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expert reaction to a preprint from the SIREN study looking at SARS-CoV-2 infection rates in antibody positive healthcare workers

A preprint, unpublished non-peer reviewed work, from the SIREN (Sarscov2 Immunity & REinfection EvaluatioN) study compares SARS-CoV-2 infection rates in antibody positive and antibody negative healthcare workers.

This Roundup accompanied an SMC Briefing.

 

Prof Paul Hunter, Professor in Medicine, The Norwich School of Medicine, University of East Anglia, said:

“The SIREN study is a very valuable contribution to our understanding of the probability of people developing a second infection after recovering from an initial infection. The two groups (one with no evidence of a previous COVID infection and the other with evidence of such an infection) were followed for up to six months. The incidence density of symptomatic infection in the previously infected group was 1.1 and 13.3 in the previously uninfected group per 100,000 person days about 8% as likely to have a symptomatic infection. By contrast the equivalent figures for all infections including symptomatic ones were 3.3 and 17.0 so about 19.4 % as likely. What this shows is that reinfection is common even in this short time period. I suspect the risk of reinfection will only increase with longer follow-up periods. But many more reinfections are asymptomatic.  In this study only 22% of people without a previous infection were asymptomatic compared to 66% of people with a previous infection.

“So repeat infections are likely to be common in people who are continually exposed to infection but they are much less likely to be symptomatic. Nevertheless, we do have to assume that these asymptomatic infections are still infectious to others albeit less infectious that symptomatic cases.”

 

Prof Eleanor Riley, Professor of Immunology and Infectious Disease, University of Edinburgh, said:

“The take home message from this study is that a primary infection with SARS-CoV-2 provides at least 94% protection against symptomatic reinfection for at least 5 months. This suggests that natural infection provides short term protection against Covid-19 that is very similar to that conferred by vaccination.

“Importantly, natural infection induces approx. 75%  protection against asymptomatic reinfection, suggesting that people who have recovered from SARS-Cov-2 infection are much less likely to transmit the virus to others. This is good news in terms of the long term trends of the pandemic. However, asymptomatic reinfections are not zero, so you cannot assume that just because you have had the virus before that you can’t be infectious.

“These data reinforce the message that, for the time being, everyone should consider themselves to be a potential source of infection for others and should behave accordingly.”

 

Dr Julian Tang, Honorary Associate Professor/Clinical Virologist, University of Leicester, said:

“The outcomes of this SIREN study have been long-awaited – and shows a useful and reassuring result for healthcare workers dealing with COVID-19 patients – that infection/recovery from COVID-19 confers a high degree of immunity (>80% for least 5 months) to reinfection.

“This was also shown in an earlier study (cited in the SIREN study) from Oxford, where the protection was reported to be around 90% for at least 6 months:

https://www.nejm.org/doi/full/10.1056/NEJMoa2034545

https://www.medscape.com/viewarticle/943154

(More accessible summary)

“Even with slight differences in the study methods, endpoints, etc. this should be very reassuring to healthcare workers.

“These results are not surprising as we already know that other coronaviruses – including SARS-COV-1 and MERS-COV, as well as seasonal common cold coronaviruses do produce long-lasting antibodies post-Infection:

SARS-COV-1 (24 months):

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851497/

MERS-COVID (34 months):

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5038413/

Seasonal coronaviruses (12 months):

https://www.nature.com/articles/s41591-020-1083-1

“These reported protective ‘efficacy’ results for natural SARS-COV-2 infection are comparable to the current COVID-19 vaccines.

“Having the vaccine after recovering from COVID-19 is not an issue or contraindication – and will likely boost the natural immunity.  We also see this with the seasonal flu vaccine.

“So hopefully the results from this paper (and the Oxford study above) will reduce the anxiety of many healthcare worker colleagues who have concerns about getting COVID-19 twice.”

 

Prof Danny Altmann, Professor of Immunology at Imperial College London and British Society for Immunology spokesperson, said:

“The Siren Study has collected a really important UK healthcare worker dataset to look at reinfection risk – a point of considerable ongoing concern to healthcare workers and the rest of us. Following over 6000 healthcare workers for 5 months through regular PCR and antibody testing, they conclude that infection confers protection of 76-87% to 5 months, calculated from the fact that 44 reinfections were seen in the previously infected group. Until now, the only other dataset in this sphere of which I’ve been aware has been a large study in Qatar, reporting much lower reinfection, at 243 reinfection cases from 133,000 people studied (0.18%), so this UK study clearly puts the risk of reinfection much higher.

“In any case, such studies enable us to put into a wider perspective the occasional case-reports of reinfections. How common are they? What one thinks of the numbers is very much a ‘glass half full or half empty?’ question: to many, it may be disappointing to put hard numbers to the idea that immunity to this virus is seemingly so variable and feeble that there is a greater than 1 in 10 chance of suffering reinfection, even at 5 months, let alone now, when many UK healthcare workers are more than 9 months out from infections in the first wave. It would be really helpful to see more detail from the SIREN dataset, especially the detail of how much antibody people had to have on board to be ‘safe’.

“In the healthcare workers cohort study that we published before Xmas (C Reynolds et al, Sci Immuniol) we showed that at 4 months, 11% of previously infected healthcare workers had no neutralising antibodies. This matches the at risk number in the Siren study.”

 

Prof Lawrence Young, Virologist and Professor of Molecular Oncology, Warwick Medical School, said:

“This study addresses a fundamentally important question with far-reaching consequences – does the immunity generated by past infection with SARS-CoV-2 protect from subsequent infection? It finds that antibodies (and presumably T cells) from past infection provides 83% protection against reinfection for at least 5 months. Reinfection was rare (44 potential reinfections out of 6,614 participants who had tested positive for antibodies). Early evidence from this on-going study suggests that some antibody-positive individuals have high virus loads and could continue to transmit the virus to others. Overall this study supports previous observations from around the world which have shown that infection with SARS-CoV-2 provides a high degree of immunity to repeat infection at least in the short to medium term. The study also indicates, along with previous work, that primary infection offers similar levels of protection from symptomatic infection as the currently licensed vaccines.

“This is a robust and well-executed multi-centre prospective study of health care workers across the UK and reports findings from 6614 participants between 18th June and 9th November 2020. The study will continue to follow participants for 12 months to determine how long immunity lasts, the effectiveness of vaccines and the degree to which people with immunity are able to carry the virus and transmit it to others.

“One extremely important message from this study is that the antibody protection after infection lasts for 5 months on average but we don’t know how long it will last beyond that time. It is therefore possible that many people who were infected during the first wave of the pandemic may now be susceptible to re-infection. Evidence from previous studies with common cold coronaviruses indicates that this re-infection is unlikely to result in severe disease but may mean that re-infected individuals are able to spread the virus. It will be interesting to know the degree to which previously infected individuals who are subsequently vaccinated are susceptible to reinfection – it could be that these individuals have an even longer-lived protective immune response. The study take place before the UK virus variant took hold so it will be important to determine whether previous infection with the old virus variant is able to offer protection from re-infection with the new virus variant.”

 

Dr Tom Wingfield, Senior Clinical Lecturer and Honorary Consultant Physician, Liverpool School of Tropical Medicine, said:

“Frontline healthcare workers have a high risk of SARS-CoV-2 infection, illness, and death.1,2 In this current Covid-19 wave in the UK, there are high rates of staff sickness and Covid-19 related absence amongst already overstretched healthcare workers. Hospitals are at or over capacity and, in some parts of the country, local NHS services are being overwhelmed.

“Therefore, it is vital that we do all that we can to understand, predict, and prevent risk of SARS-CoV-2 amongst healthcare workers. The well-conducted and extensive SIREN study findings take our knowledge forward in this field.

“The SIREN study team reviewed over 20,000 healthcare worker participants every 2 weeks over a 5-month period. About 6000 of the healthcare workers were people who had evidence of having had SARS-CoV-2 infection (termed the “positive cohort”) and about 14000 of the healthcare workers were people who had no evidence of previous SARS-CoV-2 infection (termed the “negative cohort”).

“The findings suggest that re-infection rates in the positive cohort were 83% lower than the negative cohort during the follow-up period. This is important because it suggests that having SARS-CoV-2 infection seems to lead to an immune response that confers some level of protection from reinfection with SARS-CoV-2 for at least 5 months.

“While the SIREN findings are encouraging, they take us full circle to re-emphasise that the impact of Covid-19 on healthcare workers is high. Moreover, the findings remind us that the optimal strategy to protect healthcare workers is to prevent any SARS-CoV-2 infections through vaccination roll-out and uptake and strong infection prevention and control measures including appropriate PPE.”

1. https://theconversation.com/healthcare-workers-and-coronavirus-behind-the-stiff-upper-lip-we-are-highly-vulnerable-133864

2. https://theconversation.com/we-will-not-forget-our-colleagues-who-have-died-two-doctors-on-the-frontline-of-the-second-wave-148152

 

Dr Simon Clarke, Associate Professor in Cellular Microbiology, University of Reading, said:

“The SIREN study has major implications for how we can get out of the current crisis. The good news is that this study gives further weight that reinfections of Covid is rare, at least at this stage, and that having antibodies will provide protection for a meaningful amount of time, although it may not be lifelong immunity.

“The concerning finding is that some people who have Covid antibodies appear to still be able to carry the coronavirus and could spread it to others. This means that the vast majority of the population will either need to have natural immunity or have been immunised for us to fully lift restrictions on our lives, unless we are prepared to see many more people being infected and dying from Covid-19.”

 

 

Preprint (not a paper): ‘Do antibody positive healthcare workers have lower SARS-CoV-2 infection rates than antibody negative healthcare workers? Large multi-centre prospective cohort study (the SIREN study), England: 4 June to November 2020’ by Hall et al was posted on medRxiv. This work is not peer-reviewed.

https://www.medrxiv.org/content/10.1101/2021.01.13.21249642v1

 

 

All our previous output on this subject can be seen at this weblink:

www.sciencemediacentre.org/tag/covid-19

 

 

Declared interests

Prof Riley: “No COIs.”

Prof Altmann: “DMA has received consultancy fees from Oxford Immunotec.”

Prof Young: “No conflicts or declarations of interest.”

Dr Wingfield: “None.”

Dr Clarke: “No declarations.”

None others received.

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