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By Christian Hoffmann &
Bernd S. Kamps
Lordan R, FitzGerald GA, Grosser T. Reopening schools during COVID-19. Science 04 Sep 2020: Vol. 369, Issue 6508, pp. 1146. Full-text: https://doi.org/10.1126/science.abe5765
A note from daily practice. On Thursday, September 3, at our infectious disease clinic in Hamburg, Germany, we found a young male teacher (under 40 years old) to be PCR positive. For the previous three days, he had given lectures to at least 12 classes, despite having (mild) symptoms. How to avoid, how to deal with this situation? This editorial gives some answers, recommending different mitigation strategies for the re-opening of schools.
The national COVID-19 outbreak monitoring group. COVID-19 outbreaks in a transmission control scenario: challenges posed by social and leisure activities, and for workers in vulnerable conditions, Spain, early summer 2020. Eurosurveillance Volume 25, Issue 35, 03/Sep/2020. Full-text: https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.35.2001545
From mid-June to 2 August, excluding single household outbreaks, 673 outbreaks were notified in Spain. There were two main settings where over 55% of active outbreaks (303/551) and over 60% (3,815/6,208) of active outbreak cases originated: First, social settings such as family gatherings or private parties (112 outbreaks, 854 cases), followed by those linked to leisure venues such as bars, restaurants, or clubs (34 outbreaks, over 1,230 cases). Second, occupational settings (representing 20% of all active outbreaks), mainly among workers in the fruit and vegetable sector (31 outbreaks and around 500 cases) and workers at slaughterhouses or meat processing plants (12 outbreaks and around 360 cases).
Chen X, Pan Z, Yue S, et al. Disease severity dictates SARS-CoV-2-specific neutralizing antibody responses in COVID-19. Sig Transduct Target Ther 5, 180 (2020). Full-text: https://doi.org/10.1038/s41392-020-00301-9
High neutralizing antibody (NAb) capacity in severe cases, no NAbs in asymptomatic patients: In a cohort of 59 recovered patients with various disease severity, Xiangyu Chen and colleagues observed a positive correlation between serum neutralizing capacity and disease severity, revealing the tremendous heterogeneity of SARS-CoV-2-specific NAb responses. Their findings also suggest that the collection of plasma from COVID-19 recovered patients should be restricted to those with moderate to severe symptoms for passive antibody therapy.
Singh M, Bansal V, Feschotte C, et al. A single-cell RNA expression map of human coronavirus entry factors. Cell Reports. September 03, 2020. Full-text: https://doi.org/10.1016/j.celrep.2020.108175
Using single-cell transcriptomics across various healthy human tissues, Manvendra Singh and colleagues have profiled 28 SARS-CoV-2 and coronavirus-associated receptors and factors (SCARFs) that facilitate and/or restrict viral entry. Both pro- and anti-viral factors are highly expressed within the nasal epithelium, with potential age-dependent variation. The data provide a valuable resource for future studies of the basic biology and pathology of SARS-CoV-2 and other coronaviruses. However, the authors urge caution not to overinterpret their findings. The main problem is that SCARF expression within and between individuals is bound to be heavily modulated by genetic and environmental factors, including infection by SARS-CoV-2 and other pathogens.
DeKosky BJ. A molecular trap against COVID-19. Science 04 Sep 2020: Vol. 369, Issue 6508, pp. 1167-1168. Full-text: https://doi.org/10.1126/science.abe0010
The cell surface peptidase angiotensin-converting enzyme 2 (ACE2) is the primary receptor for the spike (S) fusion protein that facilitates cell entry of SARS-CoV-2. This vasopeptidase is expressed on the surface of epithelial cells in many tissues, including the lung, heart, blood vessels, kidneys, and gastrointestinal tract. Brandon J. DeKosky from the University of Kansas gives a great overview on ACE2-mediated viral entry, the growing understanding of ACE2 interaction and potential methods of blocking it.
Lee W, Ahn JH, Park HH et al. COVID-19-activated SREBP2 disturbs cholesterol biosynthesis and leads to cytokine storm. Sig Transduct Target Ther September 3, 2020, 5, 186. Full-text: https://doi.org/10.1038/s41392-020-00292-7
Sterol regulatory element binding proteins (SREBPs) regulate the gene expressions involved in lipid cholesterol biosynthesis. During recent years, it has become increasing clear that SREBPs are involved in immunity/inflammation and several studies have demonstrated the critical importance of SREBP pathway in preventing overproduction of proinflammatory cytokines from macrophages. Wonhwa Lee and colleagues describe here how SREBP-2 is activated by SARS-CoV-2 and show that SREBP-2 can serve as an indicator for severity diagnosis and therapeutic target for preventing a cytokine storm and lung damage in severe COVID-19 patients.
Shen Y, Li C, Dong H. Community Outbreak Investigation of SARS-CoV-2 Transmission Among Bus Riders in Eastern China. JAMA Intern Med, September 1, 2020. Full-text: https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2770172
If you take the bus, choose seats near a window (and open it). On January 19, 2020, 68 individuals (including the source patient) took a bus on a 100-minute round trip to attend a worship event. In total, 24 (35%) received a diagnosis of COVID-19 after the event. The authors were able to identify seats for each passenger and divided bus seats into high-risk and low-risk zones. Passengers in the high-risk zones had moderately but non-significantly higher risk of getting COVID-19 than those in the low-risk zones. On the 3-seat side of the bus, except for the passenger sitting next to the index patient, none of the passengers sitting in seats close to the bus window developed infection. In addition, the driver and passengers sitting close to the bus door also did not develop infection, and only 1 passenger sitting by an operable window developed infection. The absence of a significantly increased risk in the part of the bus closer to the index case suggested that airborne spread of the virus may at least partially explain the markedly high attack rate observed.
Borczuk AC, Salvatore SP, Seshan SV et al. COVID-19 pulmonary pathology: a multi-institutional autopsy cohort from Italy and New York City. Mod Pathol, September 2, 2020. https://doi.org/10.1038/s41379-020-00661-1
In order to systematically evaluate a large number of lung autopsy specimens from multiple institutions, a detailed examination was performed in a series of 68 cases of COVID-19 positive patients, autopsied in New York City and Italy. A consistent pattern of tracheobronchitis, alveolar injury, and vascular/thrombotic disease was found in patients with frequent co-morbidities such as hypertension and diabetes. Correlation of immunohistochemistry and RNA in situ findings and duration of disease was performed in 23 cases. Interestingly, the majority of lung autopsies had evidence of viral infection in the lung during the first two weeks of disease but not beyond this period.
Sax P. An ID Doctor’s Confrontation with His Own Case of COVID-19 – An Interview with Dr. Michael Saag. Open Forum Infectious Diseases 04 September 2020, Volume 7, Issue 9, 1 September 2020. Full-text: https://doi.org/10.1093/ofid/ofaa395
Read how Michael Saag, a well-known HIV researcher from the University of Alabama, Birmingham, was confronted with his own infection, after picking up the virus from his son. Read about his thoughts on the evening of the sixth day, when the cytokine storm started. And how he spent the following 8 days and nights, watching his pulse race like a hawk and knowing that in the next 15 minutes, it might drop below 90 and he would end up in the hospital. Also available as a podcast.
Mato AR, Roeker LE, Lamanna N, et al. Outcomes of COVID-19 in patients with CLL: a multicenter international experience. Blood September 3, 2020, 136 (10): 1134–1143. Full-text: https://ashpublications.org/blood/article/136/10/1134/461426/Outcomes-of-COVID-19-in-patients-with-CLL-a
Among 198 CLL patients diagnosed with symptomatic COVID-19 across 43 international centers, the overall case fatality rate was 33%, although 25% remain admitted. Watch-and-wait and treated subgroups had similar rates of admission, ICU admission, intubation and mortality. Of note, CLL-directed treatment with Bruton tyrosine kinase inhibitors (BTKis, have been proposed as a potential treatment for COVID-19) at COVID-19 diagnosis did not impact survival, though BTKis were held during the COVID-19 course for most patients.