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Top 10: April 26

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By Christian Hoffmann &
Bernd S. Kamps

26 April

Epidemiology

Chinazzi M, Davis JT, Ajelli M, et al. The effect of travel restrictions on the spread of the 2019 novel coronavirus (COVID-19) outbreak. Science. 2020 Apr 24;368(6489):395-400. PubMed: https://pubmed.gov/32144116. Full-text: https://doi.org/10.1126/science.aba9757

Complex transmission models, using epidemiological data from China. Authors concluded that the travel quarantine introduced in Wuhan on 23 January 2020 only delayed epidemic progression by 3 to 5 days within China, but international travel restrictions did help to slow spread elsewhere by nearly 80% in the world until mid-February. Their results suggest that even sustained 90% travel restrictions to and from mainland China only modestly affect the epidemic trajectory. Early detection, hand washing, self-isolation, and household quarantine will likely be more effective.

 

Transmission

Canova V, Lederer Schlapfer H, Piso RJ, et al. Transmission risk of SARS-CoV-2 to healthcare workers -observational results of a primary care hospital contact tracing. Swiss Med Wkly. 2020 Apr 25;150:w20257. PubMed: https://pubmed.gov/32333603. Full-text: https://doi.org/Swiss Med Wkly. 2020;150:w20257

Good news. Among 21 healthcare workers who had contact with an initially undiagnosed COVID-19 case, transmission risk was low, especially during short contacts.

 

Comorbidities

Cai G, Bosse Y, Xiao F, Kheradmand F, Amos CI. Tobacco Smoking Increases the Lung Gene Expression of ACE2, the Receptor of SARS-CoV-2. Am J Respir Crit Care Med. 2020 Apr 24. PubMed: https://pubmed.gov/32329629. Full-text: https://doi.org/10.1164/rccm.202003-0693LE

Brand new information: Smoking is not the best idea. However, this is particularly true in the current pandemic. Ever-smoking significantly and substantially increased pulmonary ACE2 expression by 25%.The significant smoking effect on ACE2 pulmonary expression may suggest an increased risk for viral binding and entry of SARS-CoV-2 in lungs of smokers.

 

Severe COVID-19

Wadman M, Couzin-Frankel J, Kaiser J, et al. A rampage through the body. Science  24 Apr 2020: Vol. 368, Issue 6489, pp. 356-360. Full-text: https://science.sciencemag.org/content/368/6489/356

Is there anybody still twaddling about herd immunity? Let him read this detailed feature, describing the map of the devastation that COVID-19 can inflict not only on the lungs but on other organs as well, including blood vessels, heart, brain, kidneys and other organs. Scientists are just beginning to probe the nature of that harm.

 

Servick K. Survivors’ burden. Science 24 Apr 2020: Vol. 368, Issue 6489, pp. 359. https://science.sciencemag.org/content/368/6489/359

Discharge from ICU is not the end. Clinicians are now turning their attention to potential lingering effects of both the virus and the emergency treatments that allow people to survive. Scarring can cause long-term breathing problems. This feature also discusses other topics of concern such as muscle atrophy and weakness, mental problems but also cognitive impairment after leaving long-term intensive care. 

 

Marini JJ, Gattinoni L. Management of COVID-19 Respiratory Distress. JAMA. 2020 Apr 24. pii: 2765302. PubMed: https://pubmed.gov/32329799. Full-text: https://doi.org/10.1001/jama.2020.6825

Useful review on the unique lung injury induced by SARS-CoV-2 infection. It has become clear that acute respiratory distress syndrome (ARDS) in COVID-19 is different from ARDS. “CARDs” appears to include an important vascular insult that potentially mandates a different treatment approach than customarily applied for ARDS. Authors review their experiences and propose to categorize patients. In type L (low lung elastance, high compliance, low response to PEEP), infiltrates are often limited in extent and initially characterized by a ground-glass pattern on CT that signifies interstitial rather than alveolar edema. Many patients do not appear overtly dyspneic and may stabilize at this stage without deterioration. Others may transit to a clinical picture more characteristic of typical ARDS: Type H shows extensive CT consolidations, high elastance (low compliance) and high PEEP response. Clearly, types L and H are the conceptual extremes of a spectrum that includes intermediate stages.

 

Poissy J, Goutay J, Caplan M, et al. Pulmonary Embolism in COVID-19 Patients: Awareness of an Increased Prevalence. Circulation. 2020 Apr 24. PubMed: https://pubmed.gov/32330083. Full-text: https://doi.org/10.1161/CIRCULATIONAHA.120.047430

Case series from Lille/France showing a high prevalence of Pulmonary Embolism (PE) in severe COVID-19. Among the first 107 COVID-19 patients admitted to the ICU for pneumonia in March, authors identified 22 (20.6%) cases. It is of note that at the time of diagnosis of PE, 20/22 were receiving prophylactic antithrombotic treatment (UFH or LWMH) according to the current guidelines in critically ill patients.

 

Treatment

Borba MGS, Val FFA, Sampaio VS, et al. Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial. JAMA Netw Open. 2020 Apr 24;3(4.23):e208857. PubMed: https://pubmed.gov/32330277. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.8857

Less is more? This double-masked, randomized, phase IIb clinical trial in Manaus, Brazil allocated severe COVID-19 patients to receive high-dosage CQ (600 mg BID for 10 days) or low-dosage CQ (450 mg BID on day 1, QD for 4 days). The data safety monitoring board terminated the trial after 81/440 individuals had been enrolled. By day 13 of enrolment, 6 of 40 patients (15%) in the low-dose group had died, compared with 16 of 41 patients (39%) in the high-dose group. Viral RNA was detected in 78% and 76%, respectively. This trial also shows how dramatically mechanisms to execute research have accelerated: the first patient had been enrolled in this trial on March 26, 2020.

 

Mathian A, Mahevas M, Rohmer J, et al. Clinical course of coronavirus disease 2019 (COVID-19) in a series of 17 patients with systemic lupus erythematosus under long-term treatment with hydroxychloroquine. Ann Rheum Dis. 2020 Apr 24. pii: annrheumdis-2020-217566. PubMed: https://pubmed.gov/32332072. Full-text: https://doi.org/10.1136/annrheumdis-2020-217566

People with lupus (SLE) who take hydroxychloroquine (HCQ) are not protected. This case series describes 17 SLE patients with COVID-19, among them several severe cases. The duration of HCQ treatment prior to COVID-19 was relatively long, with a median of 7.5 years. Some patients were also treated with prednisone and/or with immunosuppressants.

 

Sheahan TP, Sims AC, Zhou S, et al. An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice. Sci Transl Med. 2020 Apr 6. pii: scitranslmed.abb5883. PubMed: https://pubmed.gov/32253226. Full-text: https://doi.org/10.1126/scitranslmed.abb5883

What if Remdesivir doesn’t work? The next nucleoside analog is on its way. Beta-D-N(4)-hydroxycytidine (NHC, EIDD-1931) has broad spectrum antiviral activity against all human and bat CoVs, including CoVs resistant to remdesivir. In mice, both prophylactic and therapeutic administrations improved pulmonary function and reduced virus titer.