SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19

• Julian Braun^1,2 na1,
• Lucie Loyal^1,2 na1,
• Marco Frentsch^3 na1,
• Daniel Wendisch  ORCID: orcid.org/0000-0003-1968-5751⁴,
• Philipp Georg⁴,
• Florian Kurth  ORCID: orcid.org/0000-0002-3807-473X^4,5,
• Stefan Hippenstiel  ORCID: orcid.org/0000-0002-5146-1064⁴,
• Manuela Dingeldey^1,2,
• Beate Kruse^1,2,
• Florent Fauchere  ORCID: orcid.org/0000-0002-1955-6362^1,2,
• Emre Baysal^1,2,
• Maike Mangold^1,2,
• Larissa Henze^1,2,
• Roland Lauster^1,6,
• Marcus A. Mall^7,13,
• Kirsten Beyer⁷,
• Jobst Röhmel⁷,
• Sebastian Voigt  ORCID: orcid.org/0000-0003-1544-9903⁸,
• Jürgen Schmitz⁹,
• Stefan Miltenyi⁹,
• Ilja Demuth¹⁰,
• Marcel A. Müller  ORCID: orcid.org/0000-0003-2242-5117¹¹,
• Andreas Hocke⁴,
• Martin Witzenrath⁴,
• Norbert Suttorp⁴,
• Florian Kern  ORCID: orcid.org/0000-0002-0368-8408^12,13,
• Ulf Reimer¹²,
• Holger Wenschuh¹²,
• Christian Drosten  ORCID: orcid.org/0000-0001-7923-0519^11,14,
• Victor M. Corman  ORCID: orcid.org/0000-0002-3605-0136¹¹,
• Claudia Giesecke-Thiel  ORCID: orcid.org/0000-0002-5927-7018^15 na2,
• […]
• Leif Erik Sander  ORCID: orcid.org/0000-0002-0476-9947^4 na2 &
• Andreas Thiel  ORCID: orcid.org/0000-0002-5515-4002^1,2 na2

PDF: https://www.nature.com/articles/s41586-020-2598-9_reference.pdf

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the rapidly unfolding coronavirus disease 2019 (COVID-19) pandemic^1,2. Clinical manifestations of COVID-19 vary, ranging from asymptomatic infection to respiratory failure. The mechanisms determining such variable outcomes remain unresolved. Here, we investigated SARS-CoV-2 spike glycoprotein (S)-reactive CD4⁺ T cells in peripheral blood of patients with COVID-19 and SARS-CoV-2-unexposed healthy donors (HD). We detected SARS-CoV-2 S-reactive CD4⁺ T cells in 83% of patients with COVID-19 but also in 35% of HD. S-reactive CD4⁺ T cells in HD reacted primarily to C-terminal S epitopes, which show a higher homology to spike glycoproteins of human endemic coronaviruses, compared to N-terminal epitopes. S-reactive T cell lines generated from SARS-CoV-2-naive HD responded similarly to C-terminal S of human endemic coronaviruses 229E and OC43 and SARS-CoV-2, demonstrating the presence of S-cross-reactive T cells, probably generated during past encounters with endemic coronaviruses. The role of pre-existing SARS-CoV-2 cross-reactive T cells for clinical outcomes remains to be determined in larger cohorts. However, the presence of S-cross-reactive T cells in a sizable fraction of the general population may affect the dynamics of the current pandemic, and has important implications for the design and analysis of upcoming COVID-19 vaccine trials.

https://www.nature.com/articles/s41586-020-2598-9

COVID-19 and cannabis use under study

Researchers are analyzing the effects of the coronavirus on medicinal cannabis users, one of the vulnerable populations that may be disproportionately affected by the disease. Their study includes an electronic survey to obtain epidemiologic data.

A large portion of medicinal cannabis users are people with compromised immune systems or chronic medical conditions. These are also many of the same traits that people most vulnerable to COVID-19 share. That is why a University of Miami research team is hoping to document how cannabis users are faring during the height of the coronavirus pandemic in the United States.

“The global qualifying conditions for medical cannabis, though not uniform, all include individuals with compromised immune systems and other chronic health conditions. Therefore, this is a population that we cannot forget about in our joint effort to ‘flatten the curve,'” said Denise C. Vidot, an assistant professor in the School of Nursing and Health Studies and a trained epidemiologist.

Vidot is leading the preliminary study, which involves a collaborative group of experts from the School of Nursing and Health Studies, Office of Hemispheric and Global Affairs, and Miller School of Medicine’s Department of Public Health Sciences.

Medicinal cannabis users have been advised to prepare for possible delays in health care delivery while the coronavirus continues to plague the U.S. The study seeks to collect data on the patterns and trends of this population during these unprecedented times.

Through an anonymous electronic survey, experts will obtain epidemiologic data on the mental and physical health among those who use cannabis for medicinal purposes. The survey will also help examine potential changes in frequency, dose, and route of cannabis use patterns based on COVID-19-related closures and updates. Another topic that researchers will be investigating is the sharing of inhaled cannabis products, such as joints and vapes among users, which could be a contributing factor to the spread of the novel coronavirus.

“If COVID-19 has taught us anything, it is that population-based data is vital to make informed decisions,” Vidot said. “So, we are combining our skills to do our part to provide that data. Our goal is to have cannabis users from every country complete this survey, so the data is more generalizable.”

Participate in the anonymous electronic survey here.

https://news.miami.edu/stories/2020/04/experts-study-covid-19-and-cannabis-use.html

Reduced susceptibility to SARS-CoV-2 in metropolitan regions

Thomas J. Barrett, Karen C. Patterson, Timothy M. James, View ORCID ProfilePeter Kruger

doi: https://doi.org/10.1101/2020.07.28.20163154

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2020.07.28.20163154v1.full.pdf+html

Abstract

The coronavirus pandemic is wreaking public health, social, and economic havoc across the globe, and to date a variety of strategies have been implemented to attempt to control the spread of disease [1, 2]. A critical unknown for policy planning is the number of people who have been infected and are no longer susceptible [3]. Tests for active SARS-CoV-2 infection or antibody presence can provide an indication, but both are prone to selection bias, under-representative population sampling and insufficient reliability [4, 5]. Here, we present an alternative to determine residual susceptibilities based on the analysis of observed population-wide disease dynamics data. For four highly-affected countries, we directly compared the dynamics in the largest metropolitan regions with the rest of the countries. We show that substantial susceptibility reductions are measurable in the metropolitan regions, which all continued in a phase of exponential growth of case numbers for a relatively longer time before public health interventions were introduced. Compared to these interventions, the reduction in metropolitan region susceptibility had a substantial role in the post-growth decline in infection rates. Reduced population susceptibility has far reaching consequences on future policy responses and disease forecasts including vaccine trial planning and, in the case of a second epidemic wave, higher population-normalised mortality rates for non-metropolitan regions.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This work was supported by the University of Sussex Strategic Development Fund. No authors received payment from a third party for any aspect of the submitted work.

https://www.medrxiv.org/content/10.1101/2020.07.28.20163154v1

Colchicine Cuts Lung Injury in Induced Acute Respiratory Distress Syndrome

Jocelyn Dupuis, Martin G. Sirois, Eric Rhéaume, Quang T. Nguyen, Marie-Élaine Clavet-Lanthier, Geneviève Brand, Téodora Mihalache-Avram, Gabriel Théberge-Julien, Daniel Charpentier, David Rhainds, Paul-Éduard Neagoe, Jean-Claude Tardif

DOI:

10.21203/rs.3.rs-43204/v1

Download PDF

License:

This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License

Declarations:

View author declarations.

Declarations

• This study involved the use of non-human vertebrates.
• The author has confirmed that all appropriate ethical guidelines for the handling and use of animals in research have been followed and details of the oversight board have been included in the text.
• The author has confirmed that a statement listing potential conflicts of interest or lack thereof is included in the text.

Abstract

The acute respiratory distress syndrome (ARDS) is characterized by intense dysregulated inflammation leading to lung injury and respiratory failure. We studied the effects of colchicine pre-treatment on oleic acid-induced ARDS in rats. Colchicine reduced histological lung injury by 61%, reduced lung edema, and markedly improved blood oxygenation by increasing PaO₂/FiO₂ from 66 ± 13 mmHg (mean ± SEM) to 246 ± 45 mmHg. Lung neutrophil recruitment was reduced by colchicine with evidence for reduced neutrophils activation, as assessed by flow cytometry. This study strongly supports the clinical development of colchicine, a widely available low-cost drug, for the prevention of ARDS in conditions causing acute lung injury.

https://www.researchsquare.com/article/rs-43204/v1

100 COVID-19 Positive Patients Treated with Ivermectin and Doxycycline Combo

• 

  Mohammed Tarek Alam
• 

  Rubaiul Murshed
• + 2
  

  Elias Bhiuyan
• 

  Sadia Saber

  Abstract

  Background: A definitive treatment of SARS CoV-2 is yet to arrive and the human death toll rises exponentially globally. In this health emergency, it might be useful to look into the old therapies which could be effective against the virus. In vitro research showed Ivermectin could decrease the concentration of coronavirus 4000 to 5000 folds in living lung tissue. Aim: In this prospective study a combination of Ivermectin and Doxycycline will be evaluated therapeutically to treat COVID-19 patients. Methods: 100 COVID-19 patients were enrolled in this study with a predefined inclusion and exclusion criteria. RT- PCR of the SERS-CoV-2 will be done at designated government hospitals. The clinical features and response to treatment were noted according to a dedicated protocol. Results: In this study male and female were 64 and 36 respectively, the age ranged between 8 to 84 years. Retesting was done between 4 and 18 days of starting medication. All patients tested negative and their symptoms improved within 72 hours. There were no noticeable side effects. Conclusion: Combination of Ivermectin and doxycycline was found to be very effective in viral clearance in mild and moderately sick COVID-19 patients. Medical societies and institutions should undertake larger multi center studies to validate and recommend this combination therapy to include in national guidelines.

  https://www.researchgate.net/publication/343305357_A_Case_Series_of_100_COVID-19_Positive_Patients_Treated_with_Combination_of_Ivermectin_and_Doxycyclin

Google Update on Exposure Notifications

In May, we partnered with Apple to launch the Exposure Notifications System (ENS) and made it available to public health authorities around the world in their fight against COVID-19. The ENS allows public health authorities to develop apps that augment manual contact tracing efforts while preserving the privacy of their citizens. As of today, public health authorities have used ENS to launch in 16 countries and regions across Africa, Asia, Europe, North America and South America, with more apps currently under development.

In the United States, 20 states and territories—representing approximately 45 percent of the U.S. population—are exploring apps based on ENS. We expect to see the first set of these apps roll out over the coming weeks. The Association of Public Health Laboratories also announced recently that it will host a national key server to support all U.S. states, which will allow people with Exposure Notification apps to receive alerts even if they travel across state borders.

We’ve continued to improve the technology and provide more transparency based on feedback we’ve received from public health authorities and other experts. Public health authorities will continue to make their own decisions about how exposure notifications become part of their plans in controlling COVID-19, and we will work to improve the technology in response to their feedback. Here are some of the changes we’ve already made, as well as some upcoming additional changes.

Improvements to the Exposure Notification API

Since the Exposure Notification API was publicly released in May, we’ve spoken with dozens of public health authorities to understand how the API could be improved to help them better manage the COVID-19 pandemic while preserving privacy. Based on this feedback, we recently launched an update to the API, which includes the following changes:

• When an exposure is detected, public health authorities now have more flexibility in determining the level of risk associated with that exposure based on technical information from the API.
• Bluetooth calibration values for hundreds of devices have been updated to improve the detection of nearby devices.
• The API now supports interoperability between countries, following feedback from governments that have launched Exposure Notification apps.
• To help public health authorities build apps more efficiently, we’ve added reliability improvements for apps and developer debug tools.
• We’ve improved clarity, transparency and control for users. For example, the Exposure Notifications settings on Android now include a simple on/off toggle at the top of the page. In addition, users will also see a periodic reminder if ENS is turned on.

Technical guidance and transparency

We’ve heard feedback that public health authorities and developers want more technical guidance about how ENS works. In response, we’ve published the following resources over the last few weeks:

• Reference verification server to help guide public health authorities in building a server that allows verification of test results when users report themselves as positive for COVID-19.
• Implementation code showing how the Exposure Notification API works underneath the hood.
• Telemetry design explaining what de-identified diagnostics data is collected to ensure that ENS is functioning properly and securely.

Additional technical resources will be publicly shared as we continue to improve ENS.

Education and privacy protections

The Exposure Notifications website has more information about ENS, and offers educational and technical resources, as well as the latest updates.

As a quick reminder, here are some of the core privacy protections that were built into ENS:

• You decide whether you want to use Exposure Notifications—it’s off unless you turn it on.
• ENS doesn’t use location data from your device.
• Your identity is not shared with Google, Apple or other users.
• Only public health authorities can use this system.

Finally, we’ve received questions about why your Android device location setting has to be turned on if you want to use an Exposure Notification app. We want to explain why this particular setting needs to be on, and how you can control your location settings on Android.

To be absolutely clear, ENS does not use device location, and the policies for using ENS prohibit public health authority apps from requesting or collecting device location. Instead, ENS uses Bluetooth technology to detect when two devices are near each other, without revealing the location of either device. While Bluetooth scanning doesn’t necessarily reveal location, it can in some cases be used to infer your device’s location. For example, if a shopping app scans for the Bluetooth signals of a stationary Bluetooth beacon located inside a store, then the app could infer that you went to that store. So in 2015, with privacy in mind, we designed the Android operating system to prevent Bluetooth scanning unless the device location setting is on. At that time no one could have anticipated that Bluetooth scanning might one day be helpful in controlling a global pandemic like COVID-19.

Our engineering teams have been working to update the next version of Android with Exposure Notifications in mind. On Android 11, which will soon be released, users will be able to use Exposure Notification apps without turning on the device location setting. We’re making this update for Exposure Notifications only, given that ENS has been designed in such a way that neither the system nor the apps using it can infer device location through Bluetooth scanning, and apps that are allowed to use ENS are subject to additional policies that disallow automatic collection of location. All other apps and services will still be prohibited from performing Bluetooth scanning unless the device location setting is on.

But even in current versions of Android, when you turn on the device location setting, your phone continues to prohibit access to any apps, including Google apps, that don’t have permission to use device location. The device location setting is like a circuit breaker in a house: When it’s on, power is flowing to the house, but you can turn the lights on or off in each room. If you turn on the device location setting to use ENS, it won’t affect the decisions you’ve already made about specific apps. You can always view and change which apps have access to your device location by going to Settings > Location > App permissions.

We’re committed to supporting public health authorities as they build tools to fight COVID-19. We’ll continue to improve ENS based on feedback, while ensuring that people can trust in the privacy-preserving design of this technology.

https://blog.google/inside-google/company-announcements/update-exposure-notifications/