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By Christian Hoffmann &
Bernd S. Kamps
Voice: Google Cloud Text-to-Speech: US
First, acknowledge that health care workers on the frontline are facing a substantial risk of infection during the COVID-19 outbreak. Discover that among 2,457 SARS-CoV-2-infected health care workers in Wuhan, China, more than half were nurses, while 33% were doctors. Importantly, most infected cases among health care workers were female: 72%. It is essential to improve protective measures for HCWs. Ensuring an adequate supply of PPE is just the first step. Other measures should be considered, including a nutritious food supply, adequate rest time, and societal, familial, and psychological support.
Afterwards, discuss with your colleagues a comprehensive overview about current knowledge (and knowledge gaps) about treatment of patients who develop severe disease; grant an FDA emergency use authorization for a clustered regularly interspaced short palindromic repeats (CRISPR)-based SARS-CoV-2 fluorescent assay; and use data from Germany to build a model that detects change points in the effective epidemic growth rate that correlate with the times of publicly announced interventions (including kind regards to Boris et al.).
Finally, evaluate anakinra in 29 patients with moderate-to-severe ARDS and hyperinflammation (serum C-reactive protein, CRP ≥100 mg/L) and in 8 patients with secondary hemophagocytic lymphohistocytosis (sHLH) characterized by pancytopenia, hypercoagulation, acute kidney injury and hepatobiliary dysfunction; discover that pulmonary arterial thrombosis in COVID-19 may occur despite the use of prophylactic anticoagulation; read a well-balanced editorial on the same subject; and read four critical letters about the remdesivir compassionate use program.
Dehning K, Zierenberg , Spitzner FP. Inferring change points in the spread of COVID-19 reveals the effectiveness of interventions. Science 15 May 2020. Full-text: https://doi.org/10.1126/science.abb9789
Focusing on the COVID-19 spread in Germany, these elegant models detected three change points in the effective growth rate that correlated well with interventions. First, the spreading rate decreased from 0.43 to 0.25, the decrease initiating around March 7 (cancellation of large public events, such as trade fairs and soccer matches). Second, the rate decreased further to 0.15 (around March 16, closure of schools, childcare facilities, non-essential stores). Third, the spreading rate decreased further to 0.09 (initiated around March 24, strict contact ban). While the first two change points were not sufficient to trigger a shift from the growth of novel cases to a decline, the third brought this crucial reversal. This model can be used for future scenarios – the code is freely available and can be readily adapted to any country. The paper also highlights the impact of time: delaying restrictions by only 5 days may have an incredible impact on case numbers. Sleep well, Boris, Jair, Mark etc.
Zheng L, Wang X, Zhou C, et al. Analysis of the infection status of the health care workers in Wuhan during the COVID-19 outbreak: A cross-sectional study. Clinical Infectious Diseases 2020, May 15. Full-text: https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa588/5837357
By now, the most comprehensive data on infections among HCW. Among 2,457 infected HCW in Wuhan, China, 52% were nurses, 34% were doctors and 14% were medical staff. Case infection rate of nurses (2.22%) was higher than that of doctors (1.92%). The majority (89%) came from general hospitals. The case infection rate of HCW (2.10%) was dramatically higher than that of non-HCW (0.43%). The case fatality rate of was significantly lower (0.69% versus 5.30%).
Joung J, Ladha A, Saito M, et al. Point-of-care testing for COVID-19 using SHERLOCK diagnostics. Full-text: https://doi.org/10.1101/2020.05.04.20091231.
Point-of-care testing is based on easy-to-use devices to facilitate testing outside laboratory settings. They are eagerly awaited. On May 6, the FDA granted an emergency use authorization for a clustered regularly interspaced short palindromic repeats (CRISPR)-based SARS-CoV-2 fluorescent assay marketed by Sherlock Biosciences. This method gives results in an hour and has successfully diagnosed 12 positive and 5 negative COVID-19 patients, with at least 2 of 3 replicates scoring positive in infected persons. However, use still remains limited to laboratories certified to perform high-complexity tests. On May 6, FDA also authorized Quidel’s Sofia 2 SARS Antigen Fluorescent Immunoassay. The test must be read on a dedicated analyser and detects SARS-CoV-2 nucleocapsid protein from nasopharyngeal swabs in 15 min. According to the manufacturer, the assay demonstrated acceptable clinical sensitivity and detected 47/59 infections (80%). Unfortunately, no peer-reviewed papers have been published to date.
Mackey K, King VJ, Gurley S. Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults. A Living Systematic Review. Annals Internal Medicine 2020, May 15. Full-text: https://www.acpjournals.org/doi/10.7326/M20-1515
According to this review (data cut on May 4), evidence is of moderate certainty that ACEI and ARB use is not associated with a higher likelihood of receiving a positive SARS-CoV-2 test result. Evidence is of high certainty (14 observational studies, involving 23,565 adults) that neither medication is associated with more severe COVID-19 illness. Four registered randomized trials plan to evaluate ACEIs and ARBs for treatment of COVID-19. For more information, see our special from May 4: https://covidreference.com/top-10-may-4.
Berlin DA, Gulick RM, Martinez FJ. Severe Covid-19. May 15, 2020. Full-text: https://www.nejm.org/doi/full/10.1056/NEJMcp2009575
Comprehensive overview about current knowledge (and knowledge gaps) about treatment of patients who develop severe disease. Basics of respiratory care, ventilation management and supportive care. Areas of uncertainties are also discussed.
Lax SF, Skok K, Zechner P. Pulmonary Arterial Thrombosis in COVID-19 With Fatal Outcome: Results From a Prospective, Single-Center, Clinicopathologic Case Series. Annals Int Med 2020, May 14. Full-text: https://www.acpjournals.org/doi/10.7326/M20-2566
The next autopsy study on 11 deceased patients with COVID-19 (10 selected randomly). Death may be caused by the thrombosis observed in segmental and subsegmental pulmonary arterial vessels despite the use of prophylactic anticoagulation.
Deshpande C. Thromboembolic Findings in COVID-19 Autopsies: Pulmonary Thrombosis or Embolism? Annals Int Med 2020, May 15. Full-text: https://doi.org/10.7326/M20-3255.
Well-balanced editorial, condensing current knowledge on the contributions of pulmonary thrombosis, embolism, or their combination to deaths of patients with COVID-19. Some studies have found pulmonary embolism with or without deep venous thrombosis, as well as presence of recent thrombi in prostatic venous plexus, in patients with no history of VTE, suggesting de novo coagulopathy in these patients with COVID-19. Others have highlighted changes consistent with thrombosis occurring within the pulmonary arterial circulation, in the absence of apparent embolism.
Grein J, Ohmagari N, Shin D, et al. Compassionate Use of Remdesivir for Patients with Severe Covid-19. N Engl J Med. 2020 Apr 10. PubMed: https://pubmed.gov/32275812 . To the editor: https://www.nejm.org/doi/10.1056/NEJMc2015312#sa1
Four letters, making critical comments on the NEJM paper about the remdesivir compassionate use program. We have discussed many of these issues on April 16, see here: https://covidreference.com/remdesivir
Cavalli G, De Luca G, Campochiaro C, et al. Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyper-inflammation: a retrospective cohort study. Lancet Rheumatol 2020. Full-text: https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(20)30127-2/fulltext
This retrospective cohort study at the San Raffaele Hospital in Milan, Italy, included patients with moderate-to-severe ARDS and hyperinflammation (serum C-reactive protein, CRP ≥100 mg/L) who were managed with non-invasive ventilation and HCQ and lopinavir/r. At 21 days, treatment with high-dose anakinra was associated with reductions in CRP and progressive improvements in respiratory function in 21/29 (72%) patients.
Dimopoulos G, de Mast Q, Markou N, et al. Favorable anakinra responses in severe COVID-19 patients with secondary hemophagocytic lymphohistiocytosis. Cell Host and Microbe 2020, May 14. Full-text: https://doi.org/10.1016/j.chom.2020.05.007
Another small case series of critically ill patients with secondary hemophagocytic lymphohistocytosis (sHLH) characterized by pancytopenia, hypercoagulation, acute kidney injury and hepatobiliary dysfunction. At the end of treatment, ICU patients had less need for vasopressors and significantly improved respiratory function. Although 3/8 patients died, the mortality was lower than historical series of patients with sHLH in sepsis.