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By Christian Hoffmann &
Bernd S. Kamps

11 July

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Epidemiology

Torres JP, Piñera C, De La Maza V, et al. SARS-CoV-2 antibody prevalence in blood in a large school community subject to a Covid-19 outbreak: a cross-sectional study. Clin Infect Dis. 2020 Jul 10:ciaa955. PubMed: https://pubmed.gov/32649743. Full-text: https://doi.org/10.1093/cid/ciaa955

In this school-based outbreak in Santiago, Chile identified on March 12, affecting nearly 50 people among school and household members, antibody positivity rates based on a self-administered test were 9.9% for 1,009 students and 16.6% for 235 staff. Among students, positivity was associated with younger age (p = 0.01), lower grade level (p = 0.05), prior RT-PCR positivity (p = 0.03), and history of contact with a confirmed case (p < 0.001). Among staff, positivity was higher in teachers (p = 0.01) and in those previously RT-PCR positive (p < 0.001). Teachers were more affected during the outbreak and younger children were at higher infection risk, likely because index case(s) were teachers and/or parents from preschool. Reopening schools should focus on avoiding new cases among teachers.

 

Virology

Wong YC, Lau SY, Wang KK, et al. Natural transmission of bat-like SARS-CoV-2ΔPRRA variants in COVID-19 patients. Clin Infect Dis July 10, 2020. Full-text: https://doi.org/10.1093/cid/ciaa953

SARS-CoV-2 contains the furin cleavage PRRA motif in the S1/S2 region, which enhances viral pathogenicity but is absent in closely related bat and pangolin coronaviruses. It remains unknown if bat-like coronaviral variants without PRRA (ΔPRRA) can establish natural infection in humans. In this study, these variants were readily detected among acute patients, including a family cluster showing that these variants exist naturally and are currently transmitting in COVID-19 patients. Although these variants only consisted of a very small fraction in the wild type viral challenge stock, they were also consistently detected in intranasally inoculated hamsters.

 

Immunology

Lee JS, Park S, Jeong W, et al. Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19.  Science Immunology 10 Jul 2020: Vol. 5, Issue 49. Full-text: https://doi.org/10.1126/sciimmunol.abd1554

Delayed IFN-I response contributes to pathological inflammation whereas early IFN-I response controls viral replication. The authors performed single-cell RNA-seq using tens of thousands of peripheral blood mononuclear cells (PBMCs) obtained from 4 healthy donors, 8 patients with mild or severe COVID-19, and 5 patients with severe influenza. Patients with COVID-19 exhibited hyper-inflammatory signatures across all types of cells among PBMCs, particularly up-regulation of the TNF/IL-1β-driven inflammatory response as compared to severe influenza. The IFN-I response might contribute to the hyper-inflammatory response by potentiating TNF/IL-1β-driven inflammation in severe progression of COVID-19.

 

Transmission

Dorfman D, Raz M. Mask Exemptions During the COVID-19 Pandemic—A New Frontier for Clinicians. JAMA Health Forum July 10, 2020. Full-text: https://jamanetwork.com/channels/health-forum/fullarticle/2768376

While masking remains contentious, there is bipartisan agreement among policy makers that medical exemptions for masking are necessary and appropriate. Yet there is a dearth of guidance for clinicians on how to approach a request for an exemption. The authors analyze the medical and legal standards to guide this debate. In this evidence-free zone, clinicians must make individual determinations as to whether a patient should be exempt from mask wearing. There is no obligation to provide a mask exemption to patients if it is not medically warranted.

 

Clinical

Carfi A, Bernabei R, Landi F. Persistent Symptoms in Patients After Acute COVID-19. JAMA July 9, 2020. Full-text: https://doi.org/10.1001/jama.2020.12603

Long time to recover: 143 patients discharged from the hospital after recovery from COVID-19 were assessed for follow-up post–acute care after a mean of 60 days after onset of the first COVID-19 symptom. Only 18 (12.6%) were completely free of any COVID-19 related symptom, while 32% had 1 or 2 symptoms and 55% had 3 or more. None of the patients had fever or any signs or symptoms of acute illness. Worsened quality of life was observed among 44.1% of patients. Many patients still reported fatigue (53%), dyspnea (43%), joint pain (27%) and chest pain (28%).

 

Severe COVID

Liao D, Zhou F, Luo L, et al. Haematological characteristics and risk factors in the classification and prognosis evaluation of COVID-19: a retrospective cohort study. Lancet Hematology July 10, 2020. Full-text: https://doi.org/10.1016/S2352-3026(20)30217-9

This retrospective cohort study focussed on hematological and coagulation parameters in patients with moderate, severe, and critical COVID-19, along with specific analyses of coagulopathy in non-survivors. Among 380 patients, thrombocytopenia was more frequent in patients with critical disease (49%) than in those with severe (14%) or moderate (6%). In multivariate analyses, death was associated with increased neutrophil to lymphocyte ratio (odds ratio 5.39), thrombocytopenia (OR 8.33), prolonged prothrombin time (OR 4.94), and increased D-dimer (OR 4.41). The onset of sepsis-induced coagulopathy was typically before overt disseminated intravascular coagulation.

 

Kander T. Coagulation disorder in COVID-19. Lancet Hematology July 10, 2020. Full-text: https://doi.org/10.1016/S2352-3026(20)30218-0

Careful comment on these findings. According to the author, the study is a valuable contribution to the knowledge of the coagulation profile of patients with COVID-19 and highlights the established role of routine coagulation tests as predictive variables for mortality and morbidity. However, the question of whether the observed changes in routine coagulation tests are just markers of the severity of illness or whether they show a significant and specific pathophysiology that drives morbidity and mortality in itself is still unanswered.

 

Moezinia CH, Ji-Xu A, Azari A, et al. Iloprost for COVID-19-related vasculopathy. Lancet Rheumatology July 10, 2020. Full-text: https://doi.org/10.1016/S2665-9913(20)30232-0

Interesting new finding: iloprost as a therapy to mitigate the pathological effects of COVID-19. Iloprost is a prostacyclin receptor agonist that promotes vasodilation of circulatory beds with minimal impact on hemodynamic parameters. It is licensed for the treatment of pulmonary arterial hypertension and is widely used for the management of peripheral vascular disease and digital vasculopathy, including digital ulcers and critical digital ischemia in systemic sclerosis. The authors describe three morbidly obese patients with severe COVID-19 and systemic microvasculopathy who obviously benefitted from its use. Its potential ability to reduce endothelial dysfunction and systemic inflammation could make iloprost a key player in management of COVID-19 vasculopathy.

 

Comorbidities

Ikematsu H, Hayden FG, Kawaguchi K, et al. Baloxavir Marboxil for Prophylaxis against Influenza in Household Contacts. NEJM July 8, 2020. Full-text: https://doi.org/10.1056/NEJMoa1915341

How will we deal with influenza next winter? Baloxavir marboxil (baloxavir) is a prodrug of the cap-dependent endonuclease inhibitor baloxavir acid and was approved as a single-dose treatment for uncomplicated influenza A and B in Japan and in the US in 2018. Among 752 household contacts of 545 index patients (96% influenza A) virus infection, the percentage in whom clinical influenza developed was significantly lower in the baloxavir group than in the placebo group (1.9% vs. 13.6%).

 

Uyeki TM. Baloxavir for Postexposure Prophylaxis against Influenza in Households. NEJM July 8, 2020. Full-text: https://doi.org/10.1056/NEJMe2022702

This editorial discusses some caveats of the above trial, including resistance issues. Moreover, 73% of the household contacts received baloxavir or placebo rapidly – within 24 hours after the onset of illness. Last but not least, clinicians are reminded that the primary prevention of influenza is through annual influenza vaccination. We have to be prepared next winter.