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By Christian Hoffmann &
Bernd S. Kamps
23 June
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Immunology
Yang D, Chu H, Hou Y, et al. Attenuated interferon and pro-inflammatory response in SARS-CoV-2-infected human dendritic cells is associated with viral antagonism of STAT1 phosphorylation. J Infect Dis. 2020 Jun 21:jiaa356. PubMed: https://pubmed.gov/32563187. Full-text: https://doi.org/10.1093/infdis/jiaa356
Some novel insights into pathogenesis: Dendritic cells (DCs) and macrophages are sentinel cells for innate and adaptive immunity. The authors demonstrate that these cells were permissive to SARS-CoV-2 infection but did not support productive virus replication. SARS-CoV-2 launched an attenuated interferon response in both cell types and an attenuated immune response in DCs. The latter was associated with viral antagonism of STAT1 phosphorylation (STAT1 plays a critical role in the innate immune response in the clearance of SARS-CoV).
Diagnostics
Jääskeläinen AJ, Kuivanen S, Kekäläinen E, et al. Performance of six SARS-CoV-2 immunoassays in comparison with microneutralisation. J Clin Virol. 2020 Jun 15;129:104512. PubMed: https://pubmed.gov/32563180. Full-text: https://doi.org/10.1016/j.jcv.2020.104512
“Variable” performance means that some performed badly: Among 62 COVID-19 patients with neutralising antibodies, the specificity and sensitivity values of the commercial antibody tests were as follows: 95%/81% (Abbott Architect), 95%/44% (Diasorin Liaison), 68%/88% (Euroimmun IgA), 87%/71% (Euroimmun IgG), 74%/56% (Acro IgG), 70%/46% (Acro 2019 IgM), 98%/72% (Xiamen IgG), and 89%/81% (Xiamen IgM). The variable performance highlights the need for laboratories to carefully consider their testing process in order to optimize the overall performance of SARS-CoV-2 serodiagnostics.
Atum M, Boz AAE, Çakır B, et al. Evaluation of Conjunctival Swab PCR Results in Patients with SARS-CoV-2 Infection. Ocul Immunol Inflamm. 2020 Jun 22:1-4. PubMed: https://pubmed.gov/32569495. Full-text: https://doi.org/10.1080/09273948.2020.1775261
Don’t use conjunctival swabs, even in patients with conjunctivitis. Among 40 patients (10 with conjunctivitis) who tested positive by RT-PCR of nasopharyngeal and oropharyngeal swabs, conjunctival swab rRT‐PCR was positive for 3 patients (one with conjunctivitis).
Clinical
Kronbichler A, Kresse D, Yoon S, Lee KH, Effenberger M, Shin JI. Asymptomatic patients as a source of COVID-19 infections: A systematic review and meta-analysis. Int J Infect Dis. 2020 Jun 17:S1201-9712(20)30487-2. PubMed: https://pubmed.gov/32562846. Full-text: https://doi.org/10.1016/j.ijid.2020.06.052
In total, 506 patients from 34 studies (68 single cases and 438 from case series) with an asymptomatic course were identified. Main findings: Asymptomatic patients tend to be younger and may be more socially active. Laboratory findings in most asymptomatic cases were unremarkable. However, 62% had lung opacities, most frequently ground glass opacities.
Lee YH, Hong CM, Kim DH, Lee TH, Lee J. Clinical Course of Asymptomatic and Mildly Symptomatic Patients with Coronavirus Disease Admitted to Community Treatment Centers, South Korea. Emerg Infect Dis. 2020 Jun 22;26(10). PubMed: https://pubmed.gov/32568662. Full-text: https://doi.org/10.3201/eid2610.201620
Of 632 asymptomatic and mildly symptomatic patients admitted to community treatment centers for isolation in South Korea, 75 (12%) had symptoms at admission, 186 (29%) were asymptomatic at admission but developed symptoms during their stay, and 371 (59%) remained asymptomatic during their entire clinical course. The mean virologic remission period was 20.1 days (SD + 7.7 days). The virologic remission period was longer in symptomatic patients than in asymptomatic patients. In mildly symptomatic patients, the mean duration from symptom onset to virologic remission was 11.7 days (SD + 8.2 days).
Comorbidities
Lange SJ, Ritchey MD, Goodman AB, et al. Potential Indirect Effects of the COVID-19 Pandemic on Use of Emergency Departments for Acute Life-Threatening Conditions — United States, January–May 2020. MMWR Morb Mortal Wkly Rep. ePub: 22 June 2020. Full-text: https://www.cdc.gov/mmwr/volumes/69/wr/mm6925e2.htm
National syndromic surveillance data has found that emergency department (ED) visits declined 42% during the early months of the pandemic. This report describes trends in ED visits for three acute life-threatening health conditions, immediately before and after declaration of the COVID-19 pandemic as a national emergency: in the 10 weeks following the declaration, ED visits declined 23% for heart attack, 20% for stroke, and 10% for hyperglycemic crisis. The substantial reduction might be explained by many pandemic-related factors including fear of exposure to COVID-19, unintended consequences of public health recommendations to minimize non-urgent health care, stay-at-home orders, or other reasons.
Severe COVID-19
Pfeifer M, Ewig S, Voshaar T, et al. Position Paper for the State-of-the-Art Application of Respiratory Support in Patients with COVID-19. Respiration. 2020 Jun 19:1-21. PubMed: https://pubmed.gov/32564028. Full-text: https://doi.org/10.1159/000509104
Important statements including observations about the pathophysiology of acute respiratory failure (ARF). Pulmonary damage in advanced COVID-19 often differs from acute respiratory distress syndrome (ARDS). Two types (type L and type H) are differentiated, corresponding to early- and late-stage lung damage. This differentiation should be taken into consideration in respiratory support. Based on current knowledge, inhalation therapy, nasal high-flow therapy (NHF), continuous positive airway pressure (CPAP), or non-invasive ventilation (NIV) can be performed without an increased risk of infection to staff if PPE is provided. In ARF, NIV should be carried out in an intensive care unit or a comparable setting by experienced staff. If the ARF progresses under CPAP/NIV, intubation should be implemented without delay in patients who do not have a “do not intubate”.
Treatment
Chi X, Yan R, Zhang J, et al. A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2. Science 22 Jun 2020. Full-text: https://doi.org/10.1126/science.abc6952
The authors isolated and characterized monoclonal antibodies (mAbs) from ten convalescent COVID-19 patients, among them the most interesting mAb, named 4A8. Of note, 4A8 exhibited high neutralization potency but did not bind the RBD (like most other mABs). Cryo-EM revealed that the epitope of 4A8 seems to be the N terminal domain (NTD) of the S protein.
Contini C, Enrica Gallenga C, Neri G, Maritati M, Conti P. A new pharmacological approach based on remdesivir aerosolized administration on SARS-CoV-2 pulmonary inflammation: A possible and rational therapeutic application. Med Hypotheses. 2020 May 24;144:109876. PubMed: https://pubmed.gov/32562915. Full-text: https://doi.org/10.1016/j.mehy.2020.109876
Some ideas on remdesivir as an inhalation therapy. Local instillation or aerosol in the first phase of infection, both in asymptomatic but nasopharyngeal swab positive patients, together with antiseptic-antiviral oral gargles and povidone-iodine eye drops for conjunctiva would attack the virus directly through the receptors to which it binds, significantly decreasing viral replication and risk of severe COVID-19. Gilead is working on this (knowing that “early intravenous infusions” are not feasible).
Rojas-Marte GR, Khalid M, Mukhtar O, et al. Outcomes in Patients with Severe COVID-19 Disease Treated with Tocilizumab – A Case- Controlled Study. QJM. 2020 Jun 22:hcaa206. PubMed: https://pubmed.gov/32569363. Full-text: https://doi.org/10.1093/qjmed/hcaa206
Large retrospective, case-control, single-center study in patients with severe to critical COVID-19 disease. In total, 96 patients received tocilizumab, while 97 served as control group. There was a non-statistically significant lower mortality in the treatment group (52% versus 62%). When excluding intubated patients, there was statistically significant lower mortality in patients treated with tocilizumab (6% vs. 27%, p = 0.024). Bacteremia was more common in the control group, while fungemia was similar.