Top 10: June 10

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By Christian Hoffmann &
Bernd S. Kamps

10 June

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Epidemiology

Payne DC, Smith-Jeffcoat SE, Nowak G, et al. SARS-CoV-2 Infections and Serologic Responses from a Sample of U.S. Navy Service Members — USS Theodore Roosevelt, April 2020. MMWR Morb Mortal Wkly Rep. ePub: 9 June 2020. Full-text: https://www.cdc.gov/mmwr/volumes/69/wr/mm6923e4.htm

In late March 2020, a large outbreak on the aircraft carrier USS Theodore Roosevelt was characterized by widespread transmission with relatively mild symptoms and asymptomatic infection among mostly young, healthy adults with close, congregate exposures. One fifth of infected participants reported no symptoms. Preventive measures, such as using face-coverings and observing social distancing, reduced risk for infection: among 382 service members, those who reported taking preventive measures had a lower infection rate than did those who did not report taking these measures (e.g., wearing a face-covering, 56% versus 81%; avoiding common areas, 54% versus 68%; and observing social distancing, 55% versus 70%, respectively).

Immunology

Wilk AJ, Rustagi A, Zhao NQ, et al. A single-cell atlas of the peripheral immune response in patients with severe COVID-19. Nat Med. 2020 Jun 8. PubMed: https://pubmed.gov/32514174. Full-text: https://doi.org/10.1038/s41591-020-0944-y

Using single-cell RNA sequencing, the authors profiled peripheral blood mononuclear cells from seven patients hospitalized for COVID-19 and six healthy controls. The cell atlas of the peripheral immune response to severe COVID-19 included a heterogeneous interferon-stimulated gene signature, HLA class II down-regulation and a developing neutrophil population that appeared closely related to plasmablasts appearing in patients with acute respiratory failure requiring mechanical ventilation. Of note, peripheral monocytes and lymphocytes did not express substantial amounts of pro-inflammatory cytokines.

Transmission

El-Boghdadly K, Wong DJN, Owen R, et al. Risks to healthcare workers following tracheal intubation of patients with COVID-19: a prospective international multicentre cohort study. Anaesthesia. 2020 Jun 9. PubMed: https://pubmed.gov/32516833 . Full-text: https://doi.org/10.1111/anae.15170

Around 1 in 10 HCW becomes infected: This prospective international multicentre cohort study recruited 1,718 healthcare workers participating in 5,148 tracheal intubation episodes of patients with suspected or confirmed COVID‐19 from 503 hospitals in 17 countries. The overall incidence of the primary endpoint (lab‐confirmed COVID‐19 diagnosis or new symptoms requiring self‐isolation or hospitalisation) was 10.7% over a median follow‐up of 32 days. The cumulative incidence within 7, 14 and 21 days of the first tracheal intubation episode was 3.6%, 6.1%, and 8.5%, respectively. The risk varied by country and was higher in females, but was not associated with other factors.

Diagnostics

Grifoni E, Valoriani A, Cei F. Interleukin-6 as prognosticator in patients with COVID-19. J Infection 2020, June 8. Full-text: https://doi.org/10.1016/j.jinf.2020.06.008

According to this study analysing 77 patients, IL-6 levels at hospital admission seem to be a good ”prognosticator” for the combined endpoint progression to severe disease and/or in-hospital mortality, and it seems to be the best prognosticator for negative outcome.

Clinical

Gervaise A, Bouzad C, Peroux E, Helissey C. Acute pulmonary embolism in non-hospitalized COVID-19 patients referred to CTPA by emergency department. Eur Radiol. 2020 Jun 9. PubMed: https://pubmed.gov/32518989 . Full-text: https://doi.org/10.1007/s00330-020-06977-5

Acute pulmonary embolism (APE) is not limited to severe or critical COVID-19. Five of 13 (38%) patients with APE in this small study had a moderate clinical COVID-19 type.

Lala A, Johnson KW, Januzzi JL, et al. Prevalence and Impact of Myocardial Injury in Patients Hospitalized with COVID-19 Infection. J Am Coll Cardiol. 2020 Jun 5:S0735-1097(20)35552-2. PubMed: https://pubmed.gov/32517963 . Full-text: https://doi.org/10.1016/j.jacc.2020.06.007

Myocardial injury is prevalent. Among 2,736 COVID-19 patients admitted to one of five Mount Sinai Health System hospitals in New York City who had troponin-I measured within 24 hours of admission, 985 (36%) patients had elevated troponin concentrations. After adjusting for disease severity and relevant clinical factors, even small amounts of myocardial injury (0.03-0.09 ng/mL) were significantly associated with death (adjusted HR: 1.75, 95% CI 1.37-2.24) while greater amounts (>0.09 ng/dL) were significantly associated with higher risk (adjusted HR 3.03, 95% CI 2.42-3.80).

Treatment

Williamson BN, Feldmann F, Schwarz B, et al. Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. Nature. 2020 Jun 9. PubMed: https://pubmed.gov/32516797 . Full-text: https://doi.org/10.1038/s41586-020-2423-5

In macaques, remdesivir works, if given early. Twelve rhesus macaques were inoculated with SARS-CoV-2. Twelve hours later, six animals received 10mg/kg intravenous remdesivir and the other six an equal volume of vehicle solution (2ml/kg). In contrast to vehicle-treated animals, animals treated with remdesivir did not show signs of respiratory disease and had reduced pulmonary infiltrates and reduced virus titers in bronchoalveolar lavages. Virus shedding from the upper respiratory tract was not reduced. At necropsy, lung viral loads of remdesivir-treated animals were lower and there was a reduction in damage to the lungs. According to the authors, treatment should be initiated as early as possible to achieve the maximum treatment effect. But is this realistic in clinical practice? We would need a new way of application, instead of the current infusions (i.e., tablets, inhalators).

La Rosée F, Bremer HC, Gehrke I, et al. The Janus kinase 1/2 inhibitor ruxolitinib in COVID-19 with severe systemic hyperinflammation. Leukemia. 2020 Jun 9. PubMed: https://pubmed.gov/32518419 . Full-text: https://doi.org/10.1038/s41375-020-0891-0

In this retrospective study, 12/14 patients treated with the JAK inhibitor ruxolitinib achieved significant reduction of the newly developed “COVID-19 Inflammation Score” by ≥ 25% on day 7 with sustained clinical improvement in 11/14 patients without short-term red-flag warnings of Rux-induced toxicity. Rux treatment for COVID-19 in patients with hyperinflammation was safe with some signals of efficacy to prevent or overcome multi-organ failure. A multi-center Phase II clinical trial has been initiated (NCT04338958).

Pregnancy

Knight M, Bunch K, Vousden N, et al. Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study. BMJ. 2020 Jun 8;369:m2107. PubMed: https://pubmed.gov/32513659 . Full-text: https://doi.org/10.1136/bmj.m2107

Outcome of 427 pregnant women admitted to hospital with confirmed SARS-CoV-2 infection between 1 March 2020 and 14 April 2020: Most (but not all) outcomes were good, and transmission of SARS-CoV-2 to infants was uncommon. Of note, there were 233 (56%) women from black or other ethnic minority groups, 281 (69%) were overweight or obese, 175 (41%) were aged 35 or over, and 145 (34%) had pre-existing comorbidities. 266 (62%) women gave birth or had a pregnancy loss; 196 (73%) gave birth at term. Forty one (10%) women admitted to hospital needed respiratory support, and five (1%) women died. Twelve (5%) of 265 infants tested positive for SARS-CoV-2 RNA, six of them within the first 12 hours after birth.

Martínez-Perez O, Vouga M, Cruz Melguizo S, et al. Association Between Mode of Delivery Among Pregnant Women With COVID-19 and Maternal and Neonatal Outcomes in Spain. JAMA. 2020 Jun 8. PubMed: https://pubmed.gov/32511673 . Full-text: https://doi.org/10.1001/jama.2020.10125

Of 82 pregnant patients, 4 presented with severe COVID-19 symptoms, including 1 with concomitant preeclampsia; all 4 underwent cesarean delivery and required ICU admission. Among patients with mild symptoms at presentation, all patients with a vaginal birth had excellent outcomes. In contrast, 13.5% of women undergoing cesarean delivery had severe maternal outcomes and 21.6% had clinical deterioration. Women undergoing cesarean delivery may have been at higher risk of adverse outcomes, but after adjusting for confounding factors, cesarean birth remained independently associated with an increased risk of clinical deterioration. The physiological stress induced by surgery is known to increase postpartum maternal complications