Introduction to BMJ Rapid Recommendations
BMJ 2016; 354 doi: https://doi.org/10.1136/bmj.i5191 (Published 28 September 2016) Cite this as: BMJ 2016;354:i5191![Loading Loading](https://cdn.statically.io/img/www.bmj.com/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif)
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Dear Editor
We long-haulers, people recovering from Covid-19, speak with one voice. Whether we are 1 or 150 days from knowing we had the virus, we are still experiencing symptoms – new ones and the return of old ones. We want to know what to do to give ourselves the best possible chance of recovery.
Yet we are very different. Each of us had our own version of Covid-19 with a myriad of symptoms including fever, delirium, struggling to breathe, hacking coughs, razor sharp sore throats, chest pain. There were those who lost all sense of taste, smell and couldn’t eat. Some had a heightened sense of taste, smell and were ravenously hungry.
Perhaps, given those differences, it isn’t surprising that each long-hauler has a different combination and severity of post-virus symptoms. These can appear to be asthma, thrombosis, dysautonomia, POTS, dyslexia, Alzheimer’s, heart-beat irregularity, gastro-intestinal issues, alopecia, ME and post-viral fatigue to name but a few. Problems span the whole body – the heart, lungs, brain, kidneys, liver, central nervous system and blood. So medical practitioners are being presented with patients with a massive range of symptoms and for which, often, there is no easy or immediate answer to what is wrong or what they can do to recover.
Many patients, particularly with severe, initial stage Covid-19, receive dedicated, professional treatment from nurses, doctors and health care workers in hospitals and care homes. Some long-haulers have reported fantastic help from GPs, wide ranging tests and ongoing support.
But some, particularly long-haulers and those who experienced ‘moderate’ or ‘mild’ Covid-19, are being told their on-going symptoms are the result of anxiety or the menopause. For patients explaining they are still getting spikes of what feels like fever after 100 days, when the GP starts to suggest the menopause, they are unlikely to go on to mention their heart rate almost doubles when they stand up, they’ve found they are writing ‘g’s, ‘d’s and ‘p’s the wrong way around, their hands turn blue in the shower and there are holes in their brain where words and information used to be.
As a result, very few other people are getting a true picture of the breadth, severity and potential longevity of symptoms long-haulers are coping with and trying to find ways to recover from.
Some doctors, GPs and medical staff may have, wisely in other circumstances, advised against googling symptoms on the internet or following advice from support groups. But for patients who have spent months with symptoms including unhappy lungs, an irregular heart-beat, seeing what appear to be blood clots, with rashes, brain fog, unable to digest a wide range food, getting a diagnosis of anxiety can clarify they have no choice. They do their own research. They attempt to match symptoms with treatments. They try to take account of their previous medical history and personal fitness. They become their own medical adviser and advocate for recovery.
So, what is the way to wellness?
Just as there are a whole range of long-term symptoms, a whole range of people need to come together – internationally, nationally and regionally - to create answers. We need people who have experience of and understand: post-viral issues including Sepsis Trust UK and The ME Association; asthma and breathing issues such as Asthma UK; the role diet and vitamins can play in recovery - herbalists, nutritionists; mental health specialists; medical experts in POTs, neurology, cardiology, liver function, immunology; counsellors; physios; GPs; nurses; care home staff.
We need them to collaborate, share their skills, knowledge and understanding, with those from other fields and areas of expertise. To begin to create a possible menu of options and treatments for a wide range of symptoms. To create a ‘community for wellness’, a ‘community for post-Covid-19 recovery’. And to share this widely. So how to recover is not dependent on where you live, your ability to access the internet, your finances or the person a patient consults for help.
There isn’t going to be a bottle labelled ‘Post-Covid-19 treatment’. It is going to take a personalized plan for everyone – of medical, physical, emotional and perhaps even spiritual supports and treatments. No one person or one group can hold the answer to how to get well. So many people from so many different fields, potentially, have something important they can contribute.
And patients need to be at the core of this collaboration. Patients need to be listened to, their symptoms acknowledged and collected, to take part in tests, investigations. Their experiences are a crucial part of finding the way to wellness.
Covid-19 has made us all look again at our world. It has made us look closely at what we need to change, at what is negative, is endangering us - our wildlife, ecosystems, environment, our planet’s future. It has also given us time to generate new ideas and a better understanding about what we need to protect, preserve and promote, of what is wonderful about our world, of the best things we are and can be as humans.
So, perhaps the virus and the treatment of post-Covid-19 symptoms experienced by long haulers gives us another opportunity. The opportunity to change how we develop our understanding of, diagnose and treat long-term symptoms from this virus and other illnesses. Where members of many different communities including medics, charities, alternative practitioners, mental health and recuperation specialists come together, with patients at the core, to find ways to promote recovery. Where there is listening, sharing of expertise, curiosity, determination, dedication, open mindedness, asking questions is encouraged, hitherto unmade links, connections and ideas are generated, where an understanding of the importance of and interplay between mind, body and spirit is valued.
A community for post-Covid-19 recovery. This could be our way to wellness.
Competing interests: No competing interests
Dear Editor
Ebrahim and colleagues discuss the mass gatherings and events such as Hajj should be restricted during COVID-19.
Hajj is a major annual Muslim worship gathering of about 2.5 million people from over 180 nations and occurs at a specific time of the year. During Hajj, pilgrims visit two holy cities (Makkah and Madinah ) in Saudi Arabia; they remain there for about five days in small, crowded areas (Arafat, Mina, Muzdalifah), presenting a potential risk for multiple food-, water-, and air-borne communicable diseases such as COVID-19. Participation essentially amplifies their risk of acquiring and transmitting the disease. Once they completed all aspects of Hajj, pilgrims return to their countries with a 40–90% chance of contracting or transmitting a respiratory infection. 1
In 2009, the World Health Organization (WHO) consultation group established the Jeddah Recommendations to prevent and minimize the effects of the pandemic influenza A (H1N1) virus. In 2009, recommendations included voluntarily refraining from the Hajj for high-risk groups such as pregnant women, those with chronic diseases, and people under 12 or over 65 years of age, who accounted for at least 25% of the pilgrims.2 Hajj 2009 took place without any pandemic issue. Then, the same discussion emerged again in 2013- 2014, following the discovery of a new virus known as the Middle East Respiratory Syndrome Coronavirus (MERS- CoV), an outbreak with several cases and deaths in Saudi Arabia that year. There was no vaccine or treatment, so the WHO recommended that the same high-risk individuals postpone their plans to attend the Hajj. Again, there was no significant pandemic event. 2
Today, the situation is different. The first cases of pneumonia appeared in Wuhan, China, in early December 2019. This virus (now named SARS-CoV-2) increased rapidly all over the world in a few short months, and now almost everyone is aware of COVID-19. It has affected more than four millions people and killed over 290,000. These numbers continue to increase, and it remains unknown when the SARS-CoV-2 will over. 3 So far, it had a huge negative impact on all life aspects, including socio-economic and health, and the effect will persist for a while even if a successful vaccine or treatment was discovered.
As a consequence, mainland China was the first country hit by the virus, and subsequently banned all mass gatherings after the Chinese Lunar New Year holiday and encouraged people to stay at home, even from school. All activities were banned or closed, and this policy saved many lives. Japan ultimately postponed the Tokyo 2020 Summer Olympics until 2021. 3 The Olympics brings together hundreds of thousands of attendees as well as competing athletes and other visitors and typically requires about seven years of planning. It was likely a very difficult decision; however, protecting the health of the athletes, attendants, and the global community is critically important.
This year, Hajj will begin in late July and continue until the beginning of August, which coincidentally aligns with the original schedule of the World Olympics for 2020. Pilgrims who participate in Hajj could potentially serve as indexed cases once they return home, which could have dire consequences. The high risk of pilgrims interacting with others via person-to-person contact means likely transmission of SARS CoV-2 and new infections in their home countries. Transmissions could reach and affect entire cities and families who reside there; conversely, they could infect additional Saudi citizens, overwhelming health care workers, and increasing the risk of exposure. The spreading of the disease will increase simply because it will be difficult to control it.
The current situation in Saudi Arabia is fine, so far. The first case was detected on March 2 in a case brought in from a neighboring country. The total number of cases is about 3,000 after approximately 40 days, with a reported rate of mortality less than 1.5% .4 The Saudi government took several steps to minimize the disease spreading via the enforcement of remote education, suspension of domestic and international flights, the shutdown of public offices except for those that are health-related, closures of mosques, and lockdowns of specific cities. However, the number of cases continues to increase, and we do not know the point at which this disease will end, as numbers can change rapidly at any time.
Hajj 2020 should be suspended in the interest of global safety; a further outbreak will jeopardize the health of pilgrims, workers, and national and international citizens. Hajj has been canceled several times in the past before the modern country of Saudi Arabia developed. On March 4, the Saudi government banned Saudi citizens and international visitors from Umrah, which is a minor worshipping event that can happen anytime during the year and with smaller crowd sizes.5 However, a large number of elderly and disabled individuals would participate during Hajj. Umrah visitors generally travel as singles or families in small groups and are not exposed to didactic health education programs like Hajj. International visitors spend on average 10 days, and between 43% -50% of them are over the age of 55 and have pre-existing chronic diseases; two-thirds of them are from countries with insufficient disease surveillance systems or travel health-counseling services. 6
Yes, participants can take numerous precautions during Hajj, such as handwashing, using sanitizer, gloves, and facemasks, equipping hospitals, and providing educational materials. However, such precautions will not prevent the disease from spreading if an epidemic occurs during Hajj. Consider facemasks, for example; while they can alleviate aerosolized transmission, they cannot prevent it in densely populated areas. Few people used them during the last two outbreaks (8.4% during the 2009 H1N1 influenza A pandemic and 0.02% during Middle East Respiratory Syndrome coronavirus (MERS-CoV)). 7 Moreover, there are no definitive treatments or a vaccine available yet. It will take time to have it ready to use and be available to all people. Even if it is ready by the time of Hajj, it could minimize the number of new cases, but there is always a risk of transmission and spreading the disease further.
The decision to cancel Hajj will have a significant and negative impact on the Saudi economy due to airline rescheduling and cancellations, transport and hospitality vacancies, and a reduced workforce. It will also be emotionally and mentally challenging for the many pilgrims who consider Hajj to be a cornerstone of the Muslim faith; for many, it is a lifelong dream to participate. However, this decision will have immeasurable benefits beyond Saudi Arabia to family members and cities of many people in Asia, Africa, Europe, and other Middle Eastern countries. Cancelling Hajj will prevent the numerous challenges associated with a massive volume of pilgrims during this critical time. Hajj is approaching quickly; we should not wait until the last minute to cancel it because the decision will be even more devastating to the many people who have prepared themselves for this religious experience.
References
1. Memish ZA, Steffen R, White P, et al. Mass gatherings medicine: public health issues arising from mass gathering religious and sporting events. Lancet 2019; 393:2073-84. doi: 10.1016/s0140-6736(19)30501-x pmid: 31106753.
2. Ebrahim SH, Memish ZA, Uyeki TM, et al. Public health. Pandemic H1N1 and the 2009 Hajj. Science 2009; 326:938-40. doi: 10.1126/science.1183210 pmid: 19933105.
3. Gautret P, Al-Tawfiq JA, Hoang VT. COVID 19: Will the 2020 Hajj pilgrimage and Tokyo Olympic Games be cancelled? Travel Med Infect Dis 2020; 101622. doi: 10.1016/j.tmaid.2020.101622 pmid: 32171882.
4. Worldometers. Coronavirus Cases:Saudi Arabia [April 8 , 2020]. Available from: https://www.worldometers.info/coronavirus/country/saudi-arabia/.
5. Ebrahim SH, Memish ZA. Saudi Arabia`s measures to curb the COVID-19 outbreak: temporary suspension of the Umrah pilgrimage. J Travel Med 2020; doi: 10.1093/jtm/taaa029. pmid: 32109274
6. Ebrahim SH, Memish ZA. COVID-19: preparing for superspreader potential among Umrah pilgrims to Saudi Arabia. Lancet 2020; 395:e48. doi: 10.1016/s0140-6736(20)30466-9 pmid: 32113506.
7. Elachola H, Assiri AM, Memish ZA. Mass gathering-related mask use during 2009 pandemic influenza A (H1N1) and Middle East respiratory syndrome coronavirus. Int J Infect Dis 2014; 20:77-8. doi: 10.1016/j.ijid.2013.12.001 pmid: 24355682.
Competing interests: No competing interests
Response to ‘Going viral: doctors must combat fake news in the fight against Covid-19. https://www.bmj.com/content/368/bmj.m1090/rr-10
Dear Editor,
We read with great interest ‘Covid-19: how doctors and healthcare systems are tackling coronavirus worldwide’ and the rapid response ‘Going viral: doctors must combat fake news in the fight against Covid-19.’
The year 2020 will be remembered for the COVID-19 pandemic. The uncertain and constantly evolving nature of COVID-19 has posed significant issues for ensuring correct and up to date information is circulated both within the medical community and is accurately communicated to the general public. The rate of and need for new information, and availability of information sources precludes accurate and critical analysis. This has been true not only for general information, but also peer-reviewed research that has been of questionable quality [1].
As described by O’Connor [2], the potential for the rapid dissemination of misinformation is huge and has direct implications on behaviours of those consuming such information, as well as wider implications on public opinion for public health policies implemented over the coming months. The internet and social media, never before available in a crisis such as this, has been demonstrated to have great utility for communication, especially between clinicians in countries that were already tackling COVID-19 - and those preparing for it. As seen in discussions between Italian and UK ICU doctors in March via informal communication methods, [3, 4] or more formally mediated via well-known and well-respected organisations [5]. Similarly, novel Free Open Access Meducation (FOAM) resources have been utilised to succinctly distil and communicate current best practice in managing COVID-19 patients [6].
Whilst undoubtedly many aspects of social media and other forms of novel communication methods have demonstrated their benefit during the current crisis, these methods provide the potential to facilitate the spread of anonymous and unhelpful misinformation. This is particularly true when considering the disproportionate coverage that celebrities and other well-known individuals receive when commenting on public health interventions. Celebrities are often approachable and easily empathised with, though most of these individuals are no more qualified, or experienced, than an average member of the public. Unfortunately, due to their status alone they are viewed as a trusted source and easily out-compete official sources in viewership.
Small amounts of reading in these areas can often lead to overconfidence and an inability to recognise the complexity of the situation [7], celebrities and high-status individuals are at a greater risk of this than the general population [8]. There is also history of celebrities abusing their trusted status to sell products [9].
Statements by celebrities on social media, and through television, have helped to propagate misinformation. For example, over social media, unqualified individuals have touted preferences for ventilation strategies and shared unhelpful and alarmist articles [10] to millions of people, misinterpreting the complexity of decision making and potentially undermining future attempts by clinicians to communicate management plans to patients and family members.
Through live-television, the comments of ill-informed individuals have led to further traction of conspiracy around the involvement of 5G in the COVID-19 virus [11], and a statement by one individual live on television led to shortages in Hydroxychloroquine [12], a drug that is essential for treatment of many rheumatological diseases. This statement was made despite lack of conclusive evidence [13, 14]. More recently the same individual suggested whether injecting UV light or cleaning products into the veins may help treat coronavirus infections [15]. These seemingly throw away comments have far reaching, fatal effects, likely far beyond the impact that similar comments from reputable sources on well-evidence interventions could ever achieve [16].
As previously described, the ability of public authority figures to have wide scale impact on public behaviours is not a novel one, the effects are now amplified due to the COVID-19 crisis where seemingly harmless behaviours can lead to devastating effects. Whilst attempts to address misinformation have already been taken; through adding links to official government sources, or WHO [17], to social media sites, the efforts required to dispel such propositions often far outweighs that which was made to spread the misinformation in the first instance. This is likely why it feels as if we are fighting a losing battle.
The quality of discussion around the basic science of viruses, infectious disease, and treatment of infectious disease, also serves to highlight the ineffective attempts to provide mass public health education previously, and perhaps provides a spotlight on the importance of cultural difference when implementing public health interventions. One only has to compare COVID-19 response within the UK and US as opposed to Scandinavian countries, or the likes of Germany who seems to be managing the crisis more effectively, at least in terms of testing and mortality [18].
This all serves to highlight the need for health professionals to re-emphasise our roles in the fight against misinformation. We must reconsider our position and responsibilities in the education of the public, combating misinformation as we come across it, and as a collective holding those in power or positions of influence to account for the messages they spread. We must recognise that currently our influence on public behaviour may be overestimated and we must work collaboratively with those who receive public attention to ensure the appropriate message is communicated to those in our society who may be more sheltered from direct information and therefore more vulnerable to the effects of misinformation.
References:
1. Gautret P, Lagier JC, Parola P, Meddeb L, Mailhe M, Doudier B, Courjon J, Giordanengo V, Vieira VE, Dupont HT, Honoré S. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. International journal of antimicrobial agents. 2020 Mar 20:105949.
2. O’Connor C, Murphy M. Going viral: doctors must tackle fake news in the covid-19 pandemic. bmj. 2020 Apr 24;369.
3. Van Schoor J. @jasonvanschoor From a well respected friend… [Tweet]. 2020 Available from: https://twitter.com/jasonvanschoor/status/1237142891077697538?s=20 [Accessed 2nd May 2020].
4. Cecconi M. @DrMCecconi. Our key learning points. [Tweet]. 2020 Available from: https://twitter.com/DrMCecconi/status/1235652849759137798 [Accessed 2nd May 2020].
5. European Society of Intensive Care Medicine. COVID-19 ICU Network - ESICM [Internet]. 2020 [cited 2020 Mar 14]. Available from: https://www.esicm.org/covid-19-icu-network/
6. St Emlyn’s, COVID-19 Resources. 2020. Available from https://www.stemlynsblog.org/covid-19-resources/ [Accessed 2nd May 2020].
7. Dunning D. The Dunning–Kruger effect: On being ignorant of one's own ignorance. InAdvances in experimental social psychology 2011 Jan 1 (Vol. 44, pp. 247-296). Academic Press.
8. Belmi P, Neale MA, Reiff D, Ulfe R. The social advantage of miscalibrated individuals: The relationship between social class and overconfidence and its implications for class-based inequality. Journal of personality and social psychology. 2019 May 20.
9. BBC, Celebrities warned over Instagram ads. 2017. Available from: https://www.bbc.co.uk/news/business-39650580) [Accessed 2nd May 2020].
10. Musk E. @elonmusk. Vast majority of “ventilators" are not intratracheal… [Tweet]. 2020 Available from: https://twitter.com/elonmusk/status/1250607449498775552?s=20 [Accessed 2nd May 2020].
11. BBC, Coronavirus: Eamonn Holmes under fire over 5G comments. 2020. Available from: https://www.bbc.co.uk/news/entertainment-arts-52270736 [Accessed 2nd May 2020].
12. Peschken CA. Possible Consequences of a Shortage of Hydroxychloroquine for Lupus Patients Amid the COVID-19 Pandemic. The Journal of Rheumatology. 2020 Apr 8.
13. Ferner Robin E, Aronson Jeffrey K. Chloroquine and hydroxychloroquine in covid-19 BMJ 2020; 369 :m1432
14. Taccone FS, Gorham J, Vincent JL. Hydroxychloroquine in the management of critically ill patients with COVID-19: the need for an evidence base. The Lancet Respiratory Medicine. 2020 Apr 15.
15. BBC, Coronavirus: Outcry after Trump suggests injecting disinfectant as treatment. 2020. Available from: https://www.bbc.co.uk/news/world-us-canada-52407177 [Accessed 2nd May 2020].
16. Hoffman Steven J, Tan Charlie. Following celebrities’ medical advice: meta-narrative analysis BMJ 2013; 347 :f7151
17. WHO, WHO Health Alert brings COVID-19 facts to billions via WhatsApp. 2020. Available from: https://www.who.int/news-room/feature-stories/detail/who-health-alert-br... [Accessed 2nd May 2020].
18. Financial Times, Coronavirus Tracked: the latest figures as countries fight to contain the pandemic. 2020. Available from: https://www.ft.com/coronavirus-latest [Accessed 2nd May 2020].
Competing interests: No competing interests
Dear Editor
Hugh Rayner and colleagues are to be commended for drawing attention to this important part of patient care [Writing outpatient letters to patients. BMJ 2020;568:m24]. When I asked people who had experienced cancer to "tell me all about it" one man illustrated the distress that can be caused by sending copies of letters, intended for fellow professionals, to the patient.
"Joyce had lung cancer and really didn’t want to know. I will always remember because the letter from the hospital was written professional to professional, stating the facts: very harsh, and we hadn’t asked for a copy as far as I can remember. It said that Joyce had a terminal illness, that treatment would not be beneficial and they would provide just palliative care. Joyce read the letter, threw it down and burst into tears. When it’s in black and white you can’t escape the reality. That is my one regret: if I could have stopped the letter from the hospital I would."*
Yours etc
RRHall
*From "Connecting with Cancer" by RRHall & Robert Olley, pub.Melrose Books. 2017
Competing interests: No competing interests
I was overjoyed to read about emergency paediatric and neonatal transport consultant Hazel Talbot playing netball again after an 18-year gap. As someone coming to the end of FY1 I am in a very different place in my medical career yet can agree with all of Dr Talbot's views on the sport and it’s positive affect on health and wellbeing. I have always loved team sports but did not join a club when starting FY1 believing, as many of my other FY1 friends/colleagues did, that on-call commitments alongside the busyness of daily life would not allow time for training and matches.
However 8 months into the job and I really missed the physical and social aspect to team sport. I found a summer social netball league where matches are once weekly with no training. The league was full of teams of different abilities and ages. I fully recommend to anyone considering starting a new team sport to give it a go and talk honestly and openly to the team about your situation before starting in order to find a club that suits your availability. My team was very understanding when I explained I could not commit to all matches due to on-call shifts and it turned out there were several other doctors at various stages of their careers also in the club and in the same position.
Similarly to Dr Talbot, netball has helped my work-life balance, making me work efficiently, hand over appropriately and not take on extra work that I shouldn’t so that I can leave on time to get to netball on Wednesdays. With netball being such a fast paced game I become so focused on the match that I can completely switch off all thoughts of work, something many of us find difficult to do. Other colleagues who have joined 5-a-side football and similar social sports all agree on the positive effect it has had both physically and mentally.
Competing interests: No competing interests
This type of frequently updated Rapid Recommendations on medical management are very much needed to manage patients' cases with up to date knowledge. These can also help in adopting recent advances and guidelines in patients' health care management.
Competing interests: No competing interests
COVID-19 and pre-existing immunity
Dear Editor
Since Peter Doshi’s excellent feature in the BMJ in September, entitled ‘Covid-19: Do many people have pre-existing immunity?’ [1], further studies on unexposed subjects have now been undertaken. Although all studies so far are small, they indicate that a significant proportion of individuals globally entered the SARS-CoV-2 pandemic with some pre-existing immunity. This is true of studies of IgG antibodies, memory B cells and T cells [2-14].
All studies testing memory B cells and T cells (CD4+ and CD8+) and nearly all studies testing antibodies show cross-reactivity to SARS-CoV-2 in subjects from wide geographical locations; some T cell studies showed >90% cross-reactivity. Unsurprisingly, the cross-reactivity was at a lower level to that seen in COVID-19 patients but there was clear and robust expansion of T cells in most subjects’ peripheral blood mononuclear cells on contact with SARS-CoV-2 [14].
The fact that antibodies and T cells were also cross-reactive with other human coronaviruses (the seasonal cold viruses NL63; 229E; OC43; HKU1) suggests that exposure to some of the common cold viruses can induce immunity to other coronaviruses. It is worth pointing out that >90% of the population is seropositive for at least three of these human coronaviruses [15]. Memory B and T cells were also cross-reactive with SARS-CoV-1, indicating that this type of immunity can last for at least 17 years. Importantly, T cell studies which also investigated the presence of antibodies all showed zero antibody cross-reactivity, demonstrating that the use of antibodies to indicate development of immunity is unreliable.
Patients with a previously detected human coronavirus had less severe COVID-19; despite a similar rate of infection, hospitalisation and viral burden, the milder disease seemed to be due to more subdued inflammatory responses, leading to lower ICU admission and death [16,17].
As Peter Doshi points out, the WHO and CDC acknowledged the existence of pre-existing immunity to the 2009 swine flu epidemic but then ignored the evidence 11 years later. Furthermore, cross-reactive immunity to influenza strains has been modelled to be a critical influencer of susceptibility to newly emerging, potentially pandemic, influenza strains. [1]
Epidemiologists have been calling SARS-CoV-2 a ‘novel virus’, implying no pre-existing immunity. Nevertheless, it is clear that some considerable pre-existing immunity is present but has not been incorporated into the modelling. Furthermore, government policy decisions are being made based on the number of positive PCR tests (indicating the presence of a viral RNA fragment rather than current infection) instead of investigating the proportion of the population that has developed antibody, B cell or T cell immunity.
Seroprevalence is currently the only general means of estimating the proportion of people who have developed immunity to SARS-CoV-2, yet it is clear that B and T cell immunity are not only alive and well but are more robust and longer-lasting than antibody immunity, which is known to decline with time. Since B cells are regulated by T cells, this makes it all the more important that a reliable, readily available clinical test for T cell immunity is developed. A recent Italian study showed that T cells were eight times more effective at identifying earlier SARS-CoV-2 infection and, unlike antibodies, they correlated with disease severity [18]. Moreover, memory T cell activation occurs soon after exposure, rather than having to wait before the appearance of antibodies [19].
References
[1] Doshi P, Covid-19: Do many people have pre-existing immunity? BMJ 2020;370:m3563
[2] Tso FY, Lidenge SJ, Pena PB et al. High prevalence of pre-existing serological cross-reactivity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in sub-Saharan Africa. Int J Infect Dis.102(2021)577–583
[3] Nguyen-Contant P, Embong K, Kanagaiah P et al. S Protein-Reactive IgG and Memory B Cell Production after Human SARS-CoV-2 Infection Includes Broad Reactivity to the S2 Subunit. 10.1128/mBio.01991-20. https://doi.org/10.1128/mBio.01991-20
[4] Song G, He WT, Callaghan S et al. Cross-reactive serum and memory B cell responses to spike protein in SARS-CoV-2 and endemic coronavirus infection. https://doi.org/10.1101/2020.09.22.308965
[5] Ng KW, Faulkner N, Cornish GH. Preexisting and de novo humoral immunity to SARS-CoV-2 in humans. Science. 11 Dec 2020: Vol. 370, Issue 6522, pp. 1339-1343 DOI: 10.1126/science.abe1107
[6] Braun J, Loyal L, Frentsch M et al. Presence of SARS-CoV-2-reactive T cells in COVID-19 patients and healthy donors. https://doi.org/10.1101/2020.04.17.20061440
[7] Mateus J, Grifoni A, Tarke A et al. Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans. Science. 2020; 370, 89–94
[8] Grifoni A, Weiskopf D, Ramirez SI et al. Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals. Cell. 2020; 181, 1489–1501
[9] Sekine T, Perez-Potti A, Rivera-Ballesteros O et al. Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19. Cell. 2020; 183, 158–168; https://doi.org/10.1016/j.cell.2020.08.017
[10] Nelde A, Bilich T, Walz JS et al. SARS-CoV-2-derived peptides define heterologous and COVID-19-induced T cell recognition. Nat Immunol, 2021; 22, 74–85
[11] Gallais F, Velay A, Wendling MJ et al. Intrafamilial Exposure to SARS-CoV-2 Induces Cellular Immune Response without Seroconversion. Emerging Infectious Diseases doi: 10.3201/eid2701.203611
[12] Mahajan S, Kode V, Bhojak K et al. Immunodominant T-cell epitopes from the SARS-CoV-2 spike antigen reveal robust pre-existing T-cell immunity in unexposed individuals. https://www.biorxiv.org/content/10.1101/2020.11.03.367375v1.full.pdf
[13] Weiskopf D, Schmitz KS, Raadsen MP et al. Phenotype and kinetics of SARS-CoV-2–specific T cells in COVID-19 patients with acute respiratory distress syndrome. Sci Immunol 26 Jun 2020: Vol. 5, Issue 48, eabd2071 DOI: 10.1126/sciimmunol.abd2071 http://immunology.sciencemag.org
[14] Le Bert N, Tan AT, Kunasegaran K et al. Different pattern of pre-existing SARS-COV-2 specific T cell immunity in SARS-recovered and uninfected individuals. https://doi.org/10.1101/2020.05.26.115832
[15] Gorse GJ, Patel GB, Vitale JN et al. Prevalence of antibodies to four human coronaviruses is lower in nasal secretions than in serum. Clin. Vaccine Immunol. 2010; 17, 1875–1880
[16] Sagar M, Reifler K, Rossi M et al. Recent endemic coronavirus infection is associated with less-severe COVID-19. J Clin Invest. 2021;131(1):e143380. https://doi.org/10.1172/JCI143380.
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Competing interests: No competing interests