Tagged with disease control

Coronavirus’s centre of gravity

A Centre of Gravity analysis for SARS-CoV-2 (SC2)

“If you know the enemy and know yourself, you need not fear the result of a hundred battles..” Sun Tzu

We need to know our enemy. In order to plan our return to normality, we need to consider the SARS coronavirus’s key attributes, and what makes up its centre of gravity.

SC2_outline_TLACOVID-19 is a disease caused by a new infectious agent; the SARS-CoV-2 coronavirus, for the sake of convenience shortened here to SC2. The disease, COVID-19, is the personified version of SC2, which is able to hijack its victims and turn them into coronavirus factories.

CENTRE OF GRAVITY

A key to understanding the connection between SC2, COVID-19 and all its human consequences is its prodigious transmissibility.

The word ‘transmission’ is made up of ‘trans-‘ (across) and ‘-mission’ (purpose, intent, expeditionary group). This combination signifies a dynamic process across space and time boundaries to recruit new individuals, communities, populations and even other species. Addition of ‘-ability’ denotes a notable feature of SC2, resulting in doubling of new cases in as little  three days. This is SC2’s centre of gravity, summarised here as TRANS.

COVID_COG

Key: CoG, centre of gravity; CCs, critical capabilities; CVs, critical vulnerabilities.

 

CRITICAL CAPABILITIES

SC2 achieves its centre of gravity through a series of critical capabilities:

  1. STEALTH. SC2’s capacity for undetected spread by people with asymptomatic infection, such as during the pre-symptomatic, and convalescent periods. Estimates of asymptomatic infection vary between 30 and 60% of SC2 test-positive people. A notable contributor is SC2’s ability to cause mild symptoms that may seem trivial to the index case, cand an interval of several days until more severe symptoms set in.
  2. PASSENGER. A second key attribute of SC2 is its ability to exploit and target normal human behaviour including close personal contact, prolonged proximity, social aggregation, and easing of hygiene practices in familiar company. SC2 is not self-propelled.
  3. 3-D. SC2 exposes weaknesses in the organisation of healthcare delivery, including diagnostic, therapeutic, preventive, long term residential and surveillance services. As a consequence, SC2 exploits the slow rhythms of peacetime bureaucracy that place a dead hand on lean thinking. This attribute is highlighted where health services are stretched to their limits by high service demand, at great distance for long duration in our most vulnerable remote communities. These three dimensions of logistics give COVID-19 its freedom of action.

 

CRITICAL VULNERABILITIES

COVID-19 is vulnerable to countermeasures that target these critical capabilities.

  1. INTELLIGENCE. STEALTH dictates that COVID-19 can be countered by early detection. This demands increased molecular diagnostic tests, a broadening of indications for testing to include people without any symptoms, and deployment of test capability closer to regional and remote communities. Early detection enables better targeting of control and containment efforts through laboratory evidence.
  2. DISPERSAL. PASSENGER demands an increase in interpersonal distance among social, work and recreational groups. This requires a reduction in people density to individual level for extended periods to achieve a circuit-breaker effect.
  3. LIGHTBULB. 3-D requires organisational agility, a scything elimination of bureaucratic complexity and adoption of lean thinking. SC’s freedom of action is vulnerable to just-in-time decisions that trigger actions within COVID-19’s three day doubling time. Timely solutions will do much for the most vulnerable remote communities.

 

PRIORITIES

In the current reactive stage of the COVID-19 response the current paradigm is largely one of containment. The main effort is about delay, denial, disconnection, disruption and defeat. Accepting that effective treatments and vaccines are at least months away, a comprehensive defeat of SC2 will have to be achieved by other means. The key priorities that come out of COVID-19’s centre of gravity assessment are:

  1.  increased SC2 test availability, throughput, geographic reach and repetition for the duration of the pandemic
  2. increased interpersonal distance, reduced population density, interposition of multiple layers of personal hygiene and protective physical barriers
  3. adaptive decision-making, supported by streamlined administrative support and just-in-time operational research

 

Micrognome, 19th April, 2020.

A COVID-19 READER

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Emerging Infectious Diseases (EIDs) trigger a scramble for new scientific insights to exploit in a co-ordinated public health response. The approach we have used for over a decade is to develop a systematic argument for causation, that links the proposed biological agent of infection with its effects and corresponding countermeasures. Building an argument for cause, effect and countermeasure is an iterative process of argumentation based on a series of four questions about key attributes:

  1. congruence: the point of convergence of molecular and cell biology, clinical features and community impact
  2. consistency: the degree of repetition of the congruent features in subsequent case clusters
  3. cumulative dissonance: a mechanistic understanding of how the biological agent and its effects escalate through increasing layers of biological organisation from the molecular level to the global community
  4. curtailment: demonstration of effective countermeasures at every stage of targeted intervention from diagnosis, through treatment to control and prevention

SC2

 

For a keynote summary on COVID-19 click here.

Week ending 5th April, 2020.

CONSISTENCY (case clusters, modelling). Gilbert M., et al. Preparedness and vulnerability of African countries against importations of COVID-19: a modelling study.  Lancet. 2020 Mar 14;395(10227):871-877. doi: 10.1016/S0140-6736(20)30411-6. This study identified  countries with variable capacity to respond and high vulnerability. Several clusters of African countries were found to be at risk of imported COVID-19 from Guangdong, Fujian and Beijing.

CUMULATIVE DISSONANCE (disease progression). Chen W, et al. Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity. Emerg Microbes Infect. 2020 Feb 26;9(1):469-473. doi: 10.1080/22221751.2020.1732837. In a small series, SARS-CoV-2 was found in blood from 6/57 and in anal swans from 11/28 patients. All those with coronavirus RNA detected in blood and 8/11 with positive anal swabs progressed to more severe disease.

COUNTERMEASURES. Shen C. et al. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. 2020 Mar 27. doi: 10.1001/jama.2020.4783. This small trial of convalescent plasma treatment of severe COVID-19 used plasma with antibody binding tires of more than 1:1000 at 10-22 days after patient admission. Acute Respiratory Distress Syndrome resolved in 4/5  at 12 days after their transfusions, while three were weaned off their ventilators within two weeks. These preliminary observations need confirmation in prospective trials.

Week ending 29th March, 2020.

Before we pick up the EID causality lens, let’s take a look at key questions that should drive operational research efforts in the coming months [Yuen K-S et al. SARS-CoV-2 and COVID-19: The most important research questions. Cell & Biosci 2020 10:40]

  1. How SARS-CoV-2 is transmitted currently in the epicenter of Wuhan
  2. How transmissible and pathogenic is SARS-CoV-2 in tertiary and quaternary spreading within humans.
  3. The importance of aymptomatic and presymptomatic virus shedding in SARS-CoV-2 transmission
  4. The importance of fecal-oral route in SARS-CoV-2 transmission.
  5. How COVID-19 should be diagnosed and what reagents should be made available.
  6. How COVID-19 should be treated and what treatment options should be made available.
  7. Whether inactivated vaccines are a viable option for SARS-CoV-2.
  8. The origins of SARS-CoV-2 and COVID-19.
  9. Why SARS-CoV-2 is less pathogenic.

We should bear these in mind as we pick through the recent literature.

SC2

Principia aetiologica.

Logic in a time of coronavirus.

CONGRUENCE (molecular biology). Rehman SU et al. Evolutionary trajectory for the emergence of novel coronavirus SARS-CoV-2. Pathogens 2020, 9 (3) pii: E240. This study used whole genome sequencing to show how SARS-CoV-2 is the likely descendant of bat SARS viruses, and uses mutation and recombination events in parts of the viral genome to change envelope, membrane, nucleocapsid and spike glycoproteins to become a novel infectious agent. Multiple recombinations in the S gene were detected. These are thought to improve survival and adapt to a human host.

CONSISTENCY (case clusters). Chan JF et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet 2020; 395: 514-23. This a key case-cluster report from Wuhan in the early stages of the pandemic, and therefore a good place to start assessing the consistency of clinico-pathological and epidemiological features in subsequent clusters.

CUMULATIVE DISSONANCE (mechanism of pathogenesis). Hoffmann M et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020 Mar 4. pii: S0092-8674(20)30229-4. Entry of SARS-CoV-2 relies on binding of viral spike proteins to cell surface receptors and subsequent priming by enzymes called proteases. This could help identify possible future treatments. This study showed that SARS-CoV-2 uses an ACE2 receptor to enter mammalian cells and then primes its spike protein with a protease. The study also showed that serum from convalescent patients neutralised SARS-2-S-driven cell entry.

CURTAILMENT (targeted countermeasures). Peto J. COVID-19 mass testing facilities could end the epidemic rapidly. BMJ 2020; 368: m1163. This is an interesting proposition that mass screening, performed on more than one occasion could be used to bring the UK’s national COVID-19 epidemic to an end more quickly and cheaply than a vaccine. The argument revolves around using RT-PCR assays as the key enabler for mass rapid diagnosis and subsequent control.