Effect of Suppressed Innate Immunity on Covid-19 Severity

One of the important determinants of severe Covid-19 appears to be an inappropriate response by the innate immune system. Specifically, this involves, on the one hand, insufficient or delayed expression and signaling by type 1 interferons (IFNs), which induce innate cell-mediated immunity. The interferon (IFN) response constitutes the major first line of defense against viruses. On the other hand, this involves an overly active inflammatory cytokine response, with its attendant tissue damage (this “cytokine storm” was explored in our previous Perspective at https://gvn.org/category/sars-cov-2/gvn-sars-cov-2-perspectives/). Let’s look at some of the lines of evidence for these contradictory events.

One way in which an aberrant immune response to SARS-CoV-2 is reflected at the cellular level is by a greatly increased ratio of neutrophils to lymphocytes(1). This is correlated with low expression of type I and III interferons and high expression of pro-inflammatory factors including IL-6 and a variety of chemokines(2) that act as attractants for neutrophils and monocyte/macrophages. These activities are the outcome of interactions between host factors that recognize pathogen associated molecular patterns (PAMPs), such as viral RNA in endosomes, and viral proteins that are antagonistic to these factors and their signaling pathways. Genetic differences in host factors can result in profound differences in host responses to pathogens (recent findings are described below). Different viruses also tend to have different or unique antagonists to host immune factors that can greatly influence the outcome of infection.

What are some of the molecular studies that point to defects in interferon activity in severe Covid-19? Recently, interest has been increasing in toll-like receptors (TLRs), especially TLR3 and TLR7, which recognize viral RNA and are important in interferon type I and inflammatory cytokine expression. TLRs play a key role in the recognition of PAMPs and trigger the activation of specific signaling pathways, thereby inducing the transcription of inflammatory and/or anti-inflammatory cytokine. One interesting report looked at two sets of two brothers(3) who, although young and otherwise healthy, had severe Covid-19 (one died). Whole exome sequencing revealed that both sets of brothers had mutations in TLR7, which serves as a sensor for viral RNA. One set had a missense mutation predicted to result in an inactive TLR7, while the other set had a frame shifting 4 nucleotide deletion, resulting in a nonsense protein. Stimulation of primary immune cells in vitro with the TLR agonist imiquimod resulted in defective expression of type I interferon-related genes normally regulated by TLR7. While the limited nature of the study does not permit a conclusion of causality, several factors make it likely that these loss of function mutations are significant. Exhibition of severe disease in young men is rare. Despite rare cases of loss of function mutations in TLR7, two different loss of function mutations in two young brother pairs with severe disease indicate its potential role in Covid-19 severity. It should be pointed out that TLR7 is located on the X chromosome, so a single mutant copy would cause loss of function. One of the mothers was heterozygous for wild type TLR7, making her a carrier. Thus, if problems with the TLR7 pathway exacerbate Covid-19, males might be likelier to have an insufficiency.

Another study analyzed the complete genomes or exomes of 659 patients with life threatening Covid-19 and compared them with those of 534 people with asymptomatic or benign infections(4). They characterized 13 genetic loci encoding factors in the TLR3-interferon regulatory factor 7 (IRF7) pathway, which also regulates type I interferon production and immunity to influenza virus. They found that 3.5% of the people with life threatening Covid-19 had loss of function variants at these loci. Moreover, when immune cells from patients with these variants were tested in vitro, they were found to be defective in type-I interferon immune activities, and further in vivo study confirmed impaired production of type I IFN during the course of SARS-CoV-2 infection. About half of these patients also had extremely low levels of serum interferon α, a type I interferon.

Yet, another study further implicates lack of appropriate interferon activity in severe Covid-19(5). In this study, 101 of 987 patients with life threatening Covid-19 had auto-antibodies against interferon α, interferon ω or both. These were not present in 663 patients with mild disease. The auto-antibodies were able to neutralize the antiviral effects of interferon in vitro (and likely in vivo). Interestingly, the auto-antibodies were about 5-fold more prevalent in men than in women.

None of these studies by themselves show a specific defect in interferon activity in a majority of cases. However, taken together, they certainly suggest that a great variety of different defects related to the antiviral activities of type 1 interferons may be surprisingly common. Probably, one of the factors explains why some people resist serious disease while, for others, it is life-threatening. Further, investigations in this area will be most interesting.

One other study identified a 3p21.31 gene cluster that conferred a risk of severe Covid-19. This region contains three chemokine receptor genes, all involved in innate immunity(6). It turns out to be a region derived from Neanderthals, and is present at variable incidence worldwide except in Africa. This provides yet another clue that the innate immune response to SARS-CoV-2 may be an important determinant of whether an infected individual will, or will not, develop critical Covid-19.

In this light, it has been proposed that some cross-protection could be afforded by administering live attenuated vaccines, such as measles-mumps-rubella, and oral polio vaccine(7) (non-specific effect of vaccination against SARS-CoV-2). The stimulation of innate immunity by these vaccines could provide temporary protection against Covid-19. If proven to be effective against Covid-19, emergency immunization with these vaccines could be used for protection against other unrelated emerging pathogens.

 

References

  1. Y. Liu et al., Neutrophil-to-lymphocyte ratio as an independent risk factor for mortality in hospitalized patients with COVID-19. J Infect 81, e6-e12 (2020).
  2. D. Blanco-Melo et al., Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19. Cell 181, 1036-1045 e1039 (2020).
  3. C. I. van der Made et al., Presence of Genetic Variants Among Young Men With Severe COVID-19. JAMA 324, 663-673 (2020).
  4. Q. Zhang et al., Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science, (2020).
  5. P. Bastard et al., Auto-antibodies against type I IFNs in patients with life-threatening COVID-19. Science, (2020).
  6. D. Ellinghaus et al., Genomewide Association Study of Severe Covid-19 with Respiratory Failure. N Engl J Med, (2020).
  7. K. Chumakov, C. S. Benn, P. Aaby, S. Kottilil, R. Gallo, Can existing live vaccines prevent COVID-19? Science 368, 1187-1188 (2020).

Transmission Dynamics of SARS-CoV-2: Superspreaders and Superspreading Events

The concept of Superspreaders and Superspreading events has recently attracted a lot of attention. In fact it is important to understand that most of SARS-CoV-2 infected persons are in fact not contagious! Thus, transmission is really dependent on a handful of individuals we call Superspreaders who nurture Superspreading events. Let’s distinguish between Superspreaders and Superspreading events. Superspreaders are individuals who infect a high number of persons; why?  This is not clear, and this is a most important issue to clarify in the future.  We know they yield high viral load and that they are generally, but not always, young people.  But, this cannot fully explain their massive contamination impact.  Moreover, they are frequently asymptomatic, thereby significantly increasing risk of dissemination. Superspreading events, which involve at least one Superspreader, are events which favor large scale transmission, such as close contacts in indoor situations. Secondary transmissions from infected people then result in a large number of further infections, and so on. Thus, by some estimations  only 20% of infected individuals cause 80% of infections(1).  Identification of Superspreading events depends upon contact tracing.  Furthermore, DNA sequencing of viral genomes adds a great deal to a clearer understanding of these phenomena, thus, confirming the substantial role of Superspreaders in the pandemic. Let’s look at some well-characterized superspreader events to try to better understand how the majority of SARS-CoV-2 infections occur, enabling us to gain an understanding of what might be done to prevent them.

One of the early recognized superspreading events occurred in mid-March in Skagit County, Washington(2) at a 2.5 hr-long choir practice in which 61 people sang in close proximity. Probable or confirmed infections occurred in 87% of the attendees. Given the low incidence of COVID-19 at the time of this event, it is likely that all the infections originated with a single individual, and that the act of singing vigorously launched many viral laden particles into the air. People were relatively closely positioned. Thus, it is likely that superspreading occurs in an unusually favorable environment. Looking at it another way, the virus got “lucky.”  Another study, unrelated to the choir event, analyzed the sequences of 453 viral genomes collected between February and March in Washington(3).  It is possible to infer the likelihood of how many people have been infected by a single person using viral genomic epidemiology, especially given the relative genetic stability of SARS-CoV-2. A phylogenetic analysis strongly suggested that 84% of the 453 viral genomes derived from a single introduction sometime in early February.  In the choir study, it is clear how virus was transmitted. In the genomic study, it is only clear that a single infected individual somehow infected a great number of people through primary, secondary, and other less direct routes.

Another well-studied superspreader event began with a single infected individual in a meat packing plant is Postville, Iowa. In this case, viral spread could be ascertained by both contact tracing and by genomic epidemiology. Fourteen independent viral introductions were identified in the region, but the only virus to spread widely was the one from the meat packing plant. The virus from this individual passed first to numerous other workers, then to family members, then to the community in Postville (87 cases), and finally to other locations in an area of 185 square miles in Iowa, Wisconsin and Minnesota. These conclusions were supported by genomic sequences from 27 different infected individuals. Again, it appears that prolonged close contact indoors facilitated transmission and suggests that this is a critical feature of superspreading events.

Perhaps, the best characterized superspreading event, originating from an international business meeting of Biogen in Boston(4) in which more than 90 individuals became infected.  This event recently received considerable attention. The large number of infections was indicative of a possible superspreading event. A recent study looked at this event and its consequences in detail, using genomic epidemiology(5). They were able to identify and track the virus in question by a single nucleotide polymorphism (SNP), C2416T. Among 80 separate introductions from four continents into the Boston area early in the pandemic, which they inferred from phylogenetic analyses, the C2416 SNP was unique to one virus. Comparing other viral genomes from various parts of the world with C2416T, the parental origin appears to be in Europe, perhaps France, with an estimated most recent common ancestor existing about two weeks prior to the conference aroundFebruary 26-27. Of all samples collected prior to March 10, the only instances of C2416T were from people who had attended the conference, indicating that a superspreading event had indeed occurred there.

Subsequent samples (744) from infected individuals in Boston and surrounding areas were collected over a period from February to June and genomes were sequenced. Remarkably, 35% of the samples had the C2416 SNP. Since no sample prior the March 10 had this SNP, it suggests that the superspreading event at the Biogen meeting February 26-27 resulted in virus from a single individual infecting more than a third of all infected people in the Boston area. Percentages of the C2416T SNP in regions around Boston ranged from 30-46% in four adjacent counties. In addition, a second SNP, G26233T, appears to have emerged during the event, enabling further tracking. Data from this SNP shows a likely export to other states and countries, with further community spread in Virginia, Michigan and Australia. Some caution is warranted, however, since genomic sampling is not generally done on a randomized basis.

The same report looked at infection clusters at homeless shelters, nursing facilities, and a hospital to gain a better understanding of transmission dynamics. They analyzed 193 viral genomes collected from the Boston Health Care for the Homeless Program and identified 4 clusters of 20 or more highly similar genomes, including two clusters containing the C2416T SNP. They also investigated a superspreading event at a skilled nursing facility, in which 82/97 (84%) residents and 36/97 (37%) of staff were infected. In fact, 75% of viral genomes from different individuals had highly similar genomes, suggesting that they arose from a single recent introduction. This took place even though strict interventional measures were in place. Interestingly, two other clusters of three closely related genomes were detected. This represents independent introductions, but these failed to massively spread. In the case of two clusters of infection at Massachusetts General Hospital, highly similar genomes were not found, suggesting a lack of significant in-hospital spread.

What is our conclusion? First, it is now clear that a majority of transmissions result from superspreading events, facilitated by conducive conditions. These include indoor location, close contact, lengthy contact, indoor activity such as singing or talking, poor air ventilation, and lack of mitigation procedures (i.e., wearing masks and physical distancing). Tracing Superspreading events in Hong Kong also confirmed that the largest cluster (106 cases) was traced to four bars followed by a wedding (22 cases) and attendance at a temple (19 cases) (1). This study suggests that disease control efforts should focus on avoiding gathering events and mitigating their impact.  The rapid tracing and quarantine of confirmed contacts, along with the implementation of physical distancing policies including either closures or reduced capacity measures targeting high-risk social settings such as bars, weddings, religious sites and restaurants, should be efficient to prevent the occurrence of superspreading events. Overall, the issue of Superspreaders and Superspreading events illustrates the impact of molecular epidemiology for deciphering the patterns of COVID-19 dissemination. What we still clearly lack, however, is the understanding of the very early phases of the pandemics in China. This would be very useful for the whole appraisal of transmission dynamics.

  1. D. C. Adam et al., Clustering and superspreading potential of SARS-CoV-2 infections in Hong Kong. Nat Med, (2020).
  2. L. Hamner et al., High SARS-CoV-2 Attack Rate Following Exposure at a Choir Practice – Skagit County, Washington, March 2020. MMWR Morb Mortal Wkly Rep 69, 606-610 (2020).
  3. T. Bedford et al., Cryptic transmission of SARS-CoV-2 in Washington state. Science, (2020).
  4. A. Schuchat, C. C.-R. Team, Public Health Response to the Initiation and Spread of Pandemic COVID-19 in the United States, February 24-April 21, 2020. MMWR Morb Mortal Wkly Rep 69, 551-556 (2020).
  5. J. Lemieux et al., Phylogenetic analysis of SARS-CoV-2 in the Boston area highlights the role of recurrent importation and superspreading events. medRxiv, (2020).

GVN 2020 Special Annual Meeting Executive Summary

A New Era in the Fight Against COVID-19 Pandemic: Forging a “Viral Pandemic Readiness Alliance”

A September 22-23, 2020 Special Meeting of Top Global Experts Launches “Global Virus Network’s Vision for Future Pandemic Preparedness”

We are in the midst of a pandemic that has completely upended the world with major economic, social and psychological impacts. The major threat to public health is not only connected to COVID-19-related mortalities, but also to associated morbidity and, possibly, sequelae; moreover COVID-19 impacts overall population health due to the disorganization of health systems.

We must be very humble, as we cannot predict what the future could hold: seasonal variations? Long term persistence? Or regression? We need to keep in mind that the reason behind the SARS-CoV-1 epidemic’s regression has remained in part mysterious. In fact, eradication of the virus seems impossible, and herd immunity may be very difficult to achieve. Thus, we must learn to live with the virus.

It is increasingly clearer that we are not facing “another health crisis.” We are entering a new era where novel modes of organization must be designed. We cannot wait for the current crisis to conclude to prepare for the next—we must act now!

Despite significant progress in global health following previous epidemics and pandemics (including HIV, Influenza and Ebola), and although we were aware of the potential risk of such new pandemics, we were not sufficiently prepared. There are two immediate consequences for global health policies:

  • The importance of infectious diseases, global and “one health” are only further emphasized.
  • The divergence between politics and health in many countries has led to disastrous decisions. As such, we need to provide governing leaders with science-driven and independent strategies.

The Global Virus Network (GVN) is poised to be an important partner in achieving these objectives. This is a coalition of the foremost virologists worldwide, representing 57 research centers and 10 affiliates in 33 countries, and growing by the day. The GVN coordinates scientific projects and has organized task forces on specific viruses including Zika, Chikungunya, and HTLV-1, and now SARS-CoV-2. The organization also has a major focus on education, training and mentoring others in the field. Globally, there is a lack of critical mass in scientists, medical doctors and public health professionals working on infectious diseases. The GVN plays a significant role in advocacy and providing statements (in particular through its website https://gvn.org/). Science-driven and independent expertise are key drivers of meaningful public health strategies, and through its network of outstanding virologists worldwide, GVN offers national and international institutions, as well as industrial partners, a unique source of information and recommendations.

In this context, the GVN organized a two-day workshop dedicated to COVID-19 and future pandemic preparedness with the aim to evaluate what has been improperly and properly handled during these first eight months of the COVID-19 pandemic spreading. The workshop looked at precisely identifying the challenges ahead, the actions to take and how the GVN can collaborate with the many institutions to meet these needs. The goal of the workshop was not to revisit in detail all topics and known facts.  A video of the full post-meeting press conference, can be found here.

The following summarizes the major issues discussed:

1) Preparedness: We were not prepared, and we need to prepare now; This implies novel organizational modalities.

  • Cooperation and coordination, beyond goodwill and fashionable wordings; too many institutions are still working in silos with self-interest strategies.
  • Leverage technologic innovation and scientific progress to produce diagnostics, vaccines, and therapeutics.
  • Contemplate and implement novel modes of interactions between academics and industrials, and such partnerships have been at the heart of the GVN since its inception.
  • Multi- and transdisciplinary collaborations, including social and behavioral sciences, and perception of communication.
  • International collaborations: one country alone cannot solve the problem. While this seems obvious, most countries have reacted on an isolated basis. A global collaboration network for pandemic preparedness and prevention needs to be implemented immediately.

2) Prediction: Humans are the best sentinels. Is it feasible to predict future pandemics? How to sufficiently organize surveillance?

  • We must recognize that we cannot predict future pandemics, though we can improve our strategies. Yet, we have sufficient technologies and data analysis systems (including artificial intelligence), but we need to establish implementation and global data sharing mechanisms.
  • We know that animal viruses are major risk factors for the next epidemics and pandemics. This is even increasingly at stake. During the meeting scientists emphasized that five of the seven human coronaviruses identified (229E, NL63, OC43, HKU1, SARS-CoV-1, MERS-CoV and SARS-CoV-2) in the last 20 years have emerged from bats. Humans are modifying ecosystems and are in fact accelerating transmission events.
  • Comprehensive sequencing-based analysis of all viruses worldwide (“animal viromes”) provides useful knowledge but does not predict transmission to humans. GVN scientists point to the importance of focusing surveillance efforts to the human populations who interface with animals.

3) Origin: There is no scientific evidence that SARS-CoV-2 was disseminated by human manipulation.

  • GVN scientists all concur on this controversy.
  • The mission to find out the origins of the virus was a true international collaboration and transparent process featuring scientists from China, America, Australia, Japan, France, and the Philippines.
  • There is a 1,200-nucleotide difference between the closest backbone virus and SARS-CoV-2, representing 4 to the power of 1,200 possible combinations. Even if someone had unlimited research funding and all the best virologists in the world, no one could make this virus.
  • An extensive study will be conducted starting in China and through Southeast Asia to identify the origins of the virus and to allow much better surveillance and mitigation for future emerging viruses.

4) Transmission: “Super spreaders” and “super spreading” events are major drivers of pandemics.

  • COVID-19 is a highly contagious respiratory disease with very low mortality directly induced by the virus, thus the ideal condition for a virus to spread. The importance of masks, physical distancing and handwashing is well-known. GVN scientists also emphasize the importance of research on disinfectants, an underappreciated protective measure.
  • As re-emphasized in this workshop, only a handful of those infected seem highly contagious. Thus, transmission is driven by a limited number of individuals who behave as “super spreaders.” Why do some individuals (a.k.a. “super spreaders”) transmit viruses to so many others? Although we know that such individuals show high viral load and are generally, yet not always, younger, this cannot fully account for this spreading. What are the other factors? Thus far, research focused on such individuals is mandatory. The question remains whether we can identify novel biomarkers, though we would need to fully exclude stigmatization.
  • Also, this implies for obvious statistical reasons that large gatherings are major risk factors for being in contact with such rare “super spreaders” and thus contributors to rapid viral wide spreading. Therefore, we should not only speak of “super spreaders” but also of “super spreading” events.
  • Aerosol-related transmission is still a controversial issue. Yet, GVN scientists have emphasized that the impact of short-range aerosol-driven transmission contributes to the dissemination of the virus, particularly in the context of “super spreading” events. Masks are very efficient against large droplets but are unfortunately less efficient against such aerosols.

5) Diagnostic: Efficient and rapid diagnostic testing is the key for controlling an infectious disease, and we have not benefited enough from the huge technology progress in this area.

  • Nothing is needed more than rapid diagnostic tests. We need to trace and follow infected individuals and their contacts. We need to educate the general public. This is absolutely the foundation, and we cannot do anything without it.
  • There is now ample evidence that salivary sampling can be used instead of nasal swabs in both symptomatic and asymptomatic infected individuals. This can overhaul access to testing, in particular but not only in children. Rapid tests, whether molecular or immune-based, are now available at a low cost, and presentations have been made by GVN scientists demonstrating these points. Point-of-care rapid tests should also be available.
  • Important progress has been made regarding serological assays, offering major insights not only on the epidemiology but also defining the neutralization capacity of detected antibodies as novel correlates for protection. These are fully necessary for evaluating protective measures, novel therapies and vaccines. As an example, some presentations showed that the nature of the antibodies to SARS-CoV-2 significantly differs when comparing children and elderly, possibly accounting for variations in disease severity. Yet, we need standardized protocols for neutralizing assays. Also, the protective efficacy of antibodies needs to be further substantiated. GVN scientists have emphasized the need to get access to the cellular immune response for delineating such correlates of protection.
  • Discussions have been focused on how we should provide novel organizational schemes to favor rapid translation from technology-driven research to routine testing, and partnerships between academic and industrial partners should be reinforced in an international context. Institutions such as the Coalition for Epidemic Preparedness and Innovations created for vaccine development are interesting models to get such novel consortia moving faster.

6) Therapeutics: Despite a huge effort made on drug repurposing so far, we have achieved limited results.

  • Drug repurposing must continue to be at the heart of the therapeutic strategy, providing immediate access of well characterized molecules and allowing massive screening for antiviral activities. However, we do not yet have access to drugs that can prevent transmission in high-risk groups or treat early infections. In fact, we are left with combining steroids, Remdesivir (with some but limited efficacy) and anticoagulants for severe infections with pneumonia. Though, several ongoing studies offer hope for novel prophylactic and early treatment molecules.
  • In this context, GVN scientists have emphasized the need for research agencies to fund not only drug repurposing but also drug discovery. Drug discovery will take time to lead to novel accessible molecules – this is a long battle and not a single crisis.
  • Several presentations demonstrated the potential of novel therapeutic avenues, from immunomodulatory to direct antiviral approaches. Antivirals are only meaningful in the early phase of the infection.
  • The trend will be to use drugs targeting multiple pathways and to combine antivirals and immunomodulatory molecules. Additionally, GVN scientist are addressing the possibility of developing broad spectrum antivirals, which could be effective against coronaviruses, influenza and filoviruses (involved in hemorrhagic fevers such as Ebola, Zika etc.).

7) Vaccines: Safety, efficacy and durability are predominant concerns of COVID-19 vaccine development. Nonspecific immunization procedures must be considered along with COVID-19-specific vaccines.

  • Enormous parallel efforts are being made worldwide utilizing innovative approaches to shorten the vaccine development time. There is uncertainty as to when vaccines for COVID-19 will be readily available for mass vaccination and which formula will be the most efficient. Importantly, we need to ensure the safety of vaccines by testing proper animal models and complying with regulatory requirements – we simply cannot incur adverse reactions.
  • We also need second-generation vaccines that are more focused on the cell immune response.
  • Stimulation of the Innate immune response by non-specific immunization, for example: Bacille Calmette-Guérin (BCG), Oral Polio Virus, is extremely important. GVN scientists made important presentations on this topic, illustrating how BCG-based strategies have already allowed in different contexts to decrease the neonates’ overall mortality in Africa and the rate of respiratory infections in elderly. Mechanisms accounting for stimulation of innate immune response in COVID-19 were thoroughly discussed, and ongoing trials on the impact of BCG and Oral Polio Virus-based vaccines on COVID-19 were deliberated. This approach is complementary to specific vaccine development and might offer a bridge before getting an efficient and sufficiently characterized vaccine.

Conclusions:

It is not a crisis – it is a new era. We have major challenges ahead.  We need a new organization and we need it now.  This is where the GVN is very important, and complementary to national and international agencies. This workshop has led GVN to forge a unified and multidisciplinary pandemic response strategy, tentatively named the Viral Pandemic Readiness Alliance (VPRA) by collaborations with university, industry, government and communities to merge the efforts and find solutions together.

  • True international collaborations are essential and go beyond good and fashionable wordings. Global, One Health and VPRA strategy can support future pandemic preparedness with distribution of diagnostics, vaccine and therapeutics and other interventional measures.
  • In a surge of COVID-19 publications and news releases, we need reliable channels for dissemination of scientific knowledge and information sharing. GVN and VPRA can contribute to this global collaboration effort by assisting the UN, WHO, CEPI, Wellcome Trust, the Bill and Melinda Gates Foundation, and other organizations to serve this purpose.

 

GVN 2020 Meeting Press Release

GVN International Press Conference September 24, 2020

GVN’s Top Virus Experts Meet Together To Identify Most Promising Advances To Battle COVID-19 & Strategies To Prepare For Future Pandemics

Rapid Diagnostic Testing, Repurposing Drug Therapies and Vaccines Targeting Innate Immunity, Are Integral Factors in Mitigating COVID-19

Baltimore, Maryland, USA, September 30, 2020: The Global Virus Network (GVN), a coalition of the world’s leading medical and basic virology research centers working to prevent illness and death from viral disease, convened a press conference with attendees from across the globe to discuss key takeaways from the GVN virtual 2020 Special Annual Meeting held September 23-24, 2020.

A video of the full press conference, can be found here.

“We do not know what the future holds for COVID-19 – there may be seasonal variations or chronic infections or maybe a slowdown,” said Dr. Christian Bréchot, GVN President. “However, we know that we have to prepare and that this for now and not after the end of this pandemics; in the spirit of preparation, it is very timely that we used the Special Annual Meeting to band together international experts to identify and analyze what went wrong, what has been properly handled and what recommendations we can confidently make.”

Key findings during the meeting regarding SARS-CoV-2 and COVID-19 research include:

  • “Super-spreaders” and “super-spreading” events are major drivers of the pandemic, indicating that only a handful of those infected seem be exponentially contagious. Further, short-range aerosol-driven transmission contributes to the dissemination of the virus, particularly in the context of the super spreading events.
  • Key pandemic response strategies – the need to take better advantage of the major technology progress in diagnostics, a key driver for the control of infectious diseases; salivary sampling will very much increase our testing capacity, including in school settings; novel rapid and cheap molecular rapid diagnostic tests combined with digital-based transmission of the results, tracing and isolation should be widely emphasized, an understanding of communicability and transmission and, most importantly, the creation of a unified and multidisciplinary response with mechanisms for information sharing among international virologists and independent authorities.
  • An evaluation of vaccine development – timing, an analysis of the candidates, side-effects and managing the world’s expectation for a satisfactory and timely vaccine. Until a classical, effective vaccine is available, vaccines that stimulate the body’s innate immune system, such as the oral polio vaccine and BCG, are integral in protecting against infection.
  • A very strong statement against SARS-CoV-2 being the result of human manipulation.
  • An update on the available and future therapies, emphasizing the need to combine novel antiviral and immunomodulatory molecules as well as the need to contemplate in the future antivirals with broad spectrum against several viruses.

Dr. Bréchot, who also is a professor at the University of South Florida in Tampa, continued, “This is not just a crisis – it is a new era. We have major challenges ahead, we need a new organization and we need it now.  Global collaborations will build a strong foundation. This is where the GVN is very important, and complementary to national and international agencies. The GVN is well positioned to establish with all partners a Viral Pandemic Readiness Alliance to facilitate collaborations with universities, industry, governments and communities to merge efforts and find solutions together.”

“Simple, safe, oral, inexpensive, live vaccines such as the oral polio vaccine (OPV) will have a broad benefit against COVID-19. This can also likely be used in future pandemics, particularly of respiratory viruses, by inducing innate immunity, which is immediate and not as limiting as a specific vaccine,” said Dr. Robert Gallo, co-founder of GVN; The Homer & Martha Gudelsky Distinguished Professor in Medicine, co-founder and director of the Institute of Human Virology at the University of Maryland School of Medicine.

Dr. Gallo, who is most renowned for discovering human retroviruses, co-discovering HIV as the cause of AIDS and developing the HIV blood test continued, “Nothing is needed more than a rapid diagnostic test. Molecular tests that can be done cheaply and at home, within two hours or less time – nothing could be more valuable “We need to be able to trace; we need to be able to follow people; we need to be able to educate. This is absolutely basic, and without it we can do nothing. There is singularly nothing else more important in my mind than having rapid and reliable diagnostics.”

Dr. Bréchot was joined at the press event by presenters from the annual meeting including:

  • Linfa Wang, Duke-NUS Medical School, Singapore
  • Konstantin Chumakov, FDA Office of Vaccines Research and Review, USA
  • Ab Osterhaus, TiHo Hannover, Germany
  • Johan Neyts, Rega Institute, Belgium
  • Raymond Schinazi, Emory University, USA

Next, David Scheer, an advisor and entrepreneur in life sciences with a lifelong career in global public health non-profits, moderated a discussion titled, “From HIV to SARS-CoV-2 and Beyond.” Panelists were Dr. Gallo, Dr. Bréchot and Dr. Eric Rubin, New England Journal of Medicine Editor.  The frank COVID-19 discussion included historical perspectives, the emergence of variant strains of SARS-CoV-2, vaccine development and innate immunity, the use of existing and new drug therapies, pandemic preparedness as it relates to industry, government and academia, and that SARS-CoV-2 is naturally occurring and not manmade.

The meeting program can be found here.

About the Global Virus Network (GVN)

The Global Virus Network (GVN) is essential and critical in the preparedness, defense and first research response to emerging, exiting and unidentified viruses that pose a clear and present threat to public health, working in close coordination with established national and international institutions. It is a coalition comprised of eminent human and animal virologists from 57 Centers of Excellence and 10 Affiliates in 33 countries worldwide, working collaboratively to train the next generation, advance knowledge about how to identify and diagnose pandemic viruses, mitigate and control how such viruses spread and make us sick, as well as develop drugs, vaccines and treatments to combat them. No single institution in the world has expertise in all viral areas other than the GVN, which brings together the finest medical virologists to leverage their individual expertise and coalesce global teams of specialists on the scientific challenges, issues and problems posed by pandemic viruses. The GVN is a non-profit 501(c)(3) organization. For more information, please visit www.gvn.org. Follow us on Twitter @GlobalVirusNews.

Media Contacts:
Sard Verbinnen & Co
Kelly Kimberly/Kelly Langmesser
[email protected]
+1.212.687.8080

GVN
Nora Samaranayake
410-706-1966
[email protected]

GVN International Press Conference September 24, 2020

GVN 2020 Special Annual Meeting Executive Summary

Global Virus Network (GVN) Presents Doherty Institute Director, University of Melbourne Professor Sharon Lewin with the Robert C. Gallo Award for Scientific Excellence and Leadership in Medical Virology

Baltimore, Maryland, USA, September 22, 2020: The Global Virus Network (GVN), comprising foremost experts around the world in every class of virus-causing disease in humans and some animals, today presented Doherty Institute Director, University of Melbourne Professor Sharon Lewin with the Robert C. Gallo Award for Scientific Excellence and Leadership in Medical Virology  Presented today at the GVN Special Annual Meeting, Professor Lewin was selected for her outstanding clinical virology research and clinical trials, her leadership in Australian medical science as Director of the Doherty Institute, and her leadership in the GVN.

Professor Lewin has an international reputation in the field of HIV latency and eradication and immune reconstitution and HIV-hepatitis B virus co-infection.

In 2020 she has worked tirelessly at the helm of the Doherty Institute which has been at the forefront of Australia’s response to the COVID-19 pandemic.

Professor Lewin said it was an incredible honour to be presented with the Robert Gallo Award.

“The GVN is among other things, dedicated to identifying, research, combatting and preventing current and emerging pandemic viruses, it’s reason for being has never been so relevant. It’s a privilege to receive the Robert Gallo Award, and to be so closely linked as a GVN Center of Excellence Director,” Professor Lewin said.

The Doherty Institute is one of 57 GVN global Centers of Excellence, which Professor Lewin co-leads with Professor Damian Purcell and Professor Peter Revill.

The award is named after GVN Co-Founder and International Scientific Advisor, Professor Robert Gallo, who is most widely known for his co-discovery of HIV as the cause of AIDS and the development of the HIV blood test.

“Sharon Lewin is an international leader in clinical research,” said Professor Robert C. Gallo, co-founder of GVN and the current Director of the Institute of Human Virology at the University of Maryland School of Medicine.  “Additionally, she has been, and will continue to be, a medical science thought leader for the field of clinical virology and a powerful presence in Australia and globally as a scientific leader of the Doherty Institute, quickly establishing this GVN Center as one of excellence. I know all in the GVN are very happy and proud to honor her.”

“I congratulate Sharon Lewin for such a well-deserved award,” said GVN President Professor Christian Bréchot.  “Indeed, this recognizes her major scientific achievements and her full commitment to both the fight against HIV and support for the Global Virus Network.”

About the Global Virus Network (GVN)
The GVN is essential and critical in the preparedness, defense and first research response to emerging, exiting and unidentified viruses that pose a clear and present threat to public health, working in close coordination with established national and international institutions. It is a coalition comprised of eminent human and animal virologists from 57 Centers of Excellence and 10 Affiliates in 33 countries worldwide, working collaboratively to train the next generation, advance knowledge about how to identify and diagnose pandemic viruses, mitigate and control how such viruses spread and make us sick, as well as develop drugs, vaccines and treatments to combat them. No single institution in the world has expertise in all viral areas other than the GVN, which brings together the finest medical virologists to leverage their individual expertise and coalesce global teams of specialists on the scientific challenges, issues and problems posed by pandemic viruses. The GVN is a non-profit 501(c)(3) organization. For more information, please visit www.gvn.org and follow on Twitter @GlobalVirusNews.

Current Status of COVID-19 Vaccine Development

As the COVID-19 pandemic expands, interests in the progress of vaccine development are intensifying. Despite an unprecedented rate of progress, it is still uncertain when a safe, effective vaccine will be available for wide distribution to the public. Successful vaccine development goes through a series of stages, from animal studies for the evaluation of its protective immunogenicity to phase 1 (safety and antibody production), phase 2 (safety and immunogenicity by including a placebo group), and phase 3 (verification of safety, and efficacy in, a large population group) clinical trials. This is obviously a long, drawn out process, yet it is necessary to ensure the efficacy and safety of vaccines. In addition, it takes very high numbers of participants to generate meaningful and significant statistics to prove vaccine protection. This makes these trials expensive and their enrollment process lengthy, but phase 3 trials are clearly necessary, and are the most important step for its approval.

Immunogenicity studies are especially critical because there is not yet a clear understanding of what constitutes a protective immune response. Neutralizing or IgG antibody titers against the spike (S) protein do not seem to correlate inversely with disease severity, although it may be that rapid expression of such antibodies would be protective. Another issue is that neutralizing antibodies may only last a few months. However, immune memory cells may facilitate rapid production of such antibodies after infection. Even less is known about the role or relevance of T cell responses in protection. With all these caveats in mind, we will discuss nine candidate vaccines that are in the most advanced stages of development.  Most, but not all, are focused exclusively on the S protein, in large part because it is the target of neutralizing antibodies.

There are currently two vaccines in the late stage of development that depend upon injection of mRNA encoding the spike protein or portions including the receptor binding domain (RBD) of the S protein. These have an advantage of being easy to produce but have the disadvantage of needing to be stored at 4°C, requiring a cold chain supply, thus presenting difficulties for use in low-income countries. These two vaccines are produced by Moderna and Pfizer/BioNTech. Its limitations associated with the intracellular instability and inefficient delivery of mRNA have been addressed by chemically modifying the RNA and encapsulating it in lipid nanoparticles.

The Moderna vaccine (mRNA-1273) and one of the two Pfizer vaccines (BNT162b2) encode prefusion conformation of the S proteins. The other Pfizer vaccine (BNT162b1) encodes trimerized soluble S protein receptor binding domains on a peptide linker scaffold. The Moderna vaccine was protective in rhesus macaques. Human phase 1 trial results were reported in June by demonstrating its safety and immunogenicity with induction of binding and neutralizing antibodies equivalent to the levels that are seen in natural infection. The antibody levels persisted until at least day 43 post-vaccination. A phase 2 trial with 600 participants was begun in June. Phase 3 trials to determine efficacy and safety were initiated in August and will have 30,000 participants.

Pfizer decided to concentrate on BNT162b2, as it is equally immunogenic to BNT162b1 but generates fewer side effects. There do not appear to be any reports of trials with non-human primates. Three phase 1 trials showed that both vaccines elicited binding and neutralizing antibodies, but lesser side effects led to the selection of BNT162b2 for phase 3 trials (Publication 1, Publication 2). Trials began in August and, as with the Moderna trials, aim to enroll 30,000 participants.

The other nucleic acid-based vaccine, developed by Inovio (INO-4800), is comprised of DNA encoding the S protein. The DNA vaccine, unlike the mRNA vaccines, is stable at room temperature. The DNA is injected intramuscularly and then electroporated into cells by a hand-held device delivering a brief electric pulse.  The vaccine was partially protective in rhesus monkeys against a viral challenge three months after vaccination as judged by a reduction in viral titers. Inovio claims that antibody and/or T cell responses were induced after two doses of the vaccine in 94% of the 40 participants in Phase 1 trials, but they have not yet published the results. They are scheduling Phase 3 trials for September.

The Novavax vaccine candidate, NVX-CoV2373, is a full-length stabilized spike protein produced in insect cells and formulated into a lipid nanoparticle. Reports from a phase 1-2 trial showed that binding and neutralizing antibodies were elicited(1). Antibody levels were greatly increased, and T cell activities (especially Th1) were induced when NVX-CoV2373 was combined with a saponin-based adjuvant. Phase 3 trials are planned for late 2020.

There are currently three late stage vaccines that use adenoviral vectors to deliver their payloads to express the S protein. These include AstraZeneca/University of Oxford, which uses a chimpanzee adenovirus originally isolated from a chimp stool sample, Johnson and Johnson/Janssen (adeno26) and Cansino/Beijing Institute of Biotechnology (adeno5), the two latter of which are human adenoviruses. All three adenoviral vectors have been genetically modified to render them incapable of self-replication. The reasoning behind the use of a chimp adenovirus was to avoid the possibility that vaccinees previously infected by human adenoviruses would mount in an immune response against the vector, thus diminishing the efficacy of the vaccine.

The AstraZeneca vaccine, ChAdOx1 nCoV-19, was shown to partially protect rhesus macaques from viral challenge(2). Out of 6 vaccinated animals, none showed signs of pneumonia or lung pathology, while 3 of 6 controls developed interstitial pneumonia. The vaccine elicited binding and neutralizing antibodies against the S protein as well as Th1 and Th2 responses. Protection was not, however, sterilizing. Vaccinated animals had reduced viral loads in their lower respiratory tracts compared to controls, but viral loads in the nasopharynx were equivalent in both groups. A randomized phase1/2 trial with >1,000 subjects was injected with either ChAdOx1 nCoV-19 or the same vector with an unrelated antigen(3). The vaccine elicited binding and neutralizing anti-S antibodies as well as a T cell response without exhibiting serious adverse events. ChAdOx1 nCoV-19, currently in phase 3 trials, has recently been in the news because of a potential serious adverse reaction that temporarily halted the trials. A vaccinated women developed a severe spinal inflammation (transverse myelitis), which can occasionally develop following viral infections. She has since recovered, and it is not clear whether this is related to the vaccine. Trials have since resumed in Britain, but the Food and Drug Administration (FDA) has not yet approved resumption in the US. There are two ways to view this event. It could be considered to reflect the speed with which these vaccines are being developed and might be a cause for apprehension.

The Johnson and Johnson vaccine, Ad26.COV2.S, expresses a prefusion conformation of S protein (proline-stabilized S protein) in a human adeno 26 vector. In rhesus macaques, vaccinated animals developed high levels of binding and neutralizing anti-S protein antibodies and a Th1 biased T cell response(4). The authors suggested that neutralizing antibodies, but not cell-mediated immune activities, were correlative on protection. All 20 controls were infected and developed minimal disease after intratracheal and intranasal challenge. Five of six vaccinated animals were protected from detectable infection, and the sixth had a 3-4 log reduction in virus loads. Ad26.COV2.S is currently in phase 1/2 trials with 11,000 subjects that was started in June. Phase three trials are scheduled for September with 30,000 participants.

The CanSino vaccine, Ad5-S-nb2, contains a codon-optimized gene expressing the S protein. In rhesus macaques, a single dose elicited neutralizing and S protein binding antibodies and activated cell mediated immune responses after intramuscular inoculation(5). Intranasal inoculation induced antibody production but only weak cellular immunity. In an open label non-randomized trial, the vaccine was immunogenic in humans and generally well tolerated with the main adverse effect of being pain(6).  A phase 2 trial with ~600 participants confirmed immunogenicity and safety(7).

There are three vaccines, developed by Sinovac, Beijing Institute of Biological Products, and Sinopharm, that are based upon chemically inactivated whole SARS-CoV-2. These vaccines, unlike the others, contain all the viral structural proteins, and thus, might be expected to induce a wider T cell response than the other vaccines, which contain only the S protein. The Sinovac candidate, Coronavac, elicited neutralizing and binding antibodies against the S protein(8). The highest vaccine dose protected animals completely against an intratracheal challenge, and lower doses prevented severe interstitial pneumonia and resulted in greatly reduced vial loads. In a phase 1/2 trial, Sinovac claimed that 90% of the volunteers developed neutralizing antibodies and had no serious adverse effects. There was no sign of antibody-dependent enhancement within the time frame reported. Sinovac initiated phase 3 trials in Indonesia and Brazil in August and is planning another trial in Bangladesh. Another inactivated virus vaccine (BBIBP-CorV), developed by the Beijing Institute of Biological Products, induced anti-S protein binding and neutralizing antibodies in rhesus macaques and cynomolgus monkeys and protected rhesus macaques from intratracheal challenge(9). BBIBP-CorV will soon be entering human trials. Two other similarly inactivated whole vaccines, produced by Sinopharm, induced neutralizing antibodies in phase 1 trials and had no serious adverse effects(10). Phase 3 trials with this vaccine were started in July in the UAE. 

The speed of vaccine development with which this has happened is remarkable. The general take home message gleaned from an overview of these vaccines is that they induce neutralizing antibodies, stimulate T cell-mediated activity, and partially or completely protect non-human primates from infection and/or serious disease. None appear to cause an undue level of adverse events. The most pressing question is of course when one or more will be available. However, many uncertainties remain given the lack of robust clinical data. We still need to wait for finalization of phase III trials to confirm the safety and efficacy of the vaccine candidates. In particular, potential induction of antibody-dependent enhancement could be a concern. Immunogenicity of vaccine candidates are focused on the induction of neutralizing antibodies. Furthermore, they are mostly administrated by using the intramuscular route, thus limiting the induction of mucosal immunity. Intranasal immunization approach also needs to be considered. In addition, most vaccine candidates might require two doses (prime and boost vaccinations) to enhance their protective efficacy. For a global vaccination, this poses challenges financially and logistically. Therefore, we also need to consider the non-specific protective effects of live vaccines based on stimulation of innate immunity and trained innate immunity (i.e. epigenetic changes induced by live vaccines).

References

 

  1. C. Keech et al., Phase 1-2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine. N Engl J Med, (2020).
  2. N. van Doremalen et al., ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques. Nature, (2020).
  3. P. M. Folegatti et al., Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet 396, 467-478 (2020).
  4. N. B. Mercado et al., Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques. Nature, (2020).
  5. L. Feng et al., An adenovirus-vectored COVID-19 vaccine confers protection from SARS-COV-2 challenge in rhesus macaques. Nat Commun 11, 4207 (2020).
  6. F. C. Zhu et al., Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial. Lancet 395, 1845-1854 (2020).
  7. F. C. Zhu et al., Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet 396, 479-488 (2020).
  8. Q. Gao et al., Development of an inactivated vaccine candidate for SARS-CoV-2. Science 369, 77-81 (2020).
  9. H. Wang et al., Development of an Inactivated Vaccine Candidate, BBIBP-CorV, with Potent Protection against SARS-CoV-2. Cell 182, 713-721 e719 (2020).
  10. S. Xia et al., Effect of an Inactivated Vaccine Against SARS-CoV-2 on Safety and Immunogenicity Outcomes: Interim Analysis of 2 Randomized Clinical Trials. JAMA, (2020).

 

Global Virus Network Announces 2020 Special Annual Meeting

World-Renowned Scientists Come Together to Address COVID-19, Ramifications for Future Epidemics and Pandemics  at September 22-23 Virtual Meeting

Editors’ note: Media are invited to participate in a virtual press conference on Thursday, September 24 at 9 am ET, which will highlight key outcomes/findings of the meeting. GVN founders and session chairs will present the findings, followed by a QA session for news media. To register or learn more, email [email protected]

Baltimore, Maryland, USA, September 17, 2020: The Global Virus Network (GVN), a coalition of the world’s leading medical virology research centers working to prevent illness and death from viral disease, will hold its 2020 GVN Special Annual Meeting virtually September 22-23, 2020.  The current SARS-CoV-2 (COVID-19) crisis has now been ongoing for more than seven months and it is timely to investigate what went wrong, what went right, and what GVN proposes for future pandemics.  GVN, a partner of international institutions such as the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC), looks forward to providing guidance on lessons learned from this current crisis and future preparedness, particularly as we prepare for a potential second wave of SARS-CoV-2 infections.

Discussion topics will include vaccine development, therapeutics and diagnostics, as well as ensuring that scientific truth and fact prevails. This analysis will examine key pandemic response strategies, including a universal masking policy, creating a consortium to improve diagnostics and vaccines, enhancing peer reviewed processes and establishing reliable channels for information sharing. The invitation-only meeting will bring together experts in virology, epidemiology and public health, including representatives of GVN Centers of Excellence, to facilitate international collaboration and information sharing.

“There could not be a more critical time for our organization to host a special meeting as the world continues to battle the COVID-19 pandemic. We look forward to the collaborative ideas, insights, perspectives and recommendations that our Annual Meetings consistently provide, enlightening our members and the broader global scientific community and world leaders in their work addressing virus-causing diseases,” said GVN President Christian Bréchot, MD, PhD. “And at this critical time, we need shared expertise and strategies as we work together to anticipate the second wave of COVID-19 and future pandemics.”

“If there existed a collaborative, first research response such as the GVN when I was working on AIDS, we would have distributed the fast-moving scientific developments more rapidly and saved countless more lives.  COVID-19 is no different, the world should have been better prepared, and still it is not,” said Dr. Robert C. Gallo, co-founder of GVN and the current Director of the Institute of Human Virology at the University of Maryland School of Medicine. “The GVN Special Annual Meeting will give us the opportunity to determine what we must do to address the impending second wave of COVID-19 and be better prepared for the future epidemics and pandemics to come.”

The conference will include presentations by leading international scientists from nine countries representing 15 GVN Centers of Excellence. In addition to Drs. Gallo and Bréchot, presenters include:

 

  • Sharon Lewin of Doherty Institute, Australia
  • Edward Holmes of University of Sydney, Australia
  • Joaquim Segales of Irta-Cresa, Spain
  • Wim H. M. Van Der Poel of Wageningen University, Netherlands
  • Ben Cowling of the University of Hong Kong, China
  • Raymond Schinazi of Emory University Center, USA
  • David Block of Glinknik, USA
  • John Mellors of the University of Pittsburgh, USA
  • Rabindra M. Tirovanziam of Emory University, USA
  • Franco Buonaguro of the National Cancer Institute, Italy
  • Miguel Luengo-Oroz of Un Global Pulse, USA
  • Linfa Wang of the Duke-NUS Medical School, Singapore
  • Florian Krammer of Mount Sinai, USA
  • Amy Chung of University of Melbourne, Australia
  • Sophie Valkenburg of the University of Hong Kong, China
  • Konstantin Chumakov of the FDA Office of Vaccines Research and Review, USA
  • Marion Gruber of the FDA Office of Vaccines Research and Review, USA
  • Chirstine Stabel Benn of the University of Southern Denmark, Denmark
  • Mihai Netea of Radboud University, Netherlands
  • Gavin Cloherty of Abbott Laboratories, USA
  • David Scheer of Scheer & Company, USA
  • Mark Parrington of Sanofi, USA
  • Ab Osterhaus of TiHo Hannover, Germany
  • Matthew Frieman of the University of Maryland School of Medicine, USA
  • Gene Morse of the University of Buffalo, USA

About the Global Virus Network (GVN)

The Global Virus Network (GVN) is essential and critical in the preparedness, defense and first research response to emerging, exiting and unidentified viruses that pose a clear and present threat to public health, working in close coordination with established national and international institutions. It is a coalition comprised of eminent human and animal virologists from 57 Centers of Excellence and 10 Affiliates in 33 countries worldwide, working collaboratively to train the next generation, advance knowledge about how to identify and diagnose pandemic viruses, mitigate and control how such viruses spread and make us sick, as well as develop drugs, vaccines and treatments to combat them. No single institution in the world has expertise in all viral areas other than the GVN, which brings together the finest medical virologists to leverage their individual expertise and coalesce global teams of specialists on the scientific challenges, issues and problems posed by pandemic viruses. The GVN is a non-profit 501(c)(3) organization. For more information, please visit www.gvn.org. Follow us on Twitter @GlobalVirusNews.

Media Contacts:

Sard Verbinnen & Co
Kelly Kimberly/Kelly Langmesser
[email protected]
+1.212.687.8080

GVN
Nora Samaranayake
410-706-1966
[email protected]

 

 

Abbott partners with the Global Virus Network on a new coalition to prepare for future pandemics

In late 2019, a group of infectious disease experts had an idea— to create a coalition among leaders in the public and private sectors that could help prepare for how the global health community responds to emerging pandemics and collaborate to end major viral pandemics.

As the initial program formed between Abbott and Global Virus Network (GVN) – a global coalition of medical virologists – the group quickly realized they would be developing a blueprint for pandemic preparedness, while in the middle of one.

“We are seeing first-hand the urgent need for collaboration when it comes to a novel virus that becomes a pandemic,” says Christian Bréchot, M.D., Ph.D., and president of the Global Virus Network (GVN). “By having this coalition in place, we are essentially creating the instructional manual for how we respond to emerging pandemics, while also creating the vehicle to do so.”

A global virus coalition

The GVN Corporate Centers of Excellence Coalition was first created in late 2019 as a way to bring together the world’s foremost virologists and prominent companies to catalyze and facilitate the development, evaluation and testing of diagnositcs, therapeutics, treatments and vaccines for viral epidemics and pandemics that pose a threat to public health.

As a leader in infectious disease testing and blood screening, Abbott joined as the inaugural member of the coalition.

“We know that every day matters when it comes to responding to a pandemic, which is why collaboration and preparedness are critical,” said Gavin Cloherty, Ph.D., head of Infectious Disease Research, Diagnostics, Abbott. “With this partnership, we are creating a SWAT team of highly trained scientists to share knowledge, techniques and innovative tests and technologies to better understand both existing and emerging viruses.”

The collaboration with GVN plans to focus on three initial areas:

  • Strengthening preparedness
  • Sharing research on known pathogens and emerging pathogens
  • Providing insights on the potential impact of this research

Collaboration during the COVID-19 pandemic

In the early weeks of the pandemic, Abbott brought together a team of its scientists to develop diagnostic and antibody tests to detect the virus and the antibodies that develop after an infection.

One of the key elements for developing these tests were virus samples to ensure the accuracy of our test. Through the Corporate Centers of Excellence program, Abbott collaborated with GVN to identify additional virus samples in different patient populations and has worked with GVN to determine new locations to conduct research.

The coalition is also developing the framework to collaborate and share research on the COVID-19 (SARS-CoV-2 ) virus. Abbott and GVN are establishing a SARS-CoV-2 biobank – or repository that stores biology samples – to study and validate antibody tests.

Planning for the future

From Smallpox, to HIV or the latest efforts for COVID-19, history has shown the impact infectious diseases can have and the need to stay ahead of emerging viruses.

The Centers of Excellence will take learnings developed for the fight against COVID-19 to prepare for future pandemics.

“In the early days of the pandemic, data-sharing was critical to helping the research community understand the virus. We can take the infrastructure from our SARS-CoV-2 biobank in development and use it as a template for future emerging viruses,” said Cloherty.

By developing an integrated global network of scientists and industry leaders, the healthcare community can work together to help in the fight against our current pandemic and quickly respond to future infectious disease outbreaks.

 

About the Global Virus Network (GVN)

The Global Virus Network (GVN) is essential and critical in the preparedness, defense and first research response to emerging, exiting and unidentified viruses that pose a clear and present threat to public health, working in close coordination with established national and international institutions. It is a coalition comprised of eminent human and animal virologists from 55 Centers of Excellence and 10 Affiliates in 33 countries worldwide, working collaboratively to train the next generation, advance knowledge about how to identify and diagnose pandemic viruses, mitigate and control how such viruses spread and make us sick, as well as develop drugs, vaccines and treatments to combat them. No single institution in the world has expertise in all viral areas other than the GVN, which brings together the finest medical virologists to leverage their individual expertise and coalesce global teams of specialists on the scientific challenges, issues and problems posed by pandemic viruses. The GVN is a non-profit 501(c)(3) organization. For more information, please visit www.gvn.org. Follow us on Twitter @GlobalVirusNews

 

GVN MEDIA CONTACT
Nora Samaranayake
Phone:  410-706-1966
Email:    [email protected]

 

COVID-19 Vs. Influenza: Influenza Vaccination Amid COVID-19 Pandemic

Severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2), a highly contagious virus, emerged in 2019 from Wuhan, China (1). It rapidly spread around the world causing a novel acute respiratory disease, coronavirus disease 2019 (COVID-19). The World Health Organization (WHO) declared COVID-19 a pandemic on March 11, 2020. Consequently, the current COVID-19 pandemic impacts global health and economies to unprecedented levels. As of August 17, 2020, over 21,760,000 cases have been confirmed in more than 188 countries, with over 776,580 deaths, and growing daily. The spectrum of disease with SARS-CoV-2 ranges from asymptomatic infection to severe, often fatal disease. Patients with mild disease (80%) have fever, cough, sore throat, loss of smell, headache, and body aches (2). A surge of COVID-19 patients resulted in enormous challenges for capacity and patient flow in hospitals and health care systems globally. Currently, we have limited interventional strategies in curbing COVID-19, and attention has been focused on the progress in the development of vaccines and therapeutics since the beginning of pandemic. Despite the progress, one cannot exclude that the virus would be continuously circulating as a seasonal virus even after the availability of a vaccination program.

Seasonal influenza is a major cause of morbidity, mortality, resulting in a burden on  healthcare services globally every year. According to the WHO, up to 650,000 deaths are associated with seasonal influenza respiratory infections annually. In the Northern Hemisphere, the 2020-2021 influenza season will coincide with the continued circulation of SARS-CoV-2. The nature of disease similarity between COVID-19 and influenza is cause for great concern. In addition, SARS-CoV-2 and influenza viruses have similar transmission characteristics. The two viruses are spread by contact and airborne transmission. The incubation period for influenza is short, typically 1–2 days, whereas for SARS-CoV-2, it is 4.5–5.8 days (2). The basic reproductive rate (R0, the average number of secondary transmissions from one infected person) for SARS-CoV-2 is estimated to be 2·5 (range 1·8–3·6) compared with 2·0–3·0 for the 1918 influenza pandemic, 1·5 for the 2009 influenza pandemic, and 1.3 for seasonal influenza viruses (3, 4). COVID-19 mortality risk has been highly concentrated at old ages (> 65 years old) and those, in particular, males, with underlying medical conditions (called co-morbidities), including hypertension, diabetes, cardiovascular disease, and immunocompromised states (2). Furthermore, SARS-CoV-2 can also infect younger individuals. In particular, children have shown to be susceptible to infection (5). Although most of the infections run a rather benign course, some children may develop severe primary and unique secondary inflammatory complications of infection, including multisystem inflammatory syndrome of children (6). Indeed, while children comprise 22% of the U.S. population, recent data show that 7.3% of all cases of COVID-19 in the U.S. reported to the Centers for Disease Control and Prevention (CDC) were among children (as of August 3rd, 2020). The number and rate of cases in children in the U.S. have been steadily increasing from March to July 2020, even though the incidence of SARS-CoV-2 infection in children is known to be underrated due to a lack of widespread testing. Opening schools in many locations might change a dynamic of transmission of SARS-CoV-2 and COVID-19 cases among children. Similar to COVID-19, influenza-associated excess mortality in elderly individuals related to a range of other chronic health conditions, including cardiovascular causes, diabetes, neoplasms and renal disease (2). In contrast to COVID-19, children are believed to have the highest rates of infection and complications arising from influenza, thus leading to high rates of excess outpatient visits, hospital admissions and antibiotic prescriptions (7). Infections among children can also drive influenza epidemics due to their increased susceptibility to infection and greater contribution to the spread of virus in the community.

Vaccination can be the most efficient and effective measures in controlling the current COVID-19 pandemics. Researchers are developing more than 170 vaccines against the coronavirus, and 47 vaccines are in human trials. In contrast, annual influenza vaccination is available with inactivated influenza vaccines, recombinant influenza vaccine, and live attenuated influenza vaccine. This the main public health intervention in reducing the burden of disease (8). The WHO has recognized some priority target groups for annual influenza vaccination, including pregnant women, children aged 6 months to 5 years, the elderly, subjects with specific chronic conditions, healthcare workers, and international travelers (9). However, influenza vaccination rates among children aged 6 months to 17 years remain low compared with other routinely recommended childhood vaccines. In-plan vaccination coverage during the 2016–17 season was 67.7% in infants (born 2015), 49.5% in toddlers (born 2012–2014), 35.0% in school-aged children (born 2004–2011), and 22.3% in teenagers (born 1999–2003) (10). Like vaccination coverage, vaccination opportunities decreased with age. Along with continued efforts to reduce missed opportunities, effective strategies to bring children to their doctor for annual influenza vaccination are needed, particularly for older children. Among adults, influenza vaccination coverage (≥18 years) was 45.3% in the U.S. during 2018–19 influenza season (11).

The information regarding COVID‐19 and influenza coinfection is limited. Unless screening patients with COVID‐19, the coinfection remains undiagnosed and underestimated. The severity of disease resulting from the co-infections varies by causing a more severe course with a fatal outcome or mild illness (12). Although this needs to be further evaluated, influenza immunization for high-risk groups can reduce the possibility of influenza infection and co-infection with SARS-CoV-2 and complications associated with diagnostics and antiviral treatment. A COVID-19 infection prediction model has also shown that influenza vaccines could reduce COVID-19 infection risk (13). This will also alleviate burden on the health care system by avoiding an overload of health services and hospitals associated with influenza infections (i.e., outpatient illnesses, hospitalizations, and intensive care unit admissions). Influenza vaccine is safe for elderly and children with a proven record over the past 50 years (7). Therefore, influenza vaccination can be a critical component of response to the COVID-19 pandemic. However, there has been a prediction that the COVID-19 pandemic could decrease influenza vaccination, since the pandemic resulted in a 38 percent drop in consumer spending on health care and loss of health insurance (14). In response, CDC already arranged for an additional 9.3 million doses of low-cost flu vaccine for uninsured adults, up from 500,000. The agency expanded plans to reach out to minority communities. It is uncertain how this upcoming influenza season will evolve under the current circumstance. In general, taking an influenza vaccine can be a good preventive strategy for public health.

 

Readers’ Comments are Welcome

 

References

  1. 2020. Rolling updates on coronavirus disease (COVID-19). July 31, 2020. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/events-as-they-happen.
  2. Subbarao K, Mahanty S. Respiratory Virus Infections: Understanding COVID-19. Immunity. 2020;52(6):905-909. doi:10.1016/j.immuni.2020.05.004.
  3. Petersen E, Koopmans M, Go U, Hamer DH, Petrosillo N, Castelli F, Storgaard M, Al Khalili S, Simonsen L. Comparing SARS-CoV-2 with SARS-CoV and influenza pandemics. Lancet Infect Dis. 2020 Jul 3;20(9):e238–44. doi: 10.1016/S1473-3099(20)30484-9.
  4. Biggerstaff, M., Cauchemez, S., Reed, C. et al. Estimates of the reproduction number for seasonal, pandemic, and zoonotic influenza: a systematic review of the literature. BMC Infect Dis 14, 480 (2014). https://doi.org/10.1186/1471-2334-14-480
  5. Han MS, Choi  EH, Chang  SH,  et al.  Clinical characteristics and viral RNA detection in children with coronavirus disease 2019 in the Republic of Korea.   JAMA Pediatr. Published online August 21, 2020. doi:10.1001/jamapediatrics.2020.3988.
  6. Feldstein LR, Rose  EB, Horwitz  SM,  et al; Overcoming COVID-19 Investigators and the CDC COVID-19 Response Team.  Multisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med. 2020;383(4):334-346. doi:10.1056/NEJMoa2021680.
  7. Sullivan SG, Price OH, Regan AK. Burden, effectiveness and safety of influenza vaccines in elderly, paediatric and pregnant populations. Ther Adv Vaccines Immunother. 2019 Feb 7;7:2515135519826481. doi: 10.1177/2515135519826481. PMID: 30793097; PMCID: PMC6376509.
  8. Grohskopf LA, Alyanak E, Broder KR, et al. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices – United States, 2020-21 Influenza Season. MMWR Recomm Rep. 2020;69(8):1-24. Published 2020 Aug 21. doi:10.15585/mmwr.rr6908a1.
  9. World Health Organization (WHO). Vaccines against influenza WHO position paper – November 2012. Wkly. Epidemiol. Rec. 2012, 87, 461–476.
  10. Fangjun Zhou, Megan C. Lindley, Variability in influenza vaccination opportunities and coverage among privately insured children, Vaccine, 2020, ISSN 0264-410X, https://doi.org/10.1016/j.vaccine.2020.07.061.
  11. 2019. Flu vaccination coverage, United States, 2018–19 influenza season. https://www.cdc.gov/flu/fluvaxview/coverage-1819estimates.htm#:~:text=Flu%20vaccination%20coverage%20among%20adults,than%20the%202016%E2%80%9317%20season.
  12. Co-infection with COVID-19 and influenza A virus in two died patients with acute respiratory syndrome, Bojnurd S.A. Hashemi, S. Safamanesh, M. Ghafouri, M.R. Taghavi, M.S. Mohajer Zadeh Heydari, H. Namdar Ahmadabad et al. Iran. J Med Virol (2020), 10.1002/jmv.26014
  13. Jehi L, Ji X, Milinovich A, Erzurum S, Rubin B, Gordon S, Young J, Kattan MW. Individualizing risk prediction for positive COVID-19 testing: results from 11,672 patients. Chest. 2020 Jun 10:S0012-3692(20)31654-8. doi: 10.1016/j.chest.2020.05.580.
  14. Health System Tracker. 2020. How have healthcare utilization and spending changed so far during the coronavirus pandemic? https://www.healthsystemtracker.org/chart-collection/how-have-healthcare-utilization-and-spending-changed-so-far-during-the-coronavirus-pandemic/#item-start