Management of post-acute covid-19 in primary careBMJ 2020; 370 doi: https://doi.org/10.1136/bmj.m3026 (Published 11 August 2020) Cite this as: BMJ 2020;370:m3026
All rapid responses
Please note that Dysautonomia and POTS are actually a highly occurring disorders caused by covid. I would also suggest that MCAS is looked into for those having skin issues
Competing interests: No competing interests
I would like to comment on Box 2 Breathing techniques, in particular the 'breathing control' technique which is a suggested treatment programme in this Practice Pointer.
The article states that:
“The “breathing control” technique is aimed at normalising breathing patterns and increasing the efficiency of the respiratory muscles (including the diaphragm) resulting in less energy expenditure, less airway irritation, reduced fatigue, and improvement in breathlessness.”
My understanding is that one component of a normal breathing pattern is breathing both in and out through the nose, and keeping the mouth closed throughout.
However the 'breathing control' instructions in this article state:
“The patient should sit in a supported position and breathe in and out slowly, preferably in through the nose and out through the mouth, while relaxing the chest and shoulders and allowing the tummy to rise.’
According to Dr Sarah Todd’s recent paper (1), on the Brompton Breathing Pattern Assessment Tool, during normal breathing the mouth should remain closed.
The fourth component of this Breathing Pattern Assessment is “Channel of inspiration and expiration”, that is nose or mouth breathing. Each component is given a score of 0 to 2 based on features consistent with expected normal (0) versus that present in severe dysfunctional breathing (2).
For “Channel of inspiration and expiration” the expected normal is described as “Nose (with their mouth closed throughout the minute assessed).” Using this scoring system, breathing in through the nose and out through the mouth as suggested in this Practice Pointer would score (1) and be an indicator of a breathing pattern disorder - rather than a normal breathing pattern.
1. Todd S, Walsted ES, Grillo L, Livingston R, Menzies-Gow A, Hull JH.
Novel assessment tool to detect breathing pattern disorder in patients with refractory asthma. Respirology. 2018;23(3):284-290. doi:10.1111/resp.13173
Competing interests: No competing interests
The article titled "Management of post-acute covid-19 in primary care" very well represents post COVID symptoms and care for the same. The figure explains management which can be easily understood by health professionals and general population.
However, the characteristics described are the ones which can be life-threatening and require serious care. This article does not cover symptoms of less severity such as hair fall, hearing losses, irritability, reduced immunity for other infections, skin problems, impaired nutritional status, brain fog and neurological symptoms which are seen following infection in later months. We should frame guidelines for such health problems so that we can manage post-COVID symptoms in a better manner.
Competing interests: No competing interests
While I am not a learned researcher, I would like to share my experience which may be of use to your researchers.
Covid-19 can have pneumonia as part of the illness. I have not seen clarification as to whether this is viral pneumonia or bacterial pneumonia. My observations relate to having viral pneumonia and I am sharing this on the basis that persons who are suffering long covid may in some cases be suffering from the effects of the viral pneumonia or similar.
I had viral pneumonia in 1994. As a very fit young person, the side effects of this have lasted for the rest of my life. The initial tiredness and exhaustion lasted 7 months before I could return to work 3 days a week for the following 3 months. Then I returned to full time after 10 months but still I had to manage the energy levels and tiredness. My fitness has never recovered beyond 80% of what it had been and I continue to maintain the fitness. To this date, I do have periods when exercise can cause me to want to sleep and extra couple of hours per day. If the long covid is leaving residual effects on the body owing to the virus or viral pneumonia, the managing the following may be worth considering within your research:
1. Expectation that original fitness may never be achieved
2. Expectation is that breathlessness and tiredness this may continue occasionally for the rest of one's life
3. Expectation that there will be periods when greater tiredness sets in and these periods will go away again.
4. Maintenance of fitness as best one can does help to continue a life close to what was normal before.
Competing interests: No competing interests
Specialist Multidisciplinary Rehabilitation pathways needed to tackle long COVID and chronic COVID syndromes
Re: Management of post-acute covid-19 in primary care (by Greenhalgh et al)
As highlighted by Greenhalgh and colleagues in this article, long COVID and chronic COVID are multisystem syndromes and likely to affect around 10% of survivors. Two recent studies from Italy and UK have demonstrated troublesome persistent symptoms in more than half of the hospitalised patients 2 months after contracting the illness (1,2). Post-illness fatigue, weakness, breathlessness, post-traumatic stress, joint pain and cognitive problems and reduced quality of life were commonly reported by participants. We know from previous coronavirus outbreaks of SARS and MERS that these symptoms can persist for years after the illness (3).
We need a multifaceted approach to tackle the physical, psychological, social and vocational domains of this health condition. Comprehensive, brief and pragmatic screening tools such as the newly developed C19-YRS (Yorkshire Rehabilitation Screen) can be used to identify persistent symptoms and rehabilitation needs (4). An integrated COVID-19 rehabilitation pathway is needed that provides targeted intervention to survivors based on their symptoms and needs (5). Needs in isolated health domains (for example breathlessness alone) can be met by unidisciplinary services (physiotherapy) whereas complex needs in multiple domains require a multidisiplinary team that has representation from hospital specialists (respiratory medicine, cardiology) and various rehabilitation disciplines (including physiotherapy, occupational therapy, psychology and rehabilitation medicine physician). This pandemic has also introduced a new normal of tele-consults and tele-rehabilitation protocols and programmes needs to be explored in such an integrated pathway. This is also likely to make the service delivery model efficient and cost-effective.
Health services will be judged by not only how we managed to reduce mortality but also by how the massive rehabilitation challenge was met and whether all the COVID-19 survivors were able to return to their pre-illness functional level and quality of life in time.
1. Carfi A, Bernabei R, Landi F, et al. Persistent Symptoms in Patients After Acute COVID-19. JAMA 2020; e2012603
2. Halpin SJ, McIvor C, Whyatt G, et al. Post-discharge symptoms and rehabilitation needs in survivors of COVID-19 infection: a cross-sectional evaluation. J Med Virol 2020 doi: 10.1002/jmv.26368. Online ahead of print
3. Ahmed H, Patel K, Greenwood D, et al. Long-term clinical outcomes in survivors of Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome coronavirus outbreaks after hospitalisation or ICU admission: a systematic review and meta-analysis. J Rehabil Med 2020; 52
4. Sivan M, Halpin SJ, Gee J. Assessing long-term rehabilitation needs in COVID-19 survivors using a telephone screening tool (C19-YRS tool). Advances in Clinical Neurosciences and Rehabilitation 2020; 19: 14‐17.
5. Sivan M, Halpin S, Hollingworth L, Snook N, Hickman K, Clifton IJ. Development of an integrated rehabilitation pathway for individuals recovering from COVID-19 in the community. J Rehabil Med. 2020;52(8)
Competing interests: No competing interests
We write as a group of doctors affected by persisting symptoms of suspected or confirmed COVID-19. We aim to share our insights from both our personal experiences of the illness and our perspective as physicians.
Tackling this issue will involve collaboration between politicians, healthcare services, public health professionals, scientists and society as a whole. We call for the following principles to be used so that the best possible outcomes can be achieved for all people affected by persisting symptoms of COVID-19:
1) Research and surveillance: Persisting symptoms of COVID-19 should be dealt with using a scientific methodology and without bias. People experiencing them should be counted.
The effects of the virus should be studied in the way that any other disease would be, with thorough attention paid to epidemiology, pathophysiology and management. “We still know very little about COVID-19, but we do know that we cannot fight what we do not measure.” Research and surveillance needs to capture the full spectrum of disease, including in those not hospitalised and not tested, in order to build an accurate picture of COVID-19 phenotypes. A clear definition for recovery from COVID-19 is required. Whilst further evidence is awaited clinicians should “be open about uncertainty, and transparent in the ways in which we acknowledge the limitations of the imperfect data we have no choice but to use”. We argue this means accepting an emerging picture that prolonged symptoms are having a substantial impact on a significant minority of people and acknowledging that death is not the only outcome to measure. We argue that further research into chronic COVID-19 symptoms is essential. Failure to understand the underlying biological mechanisms causing these persisting symptoms risks missing opportunities to identify risk factors for developing them, prevent chronicity and find treatment approaches both for people suffering now as well as any future patients.
2) Clinical Services: Services need to be timely, tailored to individuals’ presentations, and involve investigating and treating pathology, as well as the functional recovery of individuals.
Many patients who may, under normal circumstances, have been admitted to hospital instead managed their extremely difficult symptoms at home during this crisis. We should not assume that pathology is different between hospitalised and non-hospitalised patients. Before any active rehabilitation can start organic pathology needs to be detected and managed with appropriate investigations. A rehabilitation prescription can then be made for the individual. As Prof. Turner-Stokes (Consultant in Rehabilitation Medicine) warned in a recent RSM Webinar, “… before we get people exercising, it’s important to be sure that it’s going to be safe. We need proper evaluation of cardiac and respiratory function, and we need to take things slowly and in a paced measure.” A recent study in JAMA  of 100 patients (67 of whom had not been admitted to hospital) undergoing cardiac MRI after COVID-19 demonstrated “cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%)”. The authors discuss that “…participants… with mostly home-based recovery had frequent cardiac inflammatory involvement, which was similar to the hospitalized subgroup with regards to severity and extent.”
The establishment of one-stop clinics will allow pattern recognition and expertise to develop amongst clinicians identifying and managing sequelae of COVID-19. These clinics should reflect the multi-system nature of COVID-19 and involve multidisciplinary teams with access to relevant investigations to detect known complications of COVID-19 as indicated after clinical review. A reliance on “one-size fits all” online rehabilitation services risks serious harm to patients if pathology goes undetected, and is a missed opportunity for clinicians to develop their experience with the sequelae of this virus that is set to be an ongoing presence in our clinical practice. Where current guidance has been issued, such as the statement from NICE  cautioning against Graded Exercise Therapy in the context of COVID-19, it should be communicated quickly to clinicians on the frontline.
3) Patient involvement: Patients must be involved in the commissioning of clinical services and the design of research studies.
‘No decision without me’- Lessons learnt from other illnesses have demonstrated the importance of involving those most affected. Patients experiencing persisting symptoms of COVID-19  have a great deal to contribute to the search for solutions. Involving patients in research design  and the commissioning of clinical services will ensure that the patient perspective is listened to and will optimise the development of such studies and clinical services. This may take the form of representatives from patient-formed groups, which may include signatories of this letter, liaising with policy makers, researchers and healthcare leaders.
4) Clinical services commissioned should not unfairly discriminate against those with negative tests and a clinical diagnosis should be adequate for accessing any appropriate services.
Widespread testing was not available during the early days of the pandemic. The timing of tests for active COVID-19 infection (such as RT-PCR tests) affects test performance and even if performed at an optimal time, the test is associated with a considerable risk of false negatives. We know antibody tests have mainly been validated on hospitalised patients and are poorly sensitive early in the illness. There is little data regarding testing later in the disease course, and false negatives appear common. Some individuals do not seroconvert  despite having previously tested positive. Thus, adherence to positive test results as a criterion for access to medical services or specific COVID-19 sick pay arrangements with employers is unacceptable in the context of a clinical diagnosis of COVID-19.
We welcome increasing awareness of the problem of persisting symptoms of COVID-19. As politicians, scientists and doctors attempt to tackle this issue, these principles can act as a guide enabling the experiences of those living with the condition to inform the efforts of experts and lead to improved research and clinical care, benefiting those affected and society as a whole.
1) Alwan N. What exactly is mild covid-19? https://blogs.bmj.com/bmj/2020/07/28/nisreen-a-alwan-what-exactly-is-mil...
Date last updated: July 28 2020. Date last accessed: August 21 2020.
2) Rutter H, Wolpert M, Greenhalgh T. Managing uncertainty in the covid-19 era. https://blogs.bmj.com/bmj/2020/07/22/managing-uncertainty-in-the-covid-1...
Date last updated: July 22 2020. Date last accessed: August 21 2020.
3) RSM COVID-19 Series | Episode 32: Rehabilitation after the viral infection. https://www.youtube.com/watch?v=KW1Gdw9D_Pk
Date last updated: July 21 2020. Date last accessed: August 21 2020.
4) Puntmann VO, Carerj ML, Wieters I, et al. Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. Published online July 27, 2020. doi:10.1001/jamacardio.2020.3557.
5) Torjesen I. NICE cautions against using graded exercise therapy for patients recovering from covid-19. BMJ 2020;370:m2912.
6) Department of Health. Liberating the NHS: No decision about me, without me – Government response to the consultation. https://assets.publishing.service.gov.uk/government/uploads/system/uploa...
Date published: December 13 2012. Date last accessed: August 21 2020.
7) Lokugamage A, Taylor S, Rayner C. Patients’ experiences of “longcovid” are missing from the NHS narrative. https://blogs.bmj.com/bmj/2020/07/10/patients-experiences-of-longcovid-a...
Date published: July 10 2020. Date last accessed: August 21 2020.
8) NIHR. PPI (Patient and Public Involvement) resources for applicants to NIHR research programmes. https://www.nihr.ac.uk/documents/ppi-patient-and-public-involvement-reso...
Date last updated: December 18 2019. Date last accessed: August 21 2020.
9) Watson J, Whiting PF, Brush JE. Interpreting a covid-19 test result. BMJ 2020; 369 :m1808.
10) Deeks JJ, Dinnes J, Takwoingi Y, Davenport C, Spijker R, Taylor-Phillips S, Adriano A, Beese S, Dretzke J, Ferrante di Ruffano L, Harris IM, Price MJ, Dittrich S, Emperador D, Hooft L, Leeflang MMG, Van den Bruel A. Antibody tests for identification of current and past infection with SARS‐CoV‐2. Cochrane Database of Systematic Reviews 2020, Issue 6. Art. No.: CD013652. DOI: 10.1002/14651858.CD013652.
11) Staines HM, Kirwan DE, Clark DJ, Adams ER, Augustin Y, Byrne RL, Cocozza M, Cubas-Atienza AI, Cuevas LE, Cusinato M, Davies BMO, Davis M, Davis P, Duvoix A, Eckersley NM, Forton D, Fraser A, Garrod G, Hadcocks L, Hu Q, Johnson M, Kay GA, Klekotko K, Lewis Z, Mensah-Kane J, Menzies S, Monahan I, Moore C, Nebe-von-Caron G, Owen SI, Sainter C, Sall AA, Schouten J, Williams C, Wilkins J, Woolston K, Fitchett JRA, Krishna S, Planche T. Dynamics of IgG seroconversion and pathophysiology of COVID-19 infections. (Preprint)
medRxiv 2020.06.07.20124636; doi: https://doi.org/10.1101/2020.06.07.20124636.
12) Greenhalgh T, Knight M, A’Court C, Buxton M, Husain L. Management of post-acute covid-19 in primary care. BMJ 2020; 370 :m3026.
Competing interests: Dr Daniel Campion reports personal fees from Emergent BioSolutions, outside the submitted work; Dr Nathalie MacDermott reports grants from National Institute for Health Research (NIHR) UK , grants from Wellcome Trust, outside the submitted work; Dr Margarita Thomson is Cancer Clinical lead South West London CCG (Merton).
Re: Management of post-acute covid-19 in primary care: helping employees with covid-19 return to work
I welcome the authoritative review of post-covid-19 problems by Greenhalgh et al and in particular that those in employment may need help in returning to work (RTW).  Strangely the assistance offered by Acas  to which Greenhalgh referred makes little reference to this issue, but it is more complex than negotiating a phased RTW, helpful though that facility is. As work is known to be of great importance to individuals, their families, employers and society at large,  RTW is now seen to be an important outcome of health interventions. 
In order to minimise worry about possible job difficulties or loss, patients need to be informed early in the course of the disease that there are many ways of helping them to RTW and that it is most important that they remain in contact with their employer, [5-6] as not all employers have, or practice, good absence management. It is also helpful at an early stage to comment on the fact that RTW usually precedes full recovery by utilising such techniques as:-
• working from home
• part-time working
• adjusting working tasks and responsibilities
• allowing time off work for health-related activities e.g. appointments, physiotherapy or mental health support
• access to a quiet room for those with fatigue
• utilising the Access to Work Scheme or other advice from the Department for Work and Pensions (https://www.gov.uk/access-to-work).
Primary care teams can be very helpful when completing a fit note  which assists employers in understanding their employees' potential needs when they RTW. For those with difficulties in talking about work to their patients, advice is now available.  Early involvement of occupational health departments can also greatly facilitate a successful RTW when available.
When the clinical condition has improved sufficiently to consider when and how to effect a RTW, these issues can be reviewed and often a meeting between the employer and employee can construct a RTW plan. When conditions are complicated, a vocational rehabilitation professional should be consulted when one is not available as part of the rehabilitation available. 
The views expressed are those of the author and not necessarily those of the Vocational Rehabilitation Association.
1. Greenhalgh, T., et al., Management of post-acute covid-19 in primary care. BMJ (Clinical research ed.), 2020. 370: p. m3026.
2. Acas, Coronavirus (COVID-19): advice for employers and employees. Acas: London, 2020,
3. Black, Dame Carol. Working for a healthier tomorrow. London: TSO, 2008,
4. Academy of Medical Royal Colleges, Royal College of Nursing, Allied Health Professions Federation. Healthcare Professionals' Consensus Statement for Action, London: 2019 - https://www.aomrc.org.uk/news-and-views/healthcare-professionals-consens...
5. NICE. Managing long-term sickness absence and capability to work overview. 2019 [cited 2020 18/06/20]; Available from: https://pathways.nice.org.uk/pathways/managing-long-term-sickness-absenc...
6. Mikkelsen, M and Rosholm, M. Systematic review and meta-analysis of interventions aimed at enhancing return to work for sick-listed workers with common mental disorders, stress-related disorders, somatoform disorders and personality disorders. Occupational and Environmental Medicine, 2018. 75(9): p. 675-686.
7. Hampton, J. How to support patients in getting back to work. Pulse; , 2020(January):41-42
8. Council for Work and Health. Talking Work: A guide for Doctors discussing work and work modifications with patients. London: Council for Work and Health, 2019:
9. Frank, A. Vocational rehabilitation: supporting ill or disabled individuals in(to) work: a UK perspective. Healthcare, 2016. 4(46). doi:10.3390/healthcare4030046
Competing interests: No competing interests
I'd like to point out several dangerous factual errors that Dr. O'Leary has made in her recent letters.
In her letter on August 21, 2020 she stated, "The term “chronic fatigue syndrome” names a psychiatric condition that sometimes develops in reaction to acute viral infection. It is essentially deconditioning that arises from inactivity when patients embrace faulty illness beliefs."
After it was pointed out that Chronic Fatigue Syndrome was designated a neurological disease at G93.3 by the World Health Organization in 1992, which is the same coding for Myalgic Encephalomyelitis and that it will be categorized together with Myalgic Encephalomyelitis at 8E49 in ICD11. (1) (2) (3) Chronic Fatigue Syndrome also has no entry in the DSM. (4) Dr. O'Leary then stated on August 31, 2020, "Ms. Martell is objecting to the suggestion that patients diagnosed with CFS are suffering from a psychiatric condition rather than a biomedical disease. That is not a claim I have made or implied or in any way supported in my letter."
The idea that ME/CFS Myalgic Encephalomyelitis/Chronic Fatigue Syndrome is based on deconditioning and false illness beliefs has no basis in fact, (5) (6) and is dangerous to ME/CFS patients because the cardinal feature of ME/CFS is Post Exertional Malaise- a worsening of symptoms with exercise and exertion including emotional, and cognitive exertion. (7)
Putting forth this view to clinician's endangers ME/CFS patients because GP's may think this is purview of psychiatrists - which it is not. Clinicians may also minimize ME/CFS patients and believe it can be fixed by exercising - even though evidence shows exercise makes ME/CFS patients sicker. (8)
Dr. O'Leary then stated in error that the CDC retired the name CFS. On February 25, 2019, Dr. Elizabeth Unger of the CDC partnered with Medscape to tell the world that ME/CFS is real, it did so under the headline, "Chronic Fatigue Syndrome: It's Real, and We Can Do Better.". (9)
Dr. Ron W Davis, Science Director of Open Medicine Foundation, uses the term CFS in his slides- if you watch his presentations. For the study on Severe Patients (SIPS) and for the potential diagnostic test, the Nanoneedle, he uses CFS vs Healthy Controls rather than ME/CFS. (10)
Dr. O'Leary espouses an unscientific view when she writes, "While CFS is a condition we can hope to resolve with holistic virus recovery strategies" These "holistic virus recovery strategies" are of course not validated and replicated using phase III double blinded clinical trials with numerous physiological measures of illness and recovery in order to control for bias. (11)
As an ME/CFS patient I welcome new developments in the biomedical science of ME/CFS which is why I object to non-evidence based pseudoscientific views masquerading as Science.
(1) Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome; Board on the Health of Select Populations; Institute of Medicine. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. Washington (DC): National Academies Press (US); 2015 Feb 10. 2, Background. Available from: https://www.ncbi.nlm.nih.gov/books/NBK284897/
(5) van Campen CMC, Visser FC (2018) The Abnormal Cardiac Index and Stroke Volume Index Changes During a Normal Tilt Table Test in ME/CFS Patients Compared to Healthy Volunteers, are Not Related to Deconditioning. J Thrombo Cir: JTC -107. DOI: 10.29011/ JTC -107. 000007
(7) Ghali, A., Lacout, C., Ghali, M. et al. Elevated blood lactate in resting conditions correlate with post-exertional malaise severity in patients with Myalgic encephalomyelitis/Chronic fatigue syndrome. Sci Rep 9, 18817 (2019). https://doi.org/10.1038/s41598-019-55473-4
(11) Wilshire, C.E., Kindlon, T., Courtney, R. et al. Rethinking the treatment of chronic fatigue syndrome—a reanalysis and evaluation of findings from a recent major trial of graded exercise and CBT. BMC Psychol 6, 6 (2018). https://doi.org/10.1186/s40359-018-0218-3
Competing interests: No competing interests
“One of the most distressing aspects of living with long covid is the dismissive attitude of some doctors”, a quote used in the editorial of the BMJ1, resonates closely with views expressed by patients coming to terms with persistent olfactory dysfunction as a consequence of COVID infection. Loss of smell and taste is one of the most prevalent symptoms of COVID-19 infection2, and the best predictor of COVID status2,3. While a significant proportion of patients demonstrate at least partial recovery of their loss of smell, 10% have persistent loss of smell when reviewed 8 weeks after onset4. Moreover, parosmia, distortion of the sense of smell that can severely impair appetite due to familiar foods triggering a foul smell appears to be prevalent with COVID-19. It had already been reported by more than 50% of patients with post-viral olfactory loss prior to the COVID-19 pandemic5. A similar disruption to normal life is likely to be found among COVID-19 patients.
Greenhalgh’s otherwise excellent article on the management of post-acute COVID-19 highlights the broad range of symptoms experienced by patients with what has been termed long COVID6. We were surprised to find that there was no mention of smell or taste disturbance. A patient-led project evaluating COVID-19 recovery with a survey found that loss of smell and taste was reported by more than 50% of patients surveyed7; loss of appetite and nausea even more frequently. The terminology used in such surveys, “ loss of smell or taste’, very likely underestimates the extent and health consequences of parosmia and care is needed to rephrase the questions we put to patients as ‘alterations in smell and taste’ to better capture the impact of COVID-19 on olfactory and gustatory function if we are to provide appropriate support and advice. We are currently working with a large group of patients who are struggling to manage their persistent olfactory symptoms and feel they are being overlooked by the healthcare system. The article published this week suggests that they may be right.
1 Godlee Fiona. Living with covid-19 BMJ 2020; 370 :m3392
2 Menni C, Valdes AM, Freidin MB, et al. Real-time tracking of self-reported symptoms to predict potential COVID-19. Nat Med. 2020;26(7):1037-1040. doi:10.1038/s41591-020-0916-2
3 Gerkin RC, Ohla K, Veldhuizen MG, et al. Recent smell loss is the best predictor of COVID-19: a preregistered, cross-sectional study. Preprint. medRxiv. 2020;2020.07.22.20157263. Published 2020 Jul 26. doi:10.1101/2020.07.22.20157263
4 Boscolo-Rizzo P, Borsetto D, Fabbris C, et al. Evolution of Altered Sense of Smell or Taste in Patients With Mildly Symptomatic COVID-19 [published online ahead of print, 2020 Jul 2]. JAMA Otolaryngol Head Neck Surg. 2020;146(8):729-732. doi:10.1001/jamaoto.2020.1379
5 Reden J, Maroldt H, Fritz A, Zahnert T, Hummel T. A study on the prognostic significance of qualitative olfactory dysfunction. Eur Arch Otorhinolaryngol. 2007;264(2):139-144. doi:10.1007/s00405-006-0157-0
6 Greenhalgh Trisha, Knight Matthew, A’CourtChristine, Buxton Maria, Husain Laiba. Management of post-acute covid-19 in primary care BMJ 2020; 370 :m3026
7 Assaf G, Davis H, McCorkell A, Wei H, O’Neil B, Akrami A, Low R, Mercier J, Adetutu A, Tina L, Annie C, Monica S., Lauren N., Noel H., Davids JD et al, What Does Covid-19 Recovery Actually Look Like, May 11, 2020, Available at https://patientresearchcovid19.com/research/report-1/
Competing interests: No competing interests
Who would have imagined, just a few months ago, that we would be brought to our knees by a pandemic of the common cold; albeit a common cold which can cause severe systemic disease in a minority of those infected. SARS-Cov-2 causes a mild upper respiratory tract infection (URTI) in most young healthy people. The virus replicates in mucosal epithelial cells and induces a T cell immune response which leads to viral elimination. Mucosal secretory IgA is produced which is expected to prevent re-infection (10). This is typical of the common cold.
Severe covid-19, however, is a different disease. The risk of severe inflammation rises as a power function of age, with an exponent which is similar to that of ageing in general. The risk is also increased in a number of pre-existing conditions: ischaemic heart disease, hypertension, type 2 diabetes mellitus, and obesity. These conditions are associated with low grade chronic inflammation, and evidence in recent years indicates that pathogenic bacteria growing within our tissues contribute to the inflammation (2, 3).
In the 1980s there were approximately 1500 deaths per annum, in England and Wales, from sudden infant death syndrome (SIDS). There was a clear seasonal pattern and death was clearly related to the prevalence of URTI in the community. The link between SIDS and the common cold was complex. Prone sleeping and URTI led to increased pooling of nasopharyngeal secretions, increased growth of nasopharyngeal bacteria, toxin production and toxin induced sudden death in infants who at 2 to 3 months of age had low levels of protective anti-toxin IgG antibodies in their blood stream. The prime suspect was alpha-haemolysin produced by Staphylococcus aureus (4 -6).
We can make sense of covid-19 if we think about it in the same way. The coronavirus triggers a cytokine cascade in a minority of those exposed; it does not mean that the virus is the direct cause. SARS-CoV-2 amplifies the low-grade chronic inflammation which is associated with the above pre-existing conditions. In certain patients this can cause a cytokine cascade with the clinical features of sepsis.
Sepsis, with negative blood cultures, unresponsive to antibiotics, but mitigated by steroids is strongly indicative of toxic shock syndrome (7). The commonest cause is S. aureus. This is also the commonest cause of a cytokine cascade. Pathogenic bacteria, which grow within our tissues, need genetic mechanisms to prevent immune rejection and to protect their niche. Certain strains of S. aureus produce pyrogenic toxins, which are superantigens. They cause non-specific T cell proliferation with cytokine secretion and induce severe inflammation (2). An uneasy truce follows and the immune system leaves the organisms alone. But when the cytotoxic T cells come to eliminate the infected epithelial cells, S. aureus will defend its niche and severe inflammation will follow.
This concept fits with the observation that severe symptoms develop as the virus is eliminated. The idea also fits with the observation that symptoms of inflammation can persist for weeks or months after the virus is totally cleared from the system. There is experimental evidence that the common cold in infancy leads to increased S. aureus carriage and increased pyrogenic toxin production (8). There is no reason to believe that it is different in adults. Post-acute covid-19 could therefore leave the patient with increased carriage of S. aureus, and with intermittent release of pyrogenic toxins leading to prolonged fatigue.
I am sure I will be accused of speculation. But as a retired pathologist I am not in a position to organise the relatively simple tests which could be used to prove or disprove this hypothesis. If one of my relatives had post-acute covid-19 I would want the primary care physician to submit a specimen of faeces to the laboratory and ask for selective culture for S. aureus. Any isolates should then be submitted for genotyping to see if the strain is potentially pyrogenic (8). I would then suggest consumption of natural yoghurt daily to bring the microbial flora back to an optimal condition (9). I acknowledge that these unproven assumptions should be subject to rigorous test. But there is no excuse for the medical profession to continue to ignore the possible role of pyrogenic staphylococcal toxaemia in this pandemic.
1. Burgess S, Ponsford MJ, Dipender G. Are we underestimating seroprevalence of SARS-CoV-2? BMJ 2020;370:m3364.
2. Morris JA. Staphylococcus aureus bacteraemia: a hidden factor in the pathogenesis of human disease. JSM Microbiology, 2017; 5: 1037.
3. Morris JA. A cacophony of cytokines explains the biopsychosocial interaction model of mental and physical disease. Archives of Depression and Anxiety 2018; 4: 56 – 64.
4. Morris JA, Haran D, Smith A. Hypothesis: common bacterial toxins are a possible cause of the sudden infant death syndrome. Medical Hypotheses 1987; 22: 211 – 222.
5. Harrison LM, Morris JA, Telford DR, Brown SM, Jones K. The nasopharyngeal bacterial flora in infancy, effects of age, gender, season, viral upper respiratory infection and sleeping position. FEMS Immunology and Medical Microbiology 1999; 25: 19 – 28.
6. Morris JA, Harrison LM. Sudden unexpected death in infancy: evidence of infection. Lancet 2008; 371: 1815 – 1816.
7. Todd J, Fishault M, Kapral F, Welch T. Toxic shock syndrome associated with phage group 1 staphylococci. Lancet 1978; ii: 1116 – 1118.
8. Harrison LM, Morris JA, Lauder RM, Telford DR. Staphylococcal pyrogenic toxins in infant urine samples: a possible marker of transient bacteraemia. J Clin Pathol 2009; 62: 735 – 738.
9. Morris JA. Optimise the microbial flora with milk and yoghurt to prevent disease. Medical Hypotheses 2018; 114: 13 – 17.
Competing interests: No competing interests