#COVIDMS COVID-19 reinfection?

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Coronovirus COVID-19 Global Cases

The current UK strategy against COVID-19 is built solely around the development of herd immunity within the population (i.e. when sufficient numbers have immunity resisting the spread of the contagion). A risky strategy and relies on a number of suppositions: 1) infection results in immunity, 2) the virus doesn’t mutate resulting in a low chance of reinfection, 3) there is a viable vaccine to vaccinate those not yet exposed and thereby reduce the number of total infected (supposition 3 very much depends on supposition 2).

Let’s focus on reinfection. Reinfection by the same virus is not a new concept, and in fact the seasonal flu follows this concept leading to infection cycles. Professor Peter Openshaw (Immunologist) at the British Society for Immunology:

Professor Peter Openshaw, Past President of the British Society for Immunology and Professor of Experimental Medicine at Imperial College London, said:

“Herd immunity occurs when a large percentage of the population is protected against a particular disease, stopping the ability of that disease to spread within communities. This protection can either be gained through methods such as vaccination (which induces the body to produce antibodies which protect you against catching the disease) or through enough people in the population having been infected and generating antibodies by their body fighting the pathogen directly.  Modelling studies show that, over time, we can expect 60-80% of the population to be infected with SARS-CoV-2.  Generating herd immunity in the population, and particularly in younger individuals who are less likely to experience serious disease, is one way to stop the disease spreading and provide indirect protection to older, more vulnerable groups.

“SARS-CoV-2 is a novel virus in humans and there is still much that we need to learn about how it affects the human immune system. Because it is so new, we do not yet know how long any protection generated through infection will last.  Some other viruses in the Coronavirus family, such as those that cause common colds, tend to induce immunity that is relatively short lived, at around three months.  However, these viruses have co-evolved with the human immune system over thousands of years meaning they may well have developed methods to manipulate our immune responses.  With the novel SARS-CoV-2, the situation may be very different but we urgently need more research looking at the immune responses of people who have recovered from infection to be sure.” Date published Friday, 13 March, 2020

Like all viruses, COVID-19 is expected to mutate, undergoing small changes in its genome making an individual susceptible to reinfection. Recently published work on this from China suggests COVID-19 from Wuhan (the epicenter of the outbreak) has already mutated into one more and less aggressive strain (National Science Review, 3 March 2020), although this could be an artifact with only 103 cases studied:

ABSTRACT

The SARS-CoV-2 epidemic started in late December 2019 in Wuhan, China, and has since impacted a large portion of China and raised major global concern. Herein, we investigated the extent of molecular divergence between SARS-CoV-2 and other related coronaviruses. Although we found only 4% variability in genomic nucleotides between SARS-CoV-2 and a bat SARS-related coronavirus (SARSr-CoV; RaTG13), the difference at neutral sites was 17%, suggesting the divergence between the two viruses is much larger than previously estimated. Our results suggest that the development of new variations in functional sites in the receptor-binding domain (RBD) of the spike seen in SARS-CoV-2 and viruses from pangolin SARSr-CoVs are likely caused by mutations and natural selection besides recombination. Population genetic analyses of 103 SARS-CoV-2 genomes indicated that these viruses evolved into two major types (designated L and S), that are well defined by two different SNPs that show nearly complete linkage across the viral strains sequenced to date. Although the L type (∼70%) is more prevalent than the S type (∼30%), the S type was found to be the ancestral version. Whereas the L type was more prevalent in the early stages of the outbreak in Wuhan, the frequency of the L type decreased after early January 2020. Human intervention may have placed more severe selective pressure on the L type, which might be more aggressive and spread more quickly. On the other hand, the S type, which is evolutionarily older and less aggressive, might have increased in relative frequency due to relatively weaker selective pressure.

However, an opensource data site (nextstrain.org) have released new sequence data for COVID-19. All cases cluster around previous samples with a few mutations relative to a common ancestor, suggesting a shared common ancestor sometime in Nov-Dec 2019 (yellow is England):

Genomic epidemiology of novel coronavirus (hCoV-19)
Transmissions

But, mostly the reinfection rates (in inverted brackets) have been blamed on unreliable diagnostic tests with patients being discharged before they had cleared the infection. A recent publication found that the COVID RT-PCR test is not very sensitive (71%), whilst a CT chest was (98%):

Summary

In a series of 51 patients with chest CT and RT-PCR assay performed within 3 days, the sensitivity of CT for COVID-19 infection was 98% compared to RT-PCR sensitivity of 71% (p<.001).

Introduction

In December 2019, an outbreak of unexplained pneumonia in Wuhan [1] was caused by a new coronavirus infection named COVID-19 (Corona Virus Disease 2019). Noncontrast chest CT may be considered for early diagnosis of viral disease, although viral nucleic acid detection using real-time polymerase chain reaction (RT-PCR) remains the standard of reference. Chung et al. reported that chest CT may be negative for viral pneumonia of COVID-19 [2] at initial presentation (3/21 patients). Recently, Xie reported 5/167 (3%) patients who had negative RT-PCR for COVID-19 at initial presentation despite chest CT findings typical of viral pneumonia [3]. The purpose of this study was to compare the sensitivity of chest CT and viral nucleic acid assay at initial patient presentation.

Discussion

In our series, the sensitivity of chest CT was greater than that of RT-PCR (98% vs 71%, respectively, p<.001). The reasons for the low efficiency of viral nucleic acid detection may include: 1) immature development of nucleic acid detection technology; 2) variation in detection rate from different manufacturers; 3) low patient viral load; or 4) improper clinical sampling. The reasons for the relatively lower RT-PCR detection rate in our sample compared to a prior report are unknown (3). Our results support the use of chest CT for screening for COVD-19 for patients with clinical and epidemiologic features compatible with COVID-19 infection particularly when RT-PCR testing is negative.

However, as with all rumors there is no flame without smoke. Viral shedding patterns suggest that COVID-19 behaves more like flu than SARS/MERS. Unpublished data from the designated infectious diseases hospital in Guangzhou (Gz) – hospital no 8, where over 100 cases nose and throat swabs were studied, demonstrates the viral shedding pattern qPCR in cases (see Figure below). With SARS this is normally flat for a week, rises exponentially as the fever comes on at ~ day 8/9, then peaks before tailing off. However, with COVID-19 there is shedding before symptom onset and through the first 48h, before coming down. This is irrespective of case severity. This is flu dynamics; with a pre-symptomatic viral spread that like seasonal flu, will keep COVID-19 in recirculation.

Unpublished data from Gz No 8 Hospital nose & throat swabs (source data – Dr Gabriel Lung, from WHO collaborating centre, LSHTM lectures)

About the author

Neuro Doc Gnanapavan

4 comments

  • What does this mean for people on immunosuppressive therapies if we can get reinfected again? Washing hands to prevent infections are obvious, but will yearly vaccines keep us safe?

    • Like the flu, yes vaccines would help but may not cover everyone if the virus strain mutates as it crosses the globe. This is currently the case scenario with the flu. The original herd immunity that happens with vaccination, however, will prevent this type of epidemic

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