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By Christian Hoffmann &
Bernd S. Kamps
Rivera F, Safdar N, Ledeboer N, et al. Prevalence of SARS-CoV-2 asymptomatic infections in two large academic health systems in Wisconsin. Clinical Infectious Diseases 19 August 2020. Full-text: https://doi.org/10.1093/cid/ciaa1225
From April 6 2020 to June 4 2020, a total of 11,654 asymptomatic patients were tested for SARS-CoV-2 in two large academic health systems in two counties of Wisconsin. Since early April 2020, both health systems implemented SARS-CoV-2 testing on all hospitalizations, on all patients scheduled for elective surgeries, including deliveries, or among all patients with known SARS-CoV-2 exposure in the absence of symptoms. In total, only 61 (0.52%) were positive. In both of these counties, rates were low, despite the higher incidence of COVID-19 in Milwaukee county.
Chambers C, Krogstad P, Betrand K, et al. Evaluation for SARS-CoV-2 in Breast Milk From 18 Infected Women. JAMA August 19, 2020. Full-text: https://doi.org/10.1001/jama.2020.15580
There are some case reports on the detection of SARS-CoV-2 in breast milk. Christina Chambers and colleagues examined 64 breast milk samples from 18 infected women. Although SARS-CoV-2 RNA was detected in one milk sample, the viral culture for that sample was negative. These data suggest that SARS-CoV-2 RNA does not represent replication-competent virus and that breast milk may not be a source of infection for the infant.
Bunders M, Altfeld M. Implications of sex differences in immunity for SARS-CoV-2 pathogenesis and design of therapeutic interventions. Immunity August 14, 2020. Full-text: https://doi.org/10.1016/j.immuni.2020.08.003
Women show stronger immune responses against pathogens and vaccines, but also in higher susceptibility to autoimmune diseases. But do sex differences in immunity contribute to better control of SARS-CoV-2 in women? In their elegant review, Madeleine Bunders and Marcus Altfeld summarize current knowledge on the basic biological pathways that underlie differences in immune responses between women and men.
Neidleman J, Luo X, Frouard J, et al. SARS-CoV-2-specific T cells exhibit phenotypic features of robust helper function, lack of terminal differentiation, and high proliferative potential. Cell Rep Med 2020, August 19. Full-text: https://doi.org/10.1016/j.xcrm.2020.100081
The phenotypes of SARS-CoV-2-specific T cells remain poorly defined. Jason Neidleman and colleagues conducted an in-depth phenotypic analysis of SARS-CoV-2-specific CD4+ and CD8+ T cells circulating in the bloodstream of nine individuals who had recently recovered from COVID-19. This was achieved by combining detection of specific T cells together with CyTOF, a mass spectrometry-based single-cell phenotyping method that uses antibodies conjugated to metal lanthanides to quantify expression levels of both surface and intracellular proteins. The main results: T cells were diverse, exhibited features different from antigen-specific T cells against CMV, included cells with both lymphoid and tissue homing potential, harbored phenotypic features of functional effector cells, and were long-lived and capable of homeostatic proliferation. The results suggest that long-lived and robust T cell immunity is generated following natural SARS-CoV-2 infection and support an important role for SARS-CoV-2-specific T cells in host control of COVID-19.
Kaneko N, Kuo HH Boucau J, et al. Loss of Bcl-6-expressing T follicular helper cells and germinal centers in COVID-19. Cell August 19, 2020. Full-text: https://doi.org/10.1016/j.cell.2020.08.025
Examining postmortem thoracic lymph nodes and spleens in acute SARS-CoV-2 infection, Naoki Kaneko and colleagues from Ragon Institute (Massachusetts, USA) found a striking absence of lymph node and splenic germinal centers and Bcl-6 expressing B cells, defective Bcl-6+ T follicular helper cell generation and differentiation and dysregulated SARS-CoV-2 specific humoral immunity early in COVID-19 disease. According to the authors, the underlying basis for the loss of germinal centers is best explained by the striking failure of differentiation of Bcl-6+ T follicular helper cells likely because of dramatic changes in the extra-follicular cytokine milieu driven by TH1 cells and the aberrant local production of TNF-α in lymphoid organs. Their results provide a mechanistic explanation for the limited durability of humoral immunity and the less robust somatic hypermutation seen in this disease following natural infection.
Guervilly C, Burtey S, Sabatier F, et al. Circulating Endothelial Cells as a Marker of Endothelial Injury in Severe COVID -19. J Infect Dis 19 August 2020, jiaa528, https://doi.org/10.1093/infdis/jiaa528.
In this retrospective study, Christophe Guervilly and colleagues from Marseille measured circulating endothelial cells (CEC) in the blood of 99 patients with COVID-19. Patients in the intensive care units (ICU) had significantly higher CEC counts than non-ICU patients and the extent of endothelial injury was correlated with putative markers of disease severity and inflammatory cytokines. These data provide in vivo evidence that endothelial injury is a key feature of COVID-19.
Hassan AP, Kafai NM, Dmitriev IP. A single-dose intranasal ChAd vaccine protects upper and lower respiratory tracts against SARS-CoV-2. Cell August 19, 2020. Full-text: https://doi.org/10.1016/j.cell.2020.08.026
In their animal experiments on mice expressing the ACE receptor, Ahmed Hassan and colleagues from St. Louis, US show the protective activity of a chimpanzee adenovirus-vectored vaccine encoding a pre-fusion stabilized Spike protein. Of note, intramuscular dosing induced robust systemic humoral and cell-mediated immune responses but did not confer sterilizing immunity. In contrast, a single intranasal dose induced high levels of neutralizing antibodies, promoted systemic and mucosal IgA and T cell responses, and virtually completely prevented SARS-CoV-2 infection in both the upper and lower respiratory tracts.
Yehia BR, Winegar A, Fogel R, et al. Association of Race With Mortality Among Patients Hospitalized With Coronavirus Disease 2019 (COVID-19) at 92 US Hospitals. JAMA Netw Open. 2020;3(8):e2018039. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.18039
In this cohort study of 11,210 individuals with COVID-19 presenting for care at 92 hospitals across 12 states, there was no difference in all-cause, in-hospital mortality between white and black patients after adjusting for age, sex, insurance status, comorbidity, neighborhood economics, and site of care.
Wu F, Liu M, Wang A, et al. Evaluating the Association of Clinical Characteristics With Neutralizing Antibody Levels in Patients Who Have Recovered From Mild COVID-19 in Shanghai, China. JAMA Intern Med August 18, 2020. Full-text: https//doi.org/10.1001/jamainternmed.2020.4616
In this cohort study of 175 patients who recovered from mild COVID-19, neutralizing antibody titers (NAbs) varied substantially at the time of discharge. NAbs were detected in patients from day 4 to 6 and reached peak levels from day 10 to 15 after disease onset. Of note, there were 10 patients whose NAb titers were less than the detectable level of the assay.
Kasgari HA, Moradi S, Shabani AM, et al. Evaluation of the efficacy of sofosbuvir plus daclatasvir in combination with ribavirin for hospitalized COVID-19 patients with moderate disease compared with standard care: a single-centre, randomized controlled trial. J Antimicrob Chemoth, 19 August 2020. Full-text: https://doi.org/10.1093/jac/dkaa332
The first randomized controlled trial in adult patients hospitalized with COVID-19 in Ghaem Shahr Razi Hospital (Iran) to evaluate the efficacy and safety of the two HCV drugs sofosbuvir and daclatasvir in combination with ribavirin (SDR) compared with standard of care. Though were trends in favor of the SDR arm for recovery and lower death rates, the trial was too small to make definite conclusions. In addition, there was an imbalance in the baseline characteristics between the arms.