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By Christian Hoffmann &
Bernd S. Kamps

20 May

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Summary

First, investigate high SARS-CoV-2 attack rates at church events; show competency in putting on and removing personal protective equipment (PPE); and edit consensus guidelines and recommendations on the conduct and management of tracheostomy during the COVID-19 pandemic.

Afterwards, build multiple monoclonal antibodies targeting SARS-CoV-2 S identified from memory B cells; establish whether blood 25-hydroxyvitamin D (25(OH)D) concentration was associated with COVID-19 risk; calculate the incidence of deep vein thrombosis in 143 patients from Wuhan; and describe the dynamic relationship between D‐dimer level and the progression of COVID‐19 in 279 patients.

Finally, explain the decline in acute myocardial infarction in California after March 4; analyze 525 patients with inflammatory bowel disease from 33 countries and search for risk factors for severe COVID-19; and discuss available antifibrotic therapies with your colleagues for fibrotic lung disease following SARS-CoV-2 infection.

Transmission

Ortega R, Gonzalez M, Nozari A, et al. Personal Protective Equipment and Covid-19. NEJM 2020, May 19. Full-text: https://doi.org/1056/NEJMvcm2014809

Prevention works only through training and demonstrated competency in putting on and removing personal protective equipment (PPE). This video demonstrates a procedure for “donning and doffing“ PPE.

 

James A, Eagle L, Phillips C. High COVID-19 Attack Rate Among Attendees at Events at a Church — Arkansas, March 2020. MMWR 2020, May 19. Full-text: http://dx.doi.org/10.15585/mmwr.mm6920e2

High transmission rates of SARS-CoV-2 have been reported from hospitals, long-term care facilities, family gatherings, choir practice. This report describes church events. In total, 35 confirmed COVID-19 cases occurred among 92 attendees at church events during March 6–11; estimated attack rates ranged from 38% to 78%. Of note, a higher proportion of adults aged 19–64 years and ≥65 years received positive test results than did younger persons.

 

Hastie CE, Mackay DF, Ho F, et al. Vitamin D Concentrations and COVID-19 Infection in UK Biobank. Diabetes Metab Syndr 2020 May 7;14(4):561-565. Full-text: https://doi.org/10.1016/j.dsx.2020.04.050

No link between vitamin D and infection risk. Of 348,598 UK biobank participants, 449 had confirmed COVID-19 infection. Ethnicity was associated with COVID-19 infection (blacks versus whites OR = 5.32, South Asians versus whites OR = 2.65). Vitamin D was not associated with COVID-19 infection, after adjustment for confounders. Vitamin D did not explain ethnic differences.

 

Diagnostics

Li  Y, Zhao K, Wei H, et al. Dynamic Relationship Between D-dimer and COVID-19 Severity. Br J Haematol 2020 May 18. Full-text: https://doi.org/10.1111/bjh.16811

Testing coagulation profile for ten consecutive days since admission in 279 COVID-19 patients, this study gives some insights into the dynamic changes of D-dimer level that are of prognostic value.

 

Clinical

Michelozzi Paola, de’Donato Francesca, Scortichini Matteo, et al. Mortality impacts of the coronavirus disease (COVID-19) outbreak by sex and age: rapid mortality surveillance system, Italy, 1 February to 18 April 2020. Euro Surveill. 2020;25(19). Full-text: https://doi.org/10.2807/1560-7917.ES.2020.25.19.2000620

Old white men. From the start of the epidemic until 18 April, an overall 4,805 (+45%) excess deaths were observed in Italian cities, with a significantly higher excess in the north (+76%, +4,295 deaths) compared with the center and the south (+10%, +510 deaths). Overall, the excess in mortality was higher among men than among women in cities in the north vs the center and the south (men: +87% and +70% and women: +17% and +9%, respectively), with an increase in the trend by age. The greatest excess in the north was among elderly men (+76% in 65–74 year-olds, +89% in 75–84 year-olds and +102% in those 85 years and older). In central and southern Italy, the excess in mortality among men was lower, with a statistically significant excess only among elderly men: +13% and +28%, respectively, in the 75–84 years and ≥85 years age group.

 

Zhang L, Feng X, Zhang D, et al. Deep Vein Thrombosis in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19) in Wuhan, China: Prevalence, Risk Factors, and Outcome. Circulation 2020 May 18. Full-text: https://doi.org/10.1161/CIRCULATIONAHA.120.046702

The next study emphasizes the high thrombosis risk. Of 143 patients hospitalized with COVID-19 (aged 63 ± 14 years;  52% men), 66 patients developed lower extremity Deep Vein Thrombosis (DVT) (46.1%), among them 23 with proximal DVT. Compared with patients without DVT, patients were older and had a lower oxygenation index, a higher rate of cardiac injury, and worse prognosis. Multivariate analysis found CURB-65 score 3-5 (OR = 6.122), Padua prediction score ≥4 (OR = 4.016), and D-dimer >1.0 μg/ml (OR = 5.818) to be associated with DVT.

 

Comorbidities

Brenner Ej, Ungaro RC, Gearry RB, et al. Corticosteroids, but Not TNF Antagonists, Are Associated With Adverse COVID-19 Outcomes in Patients With Inflammatory Bowel Diseases: Results From an International Registry. Gastroenterology 2020 May 18. Full-text:  https://doi.org/10.1053/j.gastro.2020.05.032

An important and large study, analysing 525 patients with IBD from 33 countries. Thirty-seven patients (7%) had severe COVID-19, and 16 patients died (3% case fatality rate). Risk factors for severe COVID-19 among IBD patients included increasing age, ≥2 comorbidities, systemic corticosteroids (aOR 6.9, 95% CI 2.3-20.5), and sulfasalazine or 5-aminosalicylate use (aOR 3.1, 95% CI 1.3-7.7). Maintaining remission with steroid-sparing treatments will be important in managing patients with IBD through this pandemic. However, a causal relationship cannot be definitively established. Notably, TNF antagonist treatment was not associated with severe COVID-19.

 

Solomon MD, McNulty EJ, Rana JS, et al. The Covid-19 Pandemic and the Incidence of Acute Myocardial Infarction. NEJM 2020, May 19. Full-text: HTTPS://DOI.ORG/10.1056/NEJMc2015630

In a large diverse community setting in California, the incidence of hospitalization for acute myocardial infarction declined after March 4 by up to 48% more than would be expected on the basis of typical seasonal variation alone. Similar findings have been noted in northern Italy.

 

Severe COVID-19

George PM, Wells AU, Jenkins RG. Pulmonary Fibrosis and COVID-19: The Potential Role for Antifibrotic Therapy. Lancet Respir Med 2020 May 15; S2213-2600(20)30225-3. https://doi.org10.1016/S2213-2600(20)30225-3. Full-text: https://linkinghub.elsevier.com/retrieve/pii/S2213260020302253

This brilliant article gives an overview on the (potentially high) burden of fibrotic lung disease following SARS-CoV-2 infection. Post-viral fibrosis may lead to severe physiological impairment. Available antifibrotic therapies such as pirfenidone (a pyridone with a poorly understood mechanism of action) and the thyrosine kinase inhibitor nintedanib have broad antifibrotic activity regardless of etiology, and these drugs might have a role in attenuating profibrotic pathways in SARS-CoV-2 infection. Current knowledge and future strategies are discussed.

 

Treatment

Pinto D, Park YJ, Beltramello M, et al. Cross-neutralization of SARS-CoV-2 by a Human Monoclonal SARS-CoV Antibody. Nature 2020 May 18. Full-text: https://doi.org/10.1038/s41586-020-2349-y

The next interesting antibody study. The authors describe multiple monoclonal antibodies targeting SARS-CoV-2 spike identified from memory B cells of an individual who was infected with SARS-CoV in 2003. One antibody, named S309, potently neutralizes SARS-CoV-2 by engaging the S receptor-binding domain. Using cryo-electron microscopy and binding assays, authors show that S309 recognizes a glycan-containing epitope that is conserved within the sarbecovirus subgenus, without competing with receptor attachment.

 

Procedures

McGrath BA, Brenner MJ, Warrillow SJ, et al. Tracheostomy in the COVID-19 Era: Global and Multidisciplinary Guidance. Lancet Respir Med 2020 May 15. Full-text: https://doi.org/10.1016/S2213-2600(20)30230-7

This article provide detailed consensus guidelines and recommendations on the conduct and management of tracheostomy during the pandemic. All important issues such as timing of tracheostomy (delayed until at least day 10 of mechanical ventilation and considered only when patients are showing signs of clinical improvement), optimal setting (hierarchic approach to operative location, enhanced PPE), optimal procedure as well as management after tracheostomy are discussed.