SWITZERLAND, WEDNESDAY, 1 APRIL 2020 6:00 PM CET
INTRODUCTION
As the world’s first AI-biopharma company that has discovered and publicized the precise aetiology and pathology of COVID-191, we are committed to the non-profit dissemination of our COVID-19 discoveries and the public validation of our COVID-19 clinical predictions.
The prevalence of asymptomatic chronic infection of SARS-CoV-2 in discharged patients is one of our contrarian pathology-based clinical predictions, because all known coronaviridae don’t exhibit viral latency and antibodies in the convalescent plasma would eradicate residual SARS-CoV-2:
“SARS-CoV-2 is fundamentally different from all the other viruses that the world has hitherto known.”1
“Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) adopts a unique unbiased survival strategy of balancing viral replication with viral spread, in stark contrast to other viruses that typically trade off one against the other.”1
“Therefore, COVID-19 treatments must be rationally designed to avoid fueling the adaptive mutation and the latent infection of COVID-19. In accordance with the unbiased survival strategy of SARS-CoV-2 that balances viral replication and viral spread, the effective treatment for COVID-19 must also be unbiased such that both viral replication and host immunomodulation are equally targeted.”1
“While effective but biased treatments could switch SARS-CoV-2 to the asymptomatic infection mode, SARS-CoV-2 can still chronically interfere with the systemic genome, proteome, ion, energy, and immune system homeostases by affecting the baseline activities of ACE2-expressing host cells in multiple organs over the years. When the cumulative disruption of multi-level homeostases is sufficient to switch SARS-CoV-2 back to the symptomatic productive infection mode, asymptomatic SARS-CoV-2 carriers will initiate an accelerated disease progression and trigger severe cytokine storms and fatal comorbidities.”1
When that pathology-based prospective prediction was first announced to the public on March 7, 20202, there hadn’t been any data about the clinical characteristics of COVID-19 patients who were discharged upon recovery but tested positive for SARS-COV-2 later (re-detectable positive patients, or RP patients; in contrast to non-re-detectable positive patients, or NRP patients).
DATA VALIDATION
On March 30 2020, the first study on RP patients, “Clinical characteristics of the recovered COVID-19 patients with re-detectable positive RNA test”3, was uploaded to medRxiv. Its data on 262 discharged patients in China have robustly validated our contrarian prediction of the prevalence of asymptomatic chronic infection of SARS-CoV-2 in discharged patients:
The percentage of RP patients is 14.5% (38/262), and the percentage of mildly-to-moderately symptomatic RP patients is 15.7% (38/204) (Table 1)3.
Table 1
The sensitivity of the SARS-CoV-2 RNA detection Sherlock kit is 75%, whereas the sensitivity of the SARS-CoV-2 RNA detection qRT-PCR commercial kit is only 12.5% (Table 2)3.
Table 2
The Sherlock-detectability-adjusted percentage of RP patients is 19.3%, and the Sherlock-detectability-adjusted percentage of prior mildly-to-moderately symptomatic RP patients is 20.9%.
The percentage of RP patients undetected by the commercial kit is 16.9%, and the percentage of prior mildly-to-moderately symptomatic RP patients undetected by the commercial kit is 18.3%.
Surprisingly, there are no significant differences in IgM and IgG antibody levels between RP patients and NRP patients (Table 3)3:
Table 3
Therefore, our contrarian clinical prediction has been validated because about 20% of discharged COVID-19 patients are persistent carriers of SARS-CoV-2 despite the stable presence of antibodies to SARS-CoV-2 on a similar level to other discharged COVID-19 patients.
Furthermore, the percentage of mildly-to-moderately symptomatic COVID-19 patients is 74.5% (935/3665)(Table 4)4:
Table 4
FURTHER PREDICTION
The percentage of persistently infected mildly-to-moderately symptomatic patients despite multiple rounds of hospitalizations and treatments could be 15.6%.
The percentage of persistently infected mildly-to-moderately symptomatic patients that are undetected by the commercial kit could thus be 13.6%.
As there are 176,563 totally recovered COVID-19 cases worldwide5, we predict that more 24,000 discharged patients may have already become persistent carriers of SARS-CoV-2.
If the persistent carriers of SARS-CoV-2 are hospitalized and administrated with current biased treatments again (chloroquine, lopinavir/ritonavir, hydroxychloroquine, remdesivir, etc.), they are likely to become persistent spreaders of further mutated SARS-CoV-2 that may develop resistance to those treatments according to another clinical prediction that we made:
“As an RNA virus, SARS-CoV-2 has inherently strong adaptive mutability, which is further enhanced by the favorable intercellular microenvironment due to the disrupted homeostatic functions of the ACE2-expressing host cells. Consequentially, SARS-CoV-2 could develop robust resistance to effective but biased treatments that predominantly inhibit either viral replication or viral immunomodulation, and vaccines targeting the S protein can only provide temporary protection at the expense of accelerating adaptive mutation and potentially inducing immune crossreactivity.”1
We predict that those biased treatments that have been currently practiced worldwide, will exacerbate the COVID-19 pandemic in the long run by seeding asymptomatic persistent spreaders of SARS-CoV-2 who will not only unknowingly spread the infection to healthy people but also eventually take an accelerated course to become severely-to-critically ill patients themselves according to another clinical prediction that we made:
“When the cumulative disruption of multi-level homeostases is sufficient to switch SARS-CoV-2 back to the symptomatic productive infection mode, asymptomatic SARS-CoV-2 carriers will initiate an accelerated disease progression and trigger severe cytokine storms and fatal comorbidities.”1
Therefore, the rational discovery of unbiased COVID-19 treatments that target the exact mechanisms of SARS-CoV-2 for both viral replication and host immunomodulation may be the only effective means to put an end to the COVID-19 pandemic.
To that end, Demiurge is also the world's first company that has discovered the complete set of unbiased prophylactic and therapeutic treatments for COVID-19:
1. Irinotecan + etoposide as a specialized treatment for critically ill patients.
2. PI3K inhibitors as a curative treatment for moderately-to-severely ill patients.
3. Non-S-viral-protein optimal target for a broad-spectrum vaccine for the healthy population.
We are currently advancing the clinical development of those unbiased treatments.
REFERENCES
1. Lovetrue, B. The AI-Discovered Aetiology of COVID-19 and Rationale of the Irinotecan+Etoposide Combination Therapy for Critically Ill COVID-19 Patients. (2020). doi:10.20944/PREPRINTS202003.0341.V1
2. Demiurge AI Discovers the Complete Aetiology of COVID-19 and the Optimal Treatment Strategy for COVID-19. Available at: http://www.prweb.com/releases/demiurge_ai_discovers_the_complete_aetiology_of_covid_19_and_the_optimal_treatment_strategy_for_covid_19/prweb16966447.htm (Accessed: 1st April 2020)
3. An, J. et al. Clinical characteristics of the recovered COVID-19 patients with re-detectable positive RNA test. doi:10.1101/2020.03.26.20044222
4. Verity, R. et al. Estimates of the severity of coronavirus disease 2019 : a model-based analysis. Lancet Infect. Dis. 3099, 1–9 (2020).
5. COVID-19 Map - Johns Hopkins Coronavirus Resource Center. Available at: https://coronavirus.jhu.edu/map.html (Accessed: 1st April 2020).
About Demiurge Technologies AG
Demiurge Technologies is a research-based AI-biopharmaceutical company that transforms publicly available life science data into precise disease models in areas with unmet medical needs. The company pioneers a self-correcting scientific approach that validates disease models with the accuracy of AI-based predictions of phase 3 clinical trial outcomes. The company also pioneers a self-sustaining business that commercializes disease models by accelerating the AI-based discovery and development of innovative medicines. Demiurge started in 2016 with headquarters in Switzerland.
AI has been an emerging powerful approach to deeper disease understanding and faster drug discovery, yet it must be put to the most rigorous test to prove its worth under public scrutiny. Demiurge has predicted the outcomes of more than 90 phase 3 clinical trials across multiple therapeutic areas and achieved more than 80% accuracy. Furthermore, we have been inviting the public to witness our future predictions of clinical trial outcomes on Twitter (@DemiurgeTech).
Therefore, we officially put forward AI-based discoveries of the precise aetiology and pathology of COVID-19 and the candidate treatments for COVID-19 as scientific hypotheses only and invite the world to validate their potential to solve the unprecedented global crisis posed by COVID-19.
Demiurge urges everyone to refrain from believing in the efficacy and safety of any COVID-19 candidate treatments before any clinical data come in.
Disclaimers
This material is intended for information purposes only and is provided without any warranty of any kind, either expressed or implied. These statements are not guarantees of future performance, condition or results. Figures and graphs in this presentation are for illustration only and are may not match the actual scale. This presentation contains certain forward-looking statements. These forward-looking statements may be identified by words such as ‘believes’, ‘expects’, ‘anticipates’, ‘projects’, ‘intends’, ‘should’,‘seeks’, ‘estimates’, ‘future’ or similar expressions or by discussion of, among other things, strategy, goals, plans or intentions. Various factors may cause actual results to differ materially in the future from those reflected in forward-looking statements contained in this presentation, among others: 1 pricing and product initiatives of competitors; 2 legislative and regulatory developments and economic conditions; 3 delay or inability in obtaining regulatory approvals or bringing products to market; 4 fluctuations in currency exchange rates and general financial market conditions; 5 uncertainties in the discovery, development or marketing of new products or new uses of existing products, including without limitation negative results of clinical trials or research projects, unexpected side-effects of pipeline or marketed products; 6 increased government pricing pressures; 7 interruptions in production; 8 loss of or inability to obtain adequate protection for intellectual property rights; 9 litigation; 10 loss of key executives or other employees. Demiurge Technologies AG (“Demiurge”) undertakes no duty or obligation to publicly update or revise the forward-looking statements or other information contained in this presentation. You should not view information related to the past performance of Demiurge and its affiliates or information about the market, as indicative of future results, the achievement of which cannot be assured. While some information used in this document may have been obtained from various published and unpublished sources considered to be reliable, Demiurge neither guarantees its accuracy or completeness nor accepts liability for any direct or consequential losses arising from its use. Amounts and percentages may reflect rounding adjustments and consequently totals may not appear to sum. None of the information in this presentation does, by itself, constitute an offering or an offering circular according to Article 652a of the Swiss Code of Obligations and is subject to change without notice. Any offer or solicitation with respect to any securities that may be issued by Demiurge will be made only by means of definitive offering memoranda or prospectus, which will be provided to prospective investors and will contain material information that is not set forth herein, including risk factors relating to any such investment. Before making an investment, you must obtain and carefully read all information needed to evaluate the investment, including, but not limited to the documents providing important disclosures regarding risks, fees and expenses. An investment in Demiurge may be volatile and can suffer from adverse or unexpected market moves or other adverse events. Investors may suffer the loss of their entire investment. An investment in Demiurge will be discrete from an investment in any funds or other investment programs managed by Demiurge and the results or performance of such other investment programs is not indicative of the results or performance that will be achieved by Demiurge or such investment programs.
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