Coronastream: protective immunity, transmission dynamics and clinical presentations

Posted on May 18, 2020   by Dr Tim Inglis

In this special blog series, medical microbiologists led by Dr Tim Inglis summarise some of the research that will be essential to inform COVID-19 countermeasures. Find out more about the project in Dr Inglis' Editorial 'Logic in the time of coronavirus', published in the Journal of Medical Microbiology.

There are enough data at this stage in the COVID-19 epidemic to start populating a cohesive cause and effect narrative: congruence (convergence of molecular biology, clinical features and epidemiology), consistency (reproducible features of this nexus, and its temporal–spatial clustering), cumulative dissonance (upscaling through multiple levels of biological organisation) and curtailment (diagnosis, containment, control and preventive interventions).

Congruence: unusual clinical presentations

An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study

There has been a lot of speculation around a possible association between Kawasaki disease and SARS-CoV-2 infection in recent weeks. This report documents a 30-fold increase in a Kawasaki-like disease in the province of Bergamo, Italy. Verdoni and colleagues split their subjects into two cohorts around the onset of the local COVID-19 epidemic. Diagnostic tests for SARS-CoV-2 were only available for the second cohort of 10 children. SARS-CoV-2 RT-PCR was positive in only two cases, IgM antibodies were detected in three and IgG antibodies in eight. No coronavirus PCR results were reported in the first cohort.

As an infective cause of Kawasaki disease has not been established, this study opens up further questions about the possible unexplored role of other coronaviruses in the first cohort, a possible range of age-specific effects of SARS-CoV-2 infection, and the underlying reason for the rare appearance of Kawasaki-like features associated with paediatric exposure to this coronavirus.

Consistency: SARS-CoV-2 transmission dynamics

Projecting the transmission dynamics of SARS-CoV-2 through the post-pandemic period

As some countries begin to emerge from the first COVID-19 pandemic wave, there is much discussion of what the next phase of epidemic activity will look like. Predictions have immediate relevance to how to relax social restrictions, and longer-term relevance to public health preparedness. In this paper, Kissler and colleagues report what they found when they used data from the USA to model SARS-CoV-2 transmission dynamics in temperate regions through to 2025.

As in all epidemiological modelling, assumptions had to be made from the known behaviour of other coronaviruses to compensate for SARS-CoV-2 knowledge gaps. Their conclusions are not very reassuring. In the absence of measures such as new therapeutics, vaccines, aggressive contact tracing and quarantine, they foresee a need for continued surveillance and intermittent distancing into 2022. They highlight five key points:

  1. SARS-CoV-2 can proliferate at any time of year
  2. If immunity to SARS-CoV-2 is not permanent, it will likely enter into regular circulation,
  3. High seasonal variation in transmission leads to smaller peak incidences during the initial pandemic wave but larger recurrent wintertime outbreaks,
  4. If immunity to SARS-CoV-2 is permanent, the virus could disappear for five or more years after causing a major outbreak,
  5. Low levels of cross immunity from other betacoronaviruses against SARS-CoV-2 could make SARS-CoV-2 appear to die out, only to resurge after a few years.

An important philosophical question that has not been addressed is whether the COVID-19 pandemic ends after its first wave, or does it include further sporadic cases, outbreaks and waves attributable to SARS-CoV-2?

Cumulative dissonance: SARS-CoV-2 tissue tropisms

Multiorgan and Renal Tropism of SARS-CoV-2

In this case series of 27 autopsies, Puelles and co-authors used a combination of SARS-CoV-2 RT-PCR, in situ hybridisation and immunofluorescence techniques to demonstrate a putative tropism for tissues in non-respiratory organs including the kidneys, heart and liver. Of note is their observation that a greater number of coexisting conditions was associated with a SARS-CoV-2 tropism for the kidneys, which they followed up with in silico sequence analysis of public databases. They found that the RNA thought to facilitate SARS-CoV-2 infection i.e. for angiotensin converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS 2) and cathepsin L (CTSL), is enriched in kidney cells.

Curtailment: protective immunity

What policy makers need to know about COVID-19 protective immunity

While the world awaits the arrival of a safe, effective and deliverable SARS-CoV-2 vaccine, some key questions about the immune response to SARS-CoV-2 infection need to be answered. Altmann, Douek and Boyton address this article to policy-makers who are now facing big decisions that will affect all of us. They note that without certainty about the immunological measures of protection against SARS-CoV-2, and the proportion of the population who attain them, it is impossible to identify a point when this level of immunity has been reached. The authors stress the importance of considering Plotkin’s correlates of protection: the empirically defined, quantifiable immune parameters that determine protection against a specified pathogen. Knowledge of immune correlates of disease progress will likewise be informative. We are reminded that total antibody is not the same as protective, neutralising antibody. As 10–20% of symptomatic cases have little or no detectable antibody, and asymptomatic or mild, non-hospitalised cases may have much lower percentage antibody positivity, there is clear need for collection of sero-prevalence data. Whether vaccines or serology tests; caveat emptor.

Other resources:

Thanks to Dennis Shanks for recommending the first two papers in this week’s blog, and to David Smith for his thoughts on the Kawasaki-like syndrome.