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By Christian Hoffmann &
Bernd S. Kamps
27 June
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Google Translate has an excellent reputation for accuracy, but it isn’t perfect and does make mistakes. So use it with caution. In particular, be careful in relying on Google Translate for any important matter (health, treatment, etc.). In case of doubt, ask your friends.
Epidemiology
Horton R. Offline: The second wave. Lancet 2020, June 27, 395, ISSUE 10242, P1960. Full-text: https://doi.org/10.1016/S0140-6736(20)31451-3
Not in a good mood today? Then don’t read this important comment on what will likely happen during the next months. The first wave of the 1918 influenza pandemic took place between March and July. It proved relatively mild. The second wave arrived in August. It was much worse. Most of the 50–100 million deaths caused by influenza took place during 13 weeks between September and December, 1918. In many countries, the test, trace, and isolate system is still not fully functional and we have angry debates about whether physical distancing should be 1 m or 2 m. Scientists predict that a second wave will arrive in September, peaking by the end of 2020. Just sayin’.
Transmission
Ortega R, Gonzalez M, Nozari A, et al. Personal Protective Equipment and Covid-19. N Engl J Med 2020; June 25. Full-text: https://doi.org/10.1056/NEJMvcm2014809
Helpful video, demonstrating the complex procedure for putting on and removing PPE that has been recommended by the CDC to minimize the risk of exposure to infectious material during the care of patients with COVID-19.
Prather KA, Wang CC, Schooley RT. Reducing transmission of SARS-CoV-2. Science 26 Jun 2020: Vol. 368, Issue 6498, pp. 1422-1424. Full-text: https://doi.org/10.1126/science.abc6197
Aerosol transmission of viruses must be acknowledged as a key factor leading to the spread of infectious respiratory diseases. This viewpoint summarizes current research that is already leading to a better understanding of the importance of airborne transmission.
Diagnostics
Mak GC, Cheng PK, Lau SS, et al. Evaluation of rapid antigen test for detection of SARS-CoV-2 virus. J Clin Virol. 2020 Jun 8;129:104500. PubMed: https://pubmed.gov/32585619 . Full-text: https://doi.org/10.1016/j.jcv.2020.104500
Bad performance of the commercially available rapid BIOCREDIT COVID-19 antigen test. This test was 10,000 fold less sensitive than RT-PCR and detected between 11.1 % and 45.7 % of RT-PCR-positive samples from COVID-19 patients. It serves only as adjunct to RT-PCR test because of the potential for false-negative results.
Ben-Ami R, Klochendler A, Seidel M, et al. Large-scale implementation of pooled RNA extraction and RT-PCR for SARS-CoV-2 detection. Clin Microbiol Infect. 2020 Jun 22:S1198-743X(20)30349-9. PubMed: https://pubmed.gov/32585353 . Full-text: https://doi.org/10.1016/j.cmi.2020.06.009
Due to the overwhelming use of SARS-CoV-2 RT-PCR tests worldwide, availability of test kits has become a major bottleneck. The authors show how to overcome these challenges by pooling samples, performing RNA extraction and RT-PCR in pools. A comparison of 184 samples tested individually and in pools of 8 samples, showed that test results were not significantly affected.
Amanat F, White KM, Miorin L, et al. An In Vitro Microneutralization Assay for SARS-CoV-2 Serology and Drug Screening. Curr Protoc Microbiol. 2020 Sep;58(1):e108. PubMed: https://pubmed.gov/32585083 . Full-text: https://doi.org/10.1002/cpmc.108
A new microneutralization assay is described in detail. This assay can be used to assess in a quantitative manner if antibodies or drugs can block entry and/or replication of SARS‐CoV‐2 in vitro. Compared to the most common neutralization assay, the plaque reduction neutralization test (PRNT), more samples can be analyzed. Compared to RBD‐ACE2 inhibition assays, the test will also detect neutralizing antibodies binding to epitopes outside of the RBD. Different virus isolates can be used, and the assay can likely be adapted for staining antibodies other than mAbs (e.g., polyclonal sera, antibodies targeting S or M, etc.).
Deeks JJ, Dinnes J, Takwoingi Y, et al. Antibody tests for identification of current and past infection with SARS-CoV-2. Cochrane Database Syst Rev. 2020 Jun 25;6:CD013652. PubMed: https://pubmed.gov/32584464 . Full-text: https://doi.org/10.1002/14651858.CD013652
This Cochrane analysis on 57 publications with 15,976 samples says that the sensitivity of antibody tests is too low in the first week from symptom onset to have a primary role in the diagnosis of COVID‐19. However, these tests may still have a role complementing other testing in individuals presenting later, when RT‐PCR tests are negative, or are not done. Antibody tests are likely to have a useful role for detecting previous SARS‐CoV‐2 infection if used 15 or more days after the onset of symptoms. Data beyond 35 days post‐symptom onset is scarce. According to the authors, studies of the accuracy of COVID‐19 tests require considerable improvement. Studies must report data on sensitivity disaggregated by time from onset of symptoms. Updates of this living systematic review are planned.
Clinical
Lockhart SM, O’Rahilly S. When two pandemics meet: Why is obesity associated with increased COVID-19 mortality? Med 2020,June 25. Full-text: https://www.cell.com/med/fulltext/S2666-6340(20)30010-6
What a nice understatement. The authors describe “some hypotheses regarding the deleterious impact of obesity on the course of COVID-19”. This brilliant overview summarizes current knowledge on the underlying mechanisms. These are: 1. Increased inflammatory cytokines (potentiate the inflammatory response), 2. reduction in adiponectin secretion (abundant in the pulmonary endothelium), 3. increases in circulating complement components, 4. systemic insulin resistance (associated with endothelial dysfunction and with increased plasminogen activator inhibitor-1), and 5. ectopic lipid deposited in type 2 pneumocytes (pre-disposing to lung injury).
Comorbidities
Louapre C, Collongues N, Stankoff B, et al. Clinical Characteristics and Outcomes in Patients With Coronavirus Disease 2019 and Multiple Sclerosis. JAMA Neurol 2020, June 26. Full-text: https://doi.org/10.1001/jamaneurol.2020.2581
This registry-based cohort study from France has included 347 patients with MS with a confirmed or highly suspected diagnosis of COVID-19. In total, 73 patients (21.0%) had a COVID-19 severity score of 3 or more, and 12 patients (3.5%) died. Age, Expanded Disability Severity Scale score (EDSS; ranging from 0 to 10, with cutoffs at 3 and 6), and obesity were independent risk factors for severe COVID-19; there was no association found between exposure to disease-modifying therapies and severity.
Treatment
Li S, Hu Z, Song X. High-dose but not low-dose corticosteroids potentially delay viral shedding of patients with COVID-19. Clinical Infectious Diseases 2020, June 26. Full-text: https://doi.org/10.1093/cid/ciaa829
This study with 206 patients suggests that the effect of corticosteroids on viral shedding may be in a dose-response manner. High-dose (80 mg/d) but not low-dose corticosteroids (40 mg/d) delayed viral shedding of patients with COVID-19.