adolescents During the COVID-19 Pandemic. JAMA Dermatol. 2020 Jun 25. PubMed: https://pubmed.gov/32584397 . Full-text: https://doi.org/10.1001/jamadermatol.2020.2340

In this case series from Valencia following 20 patients aged 1 to 18 years with new-onset acral inflammatory lesions, all lacked systemic manifestations of COVID-19. Surprisingly, both PCR and serologic test results were negative for SARS-CoV-2, questioning an association between acral skin disease and COVID-19.

 

Herman A, Peeters C, Verroken A, et al. Evaluation of Chilblains as a Manifestation of the COVID-19 Pandemic. JAMA Dermatol. 2020 Jun 25. PubMed: https://pubmed.gov/32584377 . Full-text: https://doi.org/10.1001/jamadermatol.2020.2368

Same in Belgium. Of 31 patients (mostly teenagers) who had recently developed chilblains, histopathologic analysis of skin biopsy specimens (22 patients) confirmed the diagnosis of chilblains and showed occasional lymphocytic or microthrombotic phenomena. In all patients, PCR and serology remained negative. Chilblains appeared not to be directly associated with COVID-19 in this case series. According to the authors, lifestyle changes associated with community containment and lockdown measures are a possible explanation for these lesions.

 

Varatharaj A, Thomas N, Ellul MA, et al. Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study. Lancet Psychiatry June 25, 2020. Full-text: https://doi.org/10.1016/S2215-0366(20)30287-X

Online network study from the UK, including 125 patients with data and with neurologic/neuropsychiatric complications. Of these, 77 (62%) presented with a cerebrovascular event, of whom 57 (74%) had an ischemic stroke, nine (12%) an intracerebral hemorrhage, and one (1%) CNS vasculitis. Altered mental status was the second most common presentation (31%), comprising encephalopathy or encephalitis and primary psychiatric diagnoses, often occurring in younger patients.

 

Maugeri G, Castrogiovanni P, Battaglia G. The impact of physical activity on psychological health during Covid-19 pandemic in Italy. Heliyon June 24, 2020. Full-text: https://doi.org/10.1016/j.heliyon.2020.e04315

Maintain your exercise routine! Among 2524 subjects completing an online survey, total physical activity significantly decreased between before and during the COVID-19 pandemic. A significant positive correlation was found between the variation of physical activity and mental well-being, suggesting that the reduction of total physical activity had a profoundly negative impact on psychological health and well-being of population.

 

Mallapaty S. Mounting clues suggest the coronavirus might trigger diabetes. Nature 2020, June 24. Full-text: https://www.nature.com/articles/d41586-020-01891-8

Does COVID-19 lead to diabetes? Some comments on preprint papers indicating growing evidence from tissue studies and some clinical cases that the virus damages insulin-producing cells. It remains to be seen how relevant this problem is.

 

Comorbidities

Meca-Lallana V, Aguirre C, Beatrizdel Río, Cardeñoso L, Alarcon T, Vivancos J. COVID-19 in 7 multiple sclerosis patients in treatment with ANTI-CD20 therapies. Mult Scler Relat Disord. 2020 Jun 15;44:102306. PubMed: https://pubmed.gov/32585617 . Full-text: https://doi.org/10.1016/j.msard.2020.102306

A small case series on patients with MS and COVID-19, treated with the anti-CD20 monoclonal antibodies (mAbs) ocrelizumab and rituximab. Although the severity of the clinical picture varied, patients’ development was good, indicating that B cells and immunoglobulin may not be absolutely necessary for viral elimination. Not all patients developed antibodies against SARS-CoV-2.

 

Sivaloganathan H, Ladikou EE, Chevassut T. COVID-19 mortality in patients on anticoagulants and antiplatelet agents. Br J Haematol. 2020 Jun 25. PubMed: https://pubmed.gov/32584423 . Full-text: https://doi.org/10.1111/bjh.16968

Anticoagulants, or other antithrombotic agents such as antiplatelet drugs, might counteract the coagulopathic effects of COVID-19 resulting in improved outcomes. This small, matched-control study shows that this is probably not the case. Patients on aspirin (n=18), on clopidogrel (n=8), apixaban (n=12), warfarin (n=7) and some other drugs did not have a significantly different mortality risk to patients not taking these drugs. According to the authors, this could suggest these agents negate any potential increased mortality risk attributable to whichever disease the drugs had been prescribed, but further data on comorbidities is required to confirm this assertion.

 

Treatment

Yeleswaram S, Smith P, Burn T, et al. Inhibition of cytokine signaling by ruxolitinib and implications for COVID-19 treatment. Clin Immunol. 2020 Jun 22:108517. PubMed: https://pubmed.gov/32585295 . Full-text: https://doi.org/10.1016/j.clim.2020.108517

Comprehensive review on ruxolitinib. As many of the elevated cytokines signal through Janus kinase (JAK)1/JAK2, inhibition of these pathways with ruxolitinib has the potential to mitigate the COVID-19-associated cytokine storm and reduce mortality. This is supported by preclinical and clinical data from other diseases with hyperinflammatory states, where ruxolitinib has been shown to reduce cytokine levels and improve outcomes. However, it is important to consider that this work was supported by Incyte, a manufacturer of the drug.

 

Pediatrics

Götzinger F, Santiago-García B, Noguera-Julián A, et al. COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study. Lancet Child Adol Health June 25, 2020. Full-text: https://doi.org/10.1016/S2352-4642(20)30177-2

One of the largest registries to date, confirming that COVID-19 is generally a mild disease in children. Of 582 children and adolescents (median age 5.0 years, 25% with pre-existing conditions) with PCR-confirmed SARS-CoV-2 infection, 363 (62%) were admitted to hospital and 48 (8%) individuals required ICU admission. Significant risk factors for requiring ICU admission in multivariate analyses were being younger than 1 month (odds ratio 5.1), male sex (2.1) and pre-existing medical conditions (3.3). Four children died.